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Zheng B, Chen Z, Sun L, Quan J, Wei J, Huang B, Zhang D, Zhang P, Zhuo Y. Intravesical Tumor-Selective Mucoadhesive Hydrogel for Effective Chemotherapy In Murine Model. Int J Nanomedicine 2025; 20:7169-7183. [PMID: 40491849 PMCID: PMC12146100 DOI: 10.2147/ijn.s522421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2025] [Accepted: 05/19/2025] [Indexed: 06/11/2025] Open
Abstract
Introduction The therapeutic efficacy of intravesical agents for bladder cancer (BCa) is frequently constrained by their clearance via urine flushing and periodic bladder emptying, as well as the absence of tumor-targeting capabilities. Consequently, an effective drug delivery system must possess both tumor-targeting and adhesion properties to overcome these limitations. Methods In this study, we investigated a tumor-selective hydrogel as a potential vehicle for BCa treatment. For the first time in the field of intravesical therapy, we introduced the concept of pre-targeting, sequentially instilling modified polyarginine and membrane nanoparticles into the bladder to achieve selective gelation on the tumor surface. We comprehensively evaluated tumor selectivity, endocytosis pathways, organelle localization, and osmotic capacity, and demonstrated in vivo and in vitro degradation following drug delivery. Results The pre-targeted hydrogel exhibited superior tumor selectivity. The drug-loaded membrane nanoparticles released during hydrogel degradation were internalized by tumor cells at levels exceeding those in normal cells by more than eightfold. Our findings indicated that this internalization process was energy-dependent and mediated by caveolin. Post-internalization, the drug-loaded membrane nanoparticles localized to the endoplasmic reticulum and Golgi apparatus, with minimal colocalization with lysosomes. Moreover, the hydrogel demonstrated profound penetration into tumor tissue. In terms of antitumor efficacy, the hydrogel loaded with gemcitabine exhibited significantly enhanced therapeutic effects compared to free gemcitabine. Conclusion Our dual-functional hydrogel system exhibits robust anti-tumor activity against BCa, presenting a promising alternative for intravesical therapy. This innovative approach addresses key limitations of current treatments by combining tumor targeting with sustained drug adhesion, offering a novel strategy for the management of BCa.
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Affiliation(s)
- Bin Zheng
- Department of Urology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, People’s Republic of China
- Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China
| | - Zheng Chen
- Department of Urology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, People’s Republic of China
| | - Luping Sun
- Department of Urology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, People’s Republic of China
| | - Jing Quan
- Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China
| | - Jianwen Wei
- Department of Urology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, People’s Republic of China
| | - Baoyuan Huang
- Department of Urology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, People’s Republic of China
| | - Dahong Zhang
- Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China
| | - Pu Zhang
- Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China
| | - Yumin Zhuo
- Department of Urology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, People’s Republic of China
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Wang C, Guo K, Dalbeth N, Sun M, Lu J, Chen Y, Zhang H, Wang X, Ji X, Li X, Sun W, Han L, Cui L, Liu Z, Ji A, He Y, Terkeltaub R, Li C. Impact of adding urine alkalization therapy to xanthine oxidase inhibitor in gout management: a prospective cohort study. Rheumatology (Oxford) 2025; 64:3509-3517. [PMID: 39932882 DOI: 10.1093/rheumatology/keaf091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 01/07/2025] [Accepted: 01/30/2025] [Indexed: 02/13/2025] Open
Abstract
OBJECTIVES Gout patients frequently have decreased urine pH, related to metabolic syndrome (MetS) and chronic kidney disease. Here, we aimed to investigate whether the addition of urine alkalization to urate-lowering therapy (ULT) is associated with improvements in albuminuria, gout flares or MetS outcomes in men with gout and low urinary pH (pH < 6.2). METHODS A prospective cohort study enrolled 385 participants starting ULT with febuxostat (initially 20 mg daily, escalated to 40 mg daily if serum urate ≥360 µmol/l), with or without alkalization based on patient preference using a 3.5 g bid citrate mixture. Participants were followed every 4 weeks to week 12. The primary outcome was urine albumin-to-creatinine ratio (UACR) at week 12. RESULTS In total, 343 participants completed the week 12 visit (137 alkalization, 206 controls). At week 12, compared with controls, participants receiving alkalization required a significantly lower febuxostat dose (by ∼20%) but had no significant difference in serum urate at target <360 µmol/l. Urine pH increased significantly in the alkalization group from week 4 (P < 0.001). At week 12, the alkalization group had a significantly lower UACR compared with control (P < 0.001), without significantly different eGFR. Participants in the alkalization group experienced fewer gout flares and had lower pain visual analogue scale scores (P < 0.001). There were lower serum triglyceride levels (P < 0.01) and higher HDL-C levels (P < 0.001) in the alkalization group. No other differences in metabolic outcomes were observed. CONCLUSION Urine alkalization was associated with lower UACR, fewer gout flares, and improved serum lipid profile in febuxostat-treated men with gout and low urine pH. TRIAL REGISTRATION ChiCTR, http://www.chictr.org.cn, ChiCTR2100043573.
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Affiliation(s)
- Can Wang
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Kai Guo
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Nicola Dalbeth
- Department of Medicine, University of Auckland, Auckland, New Zealand
| | - Mingshu Sun
- Department of Rheumatology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Jie Lu
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Ying Chen
- Department of Endocrinology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Hui Zhang
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
| | - Xuefeng Wang
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiaopeng Ji
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xinde Li
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Wenyan Sun
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Lin Han
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Lingling Cui
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Zhen Liu
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Aichang Ji
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yuwei He
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Robert Terkeltaub
- Division of Rheumatology, Autoimmunity and Inflammation, Department of Medicine, University of California San Diego, La Jolla, CA, USA
| | - Changgui Li
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, The Affiliated Hospital of Qingdao University, Qingdao, China
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Ryu H, Lee S, Song SH, Lee H, Oh JJ, Hong SK, Byun SS, Song B. Acidic urine as a prognostic factor after intravesical Bacillus Calmette-Guérin induction therapy for nonmuscle-invasive bladder cancer. World J Urol 2025; 43:247. [PMID: 40278931 DOI: 10.1007/s00345-025-05648-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2025] [Accepted: 04/19/2025] [Indexed: 04/26/2025] Open
Abstract
PURPOSE To investigate the effect of acidic urine (pH ≤ 5.5) on disease recurrence or progression in patients with nonmuscle-invasive bladder cancer (NMIBC) undergoing transurethral resection of bladder tumor (TURBT) followed by intravesical Bacillus Calmette-Guérin (BCG) induction therapy. METHODS A total of 578 patients with intermediate- and high-risk NMIBC who underwent intravesical BCG induction after initial TURBT between May 2003 and April 2021 were included. Patients were subdivided into low (pH ≤ 5.5) and high (pH > 5.5) urine pH groups. RESULTS Patients with acidic urine showed higher fasting plasma glucose levels (p = 0.017), higher serum uric acid level (p = 0.011), lower estimated glomerular filtration rates (p = 0.022), and higher rates of abnormal urinary cytology (p = 0.021), but no significant differences were observed in context of adverse clinicopathological features. During a median follow-up period of 56 months, the acidic urine group had a lower recurrence-free survival rate than the high urine pH group (p = 0.009). In terms of disease progression, there was no difference according to urine pH status. CONCLUSION Acidic urine was associated with disease recurrence after intravesical BCG induction for NMIBC, despite no differences in adverse clinicopathological features according to urine acidity.
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Affiliation(s)
- Hoyoung Ryu
- Department of Urology, Ewha Womans University Mokdong Hospital, Seoul, Korea
| | - Sangchul Lee
- Department of Urology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Urology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sang Hun Song
- Department of Urology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Urology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hakmin Lee
- Department of Urology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Urology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jong Jin Oh
- Department of Urology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Urology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sung Kyu Hong
- Department of Urology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Urology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Seok-Soo Byun
- Department of Urology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Urology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Byeongdo Song
- Department of Urology, Hanyang University College of Medicine, Seoul, Korea.
- Department of Urology, Hanyang University Guri Hospital, 153, Gyeongchun-ro, Guri-si, Gyeonggi-do, 11923, Republic of Korea.
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Wu DN, Fajiculay E, Hsu CP, Hu CM, Lee LW, Tzou DLM. Investigation of pH-dependent 1H NMR urine metabolite profiles for diagnosis of obesity-related disordering. Int J Obes (Lond) 2025; 49:688-697. [PMID: 39658677 DOI: 10.1038/s41366-024-01695-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 11/14/2024] [Accepted: 11/26/2024] [Indexed: 12/12/2024]
Abstract
BACKGROUND Human urine is highly favorable for 1H NMR metabolomics analyses of obesity-related diseases, such as non-alcoholic fatty liver, type 2 diabetes, and hyperlipidemia (HL), due to its non-invasiveness and ease of large-scale collection. However, the wide range of intrinsic urine pH (5.5-8.5) results in inevitably chemical shift and signal intensity modulations in the 1H NMR spectra. For patients where acidic urine pH is closely linked to obesity-related disease phenotypes, the pH-dependent modulations complicate the spectral analysis and deteriorate quantifications of urine metabolites. METHODS We characterized human urine metabolites by NMR at intrinsic urine pH, across urine pH 4.5 to 9.5, to account for pH-dependent modulations. A pH-dependent chemical shift database for quantifiable urine metabolites was generated and integrated into a "pH intelligence" program developed for quantifications of pH-dependent modulations at various pH. The 1H NMR spectra of urines collected from patients with Ob-HL and healthy controls were compared to uncover potential metabolic biomarkers of Ob-HL disease. RESULTS Three urine metabolites were unveiled by pH-dependent NMR approach, i.e., TMAO, glycine, and pyruvic acid, with VIP score >1.0 and significant q-value < 0.05, that represent as potential biomarkers for discriminating Ob-HL from healthy controls. Further ROC-AUC analyses revealed that TMAO alone achieved the highest diagnostic accuracy (AUC 0.902), surpassed to that obtained by neutralizing pH approach (AUC 0.549) and enabled better recovering potential urine metabolites from the Ob-HL disease phenotypes. CONCLUSIONS We concluded that 1H NMR-derived urine metabolite profile represents a snapshot that can reveal the physiological condition of humans in either a healthy or diseased state under intrinsic urine pH. We demonstrated a systematic analysis of pH-dependent modulations on the human urine metabolite signals and further developed software for quantification of urine metabolite profiles with high accuracy, enabling the uncovering of potential metabolite biomarkers in clinical diagnosis applications.
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Affiliation(s)
- Dan-Ni Wu
- Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan
- TIGP, Chemical Biology and Molecular Biophysics Program, Academia Sinica, Taipei, Taiwan
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | | | - Chao-Ping Hsu
- Institute of Chemistry, Academia Sinica, Taipei, Taiwan
- Physics Division, National Center for Theoretical Sciences, Taipei, Taiwan
- Genome and Systems Biology Degree Program, National Taiwan University, Taipei, Taiwan
| | - Chun-Mei Hu
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Li-Wen Lee
- Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
| | - Der-Lii M Tzou
- TIGP, Chemical Biology and Molecular Biophysics Program, Academia Sinica, Taipei, Taiwan.
- Institute of Chemistry, Academia Sinica, Taipei, Taiwan.
- Biomedical Translational Research Center, Academia Sinica, Taipei, Taiwan.
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Ben Othman R, Bouzid K, Ben Sassi A, Naija O, Ferjani W, Mizouri R, Bartkiz A, Ammari K, Gamoudi A, Berriche O, Jamoussi H. Prospective study investigating the influence of nutritional intervention on biochemical profiles in patients with recurrent urolithiasis. Urologia 2025; 92:96-103. [PMID: 39344467 DOI: 10.1177/03915603241283874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/01/2024]
Abstract
BACKGROUND AND OBJECTIVES Urolithiasis, commonly known as kidney stones, is a condition significantly impacted by dietary habits. The objective of this study is to evaluate the impact of a tailored dietary plan on the crystalluria and biological parameters of patients with different types of kidney stones over a 3-month period. METHODS AND STUDY DESIGN We conducted a prospective study of 3 months. The study involved patients with recurrent nephrolithiasis. Alongside the medical consultation, a comprehensive dietary survey was performed to assess the patients' nutritional habits. Urinary parameters, including volume, calcium, oxalate, uric acid, and power of hydrogen (pH), were evaluated both before and after the dietary intervention. RESULTS 69 patients were involved. There were 17 patients diagnosed with cystine lithiasis, 33 with oxalocalcic lithiasis and 19 with uric lithiasis. After 3 months, only 32 patients revisited for follow-up. There were significant changes (p = 0.002 and 0.04) in urine crystalluria for cystinic and uric lithiasis. For the urinary oxalate variation, there was a significant decrease from T1 (before dietary intervention) to T2 (after dietary intervention), with levels dropping from 0.289 ± 0.10 umol/l to 0.215 ± 0.079 umol/l (p = 0.02).Regarding urinary calcium (calciuria), there was a trend toward a decrease from T1 to T2, although the change was not statistically significant, with levels decreasing from 2.42 ± 1.68 umol/l to 2.14 ± 1.62 umol/l (p = 0.1). CONCLUSIONS Our research underscores the favorable effects of a tailored and well-balanced diet on both the crystalluria and biological parameters of individuals with recurrent lithiasis.
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Affiliation(s)
- Rym Ben Othman
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
- Institut national de nutrition et de technologie alimentaire de Tunis, service A, Tunis, Tunisia
| | - Kahena Bouzid
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
- Laboratory of Clinical Biochemistry, Charles Nicolle Hospital, Tunis, Tunisia
- LR18ES03. Laboratory of Neurophysioloy Cellular Physiopathology and Biomolecules Valorisation; University of Tunis El Manar, Tunis, Tunisia
| | - Amira Ben Sassi
- Laboratory of Clinical Biochemistry, Charles Nicolle Hospital, Tunis, Tunisia
- LR00SP01. Research Laboratory of renal Pathologies; University of Tunis El Manar, Tunis, Tunisia
| | - Ouns Naija
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
- Pediatric Department, Charles Nicolle Hospital, Tunis, Tunisia
| | - Wafa Ferjani
- Laboratory of Clinical Biochemistry, Charles Nicolle Hospital, Tunis, Tunisia
| | - Ramla Mizouri
- Institut national de nutrition et de technologie alimentaire de Tunis, service A, Tunis, Tunisia
| | - Ahlem Bartkiz
- Laboratory of Clinical Biochemistry, Charles Nicolle Hospital, Tunis, Tunisia
| | - Khouloud Ammari
- Laboratory of Clinical Biochemistry, Charles Nicolle Hospital, Tunis, Tunisia
| | - Amel Gamoudi
- Institut national de nutrition et de technologie alimentaire de Tunis, service A, Tunis, Tunisia
| | - Olfa Berriche
- Institut national de nutrition et de technologie alimentaire de Tunis, service A, Tunis, Tunisia
| | - Henda Jamoussi
- Institut national de nutrition et de technologie alimentaire de Tunis, service A, Tunis, Tunisia
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Qiu X, Xu Q, Ge H, Gao X, Huang J, Zhang H, Wu X, Lin J. Label-free detection of kidney stones urine combined with SERS and multivariate statistical algorithm. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2025; 324:125020. [PMID: 39213834 DOI: 10.1016/j.saa.2024.125020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 07/30/2024] [Accepted: 08/20/2024] [Indexed: 09/04/2024]
Abstract
Kidney stones are a common urological disease with an increasing incidence worldwide. Traditional diagnostic methods for kidney stones are relatively complex and time-consuming, thus necessitating the development of a quicker and simpler diagnostic approach. This study investigates the clinical screening of kidney stones using Surface-Enhanced Raman Scattering (SERS) technology combined with multivariate statistical algorithms, comparing the classification performance of three algorithms (PCA-LDA, PCA-LR, PCA-SVM). Urine samples from 32 kidney stone patients, 30 patients with other urinary stones, and 36 healthy individuals were analyzed. SERS spectra data were collected in the range of 450-1800 cm-1 and analyzed. The results showed that the PCA-SVM algorithm had the highest classification accuracy, with 92.9 % for distinguishing kidney stone patients from healthy individuals and 92 % for distinguishing kidney stone patients from those with other urinary stones. In comparison, the classification accuracy of PCA-LR and PCA-LDA was slightly lower. The findings indicate that SERS combined with PCA-SVM demonstrates excellent performance in the clinical screening of kidney stones and has potential for practical clinical application. Future research can further optimize SERS technology and algorithms to enhance their stability and accuracy, and expand the sample size to verify their applicability across different populations. Overall, this study provides a new method for the rapid diagnosis of kidney stones, which is expected to play an important role in clinical diagnostics.
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Affiliation(s)
- Xinhao Qiu
- School of Opto-electronic and Communication Engineering, Xiamen University of Technology, Xiamen, Fujian, China
| | - Qingjiang Xu
- Department of Urology, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350001, China; Provincial Clinical Medical Colleges of Fujian Medical University, Fuzhou 350001, China
| | - Houyang Ge
- School of Opto-electronic and Communication Engineering, Xiamen University of Technology, Xiamen, Fujian, China
| | - Xingen Gao
- School of Opto-electronic and Communication Engineering, Xiamen University of Technology, Xiamen, Fujian, China
| | - Junqi Huang
- School of Opto-electronic and Communication Engineering, Xiamen University of Technology, Xiamen, Fujian, China
| | - Hongyi Zhang
- School of Opto-electronic and Communication Engineering, Xiamen University of Technology, Xiamen, Fujian, China
| | - Xiang Wu
- Department of Urology, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350001, China; Provincial Clinical Medical Colleges of Fujian Medical University, Fuzhou 350001, China.
| | - Juqiang Lin
- School of Opto-electronic and Communication Engineering, Xiamen University of Technology, Xiamen, Fujian, China.
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Luzardo ML. Effects of higher dietary acid load: a narrative review with special emphasis in children. Pediatr Nephrol 2025; 40:25-37. [PMID: 39093454 DOI: 10.1007/s00467-024-06466-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 07/05/2024] [Accepted: 07/08/2024] [Indexed: 08/04/2024]
Abstract
Metabolic effects of high diet acid load (DAL) have been studied for years in adults, although only recently in children. Contemporary diets, especially those of Western societies, owe their acidogenic effect to high animal-origin protein content and low contribution of base-forming elements, such as fruits and vegetables. This imbalance, where dietary acid precursors exceed the body's buffering capacity, results in an acid-retaining state known by terms such as "eubicarbonatemic metabolic acidosis," "low-grade metabolic acidosis," "subclinical acidosis," or "acid stress". Its consequences have been linked to chronic systemic inflammation, contributing to various noncommunicable diseases traditionally considered more common in adulthood, but now have been recognized to originate at much earlier ages. In children, effects of high DAL are not limited to growth impairment caused by alterations of bone and muscle metabolism, but also represent a risk factor for conditions such as obesity, insulin resistance, diabetes, hypertension, urolithiasis, and chronic kidney disease (CKD). The possibility that high DAL may be a cause of chronic acid-retaining states in children with growth impairment should alert pediatricians and pediatric nephrologists, since its causes have been attributed traditionally to inborn errors of metabolism and renal pathologies such as CKD and renal tubular acidosis. The interplay between DAL, overall diet quality, and its cascading effects on children's health necessitates comprehensive nutritional assessments and interventions. This narrative review explores the clinical relevance of diet-induced acid retention in children and highlights the potential for prevention through dietary modifications, particularly by increasing fruit and vegetable intake alongside appropriate protein consumption.
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Zomorodian A, Li X, Poindexter J, Maalouf NM, Sakhaee K, Moe OW. Fat Distribution and Urolithiasis Risk Parameters in Uric Acid Stone Formers and Patients with Type 2 Diabetes Mellitus. Clin J Am Soc Nephrol 2025; 20:116-123. [PMID: 39480991 PMCID: PMC11737447 DOI: 10.2215/cjn.0000000000000561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Accepted: 10/02/2024] [Indexed: 11/02/2024]
Abstract
Key Points Under a controlled diet, uric acid stone formers (UASFs) and diabetic patients have higher endogenous net acid production. Under a controlled diet, UASFs have lower ammonium-to-net acid excretion ratio. Body fat inversely correlates with urine buffer capacity in normal individuals, but this relationship is lost in diabetic patients and UASFs. Background Uric acid (UA) nephrolithiasis affects approximately 10% of kidney stones, with a greater preponderance among patients with obesity and diabetes mellitus (DM). UA lithogenicity is driven by abnormally acidic urine pH. Distinguishing the contribution of intrinsic (e.g ., body adiposity) versus external (e.g ., dietary) factors to UA stone propensity is challenging because of uncontrolled diets in outpatients in previously published studies. Methods This compilation of metabolic studies with body composition examined by dual-energy x-ray absorptiometry scan and blood and urine biochemistry collected under a controlled metabolic diet was conducted across three distinct populations: 74 UA stone formers (UASF group), 13 patients with type 2 DM without kidney stones (DM group), and 51 healthy volunteers (HV group). Results Compared with HVs, both UASFs and patients with DM exhibited higher levels of net acid excretion (NAE) and significantly lower urine pH and lower proportion of NAE excreted as ammonium (NH4+/NAE), all under controlled diets. UASFs exhibited significantly lower NH4+/NAE compared with patients with DM. UASFs also showed higher total body and truncal fat compared with HVs. Among the HVs, lower NH4+/NAE ratio correlated with higher truncal and total fat. However, this association was abolished in the UASF and DM groups who exhibit a fixed low NH4+/NAE ratio across a range of body and truncal fat. Conclusions The findings suggest a dual defect of diet-independent increase in acid production and impaired kidney NH4+ excretion as major contributors to the risk of UA stone formation. There is an inverse physiologic association between body fat content and NH4+/NAE in HVs, whereas NH4+/NAE is persistently low in UASFs and patients with DM, regardless of body fat, representing pathophysiology.
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Affiliation(s)
- Alireza Zomorodian
- Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Xilong Li
- Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas
- Department of Population and Data Science, University of Texas Southwestern Medical Center, Dallas, Texas
| | - John Poindexter
- Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Naim M. Maalouf
- Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Khashayar Sakhaee
- Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Orson W. Moe
- Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
- Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas
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9
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Prochaska M, Adeola G, Vetter N, Mirmira RG, Coe F, Worcester E. Insulin Resistance in Hypercalciuric Calcium Kidney Stone Patients. Kidney Med 2024; 6:100922. [PMID: 39634328 PMCID: PMC11615144 DOI: 10.1016/j.xkme.2024.100922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2024] Open
Abstract
Rational & Objective Diabetes and uric acid kidney stones are strongly associated. Patients with calcium kidney stones also have higher risk of developing diabetes compared with nonkidney stone patients yet this has not been further investigated. We aimed to characterize insulin resistance in calcium kidney stone patients. Study Design Observational. Setting & Population This study was performed in the University of Chicago Clinical Research Center. Kidney stone patients (N = 42) were selected for having idiopathic hypercalciuria and calcium stones with no other medical conditions, and controls (N = 27) were healthy. Exposures All participants presented to the Clinical Research Center in a fasting state and at least 2 timed fasting blood and urine collections were collected before a fixed breakfast. Six additional timed blood and urine collections were performed after breakfast. Outcomes We compared fasting and fed indices of insulin resistance between the groups. Analytic Approach We used t tests and multivariable linear regression models. A sensitivity analysis removing all patients who had ever been on a thiazide diuretic was also performed. Results In separate multivariable linear models, kidney stone patients had higher fasting serum insulin levels (24 (3-46 pmol/L), P = 0.03) and higher homeostatic model of insulin resistance (HOMA-IR) (1.0 (0.2-1.8), P = 0.02). In separate multivariable linear models, kidney stone patients had higher fed serum glucose levels (10 (2-18 mg/dL), P = 0.01). Results were similar in a sensitivity analysis removing all patients who had ever been on a thiazide diuretic. There were no differences in urine composition based on HOMA-IR levels. Limitations Single institution. Small sample size limited subanalyses by different calcium stone types. Conclusions Calcium kidney stone patients without diabetes or other medical conditions demonstrated signs of insulin resistance compared with healthy matched controls.
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Affiliation(s)
| | - Gloria Adeola
- Department of Medicine, University of Chicago, Chicago IL
| | - Noah Vetter
- Department of Medicine, University of Chicago, Chicago IL
| | | | - Fredric Coe
- Department of Medicine, University of Chicago, Chicago IL
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10
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Prochaska ML, Zisman AL. Nephrolithiasis. ADVANCES IN KIDNEY DISEASE AND HEALTH 2024; 31:529-537. [PMID: 39577887 DOI: 10.1053/j.akdh.2024.08.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Revised: 08/13/2024] [Accepted: 08/15/2024] [Indexed: 11/24/2024]
Abstract
Kidney stone prevalence is rapidly increasing worldwide, and decreasing stone growth and recurrence is critical to reducing morbidity. Preventative approaches vary with kidney stone type, so knowledge of stone composition and a thorough history and metabolic evaluation are necessary to individualize therapy. The cases presented herein highlight treatment strategies for the most common stone types seen in clinical practice with practical pearls for the nephrologist.
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Affiliation(s)
- Megan L Prochaska
- Department of Medicine, Section of Nephrology, University of Chicago Pritzker School of Medicine, Chicago, IL
| | - Anna L Zisman
- Department of Medicine, Section of Nephrology, University of Chicago Pritzker School of Medicine, Chicago, IL.
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11
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Xu S, Liu ZL, Zhang TW, Li B, Wang XN, Jiao W. Self-control study of multi-omics in identification of microenvironment characteristics in urine of uric acid stone. Sci Rep 2024; 14:25165. [PMID: 39448683 PMCID: PMC11502694 DOI: 10.1038/s41598-024-76054-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 10/10/2024] [Indexed: 10/26/2024] Open
Abstract
The aim of this study is to perform proteomic and metabolomic analyses in bilateral renal pelvis urine of patients with unilateral uric acid kidney stones to identify the specific urinary environment associated with uric acid stone formation. Using cystoscopy-guided insertion of ureteral catheters, bilateral renal pelvis urine samples are collected. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is employed to identify differentially expressed proteins and metabolites in the urine environment. Differentially expressed proteins and metabolites are further analyzed for their biological functions and potential metabolic pathways through Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In the urine from the stone-affected side, eight differential proteins were significantly upregulated, and six metabolites were dysregulated. The uric acid stone urinary environment showed an excess of α-ketoisovaleric acid and 3-methyl-2-oxovaleric acid, which may contribute to the acidification of the urine. Functional and pathway analyses indicate that the dysregulated metabolites are mainly associated with insulin resistance and branched chain amino acid metabolism.
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Affiliation(s)
- Shang Xu
- Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong Province, China
| | - Zhi-Long Liu
- Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong Province, China
| | - Tian-Wei Zhang
- Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong Province, China
| | - Bin Li
- Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong Province, China
| | - Xin-Ning Wang
- Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong Province, China.
| | - Wei Jiao
- Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong Province, China.
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12
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Julien M, Saint Gilles DD, Allou N. Pink urine syndrome in an anuric patient during continuous renal replacement therapy: A case report. Medicine (Baltimore) 2024; 103:e38986. [PMID: 39093782 PMCID: PMC11296465 DOI: 10.1097/md.0000000000038986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 06/28/2024] [Indexed: 08/04/2024] Open
Abstract
INTRODUCTION Pink urine syndrome is a rare, poorly understood condition, often prompted by obesity, insulin resistance, and the drug propofol. It is characterized by pink urine or urine sediment and occurs in the absence of a heme or food-based pigment. The pathophysiology of this syndrome is not yet fully understood but is linked to a uric acid metabolism disorder. Pink urine syndrome is less familiar to anesthesiologists than other propofol infusion complications. Our case report aims to highlight this rarely encountered syndrome, whose both diagnosis and therapeutic may be challenging. We have reported the first case of this syndrome evidenced by the change in color of the effluent bag during continuous veno-venous hemofiltration (CVVHF). CASE PRESENTATION A 61-year-old woman was admitted to the intensive care unit following a recovered cardiorespiratory arrest due to ventricular arrhythmia. She was placed in hypothermia, sedated with propofol (300 mg/h), and started on CVVHF for oligo-anuric acute kidney injury associated with severe metabolic acidosis. A few hours after initiation of CVVHF, the effluent bag turned bright pink. Given the pink color of the effluent bag and the hypothesis of propofol-induced pink urine syndrome, propofol was replaced by midazolam. After stopping propofol, the color of effluent bag lightened. Unfortunately, the patient died on the third day of hospitalization due to diffuse cerebral edema. CONCLUSIONS We report here the first case of pink urine syndrome as revealed by the change in color of the contents of the CVVHF effluent bag in an anuric patient. This syndrome is rare but significant in anesthesia/intensive care settings, where propofol is a frequently used sedative. Knowledge of this syndrome appears to be important to avoid irrelevant additional investigations and to optimize the therapeutic strategy.
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Affiliation(s)
- Marie Julien
- Réanimation Polyvalente, Centre Hospitalier Universitaire Felix Guyon La Réunion, Saint Denis, France
| | | | - Nicolas Allou
- Réanimation Polyvalente, Centre Hospitalier Universitaire Felix Guyon La Réunion, Saint Denis, France
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13
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Wen S, Arakawa H, Tamai I. Uric acid in health and disease: From physiological functions to pathogenic mechanisms. Pharmacol Ther 2024; 256:108615. [PMID: 38382882 DOI: 10.1016/j.pharmthera.2024.108615] [Citation(s) in RCA: 59] [Impact Index Per Article: 59.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 02/02/2024] [Accepted: 02/17/2024] [Indexed: 02/23/2024]
Abstract
Owing to renal reabsorption and the loss of uricase activity, uric acid (UA) is strictly maintained at a higher physiological level in humans than in other mammals, which provides a survival advantage during evolution but increases susceptibility to certain diseases such as gout. Although monosodium urate (MSU) crystal precipitation has been detected in different tissues of patients as a trigger for disease, the pathological role of soluble UA remains controversial due to the lack of causality in the clinical setting. Abnormal elevation or reduction of UA levels has been linked to some of pathological status, also known as U-shaped association, implying that the physiological levels of UA regulated by multiple enzymes and transporters are crucial for the maintenance of health. In addition, the protective potential of UA has also been proposed in aging and some diseases. Therefore, the role of UA as a double-edged sword in humans is determined by its physiological or non-physiological levels. In this review, we summarize biosynthesis, membrane transport, and physiological functions of UA. Then, we discuss the pathological involvement of hyperuricemia and hypouricemia as well as the underlying mechanisms by which UA at abnormal levels regulates the onset and progression of diseases. Finally, pharmacological strategies for urate-lowering therapy (ULT) are introduced, and current challenges in UA study and future perspectives are also described.
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Affiliation(s)
- Shijie Wen
- Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan
| | - Hiroshi Arakawa
- Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan
| | - Ikumi Tamai
- Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
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14
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Ahmed EM. Management of nephrolithiasis in the Middle East over a recent decade: A systematic review. Urol Ann 2024; 16:36-42. [PMID: 38415225 PMCID: PMC10896328 DOI: 10.4103/ua.ua_111_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 12/03/2023] [Accepted: 12/19/2023] [Indexed: 02/29/2024] Open
Abstract
Nephrolithiasis is a prevalent issue around the globe, particularly in hot climates such as Saudi Arabia. This analysis's objectives were to investigate the characteristics of kidney stones in Eastern Saudi Arabia and to provide the following findings: urinary stone composition, gender and age distribution, seasonal variations in stone formation, coexisting diseases linked to stone development, and urinary stone incidence. With comparisons to European and American populations, the primary risk factors for nephrolithiasis in Asian populations are to be determined through this systematic review and meta-analysis. We synthesized data from 13 geographically different studies using a thorough literature search through PubMed, ScienceDirect, and ResearchGate following the Preferred Reporting Items of Systematic Reviews and Meta-Analyses criteria. Potential targets for specialized public health programs were highlighted by the elucidation of differences in health-care-seeking behavior and disparities in health-care access. The results of this systematic analysis give doctors, researchers, and policymakers a thorough understanding of the condition of nephrolithiasis care in Saudi Arabia today. In addition, to maximize the care of nephrolithiasis in this particular group, this review identifies information gaps and highlights the necessity of context-specific guidelines and future research initiatives. All things considered, this systematic review addresses the unique possibilities and problems that exist within the Saudi Arabian health-care sector while also adding to the worldwide conversation on nephrolithiasis.
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Affiliation(s)
- Ehab Mahmoud Ahmed
- Department of Urology, College of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
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15
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Suarez Arbelaez MC, Nackeeran S, Shah K, Blachman-Braun R, Bronson I, Towe M, Bhat A, Marcovich R, Ramasamy R, Shah HN. Association between body mass index, metabolic syndrome and common urologic conditions: a cross-sectional study using a large multi-institutional database from the United States. Ann Med 2023; 55:2197293. [PMID: 37036830 PMCID: PMC10088970 DOI: 10.1080/07853890.2023.2197293] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 03/25/2023] [Indexed: 04/11/2023] Open
Abstract
INTRODUCTION The study aims to determine whether body mass index (BMI), metabolic syndrome (MS) or its individual components (primary hypertension, type 2 diabetes mellitus and dyslipidemias) are risk factors for common urological diseases. MATERIALS AND METHODS Cross-sectional study with data collected on February 28, 2022 from the TriNetX Research Network. Patients were divided in cohorts according to their BMI, presence of MS (BMI > 30 kg/m2, type 2 diabetes mellitus, primary hypertension and disorders of lipoprotein metabolism) and its individual components and its association with common urological conditions was determined. For each analysis, odds ratio (OR) with 95% confidence intervals were calculated. Statistical significance was assessed at p < .05. RESULTS BMI > 30 kg/m2 was associated with increased risk of lithiasis, kidney cancer, overactive bladder, male hypogonadism, benign prostatic hyperplasia, and erectile dysfunction (p < .05). On the contrary, BMI was inversely associated with ureteral, bladder and prostate cancer (p < .05). In all urological diseases, MS was the strongest risk factor, with prostate cancer (OR = 2.53) showing the weakest and male hypogonadism the strongest (OR = 13.00) associations. CONCLUSIONS MS and its individual components were significant risk factors for common urological conditions. Hence holistic approaches with lifestyle modification might prevent common urological disease.Key messagesOverall, metabolic syndrome is the strongest risk factor for all the analysed urological diseases.Abnormally high body mass index can be a risk or protective factor depending on the threshold and urological disease that are being evaluated.Metabolic syndrome and increased BMI should be considered important factors associated to the prevalence of common urological diseases.
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Affiliation(s)
| | - Sirpi Nackeeran
- Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Khushi Shah
- Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Ruben Blachman-Braun
- Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Isaac Bronson
- UMass Chann Medical School, University of Massachusetts, Amherst, MA, USA
| | - Maxwell Towe
- Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Abhishek Bhat
- Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Robert Marcovich
- Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Ranjith Ramasamy
- Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Hemendra N. Shah
- Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami, FL, USA
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16
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Khargi R, Blake RM, Yaghoubian AJ, Canning C, Fang A, Connors C, Gallante B, Ricapito A, Khusid JA, Atallah WM, Gupta M. Drivers of calcium oxalate stone formation in the octogenarian population. World J Urol 2023; 41:3713-3721. [PMID: 37847263 DOI: 10.1007/s00345-023-04619-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 09/06/2023] [Indexed: 10/18/2023] Open
Abstract
INTRODUCTION American Urological Association (AUA) guidelines suggest metabolic testing via 24-h urine studies in high-risk, interested first-time stone formers, and recurrent stone formers. If metabolic testing is not available or otherwise not feasible, clinicians may need to utilize empiric therapy. Debility and social barriers, particularly in the elderly population, may limit the practicality of metabolic testing, and therefore, empiric therapy is of particular importance. The aim of this study is to identify whether unique urinary metabolic abnormality profiles exist for octogenarians with calcium oxalate kidney stones, as this may guide empiric stone prevention therapy more precisely in this population. MATERIALS AND METHODS Patients with calcium oxalate stones from a single academic kidney stone center in New York, NY, were retrospectively identified in our prospectively managed database. Patient data, including demographic, clinical information, and baseline 24-h urine studies, were collected before initiating any treatment. Subjects were stratified by age (≤ 40, 41-59, 60-79, and ≥ 80 years) to compare the metabolic urinary abnormality profiles between octogenarians and other age groups. Subgroup analyses were also performed to compare results by gender and by the presence of underlying kidney dysfunction. Comparative statistical analysis was carried out using Chi-square tests, Mann-Whitney U tests, and t-tests where appropriate. RESULTS Hypocitraturia, low urine pH, and low urine volume were most common in older patients, particularly in octogenarians. Hypercalciuria, hypernatriuria, and hyperuricosuria were more apparent in younger groups. CONCLUSION With increasing age, hypocitraturia, low urine pH, and low urine volume were more prevalent on 24-h urine metabolic testing. We hypothesize increased comorbidity, including medical renal disease, polypharmacy, and dehydration are possible factors contributing to this unique profile. We suggest that empiric therapy targeted towards this profile is important in very elderly stone formers in whom 24-h urine testing may not be possible. Increased hydration, increased fruit and vegetable intake, and low-dose alkali therapy are easy measures to accomplish this.
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Affiliation(s)
- Raymond Khargi
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, USA.
| | - Ryan M Blake
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Alan J Yaghoubian
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Caroline Canning
- Department of Urology, SUNY Downstate Health Sciences University, New York, USA
| | - Alexander Fang
- Department of Urology, SUNY Downstate Health Sciences University, New York, USA
| | - Christopher Connors
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Blair Gallante
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Anna Ricapito
- Department of Urology and Kidney Transplant, University of Foggia, Foggia, Italy
| | - Johnathan A Khusid
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, USA
| | - William M Atallah
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Mantu Gupta
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, USA
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17
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Bargagli M, Liguori A, Napodano C, Baroni S, Tomasello L, Pizzolante F, De Matthaeis N, De Ninno G, Grieco A, Gasbarrini A, Gambaro G, Ferraro PM, Miele L. Urinary lithogenic profile of patients with non-alcoholic fatty liver disease. Nephrol Dial Transplant 2023; 38:2652-2654. [PMID: 37253621 PMCID: PMC10615628 DOI: 10.1093/ndt/gfad106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Indexed: 06/01/2023] Open
Affiliation(s)
- Matteo Bargagli
- U.O.S. Terapia Conservativa della Malattia Renale Cronica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
- Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Antonio Liguori
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
- U.O.C Medicina Interna e del Trapianto di Fegato, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Cecilia Napodano
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
- U.O.C Medicina Interna e del Trapianto di Fegato, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Silvia Baroni
- U.O.C di Chimica Biochimica e Biologia Molecolare Clinica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Lidia Tomasello
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
- U.O.C Medicina Interna e del Trapianto di Fegato, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Fabrizio Pizzolante
- CEMAD, Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Nicoletta De Matthaeis
- CEMAD, Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Grazia De Ninno
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Antonio Grieco
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
- U.O.C Medicina Interna e del Trapianto di Fegato, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Antonio Gasbarrini
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
- CEMAD, Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Giovanni Gambaro
- Division of Nephrology, Department of Medicine, University of Verona, Verona, Italy
| | - Pietro Manuel Ferraro
- U.O.S. Terapia Conservativa della Malattia Renale Cronica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Luca Miele
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
- U.O.C Medicina Interna e del Trapianto di Fegato, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- CEMAD, Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
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18
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Wang C, Sun W, Dalbeth N, Wang Z, Wang X, Ji X, Xue X, Han L, Cui L, Li X, Liu Z, Ji A, He Y, Sun M, Li C. Efficacy and safety of tart cherry supplementary citrate mixture on gout patients: a prospective, randomized, controlled study. Arthritis Res Ther 2023; 25:164. [PMID: 37679816 PMCID: PMC10483724 DOI: 10.1186/s13075-023-03152-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Accepted: 08/27/2023] [Indexed: 09/09/2023] Open
Abstract
BACKGROUND Low urine pH, which may be mediated by metabolic syndrome (MetS), is common in gout. Tart cherries are shown to improve MetS symptoms and possess anti-inflammatory properties. However, the efficacy of tart cherry supplements on urine pH has yet to be studied. OBJECTIVES This study aimed to investigate the efficacy and safety of tart cherry supplementary citrate (TaCCi) mixture on urine pH, serum urate (sUA), C-reactive protein (CRP), and gout flares in gout patients initiating urate-lowering therapy (ULT), in comparison to citrate mixture and sodium bicarbonate. METHODS A prospective, randomized (1:1:1), open-label, parallel-controlled trial was conducted among 282 men with gout and fasting urine pH ≤ 6, who were initiating ULT with febuxostat (initially 20 mg daily, escalating to 40 mg daily if serum urate ≥ 360 μmol/L). Participants were randomized to groups taking either sodium bicarbonate, citrate mixture, or TaCCi mixture. All participants were followed every 4 weeks until week 12. Urine pH and sUA were co-primary outcomes, with various biochemical and clinical secondary endpoints. RESULTS Urine pH increased to a similar extent in all three groups. SUA levels declined in all three groups as well, with no significant differences observed between the groups. At week 12, the TaCCi mixture group exhibited a greater reduction in the urine albumin/creatinine ratio (UACR) compared to the other two groups (p < 0.05). Participants taking TaCCi mixture or citrate mixture experienced fewer gout flares than those in the sodium bicarbonate group over the study period (p < 0.05). Additionally, the TaCCi mixture group had a lower CRP level at week 12 relative to the other two groups (p < 0.01). Adverse events were similar across all three groups. CONCLUSION The TaCCi mixture had similar efficacy and safety on urine alkalization and sUA-lowering as the citrate mixture and sodium bicarbonate in patients with gout. However, the TaCCi mixture resulted in greater improvements in UACR and CRP, which suggests that tart cherry supplements may provide additional benefits for renal protection and reduce inflammation in gout, particularly when starting ULT. TRIAL REGISTRATION This project was registered in ChiCTR ( www.chictr.org.cn ), with the registration number: ChiCTR2100050749.
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Affiliation(s)
- Can Wang
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Qingdao, China
| | - Wenyan Sun
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
| | - Nicola Dalbeth
- Department of Medicine, University of Auckland, Auckland, New Zealand
| | - Zhongjun Wang
- Department of Clinical Laboratory, the Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xuefeng Wang
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Qingdao, China
| | - Xiaopeng Ji
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Qingdao, China
| | - Xiaomei Xue
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Qingdao, China
| | - Lin Han
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Qingdao, China
| | - Lingling Cui
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Qingdao, China
| | - Xinde Li
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Qingdao, China
| | - Zhen Liu
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Qingdao, China
| | - Aichang Ji
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Qingdao, China
| | - Yuwei He
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, Qingdao, China
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Qingdao, China
| | - Mingshu Sun
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Qingdao, China.
- Department of Rheumatology, the Affiliated Hospital of Qingdao University, Qingdao, China.
| | - Changgui Li
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, Qingdao, China.
- Institute of Metabolic Diseases, Qingdao University, Qingdao, China.
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Qingdao, China.
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Adomako EA, Li X, Sakhaee K, Moe OW, Maalouf NM. Urine pH and Citrate as Predictors of Calcium Phosphate Stone Formation. KIDNEY360 2023; 4:1123-1129. [PMID: 37307531 PMCID: PMC10476682 DOI: 10.34067/kid.0000000000000184] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 05/28/2023] [Indexed: 06/14/2023]
Abstract
Key Points The occurrence of calcium phosphate stones has increased over the past five decades, and this is most notable in female stone formers. High urine pH and hypocitraturia are the most discriminatory urine parameters between calcium phosphate and calcium oxalate stone formers. High urine pH in calcium phosphate stone formers is independent of the effect of dietary alkali and acid. Background Urinary parameters, including urine pH and citrate, are recognized as critical in the pathophysiology of calcium-based stones. The factors contributing to variation in these parameters between calcium oxalate (CaOx) and calcium phosphate (CaP) stone formers (SFs) are, however, not well-understood. In this study, using readily available laboratory data, we explore these differences to delineate the odds of forming CaP versus CaOx stones. Methods In this single-center retrospective study, we compared serum and urinary parameters between adult CaP SFs, CaOx SFs, and non–stone formers. Results Urine pH was higher and urine citrate lower in CaP SFs compared with same-sex CaOx SFs and non–stone formers. In CaP SFs, higher urine pH and lower citrate were independent of markers of dietary acid intake and gastrointestinal alkali absorption, suggesting abnormal renal citrate handling and urinary alkali excretion. In a multivariable model, urine pH and urine citrate were most discriminatory between CaP SFs and CaOx SFs (receiver-operating characteristic area under the curve of 0.73 and 0.65, respectively). An increase in urine pH by 0.35, a decrease in urine citrate by 220 mg/d, a doubling of urine calcium, and female sex all independently doubled the risk of CaP stone formation compared with CaOx stones. Conclusions High urine pH and hypocitraturia are two clinical parameters that distinguish the urine phenotype of CaP SFs from CaOx SFs. Alkalinuria is due to intrinsic differences in the kidney independent of intestinal alkali absorption and is accentuated in the female sex.
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Affiliation(s)
- Emmanuel A. Adomako
- Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, UT Southwestern Medical Center, Dallas, Texas
| | - Xilong Li
- Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, UT Southwestern Medical Center, Dallas, Texas
- Peter O'Donnell Jr. School of Public Health, UT Southwestern Medical Center, Dallas, Texas
| | - Khashayar Sakhaee
- Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, UT Southwestern Medical Center, Dallas, Texas
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas
| | - Orson W. Moe
- Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, UT Southwestern Medical Center, Dallas, Texas
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas
- Department of Physiology, UT Southwestern Medical Center, Dallas, Texas
| | - Naim M. Maalouf
- Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, UT Southwestern Medical Center, Dallas, Texas
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas
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20
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Remer T, Kalotai N, Amini AM, Lehmann A, Schmidt A, Bischoff-Ferrari HA, Egert S, Ellinger S, Kroke A, Kühn T, Lorkowski S, Nimptsch K, Schwingshackl L, Zittermann A, Watzl B, Siener R. Protein intake and risk of urolithiasis and kidney diseases: an umbrella review of systematic reviews for the evidence-based guideline of the German Nutrition Society. Eur J Nutr 2023; 62:1957-1975. [PMID: 37133532 PMCID: PMC10349749 DOI: 10.1007/s00394-023-03143-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 04/03/2023] [Indexed: 05/04/2023]
Abstract
PURPOSE Changes in dietary protein intake metabolically affect kidney functions. However, knowledge on potential adverse consequences of long-term higher protein intake (HPI) for kidney health is lacking. To summarise and evaluate the available evidence for a relation between HPI and kidney diseases, an umbrella review of systematic reviews (SR) was conducted. METHODS PubMed, Embase and Cochrane Database of SRs published until 12/2022 were searched for the respective SRs with and without meta-analyses (MA) of randomised controlled trials or cohort studies. For assessments of methodological quality and of outcome-specific certainty of evidence, a modified version of AMSTAR 2 and the NutriGrade scoring tool were used, respectively. The overall certainty of evidence was assessed according to predefined criteria. RESULTS Six SRs with MA and three SRs without MA on various kidney-related outcomes were identified. Outcomes were chronic kidney disease, kidney stones and kidney function-related parameters: albuminuria, glomerular filtration rate, serum urea, urinary pH and urinary calcium excretion. Overall certainty of evidence was graded as 'possible' for stone risk not to be associated with HPI and albuminuria not to be elevated through HPI (above recommendations (> 0.8 g/kg body weight/day)) and graded as 'probable' or 'possible' for most other kidney function-related parameters to be physiologically increased with HPI. CONCLUSION Changes of the assessed outcomes may have reflected mostly physiological (regulatory), but not pathometabolic responses to higher protein loads. For none of the outcomes, evidence was found that HPI does specifically trigger kidney stones or diseases. However, for potential recommendations long-term data, also over decades, are required.
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Affiliation(s)
- Thomas Remer
- DONALD Study Center Dortmund, Department of Nutritional Epidemiology, Institute of Nutrition and Food Science, University of Bonn, Heinstück 11, 44225, Dortmund, Germany.
| | | | | | | | | | - Heike A Bischoff-Ferrari
- Department of Aging Medicine and Aging Research, University Hospital Zurich, University of Zurich, and City Hospital Zurich, Zurich, Switzerland
| | - Sarah Egert
- Department of Nutrition and Food Science, Nutritional Physiology, University of Bonn, Bonn, Germany
| | - Sabine Ellinger
- Department of Nutrition and Food Science, Human Nutrition, University of Bonn, Bonn, Germany
| | - Anja Kroke
- Department of Nutritional, Food and Consumer Sciences, Fulda University of Applied Sciences, Fulda, Germany
| | - Tilman Kühn
- The Institute for Global Food Security, Queen's University Belfast, Belfast, Northern Ireland, UK
- Faculty of Medicine and University Hospital, Heidelberg Institute of Global Health (HIGH), Heidelberg, Germany
- Department of Nutritional Sciences, University of Vienna, Vienna, Austria
- Center for Public Health, Medical University of Vienna, Vienna, Austria
| | - Stefan Lorkowski
- Institute of Nutritional Sciences, Friedrich Schiller, University Jena, Jena, Germany
- Competence Cluster for Nutrition and Cardiovascular, Health (nutriCARD) Halle-Jena-Leipzig, Jena, Germany
| | - Katharina Nimptsch
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Association, Berlin, Germany
| | - Lukas Schwingshackl
- Faculty of Medicine, Institute for Evidence in Medicine, Medical Center - University of Freiburg, Freiburg, Germany
| | - Armin Zittermann
- Clinic for Thoracic and Cardiovascular Surgery, Herz- Und Diabeteszentrum Nordrhein-Westfalen, Ruhr University Bochum, Bad Oeynhausen, Germany
| | - Bernhard Watzl
- Department of Physiology and Biochemistry of Nutrition, Max Rubner-Institut, Karlsruhe, Germany
| | - Roswitha Siener
- Department of Urology, University Stone Center, University Hospital Bonn, Bonn, Germany
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21
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Giha HA. Hidden chronic metabolic acidosis of diabetes type 2 (CMAD): Clues, causes and consequences. Rev Endocr Metab Disord 2023; 24:735-750. [PMID: 37380824 DOI: 10.1007/s11154-023-09816-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/09/2023] [Indexed: 06/30/2023]
Abstract
Interpretation of existing data revealed that chronic metabolic acidosis is a pathognomic feature for type 2 diabetes (T2D), which is described here as "chronic metabolic acidosis of T2D (CMAD)" for the first time. The biochemical clues for the CMAD are summarised in the following; low blood bicarbonate (high anionic gap), low pH of interstitial fluid and urine, and response to acid neutralization, while the causes of extra protons are worked out to be; mitochondrial dysfunction, systemic inflammation, gut microbiota (GM), and diabetic lung. Although, the intracellular pH is largely preserved by the buffer system and ion transporters, a persistent systemic mild acidosis leaves molecular signature in cellular metabolism in diabetics. Reciprocally, there are evidences that CMAD contributes to the initiation and progression of T2D by; reducing insulin production, triggering insulin resistance directly or via altered GM, and inclined oxidative stress. The details about the above clues, causes and consequences of CMAD are obtained by searching literature spanning between 1955 and 2022. Finally, the molecular bases of CMAD are discussed in details by interpretation of an up-to-date data and aid of well constructed diagrams, with a conclusion unravelling that CMAD is a major player in T2D pathophysiology. To this end, the CMAD disclosure offers several therapeutic potentials for prevention, delay or attenuation of T2D and its complications.
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Affiliation(s)
- Hayder A Giha
- Medical Biochemistry and Molecular Biology, Khartoum, Sudan.
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22
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Anders HJ, Li Q, Steiger S. Asymptomatic hyperuricaemia in chronic kidney disease: mechanisms and clinical implications. Clin Kidney J 2023; 16:928-938. [PMID: 37261000 PMCID: PMC10229286 DOI: 10.1093/ckj/sfad006] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Indexed: 10/19/2023] Open
Abstract
Asymptomatic hyperuricaemia (HU) is considered a pathogenic factor in multiple disease contexts, but a causative role is only proven for the crystalline form of uric acid in gouty arthritis and urate nephropathy. Epidemiological studies document a robust association of HU with hypertension, cardiovascular disease (CVD) and CKD progression, but CKD-related impaired uric acid (UA) clearance and the use of diuretics that further impair UA clearance likely accounts for these associations. Interpreting the available trial evidence is further complicated by referring to xanthine oxidase inhibitors as urate-lowering treatment, although these drugs inhibit other substrates, so attributing their effects only to HU is problematic. In this review we provide new mechanistic insights into the biological effects of soluble and crystalline UA and discuss clinical evidence on the role of asymptomatic HU in CKD, CVD and sterile inflammation. We identify research areas with gaps in experimental and clinical evidence, specifically on infectious complications that represent the second common cause of death in CKD patients, referred to as secondary immunodeficiency related to kidney disease. In addition, we address potential therapeutic approaches on how and when to treat asymptomatic HU in patients with kidney disease and where further interventional studies are required.
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Affiliation(s)
- Hans-Joachim Anders
- Division of Nephrology, Department of Medicine IV, Hospital of the Ludwig-Maximilians University, Munich, Germany
| | - Qiubo Li
- Division of Nephrology, Department of Medicine IV, Hospital of the Ludwig-Maximilians University, Munich, Germany
| | - Stefanie Steiger
- Division of Nephrology, Department of Medicine IV, Hospital of the Ludwig-Maximilians University, Munich, Germany
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23
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Bargagli M, Pinto F, De Leonardis R, Ragonese M, Totaro A, Recupero S, Vittori M, Bassi P, Gambaro G, Ferraro PM. Determinants of renal papillary appearance in kidney stone formers: An in-depth examination. Arch Ital Urol Androl 2023; 95:10748. [PMID: 36924385 DOI: 10.4081/aiua.2023.10748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 08/20/2022] [Indexed: 02/24/2023] Open
Abstract
OBJECTIVES The aim of this study is to investi-gate the association between the urinary metabolic milieu and kidney stone recurrence with a validated papillary evaluation score (PPLA). MATERIALS AND METHODS We prospectively enrolled 30 stone for-mers who underwent retrograde intrarenal surgery procedures. Visual inspection of the accessible renal papillae was performed to calculate PPLA score, based on the characterization of ductal plugging, surface pitting, loss of papillary contour and Randall's plaque extension. Stone compositions, 24h urine collections and kidney stone events during follow-up were collected. Relative supersaturation ratios (RSS) for calcium oxalate (CaOx), brushite and uric acid were calculated using EQUIL-2. PPLA score > 3 was defined as high. RESULTS Median follow-up period was 11 months (5, 34). PPLA score was inversely correlated with BMI (OR 0.59, 95% CI 0.38, 0.91, p = 0.018), type 2 diabetes (OR 0.04, 95% CI 0.003, 0.58, p = 0.018) and history of recurrent kidney stones (OR 0.17, 95%CI 0.04, 0.75, p = 0.019). The associations between PPLA score, diabetes and BMI were not confirmed after excluding patients with uric acid stones. Higher PPLA score was associated with lower odds of new kidney stone events during follow-up (OR 0.15, 95% CI 0.02, 1.00, p = 0.05). No other significant correla-tions were found. CONCLUSIONS Our results confirm the lack of efficacy of PPLA score in phenotyping patients affected by kidney stone disease or in predicting the risk of stone recurrence. Larger, long-term studies need to be performed to clarify the role of PPLA on the risk of stone recurrence.
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Affiliation(s)
- Matteo Bargagli
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma; U.O.S. Terapia Conservativa della Malattia Renale Cronica, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma.
| | - Francesco Pinto
- U.O.C. Clinica Urologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma.
| | - Rossella De Leonardis
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma.
| | - Mauro Ragonese
- U.O.C. Clinica Urologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma.
| | - Angelo Totaro
- U.O.C. Clinica Urologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma.
| | | | - Matteo Vittori
- Department of Urology, San Carlo di Nancy Hospital, Rome.
| | - PierFrancesco Bassi
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma; U.O.C. Clinica Urologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma.
| | - Giovanni Gambaro
- Renal Unit, Department of Medicine, University-Hospital of Verona, Verona.
| | - Pietro Manuel Ferraro
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma; U.O.S. Terapia Conservativa della Malattia Renale Cronica, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma.
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24
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Stamatelou K, Goldfarb DS. Epidemiology of Kidney Stones. Healthcare (Basel) 2023; 11:healthcare11030424. [PMID: 36766999 PMCID: PMC9914194 DOI: 10.3390/healthcare11030424] [Citation(s) in RCA: 99] [Impact Index Per Article: 49.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/25/2023] [Accepted: 01/29/2023] [Indexed: 02/05/2023] Open
Abstract
In the past two decades, major breakthroughs that improve our understanding of the pathophysiology and therapy of kidney stones (KS) have been lacking. The disease continues to be challenging for patients, physicians, and healthcare systems alike. In this context, epidemiological studies are striving to elucidate the worldwide changes in the patterns and the burden of the disease and identify modifiable risk factors that contribute to the development of kidney stones. Our expanding knowledge of the epidemiology of kidney stones is of paramount importance and largely upgrades the modern management of the disease. In this paper, we review the variables affecting prevalence and incidence, including age, gender, race, ethnicity, occupation, climate, geography, systemic diseases, diabetes, vascular disease, chronic kidney disease, and dietary risk factors relevant to kidney stones.
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Affiliation(s)
- Kyriaki Stamatelou
- “MESOGEIOS” Nephrology Center, Haidari and Nephros.eu Private Clinic, 11527 Athens, Greece
| | - David S. Goldfarb
- Nephrology Division, NYU Langone Health and NYU Grossman School of Medicine, NY Nephrology Section, NY Harbor VA Healthcare System, New York, NY 10016, USA
- Correspondence: ; Tel.: +1-212-686-7500 (ext. 3877); Fax: +1-212-951-6842
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25
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Siener R, Löhr P, Hesse A. Urinary Risk Profile, Impact of Diet, and Risk of Calcium Oxalate Urolithiasis in Idiopathic Uric Acid Stone Disease. Nutrients 2023; 15:nu15030572. [PMID: 36771279 PMCID: PMC9919786 DOI: 10.3390/nu15030572] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/18/2023] [Accepted: 01/20/2023] [Indexed: 01/24/2023] Open
Abstract
The role of diet in the pathogenesis of uric acid (UA) nephrolithiasis is incompletely understood. This study investigated the effect of dietary intervention on the risk of UA stone formation under standardized conditions. Twenty patients with idiopathic UA stone disease were included in the study. Dietary intake and 24 h urinary parameters were collected on the usual diet of the patients and a standardized balanced mixed diet. Although urinary UA excretion did not change, the relative supersaturation of UA decreased significantly by 47% under the balanced diet primarily due to the significant increase in urine volume and pH. Urinary pH was below 5.8 in 85% of patients under the usual diet, and in 60% of patients under the balanced diet. The supersaturation of calcium oxalate declined significantly under the balanced diet due to the significant decrease in urinary calcium and oxalate excretion and the increase in urine volume. Dietary intervention is a key component in the management of UA nephrolithiasis. Urinary calcium and oxalate excretion should also be monitored in patients with pure UA calculi to reduce the risk of mixed stone formation with calcium oxalate. Lower urinary pH in UA stone patients can only be partially explained by diet.
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26
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Naude, MTech (Hom) DF. Chronic Sub-Clinical Systemic Metabolic Acidosis - A Review with Implications for Clinical Practice. J Evid Based Integr Med 2022; 27:2515690X221142352. [PMID: 36448194 PMCID: PMC9716591 DOI: 10.1177/2515690x221142352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
When arterial serum pH remains near the lower pH limit of 7.35 for protracted periods of time, a low-grade, sub-clinical form of acidosis results, referred to in this review as chronic, sub-clinical, systemic metabolic acidosis (CSSMA). This narrative review explores the scientific basis for CSSMA, its consequences for health, and potential therapeutic interventions. The major etiology of CSSMA is the shift away from the ancestral, alkaline diet which was rich in fruit and vegetables, toward the contemporary, acidogenic 'Westernized' diet characterized by higher animal protein consumption and lack of base forming minerals. Urine pH is reduced with high dietary acid load and may be a convenient marker of CSSMA. Evidence suggests further that CSSMA negatively influences cortisol levels potentially contributing significantly to the pathophysiology thereof. Both CSSMA and high dietary acid load are associated with the risk and prognosis of various chronic diseases. Clinical trials show that CSSMA can be addressed successfully through alkalizing the diet by increasing fruit and vegetable intake and/or supplementing with alkaline minerals. This review confirms the existence of a significant body of evidence regarding this low-grade form of acidosis as well as evidence to support its diverse negative implications for health, and concludes that CSSMA is a condition warranting further research.
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Affiliation(s)
- David Francis Naude, MTech (Hom)
- Irma Schutte Foundation, Drummond, South Africa,David Francis Naude, Irma Schutte Foundation, 42 Protea Hill Rd, Drummond, KwaZulu Natal, 3626, South Africa. Postal address: P.O Box 8, Hillcrest, KwaZulu Natal, 3650, South Africa.
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27
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Siener R, Ernsten C, Bitterlich N, Alteheld B, Metzner C. Effect of Two Different Dietary Weight Loss Strategies on Risk Factors for Urinary Stone Formation and Cardiometabolic Risk Profile in Overweight Women. Nutrients 2022; 14:nu14235054. [PMID: 36501084 PMCID: PMC9736858 DOI: 10.3390/nu14235054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/17/2022] [Accepted: 11/23/2022] [Indexed: 11/29/2022] Open
Abstract
Overweight has been suggested to increase the risk of kidney stone formation. Although weight reduction might affect risk factors for urolithiasis, findings on the impact of different dietary weight loss strategies are limited. This randomized, controlled study evaluated the effect of a conventional energy-restricted modified diet with (MR group) or without meal replacement (C group) on risk factors for stone formation in overweight women without a history of urolithiasis. Of 105 participants, 78 were included into the per-protocol analysis. Anthropometric, clinical, biochemical, and 24 h urinary parameters were collected at baseline and after 12 weeks. Although both dietary interventions resulted in a significant weight reduction, relative weight loss and rate of responders were higher in the MR group. Weight loss improved cardiometabolic risk profile in both groups. Unfortunately, the benefit of decreased GPT activity in the C group was offset by a significant increase in homocysteine and a decline in GFR. While the relative supersaturation of calcium oxalate decreased significantly in both groups, a significant decline in serum uric acid concentration and relative supersaturation of uric acid was observed only in the MR group. Finally, the energy-restricted modified diet with meal replacement showed significant advantages over the energy-restricted modified diet alone.
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Affiliation(s)
- Roswitha Siener
- University Stone Center, Department of Urology, University Hospital Bonn, 53127 Bonn, Germany
- Correspondence:
| | - Charlotte Ernsten
- University Stone Center, Department of Urology, University Hospital Bonn, 53127 Bonn, Germany
| | - Norman Bitterlich
- Independent Biostatistician, Draisdorfer Str. 21, 09114 Chemnitz, Germany
| | - Birgit Alteheld
- Department of Nutrition and Food Sciences, Nutritional Physiology, University of Bonn, 53115 Bonn, Germany
| | - Christine Metzner
- Bonn Education Association for Dietetics r. A., 50935 Cologne, Germany
- Clinic for Gastroenterology, Metabolic Disorders and Internal Intensive Medicine (Medical Clinic III), RWTH Aachen, 52074 Aachen, Germany
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28
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Nephrolithiasis: A Red Flag for Cardiovascular Risk. J Clin Med 2022; 11:jcm11195512. [PMID: 36233380 PMCID: PMC9573143 DOI: 10.3390/jcm11195512] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 09/13/2022] [Accepted: 09/16/2022] [Indexed: 02/05/2023] Open
Abstract
Epidemiological evidence shows that nephrolithiasis is associated with cardiovascular (CV) morbidities. The association between nephrolithiasis and CV disease is not surprising because both diseases share conditions that facilitate their development. Metabolic conditions, encompassed in the definition of metabolic syndrome (MS), and habits that promote nephrolithiasis by altering urine composition also promote clinical manifestations of CV disease. By inducing oxidative stress, these conditions cause endothelial dysfunction and increased arterial stiffness, which are both well-known predictors of CV disease. Furthermore, the subtle systemic metabolic acidosis observed in stone formers with CV disease may have a pathogenic role by increasing bone turnover and leading to reduced mineral content and osteoporosis/osteopenia. Heart valves and/or coronary artery and aortic calcifications are frequently associated with reduced mineral density. This is known as the 'calcification paradox' in osteoporosis and has also been observed in subjects with calcium nephrolithiasis. Evidence supports the hypothesis that osteoporosis/osteopenia is an independent risk factor for the development of CV calcifications. In the long term, episodes of renal stones may occur from the onset of metabolic derangements/MS to arterial stiffness/atherosclerosis and CV morbidities. These episodes should be considered a warning sign of an ongoing and silent atherosclerotic process. The evaluation of cardiometabolic risk factors and MS components should be routine in the assessment of renal stone formers. This would allow for treatment and prevention of the development of CV complications, which are much more severe for the patient and for public health.
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29
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Averyanova IV. Occurrence of metabolic syndrome components in northerners. Klin Lab Diagn 2022; 67:444-450. [PMID: 36095080 DOI: 10.51620/0869-2084-2022-67-8-444-450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
The metabolic syndrome is currently becoming more common. It is a significant public health concern as it is epidemic affecting populations in many regions of the world. In Magadan region no research has been carried out to study the frequency of components of the metabolic syndrome among northerners. This survey was performed to assess the occurrence of the main and additional components of the metabolic syndrome among 17 to 74 year old residents of the Northern region. Two hundred and forty north born Caucasians participated in the study: male subjects at their young age, working age, and retirement age, all belonging to the territory of Magadan region. We used photometric, immunochemiluminescent research methods, as well as standard methods for assessing body mass index and cardiovascular system. The metabolic syndrome factors were determined in accordance with the criteria of the National Cholesterol Education Program (NCEP), the Adult Treatment Program III (ATP III), the International Diabetes Federation (IDF), and the Consensus of International Experts in Cardiology and Endocrinology. We analyzed five main components of the metabolic syndrome (overweight, carbohydrate metabolic impairments hypertension, hypertriglyceridemia, hypoalphacholesterolemia) and three additional components (presence of insulin resistance, purine metabolism disorder, deficient and insufficient concentrations of vitamin D). Combinations of the components were also studied through the examined age groups. According to the ATP III, NCEP and IDF criteria, the metabolic syndrome was more common in elderly subjects (47%) than in working age (21%) or young examinees (3%). Older males tended to exhibit higher frequency of both the main and additional factors of metabolic syndrome. The total index of the occurrence of metabolic syndrome factors in the group of young men was 101%; in the group of men of working age - 180%, and in men of retirement age - 274%. The results on occurrence of the metabolic syndrome components observed in the surveyed groups of northerners can make an information data base, which we assume can be applied when planning and carrying out scientifically grounded preventive measures, which will improve subjective quality of life and its expectancy under the North conditions.
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Blood and Urinary Biomarkers of Antipsychotic-Induced Metabolic Syndrome. Metabolites 2022; 12:metabo12080726. [PMID: 36005598 PMCID: PMC9416438 DOI: 10.3390/metabo12080726] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 07/29/2022] [Accepted: 08/03/2022] [Indexed: 12/15/2022] Open
Abstract
Metabolic syndrome (MetS) is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Antipsychotic (AP)-induced MetS (AIMetS) is the most common adverse drug reaction (ADR) of psychiatric pharmacotherapy. Herein, we review the results of studies of blood (serum and plasma) and urinary biomarkers as predictors of AIMetS in patients with schizophrenia (Sch). We reviewed 1440 studies examining 38 blood and 19 urinary metabolic biomarkers, including urinary indicators involved in the development of AIMetS. Among the results, only positive associations were revealed. However, at present, it should be recognized that there is no consensus on the role of any particular urinary biomarker of AIMetS. Evaluation of urinary biomarkers of the development of MetS and AIMetS, as one of the most common concomitant pathological conditions in the treatment of patients with psychiatric disorders, may provide a key to the development of strategies for personalized prevention and treatment of the condition, which is considered a complication of AP therapy for Sch in clinical practice.
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Exercise and Interorgan Communication: Short-Term Exercise Training Blunts Differences in Consecutive Daily Urine 1H-NMR Metabolomic Signatures between Physically Active and Inactive Individuals. Metabolites 2022; 12:metabo12060473. [PMID: 35736406 PMCID: PMC9229485 DOI: 10.3390/metabo12060473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 05/20/2022] [Accepted: 05/20/2022] [Indexed: 02/01/2023] Open
Abstract
Physical inactivity is a worldwide health problem, an important risk for global mortality and is associated with chronic noncommunicable diseases. The aim of this study was to explore the differences in systemic urine 1H-NMR metabolomes between physically active and inactive healthy young males enrolled in the X-Adapt project in response to controlled exercise (before and after the 3-day exercise testing and 10-day training protocol) in normoxic (21% O2), normobaric (~1000 hPa) and normal-temperature (23 °C) conditions at 1 h of 50% maximal pedaling power output (Wpeak) per day. Interrogation of the exercise database established from past X-Adapt results showed that significant multivariate differences existed in physiological traits between trained and untrained groups before and after training sessions and were mirrored in significant differences in urine pH, salinity, total dissolved solids and conductivity. Cholate, tartrate, cadaverine, lysine and N6-acetyllisine were the most important metabolites distinguishing trained and untrained groups. The relatively little effort of 1 h 50% Wpeak per day invested by the untrained effectively modified their resting urine metabolome into one indistinguishable from the trained group, which hence provides a good basis for the planning of future recommendations for health maintenance in adults, irrespective of the starting fitness value. Finally, the 3-day sessions of morning urine samples represent a good candidate biological matrix for future delineations of active and inactive lifestyles detecting differences unobservable by single-day sampling due to day-to-day variability.
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Abstract
Diet affects the body's acid-base balance by providing acid or alkali precursors in the metabolism. The importance of the acid-base balance of the diet for cardiovascular diseases, which have become the most important cause of morbidity on the global scale, has started to take its place in the literature. The prediction of endogenous acid production in dietary acid-base balance is expressed as dietary acid load. Although the available information about the effect of dietary acid load on cardiovascular diseases is limited, possible mechanisms are indicated as excessive calcium and magnesium excretion from the kidneys, reduced urinary citrate excretion, and excessive cortisol production. Metabolic acidosis has an important role in the development of cardiometabolic abnormalities, especially insulin resistance. Studies examining the relationship between dietary acid load and cardiovascular disease are limited and there is an inconsistency between studies. Practices for determining risk factors for cardiovascular diseases and preventing their effects are very important for the protection and improvement of health. Considering dietary acid load when planning a diet for individuals with cardiovascular diseases can help increase the effectiveness of the diet. The purpose of this review is to examine the effect of dietary acid load on cardiovascular diseases.
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Affiliation(s)
- Nursel Sahın
- Department of Nutrition and Dietetic, Bandirma Onyedi Eylul University, Balikesir, Turkey
| | - Ugur Gunsen
- Department of Nutrition and Dietetic, Bandirma Onyedi Eylul University, Balikesir, Turkey
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Abstract
A significant increase in the prevalence of kidney stones has been observed worldwide. In the past decades, this expansion was more pronounced among women than men. The precise mechanisms involved in the differences in the risk profile of stone disease between men and women have not been fully elucidated. Diet and lifestyle only partially can explain the differences, and the combination of factors such as the influence of sex hormones, genetics, and disorders in acid-base handling and urine pH, as well as differences in calcium tubular reabsorption and stone composition in men and women, may contribute to differences in the risk profile. In this review, we summarize the sex differences in the pathophysiologic basis of kidney stones, which may contribute to a more focused approach.
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Affiliation(s)
- Pietro Manuel Ferraro
- U.O.S. Terapia Conservativa della Malattia Renale Cronica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.
| | | | - Gary C Curhan
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
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Sheele JM, Libertin CR, Fink I, Jensen T, Dasalla N, Lyon TD. Alkaline Urine in the Emergency Department Predicts Nitrofurantoin Resistance. J Emerg Med 2022; 62:368-377. [PMID: 35000812 DOI: 10.1016/j.jemermed.2021.10.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 08/09/2021] [Accepted: 10/12/2021] [Indexed: 11/19/2022]
Abstract
BACKGROUND The Proteeae group (i.e., Proteus species, Morganella morganii, and Providencia species) frequently causes urinary tract infections (UTIs) and is generally resistant to nitrofurantoin. Proteeae species can produce urease, which can increase urine pH. OBJECTIVE Our aim was to determine whether higher urine pH in the emergency department is associated with nitrofurantoin resistance. METHODS A single health system database of emergency department patients aged 18 years and older who received urinalysis between April 18, 2014, and March 7, 2017, was examined using χ2 test and multivariable regression analysis. RESULTS Of 67,271 urine samples analyzed, 13,456 samples grew a single bacterial species. Urine cultures growing the Proteeae group were associated with significantly more alkaline urine than other bacteriuria cultures (odds ratio [OR] 2.20, 95% confidence interval [CI] 2.06-2.36; p < 0.001). The Proteeae species represented 4.4% of urine samples at pH 5-7, 24.4% at pH 8-9, and 40.0% at pH 9. At urine pH 5-7, 80.4% of urine samples were sensitive to nitrofurantoin; however, this percentage decreased to 66.1% for urine pH 8-9 and 54.6% for urine pH 9. Nitrofurantoin had the highest OR (2.10, 95% CI 1.85-2.39) among cefazolin, ciprofloxacin, and trimethoprim/sulfamethoxazole for bacteriuria sensitive to those antibiotics at urine pH 5-7. At urine pH 8-9 and 9, nitrofurantoin had the lowest OR among the antibiotics: 0.48 (95% CI 0.42-0.54) and 0.31 (95% CI 0.24-0.40), respectively (p < 0.001 for both). CONCLUSIONS Urine pH of 8 or higher is associated with high rates of nitrofurantoin resistance.
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Affiliation(s)
| | | | - Isaac Fink
- Clinical Research Internship Study Program, Mayo Clinic, Jacksonville, Florida
| | - Taylor Jensen
- Clinical Research Internship Study Program, Mayo Clinic, Jacksonville, Florida
| | - Nicole Dasalla
- Clinical Research Internship Study Program, Mayo Clinic, Jacksonville, Florida
| | - Timothy D Lyon
- Department of Urology, Mayo Clinic, Jacksonville, Florida
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Han JH, Jeong SH, Yuk HD, Jeong CW, Kwak C, Ku JH. Acidic Urine Is Associated With Poor Prognosis of Upper Tract Urothelial Carcinoma. Front Oncol 2022; 11:817781. [PMID: 35141155 PMCID: PMC8818799 DOI: 10.3389/fonc.2021.817781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 12/28/2021] [Indexed: 12/05/2022] Open
Abstract
PURPOSE To assess the prognostic role of acidic urine (low urine pH) in upper tract urothelial cancer (UTUC). MATERIALS AND METHODS We reviewed patients enrolled in Seoul National University Prospectively Enrolled Registry for Urothelial Cancer-Upper Tract Urothelial Cancer (SUPER-UC-UTUC) who underwent surgical resection from March 2016 to December 2020 in Seoul National University Hospital (SNUH). Patients with non-urothelial cancer or those who are in condition at end-stage renal disease were excluded. Acidic urine was defined as urine pH ≤ 5.5. RESULTS A total of 293 patients with a mean age of 70.7 ± 9.5 years were enrolled in this study. Pre-operative laboratory results showed a mean estimated glomerular filtration rate (eGFR) of 64.1 ± 19.2 mL/min/1.73m2 and a mean urine pH of 5.86 ± 0.66. Patients were subdivided into low (pH ≤ 5.5) and high (pH > 5.5) urine pH for comparison. As a result, all variables were comparable except for the T stage, which was significantly higher in the low urine pH group (p = 0.017). Cox regression analysis was performed to assess the clinical impact of acidic urine on patient survival. Multivariate Cox regression analysis revealed that tumor multifocality (HR 2.07, p = 0.015), higher T stage (HR 1.54, p = 0.036), lymphovascular invasion (HR 1.69, p = 0.033), eGFR < 60 mL/min per 1.73 m2 (HR 1.56, p = 0.017), and acidic urine (HR 1.63, p < 0.01) independently decreased disease-free survival (DFS), while multifocality (HR 9.50, p < 0.01), higher T stage (HR 9.51, p = 0.001) and acidic urine (HR 10.36, p = 0.004) independently reduced the overall survival (OS). CONCLUSIONS Acidic urine is independently associated with reduced DFS and OS in UTUC. Acidic urine contributing to acidic environment may promote acquisition of agressive behavior of UTUC.
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Affiliation(s)
- Jang Hee Han
- Department of Urology, Seoul National University Hospital, Seoul, South Korea
| | - Seung-hwan Jeong
- Department of Urology, Seoul National University Hospital, Seoul, South Korea
| | - Hyeong Dong Yuk
- Department of Urology, Seoul National University Hospital, Seoul, South Korea
- Department of Urology, Seoul National University College of Medicine, Seoul, South Korea
| | - Chang Wook Jeong
- Department of Urology, Seoul National University Hospital, Seoul, South Korea
- Department of Urology, Seoul National University College of Medicine, Seoul, South Korea
| | - Cheol Kwak
- Department of Urology, Seoul National University Hospital, Seoul, South Korea
- Department of Urology, Seoul National University College of Medicine, Seoul, South Korea
| | - Ja Hyeon Ku
- Department of Urology, Seoul National University Hospital, Seoul, South Korea
- Department of Urology, Seoul National University College of Medicine, Seoul, South Korea
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Choi C, Kim JK, Han K, Lee YG, Han JH. Effect of obesity and metabolic health on urolithiasis: A nationwide population-based study. Investig Clin Urol 2022; 63:63-70. [PMID: 34983124 PMCID: PMC8756157 DOI: 10.4111/icu.20210332] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 09/23/2021] [Accepted: 10/20/2021] [Indexed: 11/18/2022] Open
Abstract
Purpose To investigate the risk of symptomatic urolithiasis requiring surgical treatment according to obesity and metabolic health status using a nationwide dataset of the Korean population. Materials and Methods Of the 5,300,646 persons who underwent health examinations between the year 2009 and 2016, within one year after the health examination, 35,137 patients who underwent surgical treatment for urolithiasis were enrolled. Participants were classified as “obese” or “non-obese” using a body mass index (BMI) cutoff of 25 kg/m2. People who developed ≥1 metabolic disease component in the index year were considered “metabolically unhealthy”, while those with none were considered “metabolically healthy”. Results Out of 34,330 participants excluding 843 missing, 16,509 (48.1%), 4,320 (12.6%), 6,456 (18.8%), and 7,045 (20.5%) subjects were classified into the metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) group, respectively. Mean BMI was 22.1±1.9 kg/m2, 22.9±1.6 kg/m2, 26.9±1.8 kg/m2, and 27.9±2.4 kg/m2 respectively. After adjusting the age and sex, the subjects in the MUNO group had an HR (95% CI) of 1.192 (1.120–1.268), those in the MHO group, 1.242 (1.183–1.305), and those in the MUO group, 1.341 (1.278–1.407) for either extracorporeal shockwave lithotripsy or surgery, compared to those in the MHNO group. Conclusions Metabolically healthy, obese individuals have a higher risk of developing symptomatic urolithiasis than non-obese, unhealthy, but have a lower risk than obese, unhealthy. It suggests that metabolic health and obesity have collaborative effects, independently affecting the development of symptomatic urinary stone diseases.
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Affiliation(s)
- Changil Choi
- Department of Urology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea
| | - Jong Keun Kim
- Department of Urology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea
| | - Kyungdo Han
- Department of Medical Statistics, Soongsil University, Seoul, Korea
| | - Young Goo Lee
- Department of Urology, Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea
| | - Jun Hyun Han
- Department of Urology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea.
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Hood VL, Sternberg KM, de Waal D, Asplin JR, Mulligan C, Callas PW. Association of Urine Findings with Metabolic Syndrome Traits in a Population of Patients with Nephrolithiasis. KIDNEY360 2021; 3:317-324. [PMID: 35373120 PMCID: PMC8967639 DOI: 10.34067/kid.0002292021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 11/23/2021] [Indexed: 01/10/2023]
Abstract
Background The odds of nephrolithiasis increase with more metabolic syndrome (MetS) traits. We evaluated associations of metabolic and dietary factors from urine studies and stone composition with MetS traits in a large cohort of stone-forming patients. Methods Patients >18 years old who were evaluated for stones with 24-hour urine collections between July 2009 and December 2018 had their records reviewed retrospectively. Patient factors, laboratory values, and diagnoses were identified within 6 months of urine collection and stone composition within 1 year. Four groups with none, one, two, and three or four MetS traits (hypertension, obesity, dyslipidemia, and diabetes) were evaluated. Trends across groups were tested using linear contrasts in analysis of variance and analysis of covariance. Results A total of 1473 patients met the inclusion criteria (835 with stone composition). MetS groups were 684 with no traits, 425 with one trait, 211 with two traits, and 153 with three or four traits. There were no differences among groups for urine volume, calcium, or ammonium excretion. There was a significant trend (P<0.001) for more MetS traits being associated with decreasing urine pH, increasing age, calculated dietary protein, urine uric acid (UA), oxalate, citrate, titratable acid phosphate, net acid excretion, and UA supersaturation. The ratio of ammonium to net acid excretion did not differ among the groups. After adjustment for protein intake, the fall in urine pH remained strong, while the upward trend in acid excretion was lost. Calcium oxalate stones were most common, but there was a trend for more UA (P<0.001) and fewer calcium phosphate (P=0.09) and calcium oxalate stones (P=0.01) with more MetS traits. Conclusions Stone-forming patients with MetS have a defined pattern of metabolic and dietary risk factors that contribute to an increased risk of stone formation, including higher acid excretion, largely the result of greater protein intake, and lower urine pH.
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Affiliation(s)
- Virginia L. Hood
- Department of Nephrology, University of Vermont Medical Center, Burlington, Vermont
| | - Kevan M. Sternberg
- Department of Urology, University of Vermont Medical Center, Burlington, Vermont
| | - Desiree de Waal
- Department of Nephrology, University of Vermont Medical Center, Burlington, Vermont
| | - John R. Asplin
- Litholink Corporation, Laboratory Corporation of America Holdings, Itasca, Illinois
| | - Carley Mulligan
- Larner College of Medicine, University of Vermont, Burlington, Vermont
| | - Peter W. Callas
- Medical Biostatistics, University of Vermont, Burlington, Vermont
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Mirmiran P, Houshialsadat Z, Bahadoran Z, Khalili-Moghadam S, Shahrzad MK, Azizi F. Dietary acid load and risk of cardiovascular disease: a prospective population-based study. BMC Cardiovasc Disord 2021; 21:432. [PMID: 34511069 PMCID: PMC8436514 DOI: 10.1186/s12872-021-02243-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 09/02/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND AND AIM Considering the inconsistencies in the cardiovascular effects of dietary acid load and the impact of dietary acidity on the acid-base homeostasis within the body, we aimed to assess the association of dietary acid load and the risk of cardiovascular disease (CVD) in a prospective community-based study. MATERIALS AND METHODS Participants (n = 2369) free of CVD at baseline (2006-2008) were included from the Tehran Lipid and Glucose Study (TLGS) and followed up for a mean of 6.7 ± 1.4 years. Dietary intakes of the participants were assessed using a semi-quantitative food frequency questionnaire (FFQ). The dietary acid load was evaluated by Potential Renal Acid Load (PRAL) and Net Endogenous Acid Production (NEAP) scores. Both scores have used the macronutrient and micronutrient data of the Food Frequency Questionnaires. Multivariate Cox proportional hazard regression models were used to estimate the 6-years incident risk of CVDs across tertiles of PRAL and NEAP scores. RESULTS Mean age and body mass index of participants were 38.5 ± 13.3 years and 26.6 ± 4.8 kg/m2 at baseline. Within 6.7 ± 1.4 years of follow-up, 79 cases of cardiovascular events were reported. NEAP was significantly associated with the incidence of CVDs (HRs = 0.50, CI 0.32-0.96; P for trend = 0.032); however, after adjusting for potential confounders, no significant associations were observed between PRAL and NEAP scores and the risk of CVDs. CONCLUSIONS This study failed to obtain independent associations between dietary acid load and the incidence of CVDs among an Asian population.
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Affiliation(s)
- Parvin Mirmiran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Sahid-Erabi St, Yemen St, Chamran Exp, P.O.Box: 19395-4763, Tehran, Iran
| | - Zeinab Houshialsadat
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Sahid-Erabi St, Yemen St, Chamran Exp, P.O.Box: 19395-4763, Tehran, Iran
| | - Zahra Bahadoran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Sahid-Erabi St, Yemen St, Chamran Exp, P.O.Box: 19395-4763, Tehran, Iran.
| | - Sajjad Khalili-Moghadam
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Sahid-Erabi St, Yemen St, Chamran Exp, P.O.Box: 19395-4763, Tehran, Iran
| | - Mohammad Karim Shahrzad
- Shohada Tajrish Medical Center, Shahid Beheshti University of Medical Sciences, No. 24, Sahid-Erabi St, Yemen St, Chamran Exp, P.O.Box: 19395-4763, Tehran, Iran.
| | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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DiNicolantonio JJ, O'Keefe JH. Low-grade metabolic acidosis as a driver of insulin resistance. Open Heart 2021; 8:openhrt-2021-001788. [PMID: 34497064 PMCID: PMC8438953 DOI: 10.1136/openhrt-2021-001788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/27/2021] [Indexed: 11/03/2022] Open
Affiliation(s)
- James J DiNicolantonio
- Department of Preventive Cardiology, Saint Luke's Mid America Heart Institute, Kansas City, Missouri, USA
| | - James H O'Keefe
- University of Missouri-Kansas City, Saint Lukes Mid America Heart Institute, Kansas City, Missouri, USA
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SÖZEL H, YILMAZ F. The association between urine pH and abnormal glucose tolerance in adults. JOURNAL OF HEALTH SCIENCES AND MEDICINE 2021. [DOI: 10.32322/jhsm.941655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
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Wang Y, Wei L, Guan Y, Wang Q, Xie Q, Hao C. Diabetes is a risk factor for high-dose methotrexate-associated AKI in lymphoma patients. Ren Fail 2021; 42:1111-1117. [PMID: 33164656 PMCID: PMC7655081 DOI: 10.1080/0886022x.2020.1838926] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Purpose The aim of the study was to investigate the incidence of acute kidney injury (AKI) occurring after high-dose methotrexate (HDMTX) administration and the role of type 2 diabetes (T2D) playing in the occurrence of AKI. Methods We assessed associations between T2D along with other confounding factors mainly including baseline estimated glomerular filtration rate (eGFR), methotrexate (MTX) elimination and urine pH, and AKI occurrence. Patients who were diagnosed as primary central nervous system lymphoma with treatment of HDMTX and with eGFR ≥60 mL/min/1.73 m2 were enrolled in this study. Results Of the 507 courses enrolled in this study, 132 courses have T2D. Lower baseline eGFR, delayed MTX elimination, lower urine pH, and higher incidence of AKI were observed in T2D group. Using univariate logistic regression, several confounding factors including baseline eGFR, hypertension, MTX elimination, and urine alkalinization statistically and clinically important were screened out. After adjusting for these factors, T2D remained an independent association with AKI occurrence. AKI outcome had no significant relationship with severe hematological toxicity or hepatotoxicity. AKI was associated with faster eGFR decline after a series of HDMTX treatment courses. Conclusions Patients with T2D have a higher sensitivity to AKI when administrated with HDMTX. This conclusion addresses safety concerns for making chemotherapy regimen for this population.
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Affiliation(s)
- Yujia Wang
- Division of Nephrology, Huashan Hospital, and Nephrology Research Institute, Fudan University, Shanghai, China
| | - Li Wei
- Division of Hematology, Huashan Hospital, Fudan University, Shanghai, China
| | - Yi Guan
- Division of Nephrology, Huashan Hospital, and Nephrology Research Institute, Fudan University, Shanghai, China
| | - Qian Wang
- Division of Hematology, Huashan Hospital, Fudan University, Shanghai, China
| | - Qionghong Xie
- Division of Nephrology, Huashan Hospital, and Nephrology Research Institute, Fudan University, Shanghai, China
| | - Chuanming Hao
- Division of Nephrology, Huashan Hospital, and Nephrology Research Institute, Fudan University, Shanghai, China
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Noce A, Marrone G, Wilson Jones G, Di Lauro M, Pietroboni Zaitseva A, Ramadori L, Celotto R, Mitterhofer AP, Di Daniele N. Nutritional Approaches for the Management of Metabolic Acidosis in Chronic Kidney Disease. Nutrients 2021; 13:2534. [PMID: 34444694 PMCID: PMC8401674 DOI: 10.3390/nu13082534] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 07/20/2021] [Accepted: 07/21/2021] [Indexed: 12/11/2022] Open
Abstract
Metabolic acidosis is a severe complication of chronic kidney disease (CKD) which is associated with nefarious impairments such as bone demineralization, muscle wasting, and hormonal alterations, for example, insulin resistance. Whilst it is possible to control this condition with alkali treatment, consisting in the oral administration of sodium citrate or sodium bicarbonate, this type of intervention is not free from side effects. On the contrary, opting for the implementation of a targeted dietetic-nutritional treatment for the control of CKD metabolic acidosis also comes with a range of additional benefits such as lipid profile control, increased vitamins, and antioxidants intake. In our review, we evaluated the main dietary-nutritional regimens useful to counteract metabolic acidosis, such as the Mediterranean diet, the alkaline diet, the low-protein diet, and the vegan low-protein diet, analyzing the potentialities and limits of every dietary-nutritional treatment. Literature data suggest that the Mediterranean and alkaline diets represent a valid nutritional approach in the prevention and correction of metabolic acidosis in CKD early stages, while the low-protein diet and the vegan low-protein diet are more effective in CKD advanced stages. In conclusion, we propose that tailored nutritional approaches should represent a valid therapeutic alternative to counteract metabolic acidosis.
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Affiliation(s)
- Annalisa Noce
- UOC of Internal Medicine-Center of Hypertension and Nephrology Unit, Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (M.D.L.); (A.P.Z.); (L.R.); (A.P.M.); (N.D.D.)
| | - Giulia Marrone
- UOC of Internal Medicine-Center of Hypertension and Nephrology Unit, Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (M.D.L.); (A.P.Z.); (L.R.); (A.P.M.); (N.D.D.)
| | - Georgia Wilson Jones
- Center of Research of Immunopathology and Rare Diseases—Nephrology and Dialysis Coordinating Center of Piemonte and Aosta Valley Network for Rare Diseases, S. Giovanni Bosco Hospital, Department of Clinical and Biological Sciences, University of Turin, 10154 Turin, Italy;
| | - Manuela Di Lauro
- UOC of Internal Medicine-Center of Hypertension and Nephrology Unit, Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (M.D.L.); (A.P.Z.); (L.R.); (A.P.M.); (N.D.D.)
| | - Anna Pietroboni Zaitseva
- UOC of Internal Medicine-Center of Hypertension and Nephrology Unit, Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (M.D.L.); (A.P.Z.); (L.R.); (A.P.M.); (N.D.D.)
| | - Linda Ramadori
- UOC of Internal Medicine-Center of Hypertension and Nephrology Unit, Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (M.D.L.); (A.P.Z.); (L.R.); (A.P.M.); (N.D.D.)
- School of Specialization in Geriatrics, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
| | - Roberto Celotto
- Department of Cardiovascular Disease, Tor Vergata University of Rome, 00133 Rome, Italy;
| | - Anna Paola Mitterhofer
- UOC of Internal Medicine-Center of Hypertension and Nephrology Unit, Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (M.D.L.); (A.P.Z.); (L.R.); (A.P.M.); (N.D.D.)
| | - Nicola Di Daniele
- UOC of Internal Medicine-Center of Hypertension and Nephrology Unit, Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (M.D.L.); (A.P.Z.); (L.R.); (A.P.M.); (N.D.D.)
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Cicerello E, Ciaccia M, Cova GD, Mangano MS. The new patterns of nephrolithiasis: What has been changing in the last millennium? Arch Ital Urol Androl 2021; 93:195-199. [PMID: 34286555 DOI: 10.4081/aiua.2021.2.195] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 05/17/2021] [Indexed: 11/22/2022] Open
Abstract
Nephrolithiasis has been increasing over the last millennium. Although early epidemiologic studies have shown that kidney stones were two to three times more frequent in males than in females, recent reports have suggested that this rate is decreasing. In parallel a dramatic increase of nephrolithiasis has also been observed among children and adolescents. Furthermore, epidemiologic studies have shown a strong association between metabolic syndrome (Mets) traits and kidney stone disease. Patients with hypertension have a higher risk of stone formation and stone formers are predisposed to develop hypertension compared to the general population. An incidence of nephrolithiasis greater than 75% has been shown in overweight and obese patients compared to those of normal weight. It has also been reported that a previous diagnosis of diabetes mellitus increases the risk of future nephrolithiasis. Additionally, an association between metabolic syndrome and uric acid stone formation has been clearly recognized. Furthermore, 24-h urinary metabolic abnormalities have been decreasing among patients with nephrolithiasis over the last decades. Finally, nephrolithiasis could cause chronic kidney disease (CKD) and end stage renal disease (ESRD), especially in women and overweight patients. According to these observations, a better understanding of these new features among stone former patients may be required. Hence, the recognition and the correction of metabolic disorders could help not only to reduce the primary disease, but also stone recurrence.
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Affiliation(s)
- Elisa Cicerello
- Unità Complessa di Urologia, Dipartimento di Chirurgia Specialistica, Ospedale Ca' Foncello, Treviso.
| | - Matteo Ciaccia
- Unità Complessa di Urologia, Dipartimento di Chirurgia Specialistica, Ospedale Ca' Foncello, Treviso.
| | - Gian D Cova
- Unità Complessa di Urologia, Dipartimento di Chirurgia Specialistica, Ospedale Ca' Foncello, Treviso.
| | - Mario S Mangano
- Unità Complessa di Urologia, Dipartimento di Chirurgia Specialistica, Ospedale Ca' Foncello, Treviso.
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Lim SY, Chan YM, Ramachandran V, Shariff ZM, Chin YS, Arumugam M. Dietary Acid Load and Its Interaction with IGF1 (rs35767 and rs7136446) and IL6 (rs1800796) Polymorphisms on Metabolic Traits among Postmenopausal Women. Nutrients 2021; 13:nu13072161. [PMID: 34201855 PMCID: PMC8308464 DOI: 10.3390/nu13072161] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 02/25/2021] [Accepted: 02/27/2021] [Indexed: 02/07/2023] Open
Abstract
The objective of this study was to explore the effects of dietary acid load (DAL) and IGF1 and IL6 gene polymorphisms and their potential diet–gene interactions on metabolic traits. A total of 211 community-dwelling postmenopausal women were recruited. DAL was estimated using potential renal acid load (PRAL). Blood was drawn for biochemical parameters and DNA was extracted and Agena® MassARRAY was used for genotyping analysis to identify the signalling of IGF1 (rs35767 and rs7136446) and IL6 (rs1800796) polymorphisms. Interactions between diet and genetic polymorphisms were assessed using regression analysis. The result showed that DAL was positively associated with fasting blood glucose (FBG) (β = 0.147, p < 0.05) and there was significant interaction effect between DAL and IL6 with systolic blood pressure (SBP) (β = 0.19, p = 0.041). In conclusion, these findings did not support the interaction effects between DAL and IGF1 and IL6 single nucleotide polymorphisms (rs35767, rs7136446, and rs1800796) on metabolic traits, except for SBP. Besides, higher DAL was associated with higher FBG, allowing us to postulate that high DAL is a potential risk factor for diabetes.
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Affiliation(s)
- Sook Yee Lim
- Department of Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), Serdang 43400, Malaysia;
| | - Yoke Mun Chan
- Department of Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), Serdang 43400, Malaysia;
- Research Center of Excellence Nutrition and Non-Communicable Diseases, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), Serdang 43400, Malaysia;
- Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang 43400, Malaysia
- Correspondence: (Y.M.C.); (V.R.)
| | - Vasudevan Ramachandran
- Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang 43400, Malaysia
- Centre for Research, Bharath Institute of Higher Education and Research, 173, Agaram Main Rd, Selaiyur, Chennai, Tamil Nadu 600073, India
- Correspondence: (Y.M.C.); (V.R.)
| | - Zalilah Mohd Shariff
- Department of Nutrition, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), Serdang 43400, Malaysia;
| | - Yit Siew Chin
- Research Center of Excellence Nutrition and Non-Communicable Diseases, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), Serdang 43400, Malaysia;
- Department of Nutrition, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), Serdang 43400, Malaysia;
| | - Manohar Arumugam
- Department of Orthopedics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), Serdang 43400, Malaysia;
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45
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Zhang F, Zhu X, Zhang H, Xu L, Wu W, Hu X, Zhou H, Wei P, Li J. Case Report: Pink Urine Syndrome Following Exposure to Propofol: A Rare, Impressive but Benign Complication. Front Pharmacol 2021; 12:686619. [PMID: 34211398 PMCID: PMC8241095 DOI: 10.3389/fphar.2021.686619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 06/03/2021] [Indexed: 11/20/2022] Open
Abstract
Drug-induced changes in urine color induced by drugs may have clinical significance. Pink urine syndrome (PUS), which has been associated with urinary uric acid (UA) disorders, is most frequently reported in patients with morbid obesity undergoing gastric bypass surgery and/or from propofol anesthesia use in those who potentially have preexisting UA metabolism disorders. However, PUS has rarely occurred following exposure to propofol in non-obese patients, and literature on long-term follow-up after PUS is scarce. We report a case of PUS induced by propofol in a previously healthy non-obese woman after undergoing thoracoscopic wedge resection of pulmonary nodules under general anesthesia using propofol. The patient suddenly developed pink urine 4 h after surgery. A pink sediment rapidly precipitated at the bottom of the test tube following centrifugation of the urine. Amorphous, colorless UA-like crystals were identified under a polarizing microscope. The diagnosis of PUS was confirmed by examining the urinary UA concentration. The patient recovered and as followed-up for 1 month, during which she did not experience any urinary complications. To our knowledge, this is the first report to describe in detail a case of PUS caused by propofol in a non-obese patient with follow-up. PUS is usually benign and can resolve by rapidly on administering lactated Ringer's solution; however, the potential risk of urinary complications, particularly UA lithiasis, should be fully realized.
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Affiliation(s)
- Fangwei Zhang
- Department of Anesthesiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, China
| | - Xing Zhu
- Department of Pathology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, China
| | - Hongbo Zhang
- Department of Clinical Laboratory, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, China
| | - Lin Xu
- Department of Anesthesiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, China
| | - Weiguo Wu
- Department of Anesthesiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, China
| | - Xuelei Hu
- Department of Thoracic Surgery, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, China
| | - Haipeng Zhou
- Department of Anesthesiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, China
| | - Penghui Wei
- Department of Anesthesiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, China
| | - Jianjun Li
- Department of Anesthesiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, China
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Kahleova H, McCann J, Alwarith J, Rembert E, Tura A, Holubkov R, Barnard ND. A plant-based diet in overweight adults in a 16-week randomized clinical trial: The role of dietary acid load. Clin Nutr ESPEN 2021; 44:150-158. [PMID: 34330460 DOI: 10.1016/j.clnesp.2021.05.015] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 04/02/2021] [Accepted: 05/17/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Evidence suggests that changes in dietary acid load may influence body weight, body composition, and insulin sensitivity. METHODS Participants (n = 244) were randomly assigned to an intervention (vegan) (n = 122) or control group (n = 122) for 16 weeks. Before and after the intervention period, body composition was measured by dual X-ray absorptiometry. Insulin resistance was assessed with the Homeostasis Model Assessment (HOMA-IR) index and predicted insulin sensitivity index (PREDIM). Repeated measure ANOVA was used for statistical analysis. RESULTS Potential Renal Acid Load (PRAL) and Net Endogenous Acid Production (NEAP) decreased significantly in the vegan group with no change in the control group (treatment effect -24.7 mEq/day [95% CI -30.2 to -19.2]; p < 0.001; and -23.8 mEq/day [95% CI -29.6 to -18.0]; p < 0.001, respectively). Body weight decreased by 6.4 kg in the vegan group, compared with 0.5 kg in the control group (treatment effect -5.9 kg [95% CI -6.8 to -5.0]; Gxt, p < 0.001), largely due to a reduction in fat mass and visceral fat. HOMA-IR index decreased and PREDIM increased in the vegan group. After adjustment for energy intake, changes in PRAL and NEAP correlated positively with changes in body weight (r = +0.37; p < 0.001; and r = +0.37; p < 0.001, respectively), fat mass (r = +0.32; p < 0.001; and r = +0.32; p < 0.001, respectively), visceral fat (r = +0.19; p = 0.006; and r = +0.15; p = 0.03, respectively), and HOMA (r = +0.17; p = 0.02; and r = +0.20; p = 0.006, respectively), and negatively with changes in PREDIM (r = -0.22; p = 0.002; and r = -0.27; p < 0.001, respectively). CONCLUSION Dietary acid load as part of a plant-based diet was associated with changes in body weight, body composition, and insulin sensitivity, independent of energy intake. Mechanistic explanations suggest that the relationship may be causal. TRIAL REGISTRATION ClinicalTrials.gov number, NCT03698955.
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Affiliation(s)
- Hana Kahleova
- Physicians Committee for Responsible Medicine, Washington, DC, USA.
| | - James McCann
- Physicians Committee for Responsible Medicine, Washington, DC, USA
| | - Jihad Alwarith
- Physicians Committee for Responsible Medicine, Washington, DC, USA
| | - Emilie Rembert
- Physicians Committee for Responsible Medicine, Washington, DC, USA
| | - Andrea Tura
- Metabolic Unit, CNR Institute of Neuroscience, Padua, Italy
| | | | - Neal D Barnard
- Physicians Committee for Responsible Medicine, Washington, DC, USA; Adjunct Faculty, George Washington University School of Medicine and Health Sciences, Washington, DC, USA
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Abstract
Rationale & Objective Acid retention may occur in the absence of overt metabolic acidosis; thus it is important to identify populations at risk. Because obesity may alter renal acid-base handling, we sought to determine whether overweight and obesity are associated with increased risk for low serum bicarbonate levels, suggesting metabolic acidosis. Study Design Retrospective cohort study. Setting & Participants Adult patients (n = 96,147) visiting outpatient clinics in the Bronx, NY, between January 1, 2010, and December 31, 2015. Predictor Body mass index (BMI). Outcome Low serum bicarbonate level (≤23 mEq/L). Analytical Approach Longitudinal analyses were conducted using mixed-effects models to examine associations of BMI with serum bicarbonate levels over time and Cox proportional hazards models to examine associations of BMI with incident low bicarbonate levels. Results During a median follow-up of 4.4 (interquartile range, 2.3-6.3) years, patients had a median of 8 serum bicarbonate measurements and 34,539 patients developed low bicarbonate levels. Higher BMI was associated with progressively lower serum bicarbonate levels, with attenuation of the association in the highest BMI groups, suggesting a J-shaped relationship. Compared with the reference group (BMI, 18.5 to <25 kg.m2), patients with BMIs of 25 to <30, 30 to <35, 35 to <40, and ≥40 kg/m2 had HRs for incident low bicarbonate levels of 1.10 (95% CI, 1.05-1.14), 1.16 (95% CI, 1.11-1.21), 1.20 (95% CI, 1.14-1.26), and 1.15 (95% CI, 1.09-1.22). Results were similar after adjustment for serum urea nitrogen level and exclusion of patients with diabetes, hypertension, or estimated glomerular filtration rates < 60 mL/min/1.73 m2. Limitations Arterial pH measurements were unavailable. Conclusions Higher BMI is independently associated with progressively greater risk for developing low serum bicarbonate levels, indicating likely metabolic acidosis. Further research should explore the causes of low bicarbonate levels in patients with overweight and obesity.
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Affiliation(s)
- Douglas C Lambert
- Department of General Internal Medicine, Northwell Health, Great Neck.,Division of Obesity Medicine, Northwell Health, Great Neck
| | - Matthew K Abramowitz
- Department of Medicine, Albert Einstein College of Medicine, Bronx, NY.,Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY.,Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY.,Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of Medicine, Bronx, NY
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48
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Brito DW, Santa-Cruz F, Aquino MAR, Nascimento WA, Ferraz ÁAB, Kreimer F. Urolithiasis and sleeve gastrectomy: a prospective assessment of urinary biochemical variables. Rev Col Bras Cir 2021; 48:e20202804. [PMID: 33656135 PMCID: PMC10683422 DOI: 10.1590/0100-6991e-20202804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 10/28/2020] [Indexed: 11/21/2022] Open
Abstract
INTRODUCTION to evaluate urinary biochemical alterations related to urolithogenesis processes after sleeve gastrectomy (SG). MATERIALS AND METHODS : prospective study with 32 individuals without previous diagnosis of urolithiasis who underwent SG. A 24-h urine test was collected seven days prior to surgery and at 6-month follow-up. The studied variables were urine volume, urinary pH, oxalate, calcium, citrate, and magnesium and calcium oxalate super saturation (CaOx SS). RESULTS patients were mainly women (81.2%), with mean age of 40.6 years. Mean pre- and postoperative BMI were 47.1 ± 8.3 Kg/m2 and 35.5 ± 6.1 Kg/m2, respectively (p<0.001). Urine volume was significantly lower at the postoperative evaluation in absolute values (2,242.50 ± 798.26 mL x 1,240.94 ± 352.39 mL, p<0.001) and adjusted to body weight (18.58 ± 6.92 mL/kg x 13.92 ± 4.65 mL/kg, p<0.001). CaOx SS increased significantly after SG (0.11 ± 0.10 x 0.24 ± 0.18, p<0.001). Moreover, uric acid levels were significantly lower at the postoperative evaluation (482.34 ± 195.80 mg x 434.75 ± 158.38 mg, p=0.027). Urinary pH, oxalate, calcium, citrate, and magnesium did not present significant variations between the pre- and postoperative periods. CONCLUSION SG may lead to important alterations in the urinary profile. However, it occurs in a much milder way than that of RYGB.
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Affiliation(s)
- Denis Waked Brito
- - Hospital das Clínicas da Universidade Federal de Pernambuco (HC/UFPE), Urology Department - Recife - PE - Brasil
| | - Fernando Santa-Cruz
- - Universidade Federal de Pernambuco (UFPE), Medical course - Recife - PE - Brasil
| | | | - Wagner A Nascimento
- - Hospital das Clínicas da Universidade Federal de Pernambuco (HC/UFPE), Department of General Surgery - Recife - PE - Brasil
| | - Álvaro Antonio B Ferraz
- - Hospital das Clínicas da Universidade Federal de Pernambuco (HC/UFPE), Department of General Surgery - Recife - PE - Brasil
| | - FlÁvio Kreimer
- - Hospital das Clínicas da Universidade Federal de Pernambuco (HC/UFPE), Department of General Surgery - Recife - PE - Brasil
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Narang RK, Gamble GG, Topless R, Cadzow M, Stamp LK, Merriman TR, Dalbeth N. Assessing the Relationship Between Serum Urate and Urolithiasis Using Mendelian Randomization: An Analysis of the UK Biobank. Am J Kidney Dis 2021; 78:210-218. [PMID: 33400963 DOI: 10.1053/j.ajkd.2020.11.018] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Accepted: 11/14/2020] [Indexed: 02/04/2023]
Abstract
RATIONALE & OBJECTIVE The association between hyperuricemia and urolithiasis has been previously reported. However, this association is based on observational data, which are prone to residual confounding. The aim of this work was to use Mendelian randomization (MR) to evaluate if this relationship represents a causal effect of hyperuricemia. STUDY DESIGN MR analysis using 2 approaches: 2-stage MR and 2-sample MR. SETTING & PARTICIPANTS Participants aged 40-69 years from the UK Biobank Resource. EXPOSURE Serum urate. OUTCOME Urolithiasis. ANALYTICAL APPROACH An observational analysis testing for an association between serum urate level and urolithiasis was performed using logistic regression. For MR analyses, serum urate-associated single-nucleotide polymorphisms, identified from genome-wide association data, were used as instrumental variables for serum urate. In the 2-stage MR analysis, a weighted genetic urate score was calculated from the instrumental variables, and a control function estimation model was fit. In the 2-sample MR analysis, multiple-instrument MR via the inverse-variance weighted method was performed. RESULTS Individual-level data were available for 359,827 participants, of whom 6,398 (1.8%) reported urolithiasis. In the observational analysis, serum urate was positively associated with urolithiasis in an unadjusted analysis (odds ratio [OR], 1.47 [95% CI, 1.42-1.51]); however, after adjustment for relevant confounders, no association was observed (OR, 1.03 [95% CI, 0.99-1.08]). In the 2-stage MR analysis, no significant causal effect of serum urate level on urolithiasis was observed in the unadjusted (OR, 0.93 [95% CI, 0.81-1.08]) or adjusted (OR, 0.94 [95% CI, 0.80-1.09]) models. In the 2-sample MR analysis, multiple-instrument MR did not indicate a causal effect of serum urate on urolithiasis. LIMITATIONS Stone composition and urinalysis data, including urine pH, were not available for this study. CONCLUSIONS Our analyses do not support a causal effect of serum urate level on urolithiasis. The association between serum urate level and urolithiasis reported in observational studies is likely due to residual confounding.
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Affiliation(s)
- Ravi K Narang
- Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Greg G Gamble
- Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Ruth Topless
- Department of Biochemistry, University of Otago, Dunedin, New Zealand
| | - Murray Cadzow
- Department of Biochemistry, University of Otago, Dunedin, New Zealand
| | - Lisa K Stamp
- Department of Medicine, University of Otago, Christchurch, New Zealand
| | - Tony R Merriman
- Department of Biochemistry, University of Otago, Dunedin, New Zealand
| | - Nicola Dalbeth
- Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
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50
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Lee J, Chang HK, Lee S. Association of low urine pH as a metabolic feature with abdominal obesity. J Int Med Res 2020; 48:300060519898615. [PMID: 31992101 PMCID: PMC7113708 DOI: 10.1177/0300060519898615] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
Objective Low urine pH (LUP) is not only affected by environmental factors, but is also a feature of metabolic syndrome (MS), which is characterized by insulin resistance, abdominal obesity, dyslipidaemia and hypertension. However, it is unclear which factors contribute most to urine acidity. This study investigated factors influencing LUP and the link between LUP and metabolic traits in South Korea. Methods Participants were middle-aged subjects (age, 52.2 ± 8.9 years; average body mass index, 24.6 ± 3.2 kg/m2), of whom 4,626 had urine pH of 5.0 and were assigned to the LUP group and 4,185 had urine pH > 5.0 and were assigned to the control group. The association between LUP and various phenotypes, including environmental and metabolic traits, was analysed. Results LUP was significantly associated with MS diagnostic components and with environmental exposures such as smoking, alcohol intake and low-fibre diet. Multivariate analysis showed that the waist-to-hip ratio was the best predictor for LUP compared with other MS components (OR: 2.439). Conclusions LUP is an indicator of MS and is mainly related to the MS diagnostic criterion of abdominal obesity, even after adjusting for environmental influences on urine acidity.
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Affiliation(s)
- Juyoung Lee
- Graduate School, Kosin University, Busan, Republic of Korea.,Dongpyun-Bubu Korean Medical Clinic, Anyang, Republic of Korea
| | - Hee Kyung Chang
- Department of Pathology, Kosin University Gospel Hospital, Busan, Republic of Korea
| | - Sanghun Lee
- Department of Medical Consilience, Graduate School, Dankook University, Yongin, Republic of Korea
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