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Julius M, Lavsky HS, Kalfon L, Kfir NC, Herskovits M, Wiesmann I, Zaccai TCF. Primary hyperoxaluria type 3: from infancy to adulthood in a genetically unique cohort. Pediatr Nephrol 2025; 40:731-741. [PMID: 39476025 PMCID: PMC11753311 DOI: 10.1007/s00467-024-06536-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 09/02/2024] [Accepted: 09/03/2024] [Indexed: 01/21/2025]
Abstract
BACKGROUND Primary hyperoxaluria type 3 (PH3) is a rare autosomal recessive disorder caused by bi-allelic genetic variants in the 4 hydroxy-2 oxoglutarate aldolase (HOGA-1) gene. We report the natural history of PH3 in a 16-patient cohort, 15 from a unique genetically isolated population. METHODS This retrospective single-center study followed PH3 patients between 2003 and 2023 with demographic, clinical, radiographic, genetic, and biochemical parameters. Genetic population screening was performed in four villages to determine carrier frequency and identify couples at risk in a genetically isolated population. RESULTS Sixteen patients with biallelic (or homozygous) pathogenic variants (PV) in HOGA-1 (c.944_946 del, c.119C > A, c.208C > T) were included in the study, 15 Druze and one Jewish, aged 0-63 years at diagnosis (4 adults and 12 pediatric patients). All symptomatic patients had clinical or imaging signs of nephrolithiasis. One developed chronic kidney disease (CKD) stage 5; biopsy showed focal mesangial sclerosis and chronic tubulo-interstitial changes with few oxalate deposits. Two other patients had CKD stage 2 (eGFR 87 and 74 mL/min/1.73 m2) upon their last visit. The remaining cohort showed preserved kidney function until the latest follow-up. Of 1167 healthy individuals screened, 90 carriers were found, a rate of 1:13 in the genetically unique cohort screened. CONCLUSIONS A high prevalence of PH3 patients was found among a unique cohort, but probably still underdiagnosed due to relatively mild disease course. The carrier rate is high. There is no specific therapy for PH3, but early diagnosis can prevent redundant diagnostic efforts and provide early treatment for kidney stone disease. Even in our homogeneous cohort, kidney stone disease severity and CKD degree were variable, supporting a suspected contribution of yet unknown genetic or environmental factors.
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Affiliation(s)
- Michal Julius
- Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel
| | - Hadas Shasha Lavsky
- Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel
- Pediatric Nephrology Unit, Galilee Medical Center, Nahariya, Israel
| | - Limor Kalfon
- Galilee Medical Center, Institute of Human Genetics, Nahariya, Israel
| | - Nehama Cohen Kfir
- Galilee Medical Center, Institute of Human Genetics, Nahariya, Israel
| | | | - Irith Wiesmann
- Pediatric Nephrology Unit, Galilee Medical Center, Nahariya, Israel
| | - Tzipora C Falik Zaccai
- Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel.
- Galilee Medical Center, Institute of Human Genetics, Nahariya, Israel.
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Uy M, Molina K. Multiorgan Crystal Deposition in Acute Ethylene Glycol Toxicity. Am J Forensic Med Pathol 2025; 46:44-47. [PMID: 39392367 DOI: 10.1097/paf.0000000000000991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
Abstract
ABSTRACT Ethylene glycol (EG) is a widely available chemical and a well-known toxin in forensic pathology, which can lead to severe metabolic acidosis and death. Its metabolism in the body leads to formation of calcium oxalate (CO) crystals, which can precipitate in the kidney leading to renal failure. Although the identification of CO crystals in the kidney is widely known, the deposition of CO crystals in other organs has only occasionally been reported and seldom studied. This report examines 18 deaths due to EG toxicity for the presence of CO crystals in various organs. CO crystals were identified most often in the kidneys, followed by the brain and lungs. It is hypothesized that crystal deposition in these other organs may contribute to the toxicity of EG.
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Affiliation(s)
- Matthew Uy
- From the Department of Pathology, Mike O'Callaghan Military Medical Center, Nellis AFB, NV
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3
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FitzGerald JD, Barrios C, Liu T, Rosenthal A, McCarthy GM, Chen L, Bai B, Ma G, Ozcan A. A Novel Polarized Light Microscope for the Examination of Birefringent Crystals in Synovial Fluid. GOUT, URATE, AND CRYSTAL DEPOSITION DISEASE 2024; 2:315-324. [PMID: 39840290 PMCID: PMC11750256 DOI: 10.3390/gucdd2040022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/23/2025]
Abstract
Background The gold standard for crystal arthritis diagnosis relies on the identification of either monosodium urate (MSU) or calcium pyrophosphate (CPP) crystals in synovial fluid. With the goal of enhanced crystal detection, we adapted a standard compensated polarized light microscope (CPLM) with a polarized digital camera and multi-focal depth imaging capabilities to create digital images from synovial fluid mounted on microscope slides. Using this single-shot computational polarized light microscopy (SCPLM) method, we compared rates of crystal detection and raters' preference for image. Methods Microscope slides from patients with either CPP, MSU, or no crystals in synovial fluid were acquired using CPLM and SCPLM methodologies. Detection rate, sensitivity, and specificity were evaluated by presenting expert crystal raters with (randomly sorted) CPLM and SCPLM digital images, from FOV above clinical samples. For each FOV and each method, each rater was asked to identify crystal suspects and their level of certainty for each crystal suspect and crystal type (MSU vs. CPP). Results For the 283 crystal suspects evaluated, SCPLM resulted in higher crystal detection rates than did CPLM, for both CPP (51%. vs. 28%) and MSU (78% vs. 46%) crystals. Similarly, sensitivity was greater for SCPLM for CPP (0.63 vs. 0.35) and MSU (0.88 vs. 0.52) without giving up much specificity resulting in higher AUC. Conclusions Subjective and objective measures of greater detection and higher certainty were observed for SCPLM over CPLM, particularly for CPP crystals. The digital data associated with these images can ultimately be incorporated into an automated crystal detection system that provides a quantitative report on crystal count, size, and morphology.
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Affiliation(s)
- John D. FitzGerald
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
| | - Chesca Barrios
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
| | - Tairan Liu
- Electrical and Computer Engineering Department, University of California, Los Angeles, CA 90095, USA
- Bioengineering Department, University of California, Los Angeles, CA 90095, USA
- California NanoSystems Institute (CNSI), University of California, Los Angeles, CA 90095, USA
| | - Ann Rosenthal
- Will and Cava Ross Professor of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Geraldine M. McCarthy
- Mater Misericordiae University Hospital and School of Medicine, University College Dublin, D04 C1P1 Dublin, Ireland
| | - Lillian Chen
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
| | - Bijie Bai
- Electrical and Computer Engineering Department, University of California, Los Angeles, CA 90095, USA
- Bioengineering Department, University of California, Los Angeles, CA 90095, USA
- California NanoSystems Institute (CNSI), University of California, Los Angeles, CA 90095, USA
| | - Guangdong Ma
- Electrical and Computer Engineering Department, University of California, Los Angeles, CA 90095, USA
- Bioengineering Department, University of California, Los Angeles, CA 90095, USA
- California NanoSystems Institute (CNSI), University of California, Los Angeles, CA 90095, USA
| | - Aydogan Ozcan
- Electrical and Computer Engineering Department, University of California, Los Angeles, CA 90095, USA
- Bioengineering Department, University of California, Los Angeles, CA 90095, USA
- California NanoSystems Institute (CNSI), University of California, Los Angeles, CA 90095, USA
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Hama Rashid AK, Salih RQ, Fakhralddin SS, Mohammed AA, Muhammed HM, Ameen Ahmed NH, Salih GM, Mustafa AM, Muhammed BO, Kakamad FH. Semen uric acid crystals in azoospermia linked to Sertoli cell‑only syndrome: A rare case report. Exp Ther Med 2024; 28:397. [PMID: 39171146 PMCID: PMC11336801 DOI: 10.3892/etm.2024.12686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 07/09/2024] [Indexed: 08/23/2024] Open
Abstract
The occurrence of crystals in semen is rare, with spermine phosphate crystals being the only type commonly described. Uric acid crystal formation is significantly influenced by pH levels. The present study reported a rare case of uric acid crystals in the semen of a patient with azoospermia associated with Sertoli cell-only syndrome (SCOS). A 28-year-old male with a four-year history of primary infertility underwent clinical assessment, including a normal physical examination with small testes. Seminal fluid analysis revealed abnormal uric acid crystals. Elevated follicle-stimulating hormone, luteinizing hormone and prolactin levels were observed. The diagnosis of SCOS was confirmed through testicular sperm aspiration. Azoospermia is a medical condition characterized by the absence of sperm in the semen, specifically the absence of sperm in the pellet obtained after centrifugation. It is classified into two primary types: Obstructive and non-obstructive azoospermia. Non-obstructive azoospermia is subdivided into three categories: SCOS, hypospermatogenesis and maturation arrest. The occurrence of SCOS in azoospermic males ranges from 26.3 to 57.8%. The diagnosis of azoospermia with SCOS can be achieved through the analysis of multiple semen samples, medical history, physical examination, hormonal analysis, histopathological examination and genetic testing. The presence of uric acid crystals in seminal fluid was first reported in patients with chronic prostatitis symptoms in 2005. Despite the rarity of crystals in semen, uric acid crystals were found in the semen of an azoospermic male with SCOS.
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Affiliation(s)
- Awara K. Hama Rashid
- Scientific Affairs Department, Smart Health Tower, Sulaymaniyah, Kurdistan 46001, Iraq
| | - Rawezh Q. Salih
- Scientific Affairs Department, Smart Health Tower, Sulaymaniyah, Kurdistan 46001, Iraq
- Kscien Organization for Scientific Research, Azadi Mall, Sulaymaniyah, Kurdistan 46001, Iraq
- Biology Department, College of Science, University of Sulaimani, Sulaymaniyah, Kurdistan 46001, Iraq
| | - Saman S. Fakhralddin
- Scientific Affairs Department, Smart Health Tower, Sulaymaniyah, Kurdistan 46001, Iraq
- College of Medicine, University of Sulaimani, Sulaymaniyah, Kurdistan 46001, Iraq
- Department of Urology, Sulaymaniyah Surgical Teaching Hospital, Sulaymaniyah, Kurdistan 46001, Iraq
| | - Ayoob A. Mohammed
- Scientific Affairs Department, Smart Health Tower, Sulaymaniyah, Kurdistan 46001, Iraq
- College of Medicine, University of Sulaimani, Sulaymaniyah, Kurdistan 46001, Iraq
| | - Huda M. Muhammed
- Scientific Affairs Department, Smart Health Tower, Sulaymaniyah, Kurdistan 46001, Iraq
- College of Medicine, University of Sulaimani, Sulaymaniyah, Kurdistan 46001, Iraq
- Department of Obstetrics and Gynaecology, Sulaimani Maternity Teaching Hospital, Sulaymaniyah, Kurdistan 46001, Iraq
| | - Nahidah H. Ameen Ahmed
- Scientific Affairs Department, Smart Health Tower, Sulaymaniyah, Kurdistan 46001, Iraq
- Department of Obstetrics and Gynaecology, Sulaimani Maternity Teaching Hospital, Sulaymaniyah, Kurdistan 46001, Iraq
| | - Goran M. Salih
- Scientific Affairs Department, Smart Health Tower, Sulaymaniyah, Kurdistan 46001, Iraq
| | - Ayman M. Mustafa
- Scientific Affairs Department, Smart Health Tower, Sulaymaniyah, Kurdistan 46001, Iraq
| | - Bryar O. Muhammed
- Scientific Affairs Department, Smart Health Tower/Raparin, Sulaymaniyah, Kurdistan 46001, Iraq
| | - Fahmi H. Kakamad
- Scientific Affairs Department, Smart Health Tower, Sulaymaniyah, Kurdistan 46001, Iraq
- Kscien Organization for Scientific Research, Azadi Mall, Sulaymaniyah, Kurdistan 46001, Iraq
- College of Medicine, University of Sulaimani, Sulaymaniyah, Kurdistan 46001, Iraq
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Niessink T, Stassen RHMJ, Kischkel B, Vuscan P, Emans PJ, van den Akker GGH, Janssen M, Joosten LAB, Otto C, Welting TJM, Jansen TL. Discovery of calcite as a new pro-inflammatory calcium-containing crystal in human osteoarthritic synovial fluid. Osteoarthritis Cartilage 2024; 32:1261-1272. [PMID: 38806070 DOI: 10.1016/j.joca.2024.05.004] [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: 01/11/2024] [Revised: 05/14/2024] [Accepted: 05/21/2024] [Indexed: 05/30/2024]
Abstract
OBJECTIVE We aimed to characterize calcium-containing crystals present in synovial fluid from patients with knee osteoarthritis (OA) using Raman spectroscopy, and specifically investigate the biological effects of calcite crystals. DESIGN Thirty-two synovial fluid samples were collected pre-operatively from knee OA patients undergoing total joint arthroplasty. An integrated Raman polarized light microscope was used for identification of crystals in synovial fluid. Human peripheral blood mononuclear cells (PBMC's), human OA articular chondrocytes (HACs) and fibroblast-like synoviocytes (FLSs) were exposed to calcite crystals. Expression of relevant cytokines and inflammatory genes were measured using enzyme-linked immuno sorbent assay (ELISA) and real-time polymerase chain reaction (PCR). RESULTS Various calcium-containing crystals were identified, including calcium pyrophosphate (37.5 %) and basic calcium phosphate (21.8 %), but they were never found simultaneously in the same OA synovial fluid sample. For the first time, we discovered the presence of calcite crystals in 93.8 % of the samples, while dolomite was detected in 25 % of the cases. Characterization of the cellular response to calcite crystal exposure revealed increased production of innate immune-derived cytokines by PBMC's, when co-stimulated with lipopolysaccharide (LPS). Additionally, calcite crystal stimulation of HACs and FLSs resulted in enhanced secretion of pro-inflammatory molecules and alterations in the expression of extracellular matrix remodeling enzymes. CONCLUSIONS This study highlights the unique role of Raman spectroscopy in OA crystal research and identified calcite as a novel pro-inflammatory crystal type in OA synovial fluid. Understanding the role of specific crystal species in the OA joint may open new avenues for pharmacological interventions and personalized approaches to treating OA.
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Affiliation(s)
- Tom Niessink
- Department of Rheumatology, VieCuri Medical Centre, Tegelseweg 210, 5912 BL Venlo, the Netherlands; Personalized Therapeutics and Diagnostics, Department of Bioengineering Technology, University of Twente, Drienerlolaan 5, 7522 NB Enschede, the Netherlands.
| | - Roderick H M J Stassen
- Department of Experimental Orthopaedics, Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX Maastricht, the Netherlands
| | - Brenda Kischkel
- Department of Internal Medicine, Radboud University Medical Centre, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, the Netherlands
| | - Patricia Vuscan
- Department of Internal Medicine, Radboud University Medical Centre, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, the Netherlands
| | - Peter J Emans
- Department of Experimental Orthopaedics, Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX Maastricht, the Netherlands
| | - Guus G H van den Akker
- Department of Experimental Orthopaedics, Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX Maastricht, the Netherlands
| | - Matthijs Janssen
- Department of Rheumatology, VieCuri Medical Centre, Tegelseweg 210, 5912 BL Venlo, the Netherlands
| | - Leo A B Joosten
- Department of Internal Medicine, Radboud University Medical Centre, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, the Netherlands; Department of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Str. Pasteur, Nr. 6, 400012 Cluj-Napoca, Romania
| | - Cees Otto
- Personalized Therapeutics and Diagnostics, Department of Bioengineering Technology, University of Twente, Drienerlolaan 5, 7522 NB Enschede, the Netherlands
| | - Tim J M Welting
- Department of Experimental Orthopaedics, Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX Maastricht, the Netherlands
| | - Tim L Jansen
- Department of Rheumatology, VieCuri Medical Centre, Tegelseweg 210, 5912 BL Venlo, the Netherlands
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Niessink T, Janssen M, Giesen T, Efdé MN, Comarniceanu AC, Otto C, Jansen TL. Diagnostic Accuracy of Raman Spectroscopy Integrated With Polarized Light Microscopy for Calcium Pyrophosphate-Associated Arthritis. Arthritis Care Res (Hoboken) 2024; 76:1333-1341. [PMID: 38622108 DOI: 10.1002/acr.25350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 03/14/2024] [Accepted: 04/11/2024] [Indexed: 04/17/2024]
Abstract
OBJECTIVE We studied the performance of integrated Raman polarized light microscopy (iRPolM) for the identification of calcium pyrophosphate (CPP)-associated arthritis (CPPD). METHODS This is a diagnostic accuracy study including 400 consecutive synovial fluid samples from a single hospital in the Netherlands. Accuracy measures were calculated against polarized light microscopy (PLM) and the 2023 American College of Rheumatology (ACR)/EULAR criteria set for CPPD. RESULTS The interrater reliability between iRPolM and the 2023 ACR/EULAR criteria set for CPPD was strong (κ = 0.88). The diagnostic performance of iRPolM compared to the 2023 ACR/EULAR criteria set was sensitivity 86.0% (95% confidence interval [CI] 73.3-94.2), specificity 99.1% (95% CI 97.5-99.8), positive likelihood ratio 100.33 (95% CI 32.3-311.3), negative likelihood ratio 0.14 (95% CI 0.07-0.28), positive predictive value 93.5% (95% CI 82.2-97.8), negative predictive value 98.0% (95% CI 82.2-97.8), and accuracy 97.5% (95% CI 95.5-98.8). We allowed rheumatologists to rate the certainty of their microscopic identification of CPP and found a large correspondence between iRPolM and a certain identification (κ = 0.87), whereas only 10% of the uncertain CPP identifications could be confirmed with iRPolM. We identified several novel particle types in synovial fluid analysis, including calcium carbonate crystals, deposited carotenoids, microplastics, and three types of Maltese cross birefringent objects. CONCLUSION iRPolM can easily identify CPP crystals with a strong diagnostic performance. PLM alone is not specific enough to reliably resolve complicated cases, and the implementation of Raman spectroscopy in rheumatology practice can be of benefit to patients with suspected CPPD.
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Affiliation(s)
- Tom Niessink
- Personalized Diagnostics and Therapeutics, University of Twente, Enschede, the Netherlands
- Department of Rheumatology, VieCuri Medical Centre, Venlo, the Netherlands
| | - Matthijs Janssen
- Department of Rheumatology, VieCuri Medical Centre, Venlo, the Netherlands
| | - Tanja Giesen
- Department of Rheumatology, VieCuri Medical Centre, Venlo, the Netherlands
| | - Monique N Efdé
- Department of Rheumatology, VieCuri Medical Centre, Venlo, the Netherlands
| | | | - Cees Otto
- Personalized Diagnostics and Therapeutics, University of Twente, Enschede, the Netherlands
| | - Tim L Jansen
- Department of Rheumatology, VieCuri Medical Centre, Venlo, the Netherlands
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Hassona Y, Hassan S, Atef A, Flaifl Y, AlShammas F, Abdaljaleel M. Primary hyperoxaluria: Description of a new oral finding and review of literature. SPECIAL CARE IN DENTISTRY 2024; 44:1041-1048. [PMID: 38321570 DOI: 10.1111/scd.12968] [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: 12/16/2023] [Revised: 01/04/2024] [Accepted: 01/20/2024] [Indexed: 02/08/2024]
Abstract
OBJECTIVES Oro-dental manifestations of hyperoxaluria and dental management of affected patients are rarely reported in the literature. We describe a new oral presentation of primary hyperoxaluria (PH) and review relevant literature about oro-dental manifestations and management of dental complications of hyperoxaluria. METHODS A case report of a 44-year-old female who presented with symptoms of temporomandibular joint dysfunction due to hyperoxaluria was described according to the CARE guidelines. In addition, an extensive search of biomedical databases (PubMed, Medline, Google Scholar, and Embase) for articles describing oro-dental manifestations and/or dental management in patients with hyperoxaluria was performed using the key words ("oral" and/or "hyperoxaluria" and/or "dental" and/or "oxalosis"). Included articles were reviewed and data about patient demographics, disease type and stage, oral and dental manifestations, and dental treatment outcome were retrieved and analyzed. RESULTS A total of 14 articles describing the oral and dental manifestations in 15 patients with hyperoxaluria were included. Tooth mobility, root resorption, and radiographic alterations were consistently described in all cases. Oral manifestations were described mainly in PH at late stages, and only after the onset of chronic renal disease. Dental management in all reported cases was palliative and aimed to relive pain and treat periodontal infection. Tooth loss due to extraction or uncontrolled mobility was the ultimate outcome in almost all reported cases. CONCLUSION Oral and dental manifestations in hyperoxaluria are rarely reported in the literature. Management of tooth mobility and root resorption in hyperoxaluria is challenging and clinical guidelines and evidence-based recommendations are lacking. Early diagnosis and treatment of hyperoxaluria might be the only effective approach to prevent dental and periodontal complications of the disease.
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Affiliation(s)
- Yazan Hassona
- Faculty of Dentistry, Centre for Oral Diseases Studies (CODS), Al-Ahliyya Amman University, Amman, Jordan
- School of Dentistry, The University of Jordan, Amman, Jordan
| | - Sora Hassan
- School of Dentistry, The University of Jordan, Amman, Jordan
| | - Alaa Atef
- School of Dentistry, The University of Jordan, Amman, Jordan
| | - Yara Flaifl
- School of Dentistry, The University of Jordan, Amman, Jordan
| | - Faris AlShammas
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman, Jordan
| | - Maram Abdaljaleel
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman, Jordan
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Lathiya MK, Errabelli P, Roy S, Mareedu N. Severe acute kidney injury due to oxalate crystal induced severe interstitial nephritis: A case report. World J Nephrol 2024; 13:93976. [PMID: 38983760 PMCID: PMC11229832 DOI: 10.5527/wjn.v13.i2.93976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 05/04/2024] [Accepted: 05/21/2024] [Indexed: 06/25/2024] Open
Abstract
BACKGROUND Acute kidney injury (AKI) due to interstitial nephritis is a known condition primarily attributed to various medications. While medication-induced interstitial nephritis is common, occurrences due to non-pharmacological factors are rare. This report presents a case of severe AKI triggered by intratubular oxalate crystal deposition, leading to interstitial nephritis. The aim is to outline the case and its management, emphasizing the significance of recognizing uncommon causes of interstitial nephritis. CASE SUMMARY A 71-year-old female presented with stroke-like symptoms, including weakness, speech difficulties, and cognitive impairment. Chronic hypertension had been managed with hydrochlorothiazide (HCTZ) for over two decades. Upon admission, severe hypokalemia and AKI were noted, prompting discontinuation of HCTZ and initiation of prednisolone for acute interstitial nephritis. Further investigations, including kidney biopsy, confirmed severe acute interstitial nephritis with oxalate crystal deposits as the underlying cause. Despite treatment, initial renal function showed minimal improvement. However, with prednisolone therapy and supportive measures, her condition gradually improved, highlighting the importance of comprehensive management. CONCLUSION This case underscores the importance of a thorough diagnostic approach in identifying and addressing uncommon causes of interstitial nephritis. The occurrence of interstitial nephritis due to oxalate crystal deposition, especially without typical risk factors, emphasizes the need for vigilance in clinical practice.
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Affiliation(s)
- Maulik K Lathiya
- Department of Emergency Medicine, Mayo Clinic Health System, Eau Claire, WI 54703, United States
| | - Praveen Errabelli
- Department of Nephrology, Mayo Clinic Health System, Eau Claire, WI 54703, United States
| | - Sasmit Roy
- Department of Nephrology, Centra Lynchburg General Hospital, Lynchburg, VA 24551, United States
| | - Neeharik Mareedu
- Department of Nephrology, UPMC Western Maryland, Cumberland, MD 21502, United States
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Antoniadou C, Fytanidis N, Devetzis V, Kantartzi K, Papagoras C. Anakinra for Refractory Pseudogout in Patients with End-stage Renal Disease on Haemodialysis. Mediterr J Rheumatol 2024; 35:58-62. [PMID: 38756932 PMCID: PMC11094439 DOI: 10.31138/mjr.261123.afr] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Revised: 12/08/2023] [Accepted: 12/11/2023] [Indexed: 05/18/2024] Open
Abstract
Calcium pyrophosphate deposition (CPPD) arthritis is the second most common type of crystal-induced arthritis after gout. Acute flares are commonly treated with non-steroidal anti-inflammatory drugs, intra-articular or short-term systemic glucocorticoids or colchicine. However, since there is no pharmacological treatment to reduce CPPD crystal burden, relapsing or chronic CPPD arthritis may be challenging to treat, particularly in patients with end-stage renal disease who are at risk for toxicity of the above medications. Since IL-1β appears to be driving CPPD arthritis, we treated two patients with chronic CPPD arthritis and end-stage renal disease on haemodialysis with the IL-1β receptor antagonist anakinra. In both patients, arthritis resolved quickly, while continuation of anakinra maintained remission and allowed complete glucocorticoid withdrawal. Therefore, anakinra may be a safe and effective option both for short and long-term treatment of CPPD arthritis in patients on chronic renal replacement therapy.
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Affiliation(s)
- Christina Antoniadou
- First Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece
| | - Nikolaos Fytanidis
- First Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece
| | | | - Konstantia Kantartzi
- Department of Nephrology, University Hospital of Alexandroupolis Democritus University of Thrace, Alexandroupolis, Greece
| | - Charalampos Papagoras
- First Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece
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Mrabet S, BenHmida M. Late Presentation of Primary Oxalosis, Microcrystalline Arthropathy, and Tumoral Calcinosis: A Case Report and a Literature Review. Curr Rheumatol Rev 2024; 20:455-458. [PMID: 38243963 DOI: 10.2174/0115733971271874231118154332] [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: 07/29/2023] [Revised: 08/30/2023] [Accepted: 09/12/2023] [Indexed: 01/22/2024]
Abstract
BACKGROUND Primary hyperoxaluria consists of a group of inherited disorders with enzymatic defects in the glyoxylate pathway, leading to decreased oxalate metabolism. The resulting oxalic deposition is specifically responsible for kidney disease and joint disease. Neonatal oxalosis is the most severe form of primary hyperoxia type 1, with the onset of end-stage renal disease in childhood. CASE PRESENTATION A 55-year-old hemodialysis man was referred to Nephrology because of inflammatory polyarthralgia and periarticular swelling evolving for six months. He had been on hemodialysis for six years for end-stage chronic renal failure, diagnosed at the same time as primary hyperoxaluria. Radiological investigation showed a rugby jersey appearance on the lumbar spine, budding calcium tone opacities next to large joints and clavicles, vascular calcifications and tumoral calcinosis. The synovial fluid contained a few cells with polymorphic intracellular crystals. We ruled out hyperparathyroidism, hypoparathyroidism, and related phosphocalcic disorders, and we retained arthropathy and tumoral calcinosis secondary to primary hyperoxaliuria. The patient also had congestive heart failure. Despite intensification of hemodialysis, he did not improve and died at the age of 56 in the context of cachexia. CONCLUSION This rare case documents the possible occurrence of late clinical presentation and long survival in primary oxalosis with extra renal complications.
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Affiliation(s)
- Sanda Mrabet
- Department of Nephrology, Dialysis, and Transplantation, Sahloul University Hospital, Sousse, Tunisia
| | - Mohamed BenHmida
- Department of Nephrology, Dialysis, and Transplantation, Hedi Chaker University Hospital, Sfax, Tunisia
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11
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García JA, Millán GR, Scioli V, Britos G, Morrell E, Odriozola E, Micheloud JF, Cantón G. Amaranthus hybridus (syn. quitensis) intoxication in cattle in Argentina: Case report. Toxicon 2024; 237:107533. [PMID: 38013055 DOI: 10.1016/j.toxicon.2023.107533] [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: 09/21/2023] [Revised: 10/29/2023] [Accepted: 11/21/2023] [Indexed: 11/29/2023]
Abstract
Amaranthus spp. is a nephrotoxic plant with unknown toxic principle, affecting production animals worldwide, mainly in South America. The aim of this paper is to describe 5 spontaneous outbreaks of A. hybridus intoxication in beef cattle, where 7 autopsies were performed. Main gross findings were pale diffuse and enlarged kidneys. Microscopically, kidneys were characterized by severe tubular acute to subacute nephrosis, with dilatated tubules showing different degrees of epithelial degeneration and necrosis, and containing intraluminal eosinophilic hyaline casts. Intratubular birefringent crystals, compatible with oxalate, were observed under polarized light in kidneys from 3 autopsies. Positive von Kossa and red alizarin S staining confirmed the intratubular crystals as calcium deposits. This intoxication occurs mainly in stubble paddocks during summer and early autumn. The data from the present study suggests that oxalates were related to nephrotoxicity due to Amaranthus consumption.
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Affiliation(s)
- Juan Agustín García
- Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible (IPADS, INTA Balcarce-CONICET), RN 226 Km 73.5, Balcarce, 7620, Buenos Aires, Argentina.
| | - Gina Rustichelli Millán
- Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible (IPADS, INTA Balcarce-CONICET), RN 226 Km 73.5, Balcarce, 7620, Buenos Aires, Argentina.
| | - Valeria Scioli
- Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible (IPADS, INTA Balcarce-CONICET), RN 226 Km 73.5, Balcarce, 7620, Buenos Aires, Argentina.
| | - Gastón Britos
- Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible (IPADS, INTA Balcarce-CONICET), RN 226 Km 73.5, Balcarce, 7620, Buenos Aires, Argentina.
| | - Eleonora Morrell
- Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible (IPADS, INTA Balcarce-CONICET), RN 226 Km 73.5, Balcarce, 7620, Buenos Aires, Argentina
| | - Ernesto Odriozola
- Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible (IPADS, INTA Balcarce-CONICET), RN 226 Km 73.5, Balcarce, 7620, Buenos Aires, Argentina.
| | - Juan Francisco Micheloud
- Instituto Nacional de Tecnología Agropecuaria (INTA), Instituto de Investigación Animal del Chaco Semiárido, Área de Investigación en Salud Animal, EEA Salta, Salta, Argentina; CCT Salta-Jujuy, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina; Facultad de Ciencias Agrarias y Veterinarias - UCASAL, Salta, Argentina.
| | - Germán Cantón
- Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible (IPADS, INTA Balcarce-CONICET), RN 226 Km 73.5, Balcarce, 7620, Buenos Aires, Argentina.
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Salgado N, Silva MA, Figueira ME, Costa HS, Albuquerque TG. Oxalate in Foods: Extraction Conditions, Analytical Methods, Occurrence, and Health Implications. Foods 2023; 12:3201. [PMID: 37685134 PMCID: PMC10486698 DOI: 10.3390/foods12173201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/19/2023] [Accepted: 08/23/2023] [Indexed: 09/10/2023] Open
Abstract
Oxalate is an antinutrient present in a wide range of foods, with plant products, especially green leafy vegetables, being the main sources of dietary oxalates. This compound has been largely associated with hyperoxaluria, kidney stone formation, and, in more severe cases, systematic oxalosis. Due to its impact on human health, it is extremely important to control the amount of oxalate present in foods, particularly for patients with kidney stone issues. In this review, a summary and discussion of the current knowledge on oxalate analysis, its extraction conditions, specific features of analytical methods, reported occurrence in foods, and its health implications are presented. In addition, a brief conclusion and further perspectives on whether high-oxalate foods are truly problematic and can be seen as health threats are shown.
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Affiliation(s)
- Neuza Salgado
- Research and Development Unit, Department of Food and Nutrition, National Institute of Health Dr. Ricardo Jorge, Avenida Padre Cruz, 1649-016 Lisbon, Portugal (T.G.A.)
- Faculty of Pharmacy, University of Lisbon, Avenida Professor Gama Pinto, 1649-003 Lisbon, Portugal
| | - Mafalda Alexandra Silva
- Research and Development Unit, Department of Food and Nutrition, National Institute of Health Dr. Ricardo Jorge, Avenida Padre Cruz, 1649-016 Lisbon, Portugal (T.G.A.)
- REQUIMTE-LAQV/Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
| | - Maria Eduardo Figueira
- Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Avenida Professor Gama Pinto, 1649-003 Lisbon, Portugal
| | - Helena S. Costa
- Research and Development Unit, Department of Food and Nutrition, National Institute of Health Dr. Ricardo Jorge, Avenida Padre Cruz, 1649-016 Lisbon, Portugal (T.G.A.)
- REQUIMTE-LAQV/Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
| | - Tânia Gonçalves Albuquerque
- Research and Development Unit, Department of Food and Nutrition, National Institute of Health Dr. Ricardo Jorge, Avenida Padre Cruz, 1649-016 Lisbon, Portugal (T.G.A.)
- REQUIMTE-LAQV/Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
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13
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Loret A, Jacob C, Mammou S, Bigot A, Blasco H, Audemard-Verger A, Schwartz IV, Mulleman D, Maillot F. Joint manifestations revealing inborn metabolic diseases in adults: a narrative review. Orphanet J Rare Dis 2023; 18:239. [PMID: 37563694 PMCID: PMC10416490 DOI: 10.1186/s13023-023-02810-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 07/06/2023] [Indexed: 08/12/2023] Open
Abstract
Inborn metabolic diseases (IMD) are rare conditions that can be diagnosed during adulthood. Patients with IMD may have joint symptoms and the challenge is to establish an early diagnosis in order to institute appropriate treatment and prevent irreversible damage. This review describes the joint manifestations of IMD that may be encountered in adults. The clinical settings considered were arthralgia and joint stiffness as well as arthritis. Unspecific arthralgias are often the first symptoms of hereditary hemochromatosis, chronic low back pain may reveal an intervertebral disc calcification in relation with alkaptonuria, and progressive joint stiffness may correspond to a mucopolysaccharidosis or mucolipidosis. Gaucher disease is initially revealed by painful acute attacks mimicking joint pain described as "bone crises". Some IMD may induce microcrystalline arthropathy. Beyond classical gout, there are also gouts in connection with purine metabolism disorders known as "enzymopathic gouts". Pyrophosphate arthropathy can also be part of the clinical spectrum of Gitelman syndrome or hypophosphatasia. Oxalate crystals arthritis can reveal a primary hyperoxaluria. Destructive arthritis may be indicative of Wilson's disease. Non-destructive arthritis may be seen in mevalonate kinase deficiency and familial hypercholesterolemia.
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Affiliation(s)
- Amaury Loret
- Department of Internal Medicine, University Hospital of Tours, Tours, France.
- Department of Rheumatology, University Hospital of Tours, Tours, France.
- Department of Internal Medicine, Hôpital Bretonneau, 2 Boulevard Tonnellé, CHRU de Tours, Tours cedex, 37044, France.
| | - Claire Jacob
- Department of Internal Medicine, University Hospital of Tours, Tours, France
| | - Saloua Mammou
- Department of Rheumatology, University Hospital of Tours, Tours, France
| | - Adrien Bigot
- Department of Internal Medicine, University Hospital of Tours, Tours, France
| | - Hélène Blasco
- Biochemistry laboratory, University Hospital of Tours, Tours, France
- UMR INSERM 1253, Tours, France
- Reference center for inherited metabolic diseases, Tours, France
| | | | - Ida Vd Schwartz
- Medical Genetics Service/Genetics Department, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre - RS, Brazil
| | - Denis Mulleman
- Department of Rheumatology, University Hospital of Tours, Tours, France
| | - François Maillot
- Department of Internal Medicine, University Hospital of Tours, Tours, France
- UMR INSERM 1253, Tours, France
- Reference center for inherited metabolic diseases, Tours, France
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14
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Gaddy A, Schwantes-An TH, Moorthi RN, Phillips CL, Eadon MT, Moe SM. Incidence and Importance of Calcium Deposition in Kidney Biopsy Specimens. Am J Nephrol 2022; 53:526-533. [PMID: 35871513 PMCID: PMC10503271 DOI: 10.1159/000525647] [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: 03/14/2022] [Accepted: 06/15/2022] [Indexed: 08/05/2023]
Abstract
INTRODUCTION Calcification on native kidney biopsy specimens is often noted by pathologists, but the consequence is unknown. METHODS We searched the pathology reports in the Biopsy Biobank Cohort of Indiana for native biopsy specimens with calcification. RESULTS Of the 4,364 specimens, 416 (9.8%) had calcification. We compared clinical and histopathology findings in those with calcification (n = 429) compared to those without calcification (n = 3,936). Patients with calcification were older, had more comorbidities, lower estimated glomerular filtration rates (eGFR), were more likely to have hyaline arteriosclerosis, interstitial fibrosis/tubular atrophy, and a primary pathologic diagnosis of acute tubular injury or acute tubular necrosis when compared to patients without calcification. Patients with calcium oxalate deposition alone, compared to calcium phosphate or mixed calcifications, had fewer comorbidities but were more likely to have a history of gastric bypass surgery or malabsorption and take vitamin D. In patients with two or more years of follow-up, multivariate analyses showed the presence of calcification (HR 0.59, 0.38-0.92, p = 0.02) and higher eGFR (HR 0.76, 0.73-0.79, p < 0.001), was associated with decreased likelihood of progressing to end-stage renal disease. The presence of calcification was also associated with a reduced slope/decline in eGFR compared to known biopsy and clinical risk factors for decline in kidney function. We hypothesized this was due to more recoverable acute kidney injury (AKI) and found more severe acute kidney injury network stage in patients with kidney calcification but also greater improvement over time. DISCUSSION/CONCLUSION In summary, we demonstrated that calcification on kidney biopsy specimens was associated with a better prognosis than those without calcification due to the association with recoverable AKI.
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Affiliation(s)
- Anna Gaddy
- Division of Nephrology and Hypertension, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Tae-Hwi Schwantes-An
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Ranjani N. Moorthi
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Carrie L. Phillips
- Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Michael T. Eadon
- Division of Nephrology and Hypertension, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Sharon M. Moe
- Division of Nephrology and Hypertension, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
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15
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Dong F, Jiang S, Tang C, Wang X, Ren X, Wei Q, Tian J, Hu W, Guo J, Fu X, Liu L, Patzak A, Persson PB, Gao F, Lai EY, Zhao L. Trimethylamine N-oxide promotes hyperoxaluria-induced calcium oxalate deposition and kidney injury by activating autophagy. Free Radic Biol Med 2022; 179:288-300. [PMID: 34767921 DOI: 10.1016/j.freeradbiomed.2021.11.010] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 11/06/2021] [Accepted: 11/08/2021] [Indexed: 12/12/2022]
Abstract
Calcium oxalate (CaOx) is the most common component of kidney stones. Oxidative stress, inflammation and autophagy-induced cell death are the major causes of CaOx crystal deposition and CaOx crystal deposition can further lead to kidney injury. Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, plays an important role in the pathogenesis of many diseases, such as atherosclerosis, diabetes and chronic kidney disease, but the effect of TMAO on hyperoxaluria-induced CaOx crystal deposition and kidney injury remains unknown. We hypothesize that TMAO aggravates CaOx crystal deposition via promoting CaOx-mediated cell death. C57Bl/6 mice were given high-oxalate diet as a model of hyperoxaluria. TMAO was provided via drinking water. Serum TMAO levels increased 15 days after CaOx treatment (6.30 ± 0.17 μmol/L vs. 34.65 ± 8.95 μmol/L). High-oxalate diet induced inflammation, CaOx deposition and kidney injury, which TMAO aggravated. In accordance, TMAO intensified high-oxalate diet induced oxidative stress, autophagy and apoptosis. Moreover, TMAO enhanced CaOx crystal adhesion to HK-2 cells and reduced cell viability (from 88.9 ± 1.6% to 75.0 ± 2.7%). Protein kinase R-like endoplasmic reticulum kinase (PERK) may mediate these TMAO effects, as TMAO promoted PERK phosphorylation. Consistently, PERK knockdown alleviated TMAO-evoked CaOx-autophagy, apoptosis and oxidative stress in HK-2 cells. In conclusion, TMAO can aggravate hyperoxaluria-induced kidney injury by triggering the PERK/ROS pathway, which enhances autophagy, apoptosis and inflammation, and facilitates CaOx crystal deposition in renal tubular cells.
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Affiliation(s)
- Fang Dong
- Department of Physiology, School of Basic Medical Sciences, and Kidney Disease Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China
| | - Shan Jiang
- Department of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Chun Tang
- Department of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Xiaohua Wang
- Department of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Xiaoqiu Ren
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China
| | - Qichun Wei
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China
| | - Jiong Tian
- Department of Physiology, School of Basic Medical Sciences, and Kidney Disease Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China
| | - Weipeng Hu
- Department of Physiology, School of Basic Medical Sciences, and Kidney Disease Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China
| | - Jie Guo
- Department of Physiology, School of Basic Medical Sciences, and Kidney Disease Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China
| | - Xiaodong Fu
- Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China
| | - Linlin Liu
- Durbrain Medical Laboratory, Hangzhou, 310000, China
| | - Andreas Patzak
- Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, 10117, Germany
| | - Pontus B Persson
- Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, 10117, Germany
| | - Fei Gao
- Durbrain Medical Laboratory, Hangzhou, 310000, China.
| | - En Yin Lai
- Department of Physiology, School of Basic Medical Sciences, and Kidney Disease Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China; Department of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China; Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, 10117, Germany.
| | - Liang Zhao
- Department of Physiology, School of Basic Medical Sciences, and Kidney Disease Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China; Department of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China; Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, 10117, Germany.
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16
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Cimé-Aké E, Carranza-Enríquez F, Hurtado-Arias JJ, Muñoz-Castañeda WRA, Medina-Fonseca B, Barrera-Vargas A, Lizardo-Thiebaud MJ, Saeb-Lima M, Merayo-Chalico J. Primary meningococcal septic arthritis associated with joint calcium oxalate crystals: A case report and review of the literature. Mod Rheumatol Case Rep 2021; 6:296-300. [PMID: 34850098 DOI: 10.1093/mrcr/rxab049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Revised: 11/02/2021] [Accepted: 11/10/2021] [Indexed: 11/13/2022]
Abstract
Primary meningococcal septic arthritis (PMSA) is an extremely rare local infection by Neisseria meningitidis in the absence of meningitis or meningococcaemia syndrome. A 30-year-old healthy, immunocompetent man presented with arthralgia, fever, chest rash, and significant swelling of the right knee. On admission, a disseminated maculopapular and purpuric rash, oligoarthritis, neutrophilia, and elevated acute phase reactants were documented. Following arthrocentesis of the right knee, isolation of N. meningitidis and the presence of calcium oxalate crystals in the synovial fluid were reported. The diagnosis of PMSA was made. Histological analysis of the skin lesion showed leucocytoclastic vasculitis. He was treated with intravenous ceftriaxone plus open surgical drainage and ambulatory cefixime with adequate response. After 1 month, he presented resolution of the pathological process. We performed an extensive review of the literature, finding that the key elements supporting the diagnosis of PMSA are prodromal upper respiratory tract symptoms and skin involvement prior to or synchronous with the arthritis. Also, the most frequently involved joint is the knee. This report is the first case of a patient presenting with PMSA associated with calcium oxalate crystals in the synovial fluid. Herein, we discuss the most frequent clinical manifestations, the unusual histological features, the recommended treatment, and the reported prognosis of this rare entity.
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Affiliation(s)
- Erik Cimé-Aké
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Fabián Carranza-Enríquez
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - José Joel Hurtado-Arias
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Wallace Rafael A Muñoz-Castañeda
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Benjamín Medina-Fonseca
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Ana Barrera-Vargas
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - María J Lizardo-Thiebaud
- Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Marcela Saeb-Lima
- Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Javier Merayo-Chalico
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
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McCune TR, Toepp AJ, Sheehan BE, Sherani MSK, Petr ST, Dodani S. High dose intravenous vitamin C treatment in Sepsis: associations with acute kidney injury and mortality. BMC Nephrol 2021; 22:387. [PMID: 34800992 PMCID: PMC8606062 DOI: 10.1186/s12882-021-02599-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Accepted: 11/03/2021] [Indexed: 01/02/2023] Open
Abstract
Background The effects of vitamin C on clinical outcomes in critically ill patients remain controversial due to inconclusive studies. This retrospective observational cohort study evaluated the effects of vitamin C therapy on acute kidney injury (AKI) and mortality among septic patients. Methods Electronic medical records of 1390 patients from an academic hospital who were categorized as Treatment (received at least one dose of 1.5 g IV vitamin C, n = 212) or Comparison (received no, or less than 1.5 g IV vitamin C, n = 1178) were reviewed. Propensity score matching was conducted to balance a number of covariates between groups. Multivariate logistic regressions were conducted predicting AKI and in-hospital mortality among the full sample and a sub-sample of patients seen in the ICU. Results Data revealed that vitamin C therapy was associated with increases in AKI (OR = 2.07 95% CI [1.46–2.93]) and in-hospital mortality (OR = 1.67 95% CI [1.003–2.78]) after adjusting for demographic and clinical covariates. When stratified to examine ICU patients, vitamin C therapy remained a significant risk factor of AKI (OR = 1.61 95% CI [1.09–2.39]) and provided no protective benefit against mortality (OR = 0.79 95% CI [0.48–1.31]). Conclusion Ongoing use of high dose vitamin C in sepsis should be appraised due to observed associations with AKI and death.
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Affiliation(s)
- Thomas R McCune
- Division of Nephrology, Department of Internal Medicine, Eastern Virginia Medical School, 301 Riverview Ave, Suite 600, Norfolk, Virginia, 23510, USA.
| | - Angela J Toepp
- EVMS-Sentara Healthcare Analytics and Delivery Science Institute, Eastern Virginia Medical School, Norfolk, Virginia, USA.,Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, Virginia, USA
| | - Brynn E Sheehan
- EVMS-Sentara Healthcare Analytics and Delivery Science Institute, Eastern Virginia Medical School, Norfolk, Virginia, USA.,Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical School, Norfolk, Virginia, USA
| | | | | | - Sunita Dodani
- EVMS-Sentara Healthcare Analytics and Delivery Science Institute, Eastern Virginia Medical School, Norfolk, Virginia, USA.,Division of Cardiology, Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, Virginia, USA
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18
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Favor OK, Pestka JJ, Bates MA, Lee KSS. Centrality of Myeloid-Lineage Phagocytes in Particle-Triggered Inflammation and Autoimmunity. FRONTIERS IN TOXICOLOGY 2021; 3:777768. [PMID: 35295146 PMCID: PMC8915915 DOI: 10.3389/ftox.2021.777768] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 10/19/2021] [Indexed: 12/14/2022] Open
Abstract
Exposure to exogenous particles found as airborne contaminants or endogenous particles that form by crystallization of certain nutrients can activate inflammatory pathways and potentially accelerate autoimmunity onset and progression in genetically predisposed individuals. The first line of innate immunological defense against particles are myeloid-lineage phagocytes, namely macrophages and neutrophils, which recognize/internalize the particles, release inflammatory mediators, undergo programmed/unprogrammed death, and recruit/activate other leukocytes to clear the particles and resolve inflammation. However, immunogenic cell death and release of damage-associated molecules, collectively referred to as "danger signals," coupled with failure to efficiently clear dead/dying cells, can elicit unresolved inflammation, accumulation of self-antigens, and adaptive leukocyte recruitment/activation. Collectively, these events can promote loss of immunological self-tolerance and onset/progression of autoimmunity. This review discusses critical molecular mechanisms by which exogenous particles (i.e., silica, asbestos, carbon nanotubes, titanium dioxide, aluminum-containing salts) and endogenous particles (i.e., monosodium urate, cholesterol crystals, calcium-containing salts) may promote unresolved inflammation and autoimmunity by inducing toxic responses in myeloid-lineage phagocytes with emphases on inflammasome activation and necrotic and programmed cell death pathways. A prototypical example is occupational exposure to respirable crystalline silica, which is etiologically linked to systemic lupus erythematosus (SLE) and other human autoimmune diseases. Importantly, airway instillation of SLE-prone mice with crystalline silica elicits severe pulmonary pathology involving accumulation of particle-laden alveolar macrophages, dying and dead cells, nuclear and cytoplasmic debris, and neutrophilic inflammation that drive cytokine, chemokine, and interferon-regulated gene expression. Silica-induced immunogenic cell death and danger signal release triggers accumulation of T and B cells, along with IgG-secreting plasma cells, indicative of ectopic lymphoid tissue neogenesis, and broad-spectrum autoantibody production in the lung. These events drive early autoimmunity onset and accelerate end-stage autoimmune glomerulonephritis. Intriguingly, dietary supplementation with ω-3 fatty acids have been demonstrated to be an intervention against silica-triggered murine autoimmunity. Taken together, further insight into how particles drive immunogenic cell death and danger signaling in myeloid-lineage phagocytes and how these responses are influenced by the genome will be essential for identification of novel interventions for preventing and treating inflammatory and autoimmune diseases associated with these agents.
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Affiliation(s)
- Olivia K. Favor
- Department of Pharmacology and Toxicology, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, United States
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, United States
| | - James J. Pestka
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, United States
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, United States
- Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, United States
| | - Melissa A. Bates
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, United States
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, United States
| | - Kin Sing Stephen Lee
- Department of Pharmacology and Toxicology, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, United States
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, United States
- Department of Chemistry, Michigan State University, East Lansing, MI, United States
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19
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Fattori A, Arfeuille G, Parratte T, Gantzer J, Olagne J, Lannes B, Lhermitte B. [Histopathological diagnosis of an intoxication]. Ann Pathol 2021; 41:549-553. [PMID: 34483010 DOI: 10.1016/j.annpat.2021.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 08/13/2021] [Accepted: 08/16/2021] [Indexed: 10/20/2022]
Abstract
Ethylene glycol poisoning is relatively rare, with around a hundred cases reported each year in France. Its diagnosis is often challenging and delayed because of a several hours' free interval between ingestion of the toxic and the onset of the first symptoms. Ethylene glycol is a colorless and odorless liquid primarily found in automotive coolants, whose toxicity is linked to its hepatic metabolites. Histologically, ethylene glycol poisoning is characterized by abundant tissular deposits of calcium oxalate crystals. Under polarized light, these crystals appear birefringent and iridescent. Their microscopic appearance and their distribution are pathognomonic of oxalosis. Due to its frequent misleading presentation, the diagnosis of ethylene glycol poisoning is sometimes only made after an autopsy. Hereafter, we report the case of a 59-year-old man diagnosed with ethylene glycol intoxication after a post-mortem histopathological examination of organs.
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Affiliation(s)
- Antonin Fattori
- Département d'anatomie et de cytologie pathologiques, hôpitaux universitaires de Strasbourg, 67200 Strasbourg, France.
| | - Gaelle Arfeuille
- Service de réanimation chirurgicale, hôpitaux universitaires de Strasbourg, 67200 Strasbourg, France
| | - Timothée Parratte
- Service de neurologie, hôpitaux universitaires de Strasbourg, 67200 Strasbourg, France
| | - Justine Gantzer
- Département d'oncologie médicale, institut de cancérologie Strasbourg Europe, 67033 Strasbourg, France
| | - Jérôme Olagne
- Département d'anatomie et de cytologie pathologiques, hôpitaux universitaires de Strasbourg, 67200 Strasbourg, France
| | - Béatrice Lannes
- Département d'anatomie et de cytologie pathologiques, hôpitaux universitaires de Strasbourg, 67200 Strasbourg, France
| | - Benoît Lhermitte
- Département d'anatomie et de cytologie pathologiques, hôpitaux universitaires de Strasbourg, 67200 Strasbourg, France
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20
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Xu X, Yan J. β-Caryophyllene may attenuate hyperoxaluria-induced kidney dysfunction in rats by regulating stress marker KIM-1/MCP-1 and NF-κB signaling pathway. J Biochem Mol Toxicol 2021; 35:e22891. [PMID: 34468068 DOI: 10.1002/jbt.22891] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Revised: 07/16/2021] [Accepted: 08/11/2021] [Indexed: 12/15/2022]
Abstract
β-Caryophyllene (BCP), a bicyclic sesquiterpene, has proved to exhibit antioxidant and anti-inflammatory activities. The present study is carried out to investigate BCP impact on hyperoxaluria-induced kidney dysfunction in male Wistar rats. The animals were categorized into four groups, namely, Group I, control rats; Group II, ethylene glycol (inducer); Group III, inducer + BCP (100 µM/kg bw); Group IV, BCP alone. After the treatment period, the rate of creatinine clearance and the concentration of urea in urine and serum were assessed. Histopathology reports were conducted to study renal and liver tissues, while the reverse transcription-polymerase chain reaction studies were carried out for messenger RNA expression of inflammatory (nuclear factor kappa B) and endoplasmic reticulum (ER) stress (kidney dysfunction molecule-1, monocyte chemoattractant protein-1, glucose binding protein 78, CHOP, activating factor 4, and X-box binding protein-1) markers as well as antioxidant activity for the hyperoxaluric rats. Western blot was performed to investigate the level of protein expression by the treatment group on apoptotic (Bcl-2, Bax, caspase-3, and caspase-9) proteins. The results show BCP to possess a renoprotective effect under hyperoxaluric conditions by decreasing the level of the inflammatory and ER stress markers and restoring the enzymes' antioxidant activities. The histology reports depicted the satisfactory morphology of glomerulus in diseased rats. Furthermore, the results of Western blot suggested that BCP may possess inhibitory action on apoptosis by affecting the mitochondrial-dependent apoptotic pathway. Therefore, BCP can be considered as a potential candidate for the therapy of hyperoxaluric-induced kidney complications.
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Affiliation(s)
- Xia Xu
- Department of Pharmacy, Ankang Hospital of Traditional Chinese Medicine, Ankang, China
| | - Jiamiao Yan
- Department of Pharmacy, Ankang Hospital of Traditional Chinese Medicine, Ankang, China
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21
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Characterization of the Striatal Extracellular Matrix in a Mouse Model of Parkinson's Disease. Antioxidants (Basel) 2021; 10:antiox10071095. [PMID: 34356328 PMCID: PMC8301085 DOI: 10.3390/antiox10071095] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 06/29/2021] [Accepted: 07/01/2021] [Indexed: 02/02/2023] Open
Abstract
Parkinson’s disease’s etiology is unknown, although evidence suggests the involvement of oxidative modifications of intracellular components in disease pathobiology. Despite the known involvement of the extracellular matrix in physiology and disease, the influence of oxidative stress on the matrix has been neglected. The chemical modifications that might accumulate in matrix components due to their long half-live and the low amount of extracellular antioxidants could also contribute to the disease and explain ineffective cellular therapies. The enriched striatal extracellular matrix from a mouse model of Parkinson’s disease was characterized by Raman spectroscopy. We found a matrix fingerprint of increased oxalate content and oxidative modifications. To uncover the effects of these changes on brain cells, we morphologically characterized the primary microglia used to repopulate this matrix and further quantified the effects on cellular mechanical stress by an intracellular fluorescence resonance energy transfer (FRET)-mechanosensor using the U-2 OS cell line. Our data suggest changes in microglia survival and morphology, and a decrease in cytoskeletal tension in response to the modified matrix from both hemispheres of 6-hydroxydopamine (6-OHDA)-lesioned animals. Collectively, these data suggest that the extracellular matrix is modified, and underscore the need for its thorough investigation, which may reveal new ways to improve therapies or may even reveal new therapies.
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22
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Plasma oxalate and eGFR are correlated in primary hyperoxaluria patients with maintained kidney function-data from three placebo-controlled studies. Pediatr Nephrol 2021; 36:1785-1793. [PMID: 33515281 PMCID: PMC8172484 DOI: 10.1007/s00467-020-04894-9] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 11/06/2020] [Accepted: 12/03/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND In patients with primary hyperoxaluria (PH), endogenous oxalate overproduction increases urinary oxalate excretion, leading to compromised kidney function and often kidney failure. Highly elevated plasma oxalate (Pox) is associated with systemic oxalate deposition in patients with PH and severe chronic kidney disease (CKD). The relationship between Pox and estimated glomerular filtration rate (eGFR) in patients with preserved kidney function, however, is not well established. Our analysis aimed to investigate a potential correlation between these parameters in PH patients from three randomized, placebo-controlled trials (studies OC3-DB-01, OC3-DB-02, and OC5-DB-01). METHODS Baseline data from patients with a PH diagnosis (type 1, 2, or 3) and eGFR > 40 mL/min/1.73 m2 were analyzed for a correlation between eGFR and Pox using Spearman's rank and Pearson's correlation coefficients. Data were analyzed by individual study and additionally were pooled for Studies OC3-DB-02 and OC5-DB-01 in which the same Pox assay was used. RESULTS A total of 106 patients were analyzed. A statistically significant inverse Spearman's correlation between eGFR and Pox was observed across all analyses; correlation coefficients were - 0.44 in study OC3-DB-01, - 0.55 in study OC3-DB-02, - 0.51 in study OC5-DB-01, and - 0.49 in the pooled studies (p < 0.0064). CONCLUSIONS Baseline evaluations showed a moderate and statistically significant inverse correlation between eGFR and Pox in patients with PH already at early stages of CKD (stages 1-3b), demonstrating that a correlation is present before substantial loss in kidney function occurs.
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AlShalabi O, Ayvazoglu Soy EH, Akdur A, Karakaya E, Kahraman G, Moray G, Haberal M. Oxalosis Crystals' Redeposition in Cardiac Tissue Leading to New-Onset Fatal Cardiac Complication After Liver Transplant in Primary Oxalosis Patient: Case Report. EXP CLIN TRANSPLANT 2020; 18:744-748. [PMID: 33187466 DOI: 10.6002/ect.2020.0401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Primary oxalosis is a rare hereditary disorder of metabolism resulting in accumulation of calcium oxalate in almost all tissues of the body. All published data point out the improvement of cardiac function after transplant. Here, we report the first case in the literature of an 8-year-old patient with primary oxalosis in which oxalosis implantations increased in cardiac tissue after liver transplant and manifested as new-onset ventricular tachycardia and cardiomyopathy, leading to death.
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Affiliation(s)
- Omar AlShalabi
- From the Department of General Surgery, Division of Transplantation, Baskent University, Ankara, Turkey
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Comprehensive Clinicopathologic Analyses of Acquired Cystic Disease-associated Renal Cell Carcinoma With Focus on Adverse Prognostic Factors and Metastatic Lesions. Am J Surg Pathol 2020; 44:1031-1039. [PMID: 32271189 DOI: 10.1097/pas.0000000000001482] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Acquired cystic disease of kidney-associated renal cell carcinoma (ACD-RCC) is a distinct subtype of renal cell carcinoma with unique morphologic and clinicopathologic features. Generally, ACD-RCC is regarded as an indolent tumor; however, prognostic and outcomes data have been conflicted by the limited and relatively low number of cases with patient follow-up or adverse events. In this study, we focused on the histology of metastatic lesions and identifying prognostic factors associated with metastatic progression. From 32 cases in the cohort, 9 patients had metastasis [ACD-RCC (M+)] and 23 patients were without metastasis [ACD-RCC (M-)]. The median age of patients was 52 years; right side, n=10; left side, n=18; bilateral, n=4; median tumor size=2.6 cm; median hemodialysis duration=17 y; and the median duration of follow-up was 50 mo. Immunohistochemistry showed ACD-RCC to be racemase positive and CK7 negative to focally positive within tumor cells, with consistent positivity for renal histogenesis-associated markers (PAX8 and RCC antigen); S100A1 was a less reliable marker at metastatic sites. All metastatic ACD-RCC except 2 cases involved lymph nodes (para-aortic, renal hilar, subclavicular). Overall, 6/9 (67%) had visceral metastasis to sites including lung (n=3), liver (n=3), bone (n=5), stomach (n=1), and brain (n=1). In total, 5/9 (56%) metastatic tumors had distinctive cystic growth pattern at the metastatic site; intriguingly metastatic tumors had intrametastatic oxalate crystal deposition, a pathognomonic feature associated with primary tumors. Four of nine (44%) patients with ACD-RCC (M+) had fatal outcomes due to metastatic disease. Clinically significant adverse prognostic features associated with metastasis [median follow-up 47 mo, ACD-RCC (M+) vs. ACD-RCC (M-), 50 mo] included: duration of hemodialysis (≥20 vs. <20 y, P=0.0085) and tumor necrosis (P=0.049). Because of sufficient overlap between these parameters, the study was not able to identify parameters that would be reliable in further management strategies, in clinical settings. Our data indicate that ACD-RCC is a tumor which has distinct metastatic potential with nodal and visceral tropism and proclivity for cystic morphology at metastatic sites; this is the first report of the presence of oxalate crystals in metastatic tumors. Our data suggest that ACD-RCC patients with prolonged hemodialysis and tumoral coagulative necrosis require additional surveillance in view of the association of these parameters with metastatic progression.
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25
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Ratzinger G, Zelger BG, Zelger BW. Bar Code Reader - an algorithmic approach to cutaneous occluding vasculopathies? part II medium vessel vasculopathies. J Dtsch Dermatol Ges 2020; 17:1115-1128. [PMID: 31765098 PMCID: PMC6899693 DOI: 10.1111/ddg.13973] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 03/27/2019] [Indexed: 12/13/2022]
Abstract
Aims Classifications of occluding vasculopathies (except vasculitis [1]) may exhibit some difficulties. Firstly, classifications may follow different principles, e.g. clinicopathologic findings, etiology or pathogenesis. Secondly, authors may not distinguish between vasculitis and occluding vasculopathies. Thirdly, occluding vasculopathies are systemic diseases. Organ‐specific variations make morphologic findings difficult to compare. Moreover, subtle changes are recognized in the skin, but may be invisible in other organs. Our aim was to use the skin and subcutis as a tool and clinicopathological correlation as the basic process for classification. Methods and results We first differentiate in the skin between small and medium vessel occluding vasculopathies. Here we focus on medium vessel‐occluding vasculopathies. In the second step we differentiate the vessel subtypes. In the final step, we differentiate according to the time point of the coagulation/reorganization process and the involved inflammatory cells/stromal features. By applying the same procedure to the various entities and visualizing the findings in the style of bar codes, the overlaps and differences in the clinical picture as well as the histopathology become more apparent. Conclusions Occluding vasculopathies are often not separate entities, but reaction patterns and epiphenomena. Distinguishing them from vasculitides is crucial because of the differences in pathogenesis, therapeutic approach and prognosis.
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Affiliation(s)
- Gudrun Ratzinger
- Department of Dermatology, Venereology and Allergology, Medical University Innsbruck, Innsbruck, Austria
| | - Bettina G Zelger
- Department of Pathology, Medical University Innsbruck, Innsbruck, Austria
| | - Bernhard W Zelger
- Department of Dermatology, Venereology and Allergology, Medical University Innsbruck, Innsbruck, Austria
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26
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Lorenz EC, Lieske JC, Seide BM, Olson JB, Mehta R, Milliner DS. Recovery From Dialysis in Patients With Primary Hyperoxaluria Type 1 Treated With Pyridoxine: A Report of 3 Cases. Am J Kidney Dis 2020; 77:816-819. [PMID: 32891627 DOI: 10.1053/j.ajkd.2020.07.017] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Accepted: 07/02/2020] [Indexed: 11/11/2022]
Abstract
Primary hyperoxaluria type 1 (PH1) is a genetic disorder characterized by overproduction of oxalate and eventual kidney failure. Kidney failure is usually irreversible in PH1. However, in patients with PH1 homozygous for the G170R mutation (in which the glycine at amino acid 170 is replaced by an arginine), pyridoxine is an enzyme cofactor and decreases urinary oxalate excretion by reducing hepatic oxalate production. We report recovery from dialysis in 3 patients with PH1 homozygous for the G170R mutation in response to pharmacologic-dose pyridoxine treatment. Median age at initiation or resumption of pyridoxine treatment was 37 (range, 20-53) years, and median daily pyridoxine dose was 8.8 (range, 6.8-14.0) mg per kilogram of body weight. Duration of hemodialysis before recovery of kidney function was 10 (range, 5-19) months. Plasma oxalate concentration improved after recovery of kidney function. At a median of 3 (range, 2-46) months following discontinuation of hemodialysis, estimated glomerular filtration rate was 34 (range, 23-52) mL/min/1.73m2, plasma oxalate concentration was 8.8 (range, 4.6-11.3) μmol/L, and urinary oxalate excretion was 0.93 (range, 0.47-1.03) mmol/d. Kidney function was maintained during a median of 3.2 (range, 1.3-3.8) years of follow-up. These observations suggest that kidney failure may be reversible in a subset of patients with PH1 homozygous for the G170R mutation treated with pharmacologic-dose pyridoxine.
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Affiliation(s)
| | - John C Lieske
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN
| | - Barbara M Seide
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN
| | - Julie B Olson
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN
| | - Ramila Mehta
- Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN
| | - Dawn S Milliner
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN
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27
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Avila-Nava A, Medina-Vera I, Rodríguez-Hernández P, Guevara-Cruz M, Heredia-G Canton PK, Tovar AR, Torres N. Oxalate Content and Antioxidant Activity of Different Ethnic Foods. J Ren Nutr 2020; 31:73-79. [PMID: 32709427 DOI: 10.1053/j.jrn.2020.04.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 04/17/2020] [Accepted: 04/19/2020] [Indexed: 12/30/2022] Open
Abstract
OBJECTIVE There is not enough information on the classification of oxalate content in several foods, particularly in ethnic foods, to recommend their consumption in subjects with urolithiasis (UL). The objective of the present study was to generate reliable information on the oxalate content and antioxidant activity in different foods and classify them by very low, low, medium, high and very high oxalate content and antioxidant activity. METHODS The oxalate content of 109 foods including ethnic foods was assessed by an enzymatic assay, and the antioxidant activity was measured by the oxygen radical absorbance capacity to determine the oxalate/antioxidant activity ratio. Oxalate consumption was then evaluated in 400 subjects with overweight and obesity using 24-h dietary recalls. RESULTS The main foods with high oxalate content were raw spinach, huanzontle, purslane, chard, almond, and toasted and sweetened roasted amaranth. The highest antioxidant activity was found in strawberries, all types of chocolates, roselle, morita peppers, and pinolillo. Subjects with overweight or obesity exceed the dietary oxalate daily intake recommendation. CONCLUSIONS The classification of foods by their oxalate content and antioxidant activity will be very useful to generate nutritional recommendation in different diseases, mainly UL.
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Affiliation(s)
- Azalia Avila-Nava
- Hospital Regional de Alta Especialidad de la Península de Yucatán, Yucatán, México
| | - Isabel Medina-Vera
- Departamento de Metodología de la Investigación, Instituto Nacional de Pediatría, México, México
| | - Pamela Rodríguez-Hernández
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de, México
| | - Martha Guevara-Cruz
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de, México
| | - Pamela K Heredia-G Canton
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de, México
| | - Armando R Tovar
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de, México
| | - Nimbe Torres
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de, México.
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Abstract
Kidney stone disease (nephrolithiasis) is a common problem that can be associated with alterations in urinary solute composition including hypercalciuria. Studies suggest that the prevalence of monogenic kidney stone disorders, including renal tubular acidosis with deafness, Bartter syndrome, primary hyperoxaluria and cystinuria, in patients attending kidney stone clinics is ∼15%. However, for the majority of individuals, nephrolithiasis has a multifactorial aetiology involving genetic and environmental factors. Nonetheless, the genetic influence on stone formation in these idiopathic stone formers remains considerable and twin studies estimate a heritability of >45% for nephrolithiasis and >50% for hypercalciuria. The contribution of polygenic influences from multiple loci have been investigated by genome-wide association and candidate gene studies, which indicate that a number of genes and molecular pathways contribute to the risk of stone formation. Genetic approaches, studying both monogenic and polygenic factors in nephrolithiasis, have revealed that the following have important roles in the aetiology of kidney stones: transporters and channels; ions, protons and amino acids; the calcium-sensing receptor (a G protein-coupled receptor) signalling pathway; and the metabolic pathways for vitamin D, oxalate, cysteine, purines and uric acid. These advances, which have increased our understanding of the pathogenesis of nephrolithiasis, will hopefully facilitate the future development of targeted therapies for precision medicine approaches in patients with nephrolithiasis.
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Affiliation(s)
- Sarah A Howles
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.,Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Rajesh V Thakker
- Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
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Choi EJ, Chee CG, Kim W, Song JS, Chung HW. Bone oxaloma-a localized manifestation of bone oxalosis. Skeletal Radiol 2020; 49:651-655. [PMID: 31768582 DOI: 10.1007/s00256-019-03348-0] [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: 08/18/2019] [Revised: 11/09/2019] [Accepted: 11/12/2019] [Indexed: 02/02/2023]
Abstract
Oxalosis is a metabolic disorder characterized by the accumulation of calcium oxalate deposits in various organ systems. Bone oxalosis is a systemic manifestation of oxalosis, in which calcium oxalate deposits accumulate in the skeletal system. This report describes a 69-year-old female patient who presented with right hip pain and was later found to have an osseous mass-like lesion in the right proximal femur, with radiographic findings resembling those of a benign bone tumor. CT-guided biopsy and surgical biopsy showed that the mass had pathologic findings typical of bone oxalosis. Because the patient had no predisposing factors for systemic oxalosis and had no hyperoxalemia or hyperoxaluria, she could be diagnosed with localized bone oxalate deposition disease or bone oxaloma rather than bone oxalosis. This is the first report of this clinical entity to present as a benign-appearing bone mass and without any predisposing systemic causes.
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Affiliation(s)
- Eun Ji Choi
- Department of Radiology, Asan Medical Center, 88, Olympic-ro 43-Gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Choong Guen Chee
- Department of Radiology, Asan Medical Center, 88, Olympic-ro 43-Gil, Songpa-gu, Seoul, 05505, Republic of Korea.
| | - Wanlim Kim
- Department of Orthopedic Surgery, Asan Medical Center, 88, Olympic-ro 43-Gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Joon Seon Song
- Department of Pathology, Asan Medical Center, 88, Olympic-ro 43-Gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Hye Won Chung
- Department of Radiology, Asan Medical Center, 88, Olympic-ro 43-Gil, Songpa-gu, Seoul, 05505, Republic of Korea
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Arafa A, Eshak ES, Iso H. Oxalates, urinary stones and risk of cardiovascular diseases. Med Hypotheses 2020; 137:109570. [PMID: 31972450 DOI: 10.1016/j.mehy.2020.109570] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 12/31/2019] [Accepted: 01/12/2020] [Indexed: 12/20/2022]
Abstract
Increased level of oxalates in urine and plasma can be attributed to endogenous overproduction, increased ingestion or excessive intestinal absorption. When a supersaturation status is reached, oxalates combine with calcium and crystallize to form 80% of the urinary stones. Several cardiovascular diseases such as coronary heart disease and stroke are thought to be associated with the formation of urinary stones via sharing the same pathogenesis and/or risk factors. This review investigated the evidence linking oxalates/urinary stones to cardiovascular diseases. Eventually, two theories can explain the possible association between urinary stones and cardiovascular diseases: the theory of common origin and the theory of common risk factors. While the first theory is based on the common vascular pathophysiology of urinary stones and cardiac events, the later suggests that metabolic syndrome traits increase the risk of urinary stones and cardiovascular diseases independently. A few cohort studies showed a higher risk of coronary heart disease and stroke among people with history of urinary stones than people without it while other cohort studies did not. These studies had different definitions for cardiovascular diseases, used various methods to assess urinary stones, and some of them did not control for potential confounders. When they were pooled together in meta-analyses, a significant heterogeneity across studies was observed. In conclusion, although there is some evidence indicating that urinary stones could increase the risk of cardiovascular diseases, a substantial causal relationship cannot be settled.
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Affiliation(s)
- Ahmed Arafa
- Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan; Department of Public Health, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt
| | - Ehab S Eshak
- Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan; Department of Public Health, Faculty of Medicine, Minia University, El-Minia, Egypt
| | - Hiroyasu Iso
- Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan; Department of Public Health Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
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31
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Ratzinger G, Zelger BG, Zelger BW. Barcodeleser – ein algorithmischer Ansatz für okkludierende kutane Vaskulopathien? Teil 2: Vaskulopathien mittelgroßer Gefäße. J Dtsch Dermatol Ges 2019; 17:1115-1130. [PMID: 31765089 DOI: 10.1111/ddg.13973_g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 03/27/2019] [Indexed: 11/30/2022]
Affiliation(s)
- Gudrun Ratzinger
- Universitätsklinik für Dermatologie, Venerologie und Allergologie, Medizinische Universität Innsbruck, Innsbruck, Österreich
| | - Bettina G Zelger
- Institut für Pathologie, Medizinische Universität Innsbruck, Innsbruck, Österreich
| | - Bernhard W Zelger
- Universitätsklinik für Dermatologie, Venerologie und Allergologie, Medizinische Universität Innsbruck, Innsbruck, Österreich
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32
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Winds of change in imaging of calcium crystal deposition diseases. Joint Bone Spine 2019; 86:665-668. [DOI: 10.1016/j.jbspin.2019.04.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 04/17/2019] [Indexed: 12/26/2022]
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33
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Snijders MLH, Hesselink DA, Clahsen-van Groningen MC, Roodnat JI. Oxalate deposition in renal allograft biopsies within 3 months after transplantation is associated with allograft dysfunction. PLoS One 2019; 14:e0214940. [PMID: 30990835 PMCID: PMC6467373 DOI: 10.1371/journal.pone.0214940] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Accepted: 03/22/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Calcium oxalate (CaOx) deposition in the kidney may lead to loss of native renal function but little is known about the prevalence and role of CaOx deposition in transplanted kidneys. METHODS In patients transplanted in 2014 and 2015, all for-cause renal allograft biopsies obtained within 3 months post-transplantation were retrospectively investigated for CaOx deposition. Additionally, all preimplantation renal biopsies obtained in 2000 and 2001 were studied. RESULTS In 2014 and 2015, 388 patients were transplanted, of whom 149 had at least one for-cause renal biopsy. Twenty-six (17%) patients had CaOx deposition. In the population with CaOx deposition: Patients had significantly more often been treated with dialysis before transplantation (89 vs. 64%; p = 0.011); delayed graft function occurred more frequently (42 vs. 23%; p = 0.038); and the eGFR at the time of first biopsy was significantly worse (21 vs. 29 ml/min/1.73m2; p = 0.037). In a multivariate logistic regression analysis, eGFR at the time of first biopsy (OR 0.958, 95%-Cl: 0.924-0.993, p = 0.019), dialysis before transplantation (OR 4.868, 95%-Cl: 1.128-21.003, p = 0.034) and the time of first biopsy after transplantation (OR 1.037, 95%-Cl: 1.013-1.062, p = 0.002) were independently associated with CaOx deposition. Graft survival censored for death was significantly worse in patients with CaOx deposition (p = 0.018). In only 1 of 106 preimplantation biopsies CaOx deposition was found (0.94%). CONCLUSION CaOx deposition appears to be primarily recipient-derived and is frequently observed in for-cause renal allograft biopsies obtained within 3 months post-transplantation. It is associated with inferior renal function at the time of biopsy and worse graft survival.
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Affiliation(s)
- Malou L H Snijders
- Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.,Rotterdam Transplant Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Dennis A Hesselink
- Rotterdam Transplant Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.,Department of Internal Medicine, Division of Nephrology and Transplantation, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Marian C Clahsen-van Groningen
- Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.,Rotterdam Transplant Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Joke I Roodnat
- Rotterdam Transplant Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.,Department of Internal Medicine, Division of Nephrology and Transplantation, University Medical Center Rotterdam, Rotterdam, The Netherlands
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D'Costa MR, Winkler NS, Milliner DS, Norby SM, Hickson LJ, Lieske JC. Oxalosis Associated With High-Dose Vitamin C Ingestion in a Peritoneal Dialysis Patient. Am J Kidney Dis 2019; 74:417-420. [PMID: 30910370 DOI: 10.1053/j.ajkd.2019.01.022] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Accepted: 01/18/2019] [Indexed: 01/15/2023]
Abstract
We report a case of systemic oxalosis involving the eyes and joints due to long-term use of high-dose vitamin C in a patient receiving maintenance peritoneal dialysis (PD). This 76-year-old woman with autosomal dominant polycystic kidney disease underwent living unrelated kidney transplantation 10 years earlier. The transplant failed 6 months before presentation, and she initiated hemodialysis therapy before transitioning to PD therapy 4 months later. During the month before presentation, the patient noted worsening arthralgias and decreased vision. Ophthalmologic examination revealed proliferative retinopathy and calcium oxalate crystals. Plasma oxalate level was markedly elevated at 187 (reference range, <1.7) μmol/L, and urine oxalate-creatinine ratio was high (0.18mg/mg). The patient reported taking up to 4g of vitamin C per day for several years. Workup for causes of primary and secondary hyperoxaluria was otherwise negative. Vitamin C use was discontinued, and the patient transitioned to daily hemodialysis for 2 weeks. Plasma oxalate level before the dialysis session decreased but remained higher (30-53μmol/L) than typical for dialysis patients. Upon discharge, the patient remained on thrice-weekly hemodialysis therapy with stabilized vision and improved joint symptoms. This case highlights the risk of high-dose vitamin C use in patients with advanced chronic kidney disease, especially when maintained on PD therapy.
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Affiliation(s)
| | | | - Dawn S Milliner
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN; The Rare Kidney Stone Consortium, Mayo Clinic, Rochester, MN
| | - Suzanne M Norby
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN
| | | | - John C Lieske
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN; The Rare Kidney Stone Consortium, Mayo Clinic, Rochester, MN; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
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Mnif K, Yaich S, Mars M, Kammoun K, Fendri F, Charfeddine K, Jarraya F, Boudawara T, Hachicha J. Crystalline Nephropathy in Renal Transplant: A Series of 4 Cases. Indian J Nephrol 2019; 28:472-476. [PMID: 30647504 PMCID: PMC6309387 DOI: 10.4103/ijn.ijn_76_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Crystals are particles of endogenous inorganic or organic composition that can trigger kidney injury when deposited or formed inside the kidney. The most common forms of crystalline nephropathies (CNs) are nephrocalcinosis and oxalate nephropathy. The causes of early allograft dysfunction are changing constantly, and recently calcium oxalate (CaOx) crystal deposition has been added to this list. CaOx deposition in renal allograft is important and probably under-recognized cause of delayed graft function that requires adequate awareness with early intervention to improve the allograft outcome. Here, we describe four cases of irreversible renal graft injury due to CNs.
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Affiliation(s)
- K Mnif
- Department of Nephrology, Hedi Chaker Hospital, Sfax, Tunisia
| | - S Yaich
- Department of Nephrology, Hedi Chaker Hospital, Sfax, Tunisia
| | - M Mars
- Department of Nephrology, Hedi Chaker Hospital, Sfax, Tunisia
| | - K Kammoun
- Department of Nephrology, Hedi Chaker Hospital, Sfax, Tunisia
| | - F Fendri
- Department of Nephrology, Hedi Chaker Hospital, Sfax, Tunisia
| | - K Charfeddine
- Department of Nephrology, Hedi Chaker Hospital, Sfax, Tunisia
| | - F Jarraya
- Department of Nephrology, Hedi Chaker Hospital, Sfax, Tunisia
| | - T Boudawara
- Department of Pathology Laboratory, Habib Bourguiba Hospital, Sfax, Tunisia
| | - J Hachicha
- Department of Nephrology, Hedi Chaker Hospital, Sfax, Tunisia
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Wijayaratne DR, Bavanthan V, de Silva MVC, Nazar ALM, Wijewickrama ES. Star fruit nephrotoxicity: a case series and literature review. BMC Nephrol 2018; 19:288. [PMID: 30348106 PMCID: PMC6198447 DOI: 10.1186/s12882-018-1084-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2017] [Accepted: 10/08/2018] [Indexed: 01/30/2023] Open
Abstract
Background Star fruit is a popular medicinal fruit in the tropics. Its hypoglycaemic properties are considered useful in achieving glycaemic control in diabetes. Star fruit induced nephrotoxicity is a rare cause of acute kidney injury in individuals with both normal and reduced baseline renal function. We present three cases of acute kidney injury due to star fruit nephrotoxicity from Sri Lanka, and discuss the published literature on this topic. Case presentation Three Sri Lankan patients, all with a background of diabetes, presented to us with acute nausea and anorexia following recent consumption of star fruit. Two patients complained of diarrhoea and one patient complained of intractable hiccoughs. They all had elevated serum creatinine on admission. Two were known to have normal baseline serum creatinine levels. On renal biopsy two had evidence of oxalate crystal deposition. One did not show crystal deposition but had acute interstitial nephritis for which no alternate cause could be identified. Two were treated with short courses of prednisolone and two required acute haemodialysis. All recovered renal function, with both patients with known baselines approaching their premorbid serum creatinine levels. Conclusion Consumption of star fruit, especially on an empty stomach or in a state of dehydration may precipitate acute kidney injury. A history of star fruit ingestion must be actively looked for in patients presenting with unexplained acute kidney injury. The use of star fruit as a therapy for diabetes should be discouraged.
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Affiliation(s)
| | - V Bavanthan
- Nephrology, Dialysis and Transplant Unit, National Hospital of Sri Lanka, Colombo, Sri Lanka
| | - M V C de Silva
- Department of Pathology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
| | - A L M Nazar
- Nephrology, Dialysis and Transplant Unit, National Hospital of Sri Lanka, Colombo, Sri Lanka
| | - Eranga S Wijewickrama
- Univeristy Medical Unit, National Hospital of Sri Lanka, Colombo, Sri Lanka.,Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
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Paul E, Albert A, Ponnusamy S, Mishra SR, Vignesh AG, Sivakumar SM, Sivasamy G, Sadasivam SG. Designer probiotic Lactobacillus plantarum expressing oxalate decarboxylase developed using group II intron degrades intestinal oxalate in hyperoxaluric rats. Microbiol Res 2018; 215:65-75. [DOI: 10.1016/j.micres.2018.06.009] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Revised: 03/28/2018] [Accepted: 06/17/2018] [Indexed: 12/22/2022]
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Yang J, Fu M, Ji C, Huang Y, Wu Y. Maize Oxalyl-CoA Decarboxylase1 Degrades Oxalate and Affects the Seed Metabolome and Nutritional Quality. THE PLANT CELL 2018; 30:2447-2462. [PMID: 30201823 PMCID: PMC6241262 DOI: 10.1105/tpc.18.00266] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 08/15/2018] [Accepted: 09/10/2018] [Indexed: 05/06/2023]
Abstract
The organic acid oxalate occurs in microbes, animals, and plants; however, excessive oxalate accumulation in vivo is toxic to cell growth and decreases the nutritional quality of certain vegetables. However, the enzymes and functions required for oxalate degradation in plants remain largely unknown. Here, we report the cloning of a maize (Zea mays) opaque endosperm mutant that encodes oxalyl-CoA decarboxylase1 (EC4.1.1.8; OCD1). Ocd1 is generally expressed and is specifically induced by oxalate. The ocd1 mutant seeds contain a significantly higher level of oxalate than the wild type, indicating that the ocd1 mutants have a defect in oxalate catabolism. The maize classic mutant opaque7 (o7) was initially cloned for its high lysine trait, although the gene function was not understood until its homolog in Arabidopsis thaliana was found to encode an oxalyl-CoA synthetase (EC 6.2.1.8), which ligates oxalate and CoA to form oxalyl-CoA. Our enzymatic analysis showed that ZmOCD1 catalyzes oxalyl-CoA, the product of O7, into formyl-CoA and CO2 for degradation. Mutations in ocd1 caused dramatic alterations in the metabolome in the endosperm. Our findings demonstrate that ZmOCD1 acts downstream of O7 in oxalate degradation and affects endosperm development, the metabolome, and nutritional quality in maize seeds.
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Affiliation(s)
- Jun Yang
- National Key Laboratory of Plant Molecular Genetics, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China
| | - Miaomiao Fu
- National Key Laboratory of Plant Molecular Genetics, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China
- University of the Chinese Academy of Sciences, Beijing 100049, China
| | - Chen Ji
- National Key Laboratory of Plant Molecular Genetics, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China
- University of the Chinese Academy of Sciences, Beijing 100049, China
| | - Yongcai Huang
- National Key Laboratory of Plant Molecular Genetics, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China
- University of the Chinese Academy of Sciences, Beijing 100049, China
| | - Yongrui Wu
- National Key Laboratory of Plant Molecular Genetics, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China
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Amelioration of hyperoxaluria-induced kidney dysfunction by chemical chaperone 4-phenylbutyric acid. Urolithiasis 2018; 47:171-179. [DOI: 10.1007/s00240-018-1064-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2017] [Accepted: 06/08/2018] [Indexed: 01/11/2023]
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Abstract
OBJECTIVE Primary hyperoxaluria type 1 (PH1) is a rare metabolic disorder of oxalate overproduction. It is associated with urolithiasis and nephrocalcinosis, which progress to end-stage renal disease and systemic oxalosis. As oxalate deposits in tissues, non-parathyroid hormone (nonPTH)-mediated hypercalcemia, oxalate osteopathy, primary hypothyroidism, and primary hypogonadism develop. In this review, we will present a case of PH1 and provide an overview of this clinical entity and its endocrine manifestations. METHODS We conducted a PubMed search for articles related to PH1. The terms "primary hyperoxaluria," "nonPTH mediated hypercalcemia," "hypothyroidism," and "hypogonadism" were used to identify pertinent literature. RESULTS Given the rarity of PH1, there is scant literature regarding the incidence and clinical significance of endocrine manifestations of this disorder. There are rare reports of hypercalcemia secondary to osteoclast-stimulating activity of macrophages in bone granulomas, which occur in response to oxalate deposits. We report that hypercalcemia may also be mediated by 1,25-dihydroxyvitamin D and PTH-related protein (PTHrP). Primary hypothyroidism and primary hypogonadism are thought to be due partly to calcium oxalate deposition in thyroid and testicular tissue. The presented case is the first to report PTHrP-mediated hypercalcemia and primary hypogonadism in a patient with PH1. CONCLUSION PH1 is a metabolic disease with significant morbidity and mortality. Owing to its rarity, it is not widely recognized in the field of endocrinology, despite presenting with several endocrinopathies. Recognition of endocrine disturbances can result in early and successful treatment, limiting morbidity and improving quality of life in these challenging patients. ABBREVIATIONS 1,25(OH)2D= 1,25-dihydoxyvitamin D AGT = alanine:glyoxylate aminotransferase ESRD = end-stage renal disease GRHPR = glyoxylate reductase-hydroxypyruvate reductase nonPTH = non-parathyroid hormone PH = primary hyperoxaluria pQCT = peripheral quantitative computed tomography PTH = parathyroid hormone PTHrP = parathyroid hormone-related protein T4 = thyroxine TSH = thyroid-stimulating hormone.
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41
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Erosive Pustular Dermatosis of the Scalp with Urate-Like Crystals. Case Rep Dermatol Med 2017; 2017:1536434. [PMID: 29119028 PMCID: PMC5651126 DOI: 10.1155/2017/1536434] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Accepted: 09/07/2017] [Indexed: 11/18/2022] Open
Abstract
Follicular urate-like crystals were first described in Necrotizing Infundibular Crystalline Folliculitis (NICF), a rare cutaneous disorder with multiple waxy folliculocentric papules. Similar crystal accumulation may be seen within follicular infundibulae as an incidental finding. We describe a case showing identical crystals occurring within the horn-like crusts of a patient with erosive pustular dermatosis of the scalp (EPDS), a condition which due to its presentation can often be mistaken for nonmelanoma skin cancer. A brief overview of erosive pustular dermatosis of the scalp (EPDS) is presented in this paper.
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42
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Pijnenburg L, Caillard S, Boivin G, Rizzo S, Javier RM. Type 1 primary hyperoxaluria: A case report and focus on bone impairment of systemic oxalosis. Morphologie 2017; 102:48-53. [PMID: 29102553 DOI: 10.1016/j.morpho.2017.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Revised: 09/28/2017] [Accepted: 09/29/2017] [Indexed: 11/15/2022]
Abstract
Primary hyperoxaluria is a rare genetic disorder characterized by oxalate overproduction, leading to kidney failure due to nephrocalcinosis, and is eventually responsible for systemic oxalosis. Bone impairment, secondary to oxalate deposits, is one of the many complications that may occur. Skeletal involvement can be difficult to diagnose because of lack of clinical symptoms and therefore needs to be confirmed by invasive testing, such as transiliac bone biopsy. If confirmed, bone oxalosis is the proof of disease severity and that combined liver-kidney transplantation should be performed.
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Affiliation(s)
- L Pijnenburg
- Department of rheumatology, Strasbourg university hospital, 1, avenue Molière, 67200 Strasbourg, France.
| | - S Caillard
- Department of nephrology, transplantation unit, Strasbourg university hospital, 3, rue de la Porte-de-l'Hôpital, 67000 Strasbourg, France
| | - G Boivin
- Inserm, UMR 1033, Lyon Est university, 11, rue Guillaume-Pradadin, 69008 Lyon, France
| | - S Rizzo
- Inserm, UMR 1033, Lyon Est university, 11, rue Guillaume-Pradadin, 69008 Lyon, France
| | - R M Javier
- Department of rheumatology, Strasbourg university hospital, 1, avenue Molière, 67200 Strasbourg, France.
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Perrotta I, Perri E. Ultrastructural, Elemental and Mineralogical Analysis of Vascular Calcification in Atherosclerosis. MICROSCOPY AND MICROANALYSIS : THE OFFICIAL JOURNAL OF MICROSCOPY SOCIETY OF AMERICA, MICROBEAM ANALYSIS SOCIETY, MICROSCOPICAL SOCIETY OF CANADA 2017; 23:1030-1039. [PMID: 28874210 DOI: 10.1017/s1431927617012533] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Over the past few decades, remarkable progress has been achieved in terms of understanding the molecular and cellular mechanisms of atherosclerotic vascular calcification and the important role of matrix vesicles in initiating and propagating pathologic tissue mineralization has been widely recognized. Despite these recent advances, however, no definitive data are currently available regarding the texture and composition of the minerals that grow in the vessel wall during the course of the disease. Using different electron microscopy imaging and analysis, we demonstrate that vascular cells can produce and secrete more than one type of matrix vesicles which act as sites for initial mineral deposition independently of their structural features. Our results reveal that apatite formation in the atherosclerotic lesions of the human aorta occur through the deposition of amorphous calcium phosphate that matures over time, transforms into crystalline hydroxyapatite, and radiates towards the lumen of the vesicles, finally forming the calcified spherules. Elemental and mineralogical analyses also demonstrate that the presence of mature and stable amorphous calcium phosphate deposits in the affected tissues is linked to the incorporation of magnesium, which probably delay the conversion to the crystalline phase. Though more rarely, the presence of calcium oxalate crystals has been also documented.
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Affiliation(s)
- Ida Perrotta
- Department of Biology, Ecology and Earth Sciences (Di.B.E.S.T.), University of Calabria, Arcavacata di Rende (Cosenza) 87036, Italy
| | - Edoardo Perri
- Department of Biology, Ecology and Earth Sciences (Di.B.E.S.T.), University of Calabria, Arcavacata di Rende (Cosenza) 87036, Italy
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Perinpam M, Enders FT, Mara KC, Vaughan LE, Mehta RA, Voskoboev N, Milliner DS, Lieske JC. Plasma oxalate in relation to eGFR in patients with primary hyperoxaluria, enteric hyperoxaluria and urinary stone disease. Clin Biochem 2017; 50:1014-1019. [PMID: 28764885 DOI: 10.1016/j.clinbiochem.2017.07.017] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2017] [Revised: 07/20/2017] [Accepted: 07/27/2017] [Indexed: 01/14/2023]
Abstract
BACKGROUND Since plasma oxalate (POx) concentrations increase at lower glomerular filtration rate (GFR) levels, even among those without enteric (EH) or primary hyperoxaluria (PH), the appropriate thresholds for considering a disorder of oxalate metabolism are poorly defined. The current study was completed to establish relationships between POx, GFR, and urine oxalate excretion (UOx) among patients with PH, EH, and routine urinary stone disease (USD). METHODS The most recent POx measurement on all Mayo Clinic patients between 2005 and 2015 were electronically pulled from the Lab Information System together with the closest serum creatinine within 14days and 24h urine study within 60days. After exclusion of patients not in steady state at the time of blood draw, 270 patients were available for study. Records were reviewed for clinical diagnoses to categorize patients as PH, EH, or USD. Waste plasma for Pox was also obtained from controls without USD undergoing clinical GFR testing. RESULTS In all 3 groups POx increased as eGFR fell. For any given eGFR, POx was highest in the PH group and lowest in the USD and control groups (p<0.0001). POx was also influenced by UOx excretion (reflecting total body oxalate burden, absorption from diet and endogenous production). Generalized estimating equations of POx vs eGFR revealed higher average POx levels in PH compared to EH,USD or control, and for EH compared to USD or control. GEE prediction models were created that use POx, UOx, age, and serum creatinine to estimate the probability of a PH diagnosis. CONCLUSIONS New models were developed to help interpret POx when considering PH in clinical practice even when it was not previously suspected and/or eGFR is reduced.
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Affiliation(s)
- Majuran Perinpam
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United States
| | - Felicity T Enders
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, United States
| | - Kristin C Mara
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, United States
| | - Lisa E Vaughan
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, United States
| | - Ramila A Mehta
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, United States
| | - Nickolay Voskoboev
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States
| | - Dawn S Milliner
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United States
| | - John C Lieske
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United States; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States.
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46
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Johnson G, Gardner JM, Shalin SC. Polarizable crystals in apocrine sweat gland tumors: A series of 3 cases. J Cutan Pathol 2017; 44:698-702. [PMID: 28497640 DOI: 10.1111/cup.12962] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2017] [Revised: 04/26/2017] [Accepted: 05/08/2017] [Indexed: 11/26/2022]
Abstract
Polarizable calcium oxalate (CaOx) crystals have been well documented in breast biopsies, generally associated with benign apocrine metaplasia. In contrast, polarizable crystals are only rarely reported in skin adnexal neoplasms. We report 3 different cases of sweat gland tumors with polarizable crystals morphologically suggestive of CaOx: 1 apocrine hidrocystoma and 2 tubular apocrine adenomas. The histologic features were examined in 3 cases. Clinical presentation summary included 2 males and 1 female, ages 53 to 74 years, with lesions located on the left cheek, inferior vertex scalp and the left eyebrow. All 3 cases showed polarizable, geometric, plate-like and fractured, colorless crystals within the lumens of the neoplasm. Of note, these crystals were seen only on the toluidine blue-stained section of Case #1, but were not present on the corresponding permanent section. We hypothesize that polarizable crystals may be present in sweat gland neoplasms more often than previously documented, but that they may often dissolve with routine processing, accounting for their rare visibility. We highlight this rare finding, and suggest that it may be underreported. We only noted this finding in benign apocrine tumors; further investigation would be necessary to determine whether these crystals are also seen in other cutaneous adnexal neoplasms.
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Affiliation(s)
- Gina Johnson
- University of Arkansas for Medical Science, Department of Pathology, Little Rock, Arkansas
| | - Jerad M Gardner
- University of Arkansas for Medical Science, Department of Pathology, Little Rock, Arkansas
| | - Sara C Shalin
- University of Arkansas for Medical Science, Department of Pathology, Little Rock, Arkansas
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47
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Dill T, Sugo E, McManus B. Enteroliths and multiple neuroendocrine tumours in a Meckel's diverticulum. Pathology 2017; 49:319-322. [PMID: 28267995 DOI: 10.1016/j.pathol.2016.10.016] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2016] [Accepted: 10/26/2016] [Indexed: 10/20/2022]
Affiliation(s)
- Tony Dill
- Pathology North, John Hunter Hospital, Newcastle, NSW, Australia.
| | - Ella Sugo
- Pathology North, John Hunter Hospital, Newcastle, NSW, Australia
| | - Brendan McManus
- Newcastle Endoscopy Centre and John Hunter Hospital, Newcastle, NSW, Australia
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48
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Zanello P. The competition between chemistry and biology in assembling iron–sulfur derivatives. Molecular structures and electrochemistry. Part V. {[Fe4S4](SCysγ)4} proteins. Coord Chem Rev 2017. [DOI: 10.1016/j.ccr.2016.10.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
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Abreu R, Bento C, Oliveira L, Morgado T. Malabsorption syndrome as a rare cause of nephrocalcinosis. ACTA ACUST UNITED AC 2017; 13:247-248. [PMID: 28228792 DOI: 10.11138/ccmbm/2016.13.3.247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Nephrocalcinosis is characterized by calcification of kidney parenchyma and can be caused by an increased amount of calcium, phosphate or oxalate in urinary excretion. We report a 35-year-old female with nephrocalcinosis. She had fitful steatorrhea since last year. Physical examination was normal. Analytic exams found normal renal function and ionogram. Primary hyperparathyroidism, renal tubular acidosis and sarcoidosis were excluded. Urinalysis showed mild hematuria, without proteinuria and 24-hour urine collection exhibited hyperoxaluria. Patient was submitted to an endoscopy and duodenal biopsy whose histology sustained the diagnosis of celiac disease. Fluid intake increase and gluten and oxalate free diet were initiated.
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Affiliation(s)
- Rui Abreu
- Department of Nephrology, Centro Hospitalar Trás-os-Montes e Alto Douro, Vila Real, Portugal
| | - Cláudia Bento
- Department of Nephrology, Centro Hospitalar Trás-os-Montes e Alto Douro, Vila Real, Portugal
| | - Luís Oliveira
- Department of Nephrology, Centro Hospitalar Trás-os-Montes e Alto Douro, Vila Real, Portugal
| | - Teresa Morgado
- Department of Nephrology, Centro Hospitalar Trás-os-Montes e Alto Douro, Vila Real, Portugal
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Plasma oxalate levels in prevalent hemodialysis patients and potential implications for ascorbic acid supplementation. Clin Biochem 2016; 49:1133-1139. [DOI: 10.1016/j.clinbiochem.2016.05.025] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2016] [Revised: 05/26/2016] [Accepted: 05/27/2016] [Indexed: 12/31/2022]
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