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Kang Y, Jin Q, Zhou M, Zheng H, Li X, Li A, Zhou JW, Lv J, Wang Y. Diagnostic value of serum TGF-β1 and CysC in type 2 diabetic kidney disease: a cross-sectional study. Front Med (Lausanne) 2025; 12:1529648. [PMID: 40291021 PMCID: PMC12021808 DOI: 10.3389/fmed.2025.1529648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 03/31/2025] [Indexed: 04/30/2025] Open
Abstract
Background Diabetic kidney disease (DKD) is one of the common microvascular complications of diabetes. The exploration of serum biomarkers holds promise for improving the efficiency and accuracy of early DKD diagnosis. This study aims to investigate the diagnostic value of transforming growth factor-β1 (TGF-β1) and cystatin C (CysC) in DKD patients. Methods A total of 126 patients with type 2 diabetes mellitus (T2DM) diagnosed at Dongzhimen Hospital, Beijing University of Chinese Medicine, between May 2021 and March 2023 were enrolled. Patients were categorized based on proteinuria levels and estimated glomerular filtration rate (eGFR). Correlation analyses were conducted to examine the relationships between serum TGF-β1, CysC, and clinical parameters. Logistic regression was applied to identify correlation factors for DKD and renal function impairment in T2DM patients. Furthermore, receiver operating characteristic (ROC) curve analysis was performed to assess diagnostic efficacy. Results Significant differences in TGF-β1 and CysC levels were observed across groups with varying proteinuria levels. CysC was positively correlated with TGF-β1 (r = 0.640, p < 0.001). TGF-β1 has been associated with proteinuria levels in T2DM patients. Each unit increase in TGF-β1 was associated with a 1.122-fold and 1.470-fold higher odds of the presence of microalbuminuria and proteinuria, respectively, in the normal proteinuria (NP) group. TGF-β1 and CysC showed varying diagnostic performance. TGF-β1 better distinguished microalbuminuria group (MP) from NP, while CysC alone was less effective. T2DM patients with impaired renal function exhibited significantly higher CysC and TGF-β1 levels compared to those with normal renal function. CysC emerged as an associated factor of renal function decline (OR = 2.255, p = 0.008). CysC demonstrated superior diagnostic efficacy compared to TGF-β1 in predicting renal function impairment (AUC = 0.974). Conclusion CysC and TGF-β1 can serve as potential biomarkers for assessing renal impairment and proteinuria in T2DM patients. Their combined evaluation demonstrates diagnostic value and clinical application potential.
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Affiliation(s)
- Yi Kang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Renal Research Institution of Beijing University of Chinese Medicine, Beijing, China
- Graduate School of Beijing University of Chinese Medicine, Beijing, China
| | - Qian Jin
- Graduate School of Beijing University of Chinese Medicine, Beijing, China
| | - Mengqi Zhou
- Department of Traditional Chinese Medicine, Beijing Puren Hospital, Beijing, China
| | - Huijuan Zheng
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Renal Research Institution of Beijing University of Chinese Medicine, Beijing, China
| | - Xiaobin Li
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Aoshuang Li
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Renal Research Institution of Beijing University of Chinese Medicine, Beijing, China
| | - Jing Wei Zhou
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Renal Research Institution of Beijing University of Chinese Medicine, Beijing, China
| | - Jie Lv
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Renal Research Institution of Beijing University of Chinese Medicine, Beijing, China
| | - Yaoxian Wang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Renal Research Institution of Beijing University of Chinese Medicine, Beijing, China
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Attieh RM, Ibrahim RM, Ghali P, Keaveny A, Croome K, Hodge D, White L, Wadei HM. Improved outcomes of kidney after liver transplantation after the implementation of the safety net policy. Liver Transpl 2024; 30:582-594. [PMID: 38015446 DOI: 10.1097/lvt.0000000000000302] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Accepted: 11/10/2023] [Indexed: 11/29/2023]
Abstract
The number of kidney after liver transplants (KALT) increased after the implementation of the United Network of Organ Sharing (UNOS) safety net policy, but the effects of the policy on KALT outcomes remain unknown. Using the UNOS database, we identified KALT between 60 and 365 days from liver transplant from January 1, 2010, to December 31, 2020. The main outcome was 1- and 3-year patient, liver, and kidney graft survival. Secondary outcomes included 6-month and 1-year acute rejection (AR) of liver and kidney, and 1-year kidney allograft function. Of the 256 KALT, 90 were pre-policy and 166 post-policy. Compared to pre-policy, post-policy 1- and 3-year liver graft survival was higher (54% and 54% vs. 86% and 81%, respectively, p <0.001), while 1- and 3-year kidney graft survival (99% and 75% vs. 92% and 79%, respectively, p =0.19), and 1- and 3-year patient survival (99% and 99% vs. 95% and 89%, respectively, p =0.11) were not significantly different. Subgroup analysis revealed similar trends in patients with and without renal failure at liver transplant. Liver AR at 6 months was lower post-policy (6.3% vs. 18.3%, p =0.006) but was similar (10.5% vs. 13%, p =0.63) at 1 year. Kidney AR was unchanged post-policy at 6 months and 1 year. Creatinine at 1 year did not differ post-policy versus pre-policy (1.4 vs. 1.3 mg/dL, p =0.07) despite a higher proportion of deceased donors, higher Kidney Donor Profile Index, and longer kidney cold ischemia time post-policy ( p <0.05 for all). This 3-year follow-up after the 2017 UNOS policy revision demonstrated that the safety net implementation has resulted in improved liver outcomes for patients who underwent KALT with no increased AR of the liver or the kidney allografts.
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Affiliation(s)
- Rose Mary Attieh
- Department of Transplant, Mayo Clinic, Jacksonville, Florida, USA
- Department of Medicine, Division of Kidney Diseases and Hypertension, Glomerular Center at Northwell Health, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York, USA
| | - Ramez M Ibrahim
- Department of Transplant, Mayo Clinic, Jacksonville, Florida, USA
| | - Peter Ghali
- Department of Medicine, Division of Gastroenterology, University of Florida, Gainesville, Florida, USA
| | - Andrew Keaveny
- Department of Transplant, Mayo Clinic, Jacksonville, Florida, USA
| | | | - David Hodge
- Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, Florida, USA
| | - Launia White
- Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, Florida, USA
| | - Hani M Wadei
- Department of Transplant, Mayo Clinic, Jacksonville, Florida, USA
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Asal FE, Yousef M, Abdraboh HAA, Abd-Elsalam S, Abdelaziz Shama AA, Elbahnasawy M, Elnaggar MH, Alsrogy HA, Elashry H. Role of Serum Cystatin C as a Diagnostic Tool for Renal Function in Cirrhotic Patients. THE OPEN BIOMARKERS JOURNAL 2022; 12. [DOI: 10.2174/18753183-v12-e2203210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 12/13/2021] [Accepted: 01/20/2022] [Indexed: 09/01/2023]
Abstract
Background:
Assessment of cystatin C levels could be valuable in the early detection of renal dysfunction because they increase faster than the creatinine levels as the GFR decreases. The aim of this work was to evaluate serum cystatin C as a diagnostic tool for renal dysfunction in cirrhotic patients with and without hepatorenal syndrome (HRS).
Methods:
This case-control study was conducted on 60 patients from the Tropical Medicine Department of Tanta University Hospitals and 10 people served as healthy control volunteers. Serum cystatin C was measured in the three groups.
Results:
A significant difference was observed among the three groups as cystatin C was higher in patients with HRS compared to the cirrhotic group and healthy controls.
Conclusion:
Serum cystatin C is a good predictor for hepatorenal syndrome with a good correlation with serum creatinine, blood urea, GFR, and creatinine clearance.
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Asrani SK, Shankar N, da Graca B, Nadim MK, Cardenas A. Role of Novel Kidney Biomarkers in Patients With Cirrhosis and After Liver Transplantation. Liver Transpl 2022; 28:466-482. [PMID: 34714972 DOI: 10.1002/lt.26344] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 10/19/2021] [Accepted: 10/21/2021] [Indexed: 01/13/2023]
Abstract
Acute kidney injury (AKI) and chronic kidney disease (CKD) are important drivers of morbidity and mortality in patients with cirrhosis before and after liver transplantation (LT). In this review, we examine the role of novel kidney biomarkers for early recognition of kidney injury. Studies are limited by lack of reference standards, heterogeneous definitions of outcomes and biomarker cutoffs, and inconsistent diagnostic performance. Overall, a change in biomarker is more relevant than an absolute cutoff. Cystatin C and urinary neutrophil gelatinase-associated lipocalin (uNGAL) are the most studied candidate biomarkers and identify AKI or progression of AKI earlier than serum creatinine (sCr). Kidney injury molecule 1 and liver-type fatty acid-binding protein (L-FABP) also show potential. NGAL and interleukin 18 may play a role in differentiating acute tubular necrosis from other forms of AKI. Combining novel biomarkers with the Model for End-Stage Liver Disease score may assist prognosis. Persistent elevations in select markers (eg, NGAL) can portend irreversible injury. Several pretransplantation markers (including sCr) predict posttransplantation kidney dysfunction. Pretransplantation assessment of clinical factors (eg, age, diabetes) and novel markers (osteopontin and tissue inhibitor of metalloproteinases 1 [TIMP-1]) may predict renal kidney recovery after LT. Intraoperative changes in biomarkers predict early post-LT AKI. Prediction of CKD remains difficult, although a combination of biomarkers (eg, beta-2 microglobulin, CD40) is promising. Novel biomarkers have yet to replace sCr in guideline-based evaluation and management of kidney dysfunction in patients with cirrhosis. We propose a theoretical framework for practical incorporation of these biomarkers that considers patient characteristics (risk for irreversible injury), markers of functional and structural change, and assessment of the AKI-CKD continuum to identify patients at the highest risk for progressive kidney disease before and after LT.
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Affiliation(s)
| | | | | | - Mitra K Nadim
- Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Andres Cardenas
- GI/Liver Transplant Unit, Institut de Malalties Digestives i Metaboliques, Hospital Clinic, Barcelona, Spain.,Faculty of Medicine, University of Barcelona, Barcelona, Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Ciber de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
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Jha P, Jha AK, Dayal VM, Jha SK, Kumar A. Baseline serum cystatin C as a marker of acute kidney injury in patients with acute-on-chronic liver failure. Indian J Gastroenterol 2021; 40:563-571. [PMID: 34981441 DOI: 10.1007/s12664-021-01201-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Accepted: 05/24/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND A creatinine-based estimation of the renal function lags behind the onset of disease process. Cystatin C is a new marker for acute kidney injury (AKI). However, data are limited in patients with acute-on-chronic liver failure (ACLF). We evaluated serum cystatin C as an early predictor of AKI in patients with ACLF. METHODS In a prospective observational study, patients with ACLF and normal serum creatinine level were included in the study. Serum cystatin C was analyzed with the development of AKI and the disease outcome. RESULT Forty-seven patients (mean age: 43.26±16.34 years; male:female: 2.35:1) were included in the study. AKI developed in 34% of patients during the hospital stay. Receiver operating characteristic (ROC) curve analysis revealed that the best cutoff for baseline cystatin C was 1.47 mg/L with a sensitivity of 0.94 and specificity of 0.68. The cystatin C ((area under the curve [AUC]=0.853) performance was better than that of the creatinine (AUC=0.699), Child-Turcotte-Pugh (CTP) (AUC=0.661), and model for end-stage liver disease-sodium (MELD-Na) (AUC=0.641). In the univariate analysis, age, platelet count, creatinine, estimated glomerular filtration rate (eGFR)-modification of diet in renal disease (MDRD), cystatin C, and estimated glomerular filtration rate-serum cystatin C (eGFRcysC) were significantly associated with AKI in ACLF patients. Cystatin C was an independent positive predictor of AKI. Cystatin C was positively correlated with the MELD-Na scores (r=0.374 and p=0.009). CONCLUSION Our study supports previous studies reporting that serum cystatin C is a better predictor for AKI development compared to serum creatinine. Cystatin C may be used as an early marker for new-onset AKI in hospitalized patients with ACLF.
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Affiliation(s)
- Praveen Jha
- Department of Gastroenterology, Indira Gandhi Institute of Medical Sciences, Sheikhpura, Patna, 800 014, India
| | - Ashish Kumar Jha
- Department of Gastroenterology, Indira Gandhi Institute of Medical Sciences, Sheikhpura, Patna, 800 014, India.
| | - Vishwa Mohan Dayal
- Department of Gastroenterology, Indira Gandhi Institute of Medical Sciences, Sheikhpura, Patna, 800 014, India
| | - Sanjeev Kumar Jha
- Department of Gastroenterology, Indira Gandhi Institute of Medical Sciences, Sheikhpura, Patna, 800 014, India
| | - Amarendra Kumar
- Department of Gastroenterology, Indira Gandhi Institute of Medical Sciences, Sheikhpura, Patna, 800 014, India
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Singapura P, Ma TW, Sarmast N, Gonzalez SA, Durand F, Maiwall R, Nadim MK, Fullinwider J, Saracino G, Francoz C, Sartin R, Trotter JF, Asrani SK. Estimating Glomerular Filtration Rate in Cirrhosis Using Creatinine-Based and Cystatin C-Based Equations: Systematic Review and Meta-Analysis. Liver Transpl 2021; 27:1538-1552. [PMID: 34143570 DOI: 10.1002/lt.26216] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 05/20/2021] [Accepted: 06/07/2021] [Indexed: 12/12/2022]
Abstract
Accurate estimation of kidney function in cirrhosis is crucial for prognosis and decisions regarding dual-organ transplantation. We performed a systematic review/meta-analysis to assess the performance of creatinine-based and cystatin C (CysC)-based eGFR equations compared with measured GFR (mGFR) in patients with cirrhosis. A total of 25 studies (n = 4565, 52.0 years, 37.0% women) comprising 18 equations met the inclusion criteria. In all GFR equations, the creatinine-based equations overestimated GFR (standardized mean difference, SMD, 0.51; 95% confidence interval [CI], 0.31-0.71) and CysC-based equations underestimated GFR (SMD, -0.3; 95% CI, -0.60 to -0.02). Equations based on both creatinine and CysC were the least biased (SMD, -0.14; 95% CI, -0.46 to 0.18). Chronic kidney disease-Epi-serum creatinine-CysC (CESC) was the least biased but had low precision and underestimated GFR by -3.6 mL/minute/1.73 m2 (95% CI, -17.4 to 10.3). All equations significantly overestimated GFR (+21.7 mL/minute/1.73 m2 ; 95% CI, 17.7-25.7) at GFR <60 mL/minute/1.73 m2 ; of these, chronic kidney disease-Epi-CysC (10.3 mL/minute/1.73 m2 ; 95% CI, 2.1-18.4) and GFR Assessment in Liver Disease (12.6 mL/minute/1.73 m2 ; 95% CI, 7.2-18.0) were the least biased followed by Royal Free Hospital (15 mL/minute/1.73 m2 ; 95% CI, 5.5-24.6) and Modification of Diet in Renal Disease 6 (15.7 mL/minute/1.73 m2 ; 95% CI, 10.6-20.8); however, there was an overlap in the precision of estimates, and the studies were limited. In ascites, overestimation of GFR was common (+8.3 mL/minute/1.73 m2 ; 95% CI, -3.1 to 19.7). However, overestimation of GFR by 10 to 20 mL/minute/1.73m2 is common in patients with cirrhosis with most equations in ascites and/or kidney dysfunction. A tailored approach is required especially for decisions regarding dual-organ transplantation.
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Affiliation(s)
- Prianka Singapura
- Baylor University Medical Center, Baylor Scott and White, Dallas, TX
| | - Tsung-Wei Ma
- Baylor University Medical Center, Baylor Scott and White, Dallas, TX
| | - Naveed Sarmast
- Baylor University Medical Center, Baylor Scott and White, Dallas, TX
| | - Stevan A Gonzalez
- Baylor University Medical Center, Baylor Scott and White, Dallas, TX
| | - François Durand
- Hepatology & Liver Intensive Care, Hospital Beaujon, Clichy, University of Paris, Paris, France
| | - Rakhi Maiwall
- Institute of Liver & Biliary Sciences, New Delhi, India
| | - Mitra K Nadim
- Division of Nephrology, University of Southern California, Los Angeles, CA
| | - John Fullinwider
- Baylor University Medical Center, Baylor Scott and White, Dallas, TX
| | - Giovanna Saracino
- Baylor University Medical Center, Baylor Scott and White, Dallas, TX
| | - Claire Francoz
- Hepatology & Liver Intensive Care, Hospital Beaujon, Clichy, University of Paris, Paris, France
| | - Rebecca Sartin
- Baylor University Medical Center, Baylor Scott and White, Dallas, TX
| | - James F Trotter
- Baylor University Medical Center, Baylor Scott and White, Dallas, TX
| | - Sumeet K Asrani
- Baylor University Medical Center, Baylor Scott and White, Dallas, TX
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Velayudham B, Thomas RG, Vasudevan C, Senthilkumar RP, Thirumalvalavan, Murugesan. Serum cystatin C unmasks renal dysfunction in cirrhosis and performs better in estimation of glomerular filtration rate. SAUDI JOURNAL OF KIDNEY DISEASES AND TRANSPLANTATION 2020; 31:1320-1330. [PMID: 33565444 DOI: 10.4103/1319-2442.308341] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
In this study, we aimed to measure glomerular filtration rate (mGFR) using 99Tc DTPA in patients with Child-Pugh C cirrhosis and normal serum creatinine levels; and to compare the performance of creatinine and cystatin C-based equations [estimated GFRs (eGFRs)] to 99TcDTPA GFR in the same group. We selected a group of 65 consecutive patients with advanced liver cirrhosis and apparently normal renal function by serum creatinine alone. Patients with confounding and reversible factors were excluded. Demographic data, blood, urine, and imaging tests along with simultaneous measurement of serum creatinine and cystatin C were analyzed. The GFR was measured by 99Tc DTPAscintigraphy (mGFR) in 41 patients. We compared the performance of chronic kidney disease epidemiology collaboration (CKD-EPI-creatinine, CKD-EPI-cystatinC, CKD-EPI-creatinine-cystatinC) and Modification of Diet in Renal Disease equation equations for bias (mean difference), precision (root mean square error), and accuracy (P10 and P30). Bland-Altman plots were used to show the agreement of eGFR and mGFR. Twenty-five out of 41 patients (61%) had significant renal dysfunction (GFR ≤60 mL/min/ 1.73m2) by 99TcDTPA in our study and three patients were already in Stage 4 CKD. Unlike serum creatinine, serum cystatin C values were deranged in these patients. Among all GFR estimating formulae, CKD-EPI-creatinine-cystatinC combined equation had the least bias (-2.3), superior precision (7.1), highest P30 accuracy (78%), good sensitivity (87.5%), and best specificity (96%) in our study. Two-thirds of patients with cirrhosis had significant renal impairment despite having normal serum creatinine. Isolated serum creatinine values are misleading in cirrhosis. Cystatin C unmasks renal dysfunction in these patients. CKD-EPI-creatinine-cystatinC equation showed the best correlation and accuracy with 99TcDTPA GFR in our study. Creatinine based GFR estimation is fallacious in cirrhosis. Cystatin C and equations based on it may be worthwhile in liver disease.
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Affiliation(s)
- Balaraman Velayudham
- Department of Nephrology, Government Kilpauk Medical College, Chennai, Tamil Nadu, India
| | - Remi George Thomas
- Department of Nephrology, Government Kilpauk Medical College, Chennai, Tamil Nadu, India
| | - C Vasudevan
- Department of Nephrology, Government Kilpauk Medical College, Chennai, Tamil Nadu, India
| | - R P Senthilkumar
- Department of Nephrology, Government Kilpauk Medical College, Chennai, Tamil Nadu, India
| | - Thirumalvalavan
- Department of Nephrology, Government Kilpauk Medical College, Chennai, Tamil Nadu, India
| | - Murugesan
- Department of Nephrology, Government Kilpauk Medical College, Chennai, Tamil Nadu, India
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Zhang J, Liu J, Wu Y, Romeiro FG, Levi Sandri GB, Zhou X, Li M, Qi X. Effect of terlipressin on renal function in cirrhotic patients with acute upper gastrointestinal bleeding. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:340. [PMID: 32355784 PMCID: PMC7186671 DOI: 10.21037/atm.2020.02.135] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/10/2019] [Accepted: 02/07/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND Renal dysfunction is a serious morbidity in cirrhotic patients with acute upper gastrointestinal bleeding (AUGIB). Terlipressin is the first-line treatment choice for acute variceal bleeding and hepatorenal syndrome (HRS). This study aimed to assess the effect of terlipressin on renal function in patients with liver cirrhosis and AUGIB. METHODS We retrospectively reviewed 40 cirrhotic patients with AUGIB treated with terlipressin by an attending physician between January 2016 and June 2018. We analyzed the change of renal function parameters, including cystatin C (CysC) and creatinine (Cr), during the use of terlipressin and after terlipressin was stopped. We also identified the factors associated with renal function improvement in patients without active bleeding during the use of terlipressin. RESULTS During the use of terlipressin, CysC value was significantly reduced (1.3±0.8 vs. 1.1±0.7, P=0.001); Cr value was reduced, but the reduction was not statistically significant (68.8±24 vs. 65.5±23, P=0.817); the rate of CysC reduction was significantly higher in patients treated with terlipressin than those treated with somatostatin/octreotide (73.1% vs. 0%, P=0.005); the rate of Cr reduction was not significantly different between patients treated with terlipressin and somatostatin/octreotide (61.5% vs. 20%, P=0.148); no factor associated with CysC reduction was identified; higher hemoglobin, red blood cell, and platelet and lower prothrombin time and international normalized ratio at baseline were significantly associated with Cr reduction. After terlipressin was stopped, neither CysC nor Cr value was significantly reduced (P=0.852 and P=0.296). CONCLUSIONS Terlipressin may be beneficial on preventing renal function impairment in cirrhotic patients with AUGIB.
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Affiliation(s)
- Jingqiao Zhang
- Liver Cirrhosis Group, Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang 110840, China
- Postgraduate College, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Jie Liu
- Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Yunhai Wu
- ICU, The Sixth Hospital of Shenyang, Shenyang 110006, China
| | - Fernando Gomes Romeiro
- Department of Internal Medicine, Botucatu Medical School, Universidade Estadual Paulista (UNESP), Botucatu, SP, Brazil
| | | | - Xinmiao Zhou
- Liver Cirrhosis Group, Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang 110840, China
- Postgraduate College, Jinzhou Medical University, Jinzhou 121001, China
| | - Miaomiao Li
- Liver Cirrhosis Group, Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang 110840, China
- Postgraduate College, Dalian Medical University, Dalian 116044, China
| | - Xingshun Qi
- Liver Cirrhosis Group, Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang 110840, China
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9
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KASL clinical practice guidelines for liver cirrhosis: Ascites and related complications. Clin Mol Hepatol 2018; 24:230-277. [PMID: 29991196 PMCID: PMC6166105 DOI: 10.3350/cmh.2018.1005] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Accepted: 04/06/2018] [Indexed: 02/07/2023] Open
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Elevated cystatin C: is it a reflection for kidney or liver impairment in hepatic children? Clin Exp Hepatol 2017; 3:159-163. [PMID: 29062906 PMCID: PMC5649481 DOI: 10.5114/ceh.2017.68399] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Accepted: 05/14/2017] [Indexed: 11/17/2022] Open
Abstract
Aim of the study To assess if elevated serum cystatin C (Cyst-C) is an indicator for renal or hepatic dysfunction in presence of liver fibrosis. Material and methods Data of 50 children with chronic liver diseases (CLDs), out of which 25 were without renal impairment, and 25 with renal impairment were analyzed. Twenty healthy children served as a healthy control group. Routine investigations, creatinine clearance, hepatitis viral markers, abdominal ultrasonography, and liver biopsy were performed for patients with CLDs. Measurement of serum Cyst-C concentration by particle induced immunonephelometry were completed for both patients and control group. Results Results showed that serum Cyst-C is not correlated with the degree of hepatic impairment (p > 0.05). Cyst-C levels were significantly higher in patients with renal impairment (3.66 ± 0.85) than those without (0.71 ± 0.12), and healthy control group (0.63 ± 0.85). Cystatin-C showed significant elevation in patients with severe fibrosis with renal impairment (3.66 ± 0.85) than those without (0.76 ± 0.04) (p < 0.0001). Cyst-C at cutoff levels of 1.65 mg/l showed 100% accuracy in discrimination between those with and those without renal impairment. Cyst-C > 2.34 mg/l predicting GFR < 40 ml/min with accuracy of 90%. Cyst-C > 2.73 mg/l predicting GFR < 20 ml/min with accuracy of 81.5%. Conclusions Serum Cyst-C is a promising marker to estimate renal impairment in children with CLDs. Further studies are needed to estimate the accuracy of serum Cyst-C for early detection of renal impairment and close monitoring of the hepatic children.
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Aiello FI, Bajo M, Marti F, Musso CG. How to evaluate renal function in stable cirrhotic patients. Postgrad Med 2017; 129:866-871. [DOI: 10.1080/00325481.2017.1365569] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Florencia I. Aiello
- Human Physiology Department, Instituto Universitario del Hospital, Italiano de Buenos Aires, Argentina
| | - Magdalena Bajo
- Human Physiology Department, Instituto Universitario del Hospital, Italiano de Buenos Aires, Argentina
| | - Fernanda Marti
- Human Physiology Department, Instituto Universitario del Hospital, Italiano de Buenos Aires, Argentina
| | - Carlos G. Musso
- Human Physiology Department, Instituto Universitario del Hospital, Italiano de Buenos Aires, Argentina
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Wang D, Feng JF, Wang AQ, Yang YW, Liu YS. Role of Cystatin C and glomerular filtration rate in diagnosis of kidney impairment in hepatic cirrhosis patients. Medicine (Baltimore) 2017; 96:e6949. [PMID: 28514315 PMCID: PMC5440152 DOI: 10.1097/md.0000000000006949] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2016] [Revised: 04/09/2017] [Accepted: 04/27/2017] [Indexed: 12/21/2022] Open
Abstract
Hepatic cirrhosis is often accompanied by functional kidney impairment, which may be reversed if early treatment is promptly administered. This study aimed to investigate the role of Cystatin C and Cystatin C estimated glomerular filtration rate in the diagnosis of kidney impairment in patients with hepatic cirrhosis.Four hundred sixty five patients with hepatic cirrhosis were recruited. Serum creatinine and Cystatin C were determined, and their estimated glomerular filtration rates were calculated.The area under the receiver-operating characteristic curve (area under curve [AUC]) of Cystatin C and Cystatin C estimated glomerular filtration rate was significantly larger than that of serum creatinine and serum creatinine estimated glomerular filtration rate, respectively (P = .000). When the optimal cut-off value and upper reference limit were used, similar sensitivity, misdiagnosis rate, and diagnostic consistency were only observed in Cystatin C estimated glomerular filtration rate (P > .05).Cystatin C and Cystatin C estimated glomerular filtration rate are superior to serum creatinine and serum creatinine estimated glomerular filtration rate in diagnosis of secondary kidney impairment, and Cystatin C estimated glomerular filtration rate has a better performance as compared with Cystatin C. However, it is not a measured parameter, and thus the lab should determine its own optimal cut-off value.
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Affiliation(s)
| | | | - An-Qun Wang
- Department of Pathology, Mianyang Central Hospital, Affiliated to Southwest Medical University, Sichuan Province, China
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Appréciation du débit de filtration glomérulaire et de la dysfonction rénale chez le cirrhotique. MEDECINE INTENSIVE REANIMATION 2016. [DOI: 10.1007/s13546-016-1215-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Abstract
It is important to accurately assess the glomerular filtration rate (GFR) of patients with liver disease to deliver care and allocate organs for transplantation in a way that improves outcomes. The most commonly used methods to estimate GFR in this population are based on creatinine, which is biased by these patients' low creatinine production and potentially by elevated serum bilirubin and decreased albumin levels. None of the creatinine-based estimated glomerular filtration rate (eGFR) equations have been specifically modified for a population with liver disease, and even measurement of a 24-hour creatinine clearance has limitations. In liver disease, all creatinine-based estimates of GFR overestimate gold standard-measured GFR, and the degree of overestimation is highest at lower measured GFR values and in more severe liver disease. Cystatin C-based eGFR has shown promise in general population studies by demonstrating less bias than creatinine-based eGFR and improved association with clinically important outcomes, but results in the liver disease population have been mixed, and further studies are necessary. Ultimately, specific eGFR equations for liver disease or novel methods for estimating GFR may be necessary. However, for now, the limitations of currently available methods need to be appreciated to understand kidney function in liver disease.
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Affiliation(s)
- Tomasz Beben
- University of California, San Diego, California Veterans Affairs San Diego Healthcare System, San Diego, CA
| | - Dena E Rifkin
- University of California, San Diego, California Veterans Affairs San Diego Healthcare System, San Diego, CA.
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15
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Beben T, Rifkin DE. GFR Estimating Equations and Liver Disease. Adv Chronic Kidney Dis 2015; 22:337-42. [PMID: 26311594 DOI: 10.1053/j.ackd.2015.05.003] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2014] [Revised: 03/05/2015] [Accepted: 05/11/2015] [Indexed: 12/20/2022]
Abstract
It is important to accurately assess the glomerular filtration rate (GFR) of patients with liver disease to deliver care and allocate organs for transplantation in a way that improves outcomes. The most commonly used methods to estimate GFR in this population are based on creatinine, which is biased by these patients' low creatinine production and potentially by elevated serum bilirubin and decreased albumin levels. None of the creatinine-based estimated glomerular filtration rate (eGFR) equations have been specifically modified for a population with liver disease, and even measurement of a 24-hour creatinine clearance has limitations. In liver disease, all creatinine-based estimates of GFR overestimate gold standard-measured GFR, and the degree of overestimation is highest at lower measured GFR values and in more severe liver disease. Cystatin C-based eGFR has shown promise in general population studies by demonstrating less bias than creatinine-based eGFR and improved association with clinically important outcomes, but results in the liver disease population have been mixed, and further studies are necessary. Ultimately, specific eGFR equations for liver disease or novel methods for estimating GFR may be necessary. However, for now, the limitations of currently available methods need to be appreciated to understand kidney function in liver disease.
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Lopez-Giacoman S, Madero M. Biomarkers in chronic kidney disease, from kidney function to kidney damage. World J Nephrol 2015; 4:57-73. [PMID: 25664247 PMCID: PMC4317628 DOI: 10.5527/wjn.v4.i1.57] [Citation(s) in RCA: 212] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2014] [Revised: 10/21/2014] [Accepted: 11/10/2014] [Indexed: 02/06/2023] Open
Abstract
Chronic kidney disease (CKD) typically evolves over many years, with a long latent period when the disease is clinically silent and therefore diagnosis, evaluation and treatment is based mainly on biomarkers that assess kidney function. Glomerular filtration rate (GFR) remains the ideal marker of kidney function. Unfortunately measuring GFR is time consuming and therefore GFR is usually estimated from equations that take into account endogenous filtration markers like serum creatinine (SCr) and cystatin C (CysC). Other biomarkers such as albuminuria may precede kidney function decline and have demonstrated to have strong associations with disease progression and outcomes. New potential biomarkers have arisen with the promise of detecting kidney damage prior to the currently used markers. The aim of this review is to discuss the utility of the GFR estimating equations and biomarkers in CKD and the different clinical settings where these should be applied. The CKD-Epidemiology Collaboration equation performs better than the modification of diet in renal disease equation, especially at GFR above 60 mL/min per 1.73 m2. Equations combining CysC and SCr perform better than the equations using either CysC or SCr alone and are recommended in situations where CKD needs to be confirmed. Combining creatinine, CysC and urine albumin to creatinine ratio improves risk stratification for kidney disease progression and mortality. Kidney injury molecule and neutrophil gelatinase-associated lipocalin are considered reasonable biomarkers in urine and plasma to determine severity and prognosis of CKD.
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17
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Evaluation of Serum Cystatin C as a Marker of Early Renal Impairment in Patients with Liver Cirrhosis. Int J Hepatol 2015; 2015:309042. [PMID: 26550493 PMCID: PMC4621358 DOI: 10.1155/2015/309042] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2015] [Revised: 09/17/2015] [Accepted: 09/17/2015] [Indexed: 12/18/2022] Open
Abstract
Background. Serum cystatin C (CysC) was proposed as an effective reflection of the glomerular filtration rate (GFR). However, its role in patients with liver cirrhosis has not been extensively verified especially in the detection of early RI. Patients and Methods. Seventy consecutive potential candidates for living donor liver transplantation with serum creatinine (Cr) <1.5 mg/dL were included. CysC, Cr, and estimated GFR [creatinine clearance (CCr), Cockcroft-Gault formula (C-G), MDRD equations with 4 and 6 variables, CKD-EPI-Cr, CKD-EPI-CysC, and CKD-EPI-Cr-CysC] were all correlated to isotopic GFR. Early RI was defined as GFR of 60-89 mL/min/1.73 m(2). Results. Patients were 25.7% and 74.3% Child-Pugh classes B and C, respectively. GFR was ≥90, 60-89, and 30-59 mL/min/1.73 m(2) in 31.4%, 64.3%, and 4.3% of the patients, respectively. All markers and equations, except C-G, were significantly correlated to GFR with CKD-EPI-Cr-CysC formula having the highest correlation (r = 0.474) and the largest area under the ROC curve (0.808) for discriminating early RI. At a cutoff value of 1.2 mg/L, CysC was 89.6% sensitive and 63.6% specific in detecting early RI. Conclusion. In patients with liver cirrhosis, CysC and CysC-based equations showed the highest significant correlation to GFR and were measures that best discriminated early RI.
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18
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Prognostic value of serum cystatin C levels in cirrhotic patients with normal serum creatinine. Open Med (Wars) 2014. [DOI: 10.2478/s11536-013-0287-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Abstract
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Ćulafić Đ, Štulić M, Obrenović R, Miletić D, Mijač D, Stojković M, Jovanović M, Ćulafić M. Role of cystatin C and renal resistive index in assessment of renal function in patients with liver cirrhosis. World J Gastroenterol 2014; 20:6573-6579. [PMID: 24914379 PMCID: PMC4047343 DOI: 10.3748/wjg.v20.i21.6573] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2014] [Revised: 02/18/2014] [Accepted: 03/19/2014] [Indexed: 02/07/2023] Open
Abstract
AIM: To evaluate the clinical significance of cystatin C and renal resistive index for the determination of renal function in patients with liver cirrhosis.
METHODS: We conducted a study of 63 patients with liver cirrhosis. A control group comprised of 30 age and gender-matched healthy persons. Serum cystatin C was determined in all study subjects and renal Doppler ultrasonography was made. Estimated glomerular filtration rate from serum creatinine (GFRCr) and cystatin C (GFRCys) was calculated.
RESULTS: We confirmed significant differences in values of cystatin C between patients with different stages of liver cirrhosis according to Child-Pugh (P = 0.01), and a significant correlation with model of end stage liver disease (MELD) score (rs = 0.527, P < 0.001). More patients with decreased glomerular filtration rate were identified based on GFRCys than on GFRCr (P < 0.001). Significantly higher renal resistive index was noted in Child-Pugh C than in A (P < 0.001) and B stage (P = 0.001). Also, a significant correlation between renal resistive index and MELD score was observed (rs = 0.607, P < 0.001). Renal resistive index correlated significantly with cystatin C (rs = 0.283, P = 0.028) and showed a negative correlation with GFRCys (rs = -0.31, P = 0.016).
CONCLUSION: Cystatin C may be a more reliable marker for assessment of liver insufficiency. Additionally, cystatin C and renal resistive index represent sensitive indicators of renal dysfunction in patients with liver cirrhosis.
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Rognant N, Lemoine S. Evaluation of renal function in patients with cirrhosis: Where are we now? World J Gastroenterol 2014; 20:2533-2541. [PMID: 24627589 PMCID: PMC3949262 DOI: 10.3748/wjg.v20.i10.2533] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Accepted: 01/20/2014] [Indexed: 02/06/2023] Open
Abstract
In the clinical context of the patients with liver cirrhosis, accurate evaluation of the renal function is potentially crucial. Indeed, it can lead to early diagnosis of both acute kidney injury and chronic kidney disease and to reliable characterization of the renal status of the patient before performing a liver transplantation. Despite some limitations, the assay of serum creatinine (SCr) is universally used to estimate glomerular filtration rate (GFR) because of its wide availability, its simplicity and because it is inexpensive. Nevertheless, several reports show that the value of this assay to estimate GFR is strongly challenged in cirrhotic patients, especially in patients with liver failure and/or severely impaired renal function. This has led to seek new alternatives to estimate more reliably the GFR in these patients. Although the reference methods, based on the utilization of exogenous markers, allow measuring GFR and thereby constitute the “gold standard” to evaluate renal function, they are not feasible in routine clinical practice. Several studies have shown that a cystatin C (CysC) based formula perform better than the SCr-based estimates in cirrhotic patients and the estimation of GFR by these formulas could therefore lead to optimize the management of the patients. A new estimate based on CysC has been recently developed using a large number of patients and the first results regarding the evaluation of its performance are promising, making this new formula the best candidate for a reference estimate of the renal function in cirrhotic patients.
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Shlipak MG, Mattes MD, Peralta CA. Update on cystatin C: incorporation into clinical practice. Am J Kidney Dis 2013; 62:595-603. [PMID: 23701892 DOI: 10.1053/j.ajkd.2013.03.027] [Citation(s) in RCA: 180] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2013] [Accepted: 03/08/2013] [Indexed: 01/08/2023]
Abstract
Kidney function monitoring using creatinine-based glomerular filtration rate estimation is a routine part of clinical practice. Emerging evidence has shown that cystatin C may improve classification of glomerular filtration rate for defining chronic kidney disease in certain clinical populations and assist in understanding the complications of chronic kidney disease. In this review and update, we summarize the overall literature on cystatin C, critically evaluate recent high-impact studies, highlight the role of cystatin C in recent kidney disease guidelines, and suggest a practical approach for clinicians to incorporate cystatin C into practice. We conclude by addressing frequently asked questions related to implementing cystatin C use in a clinical setting.
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Sirota JC, Walcher A, Faubel S, Jani A, McFann K, Devarajan P, Davis CL, Edelstein CL. Urine IL-18, NGAL, IL-8 and serum IL-8 are biomarkers of acute kidney injury following liver transplantation. BMC Nephrol 2013; 14:17. [PMID: 23327592 PMCID: PMC3562144 DOI: 10.1186/1471-2369-14-17] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2012] [Accepted: 01/11/2013] [Indexed: 01/23/2023] Open
Abstract
BACKGROUND AKI is common following liver transplantation and is associated with significant morbidity and mortality. Biomarkers of AKI have not been well established in this setting but are needed to help guide patient care and facilitate development of novel therapeutics. METHODS Serum creatinine, cystatin C, IL-6, and IL-8 and urine IL-18, NGAL, IL-6, and IL-8 were measured before and within 24 hours after liver transplantation in 40 patients. AKI was defined as a ≥50% sustained increase in creatinine above pre-operative values occurring within 24 hours of transplantation and persisting for at least 24 hours. RESULTS Seven patients met criteria for AKI (17.5%), with mean creatinines of 0.81 mg/dL pre-operatively and 1.75 mg/dL post-operatively. While pre-operative biomarker levels in patients with AKI were similar to those in patients without AKI, differences were seen between the groups with regard to median post-operative serum IL-8 (pg/mL) (242.48 vs. 82.37, p = 0.0463) and urine NGAL (ng/mL) (386.86 vs. 24.31, p = 0.0039), IL-6 (pg/mL) (52 vs. 7.29, p=0.0532), IL-8 (pg/mL) (14.3 vs. 0, p = 0.0224), and IL-18 (pg/mL) (883.09 vs. 0, p = 0.0449). The areas under receiver operating characteristic (ROC) curves were 0.749 for urine IL-18, 0.833 for urine NGAL, 0.745 for urine IL-6, 0.682 for serum IL-6, 0.773 for urine IL-8, and 0.742 for serum IL-8. Post-operative cystatin C was not significantly different between AKI and no AKI groups. CONCLUSION Serum IL-8 and urine IL-18, NGAL, IL-6, and IL-8 are elevated in AKI within the first 24 hours following liver transplantation.
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Affiliation(s)
- Jeffrey C Sirota
- Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Sciences Center, Box C281, 12700 East 19th Ave, Aurora, CO 80262, USA
| | - Angela Walcher
- Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Sciences Center, Box C281, 12700 East 19th Ave, Aurora, CO 80262, USA
| | - Sarah Faubel
- Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Sciences Center, Box C281, 12700 East 19th Ave, Aurora, CO 80262, USA
| | - Alkesh Jani
- Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Sciences Center, Box C281, 12700 East 19th Ave, Aurora, CO 80262, USA
| | - Kim McFann
- Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Sciences Center, Box C281, 12700 East 19th Ave, Aurora, CO 80262, USA
| | - Prasad Devarajan
- Division Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, ML 7022, Cincinnati, OH, USA
| | - Connie L Davis
- Division of Nephrology, Department of Medicine, School of Medicine, University of Washington, Seattle, WA, USA
| | - Charles L Edelstein
- Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Sciences Center, Box C281, 12700 East 19th Ave, Aurora, CO 80262, USA
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Hermida-Cadahia EF, Lampon N, Tutor JC. Impact of creatinine production on the agreement between glomerular filtration rate estimates using cystatin C-derived, and 4- and 6-variable Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Ups J Med Sci 2012; 117:402-10. [PMID: 22746300 PMCID: PMC3497221 DOI: 10.3109/03009734.2012.696154] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
BACKGROUND It has recently been reported that patient selection has a strong impact on the agreement between glomerular filtration rate (GFR) estimates from serum cystatin C and creatinine. The aim of our study was to evaluate the effect of creatinine production rate (CPR) on this subject. MATERIAL AND METHODS GFR was estimated from serum cystatin C and from creatinine using the 4- and 6-variable Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in 50 healthy subjects, 43 patients with renal failure, 794 kidney and 104 liver transplant recipients, 61 patients with heart failure, 59 patients with biliary obstruction, and 113 critically ill patients. RESULTS In the 295 patients with impaired CPR (< 900 mg/24 h/1.73 m(2)), discordances of more than 40% between GFR(MDRD4) and GFR(cystatinC) were observed in 38% of cases, between GFR(MDRD6) and GFR(cystatinC) in 22%, and between GFR(CKD-EPI) and GFR(cystatinC) in 27% (in all cases due to GFR overestimation from creatinine). In the 929 patients with maintained CPR (> 900 mg/24 h/1.73 m(2)), greater discordances than 40% between GFR(MDRD4) and GFR(cystatinC) were observed in 8% of cases, between GFR(MDRD6) and GFR(cystatinC) in 9%, and between GFR(CKD-EPI) and GFR(cystatinC) in 7% (in the major part of cases due to GFR overestimation from cystatin C). CONCLUSION The main source of differences of more than 40% between GFR estimates from serum creatinine and cystatin C is a GFR overestimation in patients with low CPR and GFR underestimation in patients with high CPR by the creatinine-derived equations.
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Affiliation(s)
- Esperanza F. Hermida-Cadahia
- Unidad Monitorización Fármacos, Laboratorio Central, Hospital Clínico Universitario, Instituto de Investigación Sanitaria (IDIS), 15706 Santiago de Compostela, Spain
| | - Natalia Lampon
- Unidad Monitorización Fármacos, Laboratorio Central, Hospital Clínico Universitario, Instituto de Investigación Sanitaria (IDIS), 15706 Santiago de Compostela, Spain
| | - J. Carlos Tutor
- Unidad Monitorización Fármacos, Laboratorio Central, Hospital Clínico Universitario, Instituto de Investigación Sanitaria (IDIS), 15706 Santiago de Compostela, Spain
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Waring WS, Moonie A. Earlier recognition of nephrotoxicity using novel biomarkers of acute kidney injury. Clin Toxicol (Phila) 2011; 49:720-8. [PMID: 21970770 DOI: 10.3109/15563650.2011.615319] [Citation(s) in RCA: 118] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
CONTEXT A broad range of drugs and chemicals are capable of evoking acute kidney injury, which is conventionally determined by rising serum creatinine concentrations. However there are important limitations to this approach, and there has been interest in alternative biomarkers that might provide a more sensitive and rapid means of detecting acute kidney injury. Most of the available clinical data have thus far been ascertained in patients requiring critical care or with acute sepsis. However, if a sensitive indicator of acute kidney injury were developed, then this could provide a significantly improved means of detecting the effects of acute drug or toxin exposure. OBJECTIVE To review the available data concerning potential biomarkers of acute kidney injury and to assess their relative strengths and weaknesses in comparison to existing methods based on serum creatinine concentrations. A large number of possible biomarkers have been proposed. Evidence for individual biomarkers is reviewed with a particular emphasis on those with potential application in clinical toxicology. Where available, comparative data are presented. METHODS There were 236 papers identified using Medline, Embase, and Google Scholar databases, of which 52 were considered directly relevant. CREATININE: Creatinine is subject to glomerular filtration and, to a lesser extent tubular secretion. Serum concentrations are an insensitive marker of acute kidney injury, and the speed of an increase from baseline depends on the magnitude of the acute injury and pre-existing kidney functional reserve. A wide range of inter-individual concentrations means that single time-point determinations are difficult to interpret, and acute kidney injury may not manifest as a detectable increase in serum creatinine concentrations until at least 24-48 h after the primary insult. KIDNEY ENZYMES: Enzymes are often localised to specific anatomical locations, and acute injury may cause a detectable increase in urinary activity due to up-regulated activity or leakage due to cell membrane disruption. Key examples include gamma-glutamyl transpeptidase (GGT), glutathione-S-transferase (GST), and N-acetyl-glucosaminidase (NAG), which are found predominantly in the proximal tubule and urinary enzyme activity increases after acute exposure to heavy metals and other nephrotoxins. NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN: Neutrophil gelatinase-associated lipocalin (NGAL) is expressed by renal tubular epithelium, and a rise in urinary concentrations may provide an indicator of acute renal injury caused by any one of a broad range of provoking factors that is detectable before a rise in serum creatinine concentrations. CYSTATIN C: Serum and urinary cystatin C concentrations are closely related to kidney function and, for example, in acute tubular necrosis allow better prediction of the need for renal replacement therapy than serum creatinine concentrations. KIDNEY INJURY MOLECULE 1: Kidney injury molecule 1 (KIM-1) is expressed in the proximal tubule in the setting of acute ischaemia. For example, urinary KIM-1 concentrations becomes detectable within 24 h of acute tubular necrosis. Urinary KIM-1 expression may be detected after exposure to a variety of nephrotoxic agents, even when serum creatinine concentrations do not increase, and this has been accepted by regulatory authorities as a sensitive biomarker of acute kidney injury during early drug development. CONCLUSIONS Novel biomarkers appear capable of offering a more sensitive means of detecting acute kidney injury than existing approaches. Certain of these allow discrimination between the various mechanisms and anatomical site of acute injury. Ultimately, clinical assessment might incorporate a panel of different biomarkers, each informing on the integrated aspects of glomerular, tubular and interstitial function. Presence of biomarkers may in some cases detect mild or transient renal dysfunction that is presently undetected, and the clinical relevance needs further exploration. Whilst many potentially useful biomarkers have been proposed, comparatively few clinical data exist to support their validity in routine practice. Further prospective clinical studies are required to examine the validity of biomarkers after acute drug or toxin exposure, and to establish whether they might offer improved clinical outcomes in the setting of clinical toxicology.
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