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Huynh BA, Ho NHH, Bui TTA, Hoang KC, Tran TTT. New equation for estimating glomerular filtration rate in Vietnamese kidney transplant recipients. Int Urol Nephrol 2025:10.1007/s11255-025-04458-6. [PMID: 40128434 DOI: 10.1007/s11255-025-04458-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Accepted: 03/09/2025] [Indexed: 03/26/2025]
Abstract
PURPOSE Accurate assessment of kidney function is essential for post-kidney transplant management. This study aims to develop a new equation tailored to Vietnamese kidney transplant recipients and validate its performance against established equations. METHODS A total of 299 kidney transplant recipients underwent glomerular filtration rate (GFR) measurement using technetium-99m-diethylenetriaminepentaacetate renal dynamic scintigraphy, along with demographic, clinical, and laboratory assessments. Participants were divided into a development cohort (n = 150) to generate a new GFR-estimating equation and a validation cohort (n = 149) for internal validation against six equations. RESULTS The new equation, G F R = 100.430 × 1 . 080 sex × a g e - 0.097 × S c r - 0.524 × S c y s - 0.435 (sex: 0 = female; 1 = male), showed the smallest median bias (-0.11 [-1.40; 1.11]), highest P30 accuracy (94.0% [88.6; 96.6]), highest precision (interquartile range = 9.82 [7.63; 12.37]), and strongest correlation with measured GFR (r = 0.824 [0.752; 0.880]) among tested equations in the validation cohort. Among creatinine-based equations, the Modification of Diet in Renal Disease equation was the most accurate. CONCLUSION The new equation outperformed established equations and is recommended for Vietnamese kidney transplant recipients. The Modification of Diet in Renal Disease equation may serve as an alternative in centers lacking access to serum cystatin C. Further studies with larger cohorts, external validation, and comparisons with gold-standard GFR measurement methods are needed to confirm these results.
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Affiliation(s)
- Bao An Huynh
- Faculty of Medicine, Can Tho University of Medicine and Pharmacy, No. 179 Nguyen Van Cu Street, An Khanh Ward, Ninh Kieu District, Can Tho City, 900000, Vietnam
| | - Nguyen Huy Hoang Ho
- Faculty of Medicine, Can Tho University of Medicine and Pharmacy, No. 179 Nguyen Van Cu Street, An Khanh Ward, Ninh Kieu District, Can Tho City, 900000, Vietnam
| | - Thi Tram Anh Bui
- Faculty of Medicine, Can Tho University of Medicine and Pharmacy, No. 179 Nguyen Van Cu Street, An Khanh Ward, Ninh Kieu District, Can Tho City, 900000, Vietnam
| | - Khac Chuan Hoang
- Department of Urology, Cho Ray Hospital, No. 201B Nguyen Chi Thanh, Ward 12, District 5, Ho Chi Minh City, 700000, Vietnam
| | - Thai Thanh Tam Tran
- Department of Physiology, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Ninh Kieu District, No. 179 Nguyen Van Cu Street, An Khanh Ward, Can Tho City, 900000, Vietnam.
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Wang X, Mu J, Ma K, Ma Y. Challenges of Serum Creatinine Level in GFR Assessment and Drug Dosing Decisions in Kidney Injury. Adv Pharm Bull 2024; 14:745-758. [PMID: 40190670 PMCID: PMC11970497 DOI: 10.34172/apb.42345] [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: 10/12/2023] [Revised: 11/23/2024] [Accepted: 12/03/2024] [Indexed: 04/09/2025] Open
Abstract
Serum creatinine (SCr) is widely regarded as a standard biomarker for assessing glomerular filtration rate (GFR) and is commonly used to guide dose adjustments for renally eliminated drugs. However, the application of SCr as a marker for evaluating GFR and drug dosing in kidney injury has significant limitations that are often overlooked in clinical practice. This oversight can result in subtherapeutic drug concentrations or adverse drug reactions due to inappropriate dosing adjustments based on SCr levels alone. This review aimed to highlight the factors affecting serum creatinine (SCr) and the challenges associated with using SCr as a biomarker for assessing GFR and adjusting drug doses with regard to its limitations and variability. The findings of this review underscore the complexity of SCr regulation, which is affected by its synthesis, metabolism, and excretion processes (glomerular filtration, tubular secretion, tubular reabsorption and extra-renal elimination), and disease states (such as trauma-induced hyperfiltration and HIV) and the use of medications (drug-creatinine interactions) lead to altered renal excretion of creatinine, either increasing or decreasing its levels. Additionally, the renal excretion pathways for drugs and creatinine are not entirely the same, making it difficult to use creatinine to evaluate drug renal excretion. In conclusion, SCr is an imperfect index of GFR and adjusting drug dosing, and the development of multi-biomarker panels, incorporating biomarkers from different excretory pathways-particularly those involving tubular transport-holds promise for improving the evaluation of renal excretory function and ensuring safer and more effective drug dosing.
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Affiliation(s)
- Xinyi Wang
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China
| | - Jing Mu
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China
| | - Kexin Ma
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China
| | - Yanrong Ma
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China
- Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou 730000, China
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Raynaud M, Al-Awadhi S, Juric I, Divard G, Lombardi Y, Basic-Jukic N, Aubert O, Dubourg L, Masson I, Mariat C, Prié D, Pernin V, Le Quintrec M, Larson TS, Stegall MD, Bikbov B, Ruggenenti P, Mesnard L, Ibrahim HN, Nielsen MB, Matas AJ, Nankivell BJ, Benjamens S, Pol RA, Bakker SJL, Jouven X, Legendre C, Kamar N, Smith BH, Wadei HM, Durrbach A, Vincenti F, Remuzzi G, Lefaucheur C, Bentall AJ, Loupy A. Race-free estimated glomerular filtration rate equation in kidney transplant recipients: development and validation study. BMJ 2023; 381:e073654. [PMID: 37257905 PMCID: PMC10231444 DOI: 10.1136/bmj-2022-073654] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/17/2023] [Indexed: 06/02/2023]
Abstract
OBJECTIVE To compare the performance of a newly developed race-free kidney recipient specific glomerular filtration rate (GFR) equation with the three current main equations for measuring GFR in kidney transplant recipients. DESIGN Development and validation study SETTING: 17 cohorts in Europe, the United States, and Australia (14 transplant centres, three clinical trials). PARTICIPANTS 15 489 adults (3622 in development cohort (Necker, Saint Louis, and Toulouse hospitals, France), 11 867 in multiple external validation cohorts) who received kidney transplants between 1 January 2000 and 1 January 2021. MAIN OUTCOME MEASURE The main outcome measure was GFR, measured according to local practice. Performance of the GFR equations was assessed using P30 (proportion of estimated GFR (eGFR) within 30% of measured GFR (mGFR)) and correct classification (agreement between eGFR and mGFR according to GFR stages). The race-free equation, based on creatinine level, age, and sex, was developed using additive and multiplicative linear regressions, and its performance was compared with the three current main GFR equations: Modification of Diet in Renal Disease (MDRD) equation, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, and race-free CKD-EPI 2021 equation. RESULTS The study included 15 489 participants, with 50 464 mGFR and eGFR values. The mean GFR was 53.18 mL/min/1.73m2 (SD 17.23) in the development cohort and 55.90 mL/min/1.73m2 (19.69) in the external validation cohorts. Among the current GFR equations, the race-free CKD-EPI 2021 equation showed the lowest performance compared with the MDRD and CKD-EPI 2009 equations. When race was included in the kidney recipient specific GFR equation, performance did not increase. The race-free kidney recipient specific GFR equation showed significantly improved performance compared with the race-free CKD-EPI 2021 equation and performed well in the external validation cohorts (P30 ranging from 73.0% to 91.3%). The race-free kidney recipient specific GFR equation performed well in several subpopulations of kidney transplant recipients stratified by race (P30 73.0-91.3%), sex (72.7-91.4%), age (70.3-92.0%), body mass index (64.5-100%), donor type (58.5-92.9%), donor age (68.3-94.3%), treatment (78.5-85.2%), creatinine level (72.8-91.3%), GFR measurement method (73.0-91.3%), and timing of GFR measurement post-transplant (72.9-95.5%). An online application was developed that estimates GFR based on recipient's creatinine level, age, and sex (https://transplant-prediction-system.shinyapps.io/eGFR_equation_KTX/). CONCLUSION A new race-free kidney recipient specific GFR equation was developed and validated using multiple, large, international cohorts of kidney transplant recipients. The equation showed high accuracy and outperformed the race-free CKD-EPI 2021 equation that was developed in individuals with native kidneys. TRIAL REGISTRATION ClinicalTrials.gov NCT05229939.
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Affiliation(s)
- Marc Raynaud
- Université de Paris Cité, INSERM, PARCC, Paris Translational Research Centre for Organ Transplantation, F-75015 Paris, France
| | - Solaf Al-Awadhi
- Université de Paris Cité, INSERM, PARCC, Paris Translational Research Centre for Organ Transplantation, F-75015 Paris, France
| | - Ivana Juric
- Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Gillian Divard
- Université de Paris Cité, INSERM, PARCC, Paris Translational Research Centre for Organ Transplantation, F-75015 Paris, France
| | - Yannis Lombardi
- Department of Nephrology and Acute Kidney Intensive Care, Tenon Hospital, Paris, France
| | - Nikolina Basic-Jukic
- Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Olivier Aubert
- Université de Paris Cité, INSERM, PARCC, Paris Translational Research Centre for Organ Transplantation, F-75015 Paris, France
- Department of Nephrology and Kidney Transplantation, Necker Hospital, Paris, France
| | - Laurence Dubourg
- Centre de Référence des Maladies Rénales Rares, Service de Néphrologie et Rhumatologie Pédiatriques, Hospices Civils de Lyon, Lyon, France
| | - Ingrid Masson
- Department of Nephrology, Dialysis and Renal Transplantation, Nord Hospital, Jean Monnet University, Saint-Etienne, France
| | - Christophe Mariat
- Department of Nephrology, Dialysis and Renal Transplantation, Nord Hospital, Jean Monnet University, Saint-Etienne, France
| | - Dominique Prié
- Department of Nephrology and Kidney Transplantation, Necker Hospital, Paris, France
| | - Vincent Pernin
- Department of Nephrology, University Hospital Centre, Montpellier, France
| | - Moglie Le Quintrec
- Department of Nephrology, University Hospital Centre, Montpellier, France
| | - Timothy S Larson
- William J von Liebig Centre for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA
| | - Mark D Stegall
- William J von Liebig Centre for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA
| | - Boris Bikbov
- Department of Health Policy, Instituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - Piero Ruggenenti
- Department of Renal Medicine, Clinical Research Centre for Rare Diseases "Aldo e Cele Daccò": Instituto di Ricerche Farmacologiche Mario Negri IRCCS, Ranica, Bergamo, Italy
- Unit of Nephrology and Dialysis, Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy
| | - Laurent Mesnard
- Department of Nephrology and Acute Kidney Intensive Care, Tenon Hospital, Paris, France
| | - Hassan N Ibrahim
- University of Texas Health Sciences Centre at Houston, Texas, USA
| | | | - Arthur J Matas
- Division of Transplantation, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA
| | | | - Stan Benjamens
- Department of Surgery, University of Groningen and University Medical Centre Groningen, Groningen, Netherlands
| | - Robert A Pol
- Department of Surgery, University of Groningen and University Medical Centre Groningen, Groningen, Netherlands
| | - Stephan J L Bakker
- Division of Nephrology, Department of Internal Medicine, University of Groningen and University Medical Centre Groningen, Groningen, Netherlands
| | - Xavier Jouven
- Université de Paris Cité, INSERM, PARCC, Paris Translational Research Centre for Organ Transplantation, F-75015 Paris, France
| | - Christophe Legendre
- Department of Nephrology and Kidney Transplantation, Necker Hospital, Paris, France
| | - Nassim Kamar
- Department of Nephrology and Organ Transplantation, Paul Sabatier University, INSERM, Toulouse, France
| | - Byron H Smith
- Division of Nephrology and Hypertension, Mayo Clinic, Jacksonville, Florida, USA
| | - Hani M Wadei
- Division of Nephrology and Hypertension, Mayo Clinic, Jacksonville, Florida, USA
| | - Antoine Durrbach
- Department of Nephrology and Renal Transplantation, Henri-Mondor Hospital, Paris-Saclay University, Creteil, France
| | - Flavio Vincenti
- Department of Surgery, Kidney Transplant Service, University of California San Francisco, San Francisco, California, USA
| | - Giuseppe Remuzzi
- Department of Renal Medicine, Clinical Research Centre for Rare Diseases "Aldo e Cele Daccò": Instituto di Ricerche Farmacologiche Mario Negri IRCCS, Ranica, Bergamo, Italy
| | - Carmen Lefaucheur
- Department of Kidney Transplantation, Saint Louis University Hospital, Paris, France
| | - Andrew J Bentall
- William J von Liebig Centre for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA
| | - Alexandre Loupy
- Université de Paris Cité, INSERM, PARCC, Paris Translational Research Centre for Organ Transplantation, F-75015 Paris, France
- Department of Nephrology and Kidney Transplantation, Necker Hospital, Paris, France
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Performance of the various serum creatinine-based GFR estimating equations in pediatric kidney transplant recipients, stratified by age and CKD staging. Pediatr Nephrol 2021; 36:3221-3228. [PMID: 33893542 DOI: 10.1007/s00467-021-05024-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Revised: 02/12/2021] [Accepted: 02/22/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Numerous equations are used to estimate glomerular filtration rate (eGFR), based on serum creatinine (SCr), demographic and anthropometric data, none established in pediatric kidney transplant recipients. This study aimed to validate the available SCr-based eGFR equations in comparison with a measured (mGFR), stratified by chronic kidney disease (CKD) stage and age at the time of testing. METHODS One hundred twenty-seven pediatric kidney transplant recipients with 411 mGFR values (plasma clearance of iothalamate) were enrolled in this retrospective study. The bias, precision, and accuracy (percentage of estimates within 10% and 30% of mGFR) of five SCr eGFR equations (original Schwartz, CKiDSCr equation, Pottel, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) were assessed. RESULTS Height-independent Pottel equation performed well across all the categories of age and CKD staging. CKiDSCr equation performed well in CKD stages II-V. The CKiDSCr equation had a lower bias in children < 15 years of age, while MDRD and CKD-EPI equations had less bias in children > 15 years. Overall, both the Pottel and CKiDSCr equations had high accuracy (80%) and low bias (< 5 ml/min/1.73 m2). In contrast, the original Schwartz, MDRD, and CKD-EPI equations displayed high bias and low precision/accuracy. CONCLUSIONS Given their low bias and high accuracy across ages and CKD stages, the Pottel or the CKiDSCr equation is better to assess eGFR in pediatric kidney transplant recipients. The Pottel equation outperformed other eGFR equations in adolescents.
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Abstract
Since 1957, over 70 equations based on creatinine and/or cystatin C levels have been developed to estimate glomerular filtration rate (GFR). However, whether these equations accurately reflect renal function is debated. In this Perspectives article, we discuss >70 studies that compared estimated GFR (eGFR) with measured GFR (mGFR), involving ~40,000 renal transplant recipients and patients with chronic kidney disease (CKD), type 2 diabetes mellitus or polycystic kidney disease. Their results show that eGFR often differed from mGFR by ±30% or more, that eGFR values incorrectly staged CKD in 30-60% of patients, and that eGFR and mGFR gave different rates of GFR decline. Errors were unpredictable, and comparable for equations based on creatinine and/or cystatin C. We argue, therefore, that the persistence of these errors (despite intensive research) suggests that the problem lies with using creatinine and/or cystatin C as markers of renal function, rather than with the mathematical methods used for GFR estimation.
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Nabiee M, Dashti-Khavidaki S. Donor's Versus Recipient's Demographic Data for Estimating Kidney Function in Kidney Transplant Recipients. J Res Pharm Pract 2019; 8:179-180. [PMID: 31728352 PMCID: PMC6830020 DOI: 10.4103/jrpp.jrpp_19_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Affiliation(s)
- Morteza Nabiee
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Simin Dashti-Khavidaki
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
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Lanznaster D, Bejan-Angoulvant T, Patin F, Andres CR, Vourc'h P, Corcia P, Blasco HÉ. Plasma creatinine and amyotrophic lateral sclerosis prognosis: a systematic review and meta-analysis. Amyotroph Lateral Scler Frontotemporal Degener 2019; 20:199-206. [PMID: 30961401 DOI: 10.1080/21678421.2019.1572192] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Background: Plasma creatinine has been described as a prognostic biomarker for Amyotrophic Lateral Sclerosis (ALS), but with conflicting results in the literature. We performed a systematic review followed by a meta-analysis to address this question. Methods: We performed a systematic review of Pubmed, Embase and Cochrane databases and retrieved 14 distinct cohorts (19 studies) reporting results regarding the relationship between plasma creatinine and a clinical marker for ALS progression, notably ALSFRS (ALS Functional Rating Scale) and survival. Results: For baseline plasma creatinine, mortality risk was 28% lower when creatinine was higher than 88.4 µmol/L (hazard ratio (HR): 0.72; 95% confidence interval (CI): 0.58 to 0.88; p = 0.0003) and was 25% lower if creatinine was above versus below the median (HR: 0.75; 95% CI: 0.63 to 0.89; p = 0.0008). We found a significant positive correlation between plasma creatinine at baseline and functional score, and between creatinine decline and functional score decline (p < 0.0001 for both); but a negative correlation between plasma creatinine and functional score decline (p = 0.033). The overall quality of the studies was low mainly due to potential attrition bias, and several studies did not report analyzable results raising concern regarding a potential reporting bias. Conclusions: Plasma creatinine seems to be a promising prognostic biomarker for ALS. However, new studies with sound methodology and standardized criteria for the evaluation of ALS progression should be conducted to validate plasma creatinine as a clinical biomarker for ALS prognosis.
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Affiliation(s)
| | | | - Franck Patin
- a UMR 1253, Team 2, INSERM/University of Tours , Tours , France and
| | | | - Patrick Vourc'h
- a UMR 1253, Team 2, INSERM/University of Tours , Tours , France and
| | - Phillipe Corcia
- a UMR 1253, Team 2, INSERM/University of Tours , Tours , France and
| | - HÉlÉne Blasco
- a UMR 1253, Team 2, INSERM/University of Tours , Tours , France and
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8
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Glassock RJ. Evaluation of proteinuria redux. Kidney Int 2016; 90:938-940. [DOI: 10.1016/j.kint.2016.07.044] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Accepted: 07/11/2016] [Indexed: 11/25/2022]
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Yadav P, Cook M, Cockwell P. Current Trends of Renal Impairment in Multiple Myeloma. KIDNEY DISEASES 2016; 1:241-57. [PMID: 27536684 DOI: 10.1159/000442511] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/10/2015] [Accepted: 11/18/2015] [Indexed: 12/20/2022]
Abstract
BACKGROUND Renal impairment (RI) is a common complication of multiple myeloma (MM). Around 50% of patients with MM have RI at presentation, and up to 5% require dialysis treatment. Severe acute kidney injury (AKI) as a cause of RI is a particular challenge as historically the survival of patients who sustain this complication and require dialysis is very poor. However, in this current period, survival is improving and the focus is on optimum use of novel chemotherapies and the evaluation of extra-corporeal therapies for removal of serum immunoglobulin light chains. SUMMARY RI in patients with MM is commonly associated with excess monoclonal free light chain (FLC) production; myeloma cast nephropathy is the predominant renal pathology in patients presenting with severe RI secondary to AKI. The majority of patients have mild to moderate RI and recover renal function. However, patients with more severe RI, in particular those with a requirement for dialysis, are less likely to recover renal function. Rapid diagnosis and prompt institution of anti-myeloma therapy is an important determinant of renal function recovery, through targeting early and sustained reduction of involved monoclonal FLC. Novel agents are associated with excellent disease response, and bortezomib is now widely used as a first-line agent in the management of MM in patients with severe RI. Extended haemodialysis using high cut-off dialysers is more effective for extracorporeal removal of FLC than plasma exchange, and clinical trials are in process. High-dose chemotherapy with autologous stem cell transplantation does have a role in patients with severe RI but requires careful patient selection. KEY MESSAGES RI is very common in patients with MM, and renal function recovery is associated with improved clinical outcomes. We summarise the epidemiology of MM in the UK, present the impact of RI and renal function recovery on patient outcome, and describe the current management of MM in western countries. FACTS FROM EAST AND WEST (1) A serum creatinine level >2 mg/dl has been reported in 16, 21, 24, and 33% of patients with MM in cohort studies from Japan, Europe, China, and Korea, respectively. A creatinine clearance rate <30 ml/min was observed in 30 and 15% of patients in Chinese and Western MM cohorts, respectively. The commonest cause of severe RI in patients with MM is myeloma cast nephropathy. (2) The efficacy of novel treatments (bortezomib, carfilzomib, thalidomide, and lenalidomide) has predominantly been assessed in Western patients. Bortezomib and dexamethasone are the current standard of care for MM and severe RI in the West. Severe RI is not a contraindication to autologous stem cell transplantation (ASCT). Most of the data are from the West; there are case reports from China describing good outcomes with ASCT. The removal of FLC by high-cut-off hemodialysis is under evaluation in randomized controlled trials (RCTs) in the West. Studies in this area are not yet conducted in China. In China, new treatments, such as bortezomib, are more widely used than before, and favorable results are being reported; however, RCT studies are still needed in this area to confirm the efficacy and safety of this and other novel treatments.
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Affiliation(s)
- Punit Yadav
- Department of Renal Medicine, Queen Elizabeth Hospital, Birmingham, UK; School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK; Birmingham Institute of Translational Medicine, Birmingham, UK
| | - Mark Cook
- Birmingham Institute of Translational Medicine, Birmingham, UK; Department of Haematology, Queen Elizabeth Hospital, Birmingham, UK
| | - Paul Cockwell
- Department of Renal Medicine, Queen Elizabeth Hospital, Birmingham, UK; School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK; Birmingham Institute of Translational Medicine, Birmingham, UK
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Santos J, Martins LS. Estimating glomerular filtration rate in kidney transplantation: Still searching for the best marker. World J Nephrol 2015; 4:345-53. [PMID: 26167457 PMCID: PMC4491924 DOI: 10.5527/wjn.v4.i3.345] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Revised: 05/06/2015] [Accepted: 05/07/2015] [Indexed: 02/06/2023] Open
Abstract
Kidney transplantation is the treatment of choice for end-stage renal disease. The evaluation of graft function is mandatory in the management of renal transplant recipients. Glomerular filtration rate (GFR), is generally considered the best index of graft function and also a predictor of graft and patient survival. However GFR measurement using inulin clearance, the gold standard for its measurement and exogenous markers such as radiolabeled isotopes ((51)Cr EDTA, (99m)Tc DTPA or (125)I Iothalamate) and non-radioactive contrast agents (Iothalamate or Iohexol), is laborious as well as expensive, being rarely used in clinical practice. Therefore, endogenous markers, such as serum creatinine or cystatin C, are used to estimate kidney function, and equations using these markers adjusted to other variables, mainly demographic, are an attempt to improve accuracy in estimation of GFR (eGFR). Nevertheless, there is some concern about the inability of the available eGFR equations to accurately identify changes in GFR, in kidney transplant recipients. This article will review and discuss the performance and limitations of these endogenous markers and their equations as estimators of GFR in the kidney transplant recipients, and their ability in predicting significant clinical outcomes.
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11
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Serum cystatin C and microalbuminuria in children with immune thrombocytopenia under short course of corticosteroids. EGYPTIAN PEDIATRIC ASSOCIATION GAZETTE 2015. [DOI: 10.1016/j.epag.2015.05.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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Estimating glomerular filtration rate in older people. BIOMED RESEARCH INTERNATIONAL 2014; 2014:916542. [PMID: 24772439 PMCID: PMC3977451 DOI: 10.1155/2014/916542] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/23/2013] [Accepted: 02/15/2014] [Indexed: 12/23/2022]
Abstract
We aimed at reviewing age-related changes in kidney structure and function, methods for estimating kidney function, and impact of reduced kidney function on geriatric outcomes, as well as the reliability and applicability of equations for estimating glomerular filtration rate (eGFR) in older patients. CKD is associated with different comorbidities and adverse outcomes such as disability and premature death in older populations. Creatinine clearance and other methods for estimating kidney function are not easy to apply in older subjects. Thus, an accurate and reliable method for calculating eGFR would be highly desirable for early detection and management of CKD in this vulnerable population. Equations based on serum creatinine, age, race, and gender have been widely used. However, these equations have their own limitations, and no equation seems better than the other ones in older people. New equations specifically developed for use in older populations, especially those based on serum cystatin C, hold promises. However, further studies are needed to definitely accept them as the reference method to estimate kidney function in older patients in the clinical setting.
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White CA, Knoll GA, Poggio ED. Measuring vs estimating glomerular filtration rate in kidney transplantation. Transplant Rev (Orlando) 2010; 24:18-27. [PMID: 19942102 DOI: 10.1016/j.trre.2009.10.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Evaluation of kidney function is crucial in the care of kidney transplant recipients and in the design and interpretation of clinical trials in transplantation. Kidney function is most commonly assessed in both instances using serum creatinine concentration or an estimate of glomerular filtration rate (GFR) based on serum creatinine. These are inexpensive, widely available, and easily administered. Both have significant drawbacks, notably with respect to their inability to accurately identify changes in GFR. Novel markers of GFR such as cystatin C and beta-trace protein show promise as accurate and sensitive markers of GFR but have not yet been adequately evaluated in kidney transplantation. In addition, they are relatively expensive compared to creatinine and their assays are not available in most clinical laboratories. Glomerular filtration rate measurement using a variety of different available tracers and techniques is infrequently used in either clinical care or research protocols because of its cost and cumbersomeness. This review will discuss the merits and pitfalls of the various tools available to evaluate GFR in kidney transplantation.
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Affiliation(s)
- Christine A White
- Division of Nephrology, Department of Medicine, Queen's University, Kingston, Canada K7L 2V6
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Kukla A, El-Shahawi Y, Leister E, Kasiske B, Mauer M, Matas A, Ibrahim HN. GFR-estimating models in kidney transplant recipients on a steroid-free regimen. Nephrol Dial Transplant 2010; 25:1653-61. [PMID: 20118486 DOI: 10.1093/ndt/gfp668] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND How to best estimate glomerular filtration rate (GFR) in kidney transplant recipients on steroid-free immunosuppression has not been established. METHODS Within 3 months of transplantation, iothalamate GFR (iGFR) was measured in 107 recipients on steroid-free and 27 on steroid-maintenance immunosuppression. A year later, a second GFR was performed. Serum creatinine was calibrated against a reference laboratory, and GFR was estimated (eGFR) using the re-expressed Cockcroft-Gault equation, eGFRCG; the Mayo Clinic equation, eGFRMC; the Modification of Diet in Renal Disease (MDRD) study equation, eGFRMDRD; and the newly introduced Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. RESULTS All models overestimated GFR regardless of steroid use or timing of GFR. In those not receiving steroids, eGFRCG was least biased: 1.85 +/- 15.2 ml/min at the first GFR and 0.23 +/- 15.2 ml/min at the second. eGFRMC and eGFRCKD-EPI were most biased and were within 30% of iGFR less than 60% of the time in contrast to eGFRCG which was within 30% of iGFR 80.2% of the time. eGFRMDRD was intermediate in its performance at the first GFR but was comparable to eGFRCG at the second measurement. Importantly, the four models had comparable but poor precision. Exposure to steroids for a whole year did not appreciably alter the models' bias or relative accuracy but resulted in a dramatic fall in their precision, R2 = 0.05-0.12. CONCLUSIONS GFR prediction equations overestimate measured GFR in recipients on and off steroid regimens. Long-term exposure to steroids results in a marked reduction in the precision of all models. In all, eGFRCG and eGFRMDRD are the two best available models.
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Affiliation(s)
- Aleksandra Kukla
- Division of Renal Diseases and Hypertension, University of Minnesota, Minneapolis, MN, USA
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Halacova M, Kotaska K, Kukacka J, Vavrova V, Kuzelova M, Ticha J, Prusa R. Serum cystatin C level for better assessment of glomerular filtration rate in cystic fibrosis patients treated by amikacin. J Clin Pharm Ther 2008; 33:409-17. [PMID: 18613859 DOI: 10.1111/j.1365-2710.2008.00932.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND AND OBJECTIVE Monitoring of renal function in cystic fibrosis (CF) patients is essential. The dosage regimen of amikacin is regularly modified according to the patient's glomerular filtration rate (GFR). The aim of the study was to evaluate the use of cystatin C (CyC) for monitoring amikacin therapy along with other markers of renal tubular and glomerular function, and damage [N-acetyl-beta-d glucosaminidase (NAG), creatinine level and creatinine clearance]. METHODS We compared the GFR, estimated from the serum concentrations of creatinine (Cockcroft-Gault formula) and CyC (Grubb's formula). Seventy-one patients (mean age 12 years; range 4-28 years) with CF were treated by intermittent intravenous infusion of amikacin. Tubular nephrotoxicity was investigated by measurement of urine NAG/urine creatinine ratio (U-NAG/U-creatinine). Concentrations of all markers were measured before starting amikacin therapy and at days 3, 5, 7, 10 and 12. Fluorescence polarization analysis, turbidimetry, enzymatic phototometric creatinine deaminase method and fluorimetry were used for determination of serum amikacin, serum CyC, creatinine and urine NAG activity. Receiver operating characteristic (ROC) analysis was performed to assess the influence of GFR estimated from serum creatinine and serum CyC for the prediction of amikacin clearance during aminoglycoside therapy. RESULTS Significant differences in the rate of U-NAG/U-creatinine were noted before and after treatment with amikacin (P < 0.001). Serum creatinine levels and creatinine clearance at the end of amikacin therapy (12th day) did not show any significant differences in comparison with the levels measured before the start of therapy (0th day). At days 5, 7, 10 and 12, serum CyC levels showed a significant elevation (P < 0.001), and CyC clearance showed a significant decrease (P < 0.001) in comparison with the levels measured at day 0. The ratio of amikacin clearance/creatinine clearance decreased with therapy whereas the amikacin clearance/CyC and amikacin clearance/CyC clearance increased. CONCLUSION We showed that the rate of U-NAG/U-creatinine is a suitable marker for monitoring tubular nephrotoxicity in CF patients. Serum creatinine and estimated creatinine clearance are modest predictors of GFR in CF patients. CyC appears to be a better marker of GFR than serum creatinine concentration or creatinine clearance in our study. Serum CyC levels and CyC clearance showed greater ability to predict amikacin clearance during therapy than creatinine clearance.
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Affiliation(s)
- M Halacova
- Department of Clinical Biochemistry and Pathobiochemistry, Charles University, 2nd Medical Faculty and University Hospital Motol, Prague, Czech Republic.
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White CA, Huang D, Akbari A, Garland J, Knoll GA. Performance of creatinine-based estimates of GFR in kidney transplant recipients: a systematic review. Am J Kidney Dis 2008; 51:1005-15. [PMID: 18455847 DOI: 10.1053/j.ajkd.2008.02.308] [Citation(s) in RCA: 81] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2007] [Accepted: 02/29/2008] [Indexed: 11/11/2022]
Abstract
BACKGROUND Glomerular filtration rate (GFR) commonly is estimated in kidney transplantation by using creatinine-based estimation equations. The performance of these equations in kidney transplant recipients is unclear, with conflicting results between studies. STUDY DESIGN Systematic review. SETTING & POPULATION Stable adult kidney transplant recipients more than 6 months posttransplantation. SELECTION CRITERIA Reporting of or ability to calculate from available data the GFR estimation equation bias (mean difference between measured GFR and estimated GFR) and percent accuracy (percentage of GFR estimates within 10%, 20%, or 30% of measured GFR). INDEX TESTS Creatinine-based GFR estimation equations (Cockcroft-Gault, 6-variable Modification of Diet in Renal Disease [MDRD] Study, 4-variable MDRD Study, and Nankivell). REFERENCE TESTS GFR determination using plasma or renal clearance of inulin, radioisotopes, or nonradiographic contrast. RESULTS The search yielded 23 studies. For the 4-variable MDRD Study equation, bias ranged from -11.4 to +9.2 mL/min/1.73 m(2) (0.15 mL/s/1.73 m(2)). Only 76% of estimates were within 30% of measured GFR. For the Cockcroft-Gault equation, bias ranged from -4.0 to +16 mL/min/1.73 m(2) and 73% of estimates were within 30% of measured GFR. For the Nankivell equation, bias ranged from -1.4 mL/min to 36.3 mL/min with a 30% accuracy of only 68%. LIMITATIONS This review is limited by the inability to pool bias data, lack of calibration of serum creatinine in the majority of studies, and inclusion of nonindependent observations in many studies. CONCLUSIONS Differences in patient populations, baseline GFRs of the study group, reference standard GFR used, and creatinine assay calibration likely account for the heterogeneity in results. These factors need to be considered by investigators and clinicians when interpreting estimates of GFR in kidney transplant recipients.
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Affiliation(s)
- Christine A White
- Department of Medicine, Division of Nephrology, Queen's University, Kingston, Ottawa, Ontario, Canada.
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Bianchi C, Donadio C, Tramonti G, Consani C, Lorusso P, Rossi G. Reappraisal of serum beta2-microglobulin as marker of GFR. Ren Fail 2001; 23:419-29. [PMID: 11499557 DOI: 10.1081/jdi-100104725] [Citation(s) in RCA: 65] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
INTRODUCTION Beta 2 microglobulin (beta2M) is filtered by the glomeruli and reabsorbed by the proximal tubular cells where it is metabolized. Its plasma concentration increases with decreasing renal function. AIM To compare serum creatinine (Cr) and serum beta2M as markers of GFR. PATIENTS AND METHODS In 160 adult patients, with various kidney diseases and different GFR, serum Cr (autoanalyzer), serum beta2M (RIA) and GFR (bladder cumulative method using 99mTc-DTPA as glomerular tracer) were measured in the same day. RESULTS A linear relationship was observed between In GFR and both In serum Cr (lnCr=3.112-0.716 lnGFR; r=0.92) and ln serum beta2M (lnbeta2M= 4.274-0.814 lnGFR; r = 0.90). With decreasing GFR the increase in serum beta2M was higher than that of serum Cr (see regression coefficients that are significantly different). The normal upper limit of serum Cr corresponds to a GFR 48.1 mL/min while that of serum beta2M to a GFR 65.0. With decreasing GFR the increase of serum beta2M occurs before than that of serum Cr. CONCLUSIONS With declining renal function, serum beta2M increases more and before than serum Cr. Serum beta2M is a good endogenous marker of GFR, better than serum Cr.
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Affiliation(s)
- C Bianchi
- U.O. Nefrologia Universitaria, Department of Internal Medicine, University of Pisa, Italy.
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Andreev E, Koopman M, Arisz L. A rise in plasma creatinine that is not a sign of renal failure: which drugs can be responsible? J Intern Med 1999; 246:247-52. [PMID: 10475992 DOI: 10.1046/j.1365-2796.1999.00515.x] [Citation(s) in RCA: 118] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
This is a review of the available information about drugs which cause an increase in plasma creatinine concentration without decreasing glomerular filtration rate (GFR). The GFR is the main, but not the single, determinant of the plasma creatinine levels. Several drugs, such as cimetidine, trimethoprim, corticosteroids, pyrimethamine, phenacemide, salicylates and active vitamin D metabolites, have been reported to increase plasma creatinine without influencing its glomerular filtration. Cimetidine, trimethoprim, pyrimethamine and salicylates can inhibit secretion of creatinine by the proximal tubule. Corticosteroids and vitamin D metabolites probably modify the production rate and the release of creatinine. The exact mechanism of phenacemide-creatinine interaction is not fully explained. These drug-induced alterations in plasma creatinine concentration have clinical significance when GFR is estimated by using plasma creatinine.
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Affiliation(s)
- E Andreev
- Clinic of Nephrology, Medical University-Sofia, Bulgaria
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Bertino JS. Measured versus estimated creatinine clearance in patients with low serum creatinine values. Ann Pharmacother 1993; 27:1439-42. [PMID: 8305771 DOI: 10.1177/106002809302701203] [Citation(s) in RCA: 27] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
OBJECTIVE To examine, in patients with a serum creatinine (SCr) < 85 mumol/L, whether the use of actual SCr versus the use of an SCr set at 85 mumol/L and applied to the Cockcroft-Gault method for calculation of creatinine clearance (Clcr), resulted in a similar ability to explain variance in prediction of Clcr. DESIGN Included in the study were patients with stable renal function receiving total parenteral nutrition, who underwent a 24-hour urine collection and had an SCr < 85 mumol/L. Clcr was calculated (CalcClcr) using the Cockcroft-Gault method, and actual SCr, and an SCr value set at 85 mumol/L (AdjCalcClcr). Calculated values were compared with 24-hour measured Clcr (MeasClcr). SETTING Inpatient, acute-care hospital. PATIENTS 33 patients having 33 urine-collection periods. All patients were receiving total parenteral nutrition as their only form of nutritional supplement. Patients who had liver disease, trauma, or burns, or who were receiving certain pharmacologic agents, were excluded from the study. MAIN OUTCOME MEASURES MeasClcr based on the 24-hour urine collection, CalcClcr computed using the actual measured SCr, and SCr adjusted to 85 mumol/L. RESULTS A higher proportion of the variance of measured versus calculated Clcr was explained by the using the actual measured SCr value (r2 = 0.68) than SCr adjusted to 85 mumol/L (r2 = 0.32). When analyzed by gender, adjusting the SCr to 85 mumol/L was somewhat better at explaining the variance of measured versus calculated Clcr, but still explained less than 50 percent of the variance. However, the use of the actual SCr explained more of the variance of measured versus calculated Clcr than the use of the SCr value adjusted to 85 mumol/L. CONCLUSIONS In patients with an SCr < 85 mumol/L, the actual measured SCr should be used when calculating Clcr (regardless of the patient's gender), by the Cockcroft-Gault method.
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Affiliation(s)
- J S Bertino
- Department of Pharmacy Services, Mary Imogene Bassett Hospital, Cooperstown, NY 13326
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Horber FF, Haymond MW. Human growth hormone prevents the protein catabolic side effects of prednisone in humans. J Clin Invest 1990; 86:265-72. [PMID: 2195062 PMCID: PMC296716 DOI: 10.1172/jci114694] [Citation(s) in RCA: 301] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Prednisone treatment causes protein wasting and adds additional risks to a patient, whereas human growth hormone (hGH) treatment causes positive nitrogen balance. To determine whether concomitant administration of hGH prevents the protein catabolic effects of prednisone, four groups of eight healthy volunteers each were studied using isotope dilution and nitrogen balance techniques after 7 d of placebo, hGH alone (0.1 mg.kg-1.d-1), prednisone alone (0.8 mg.kg-1.d-1), or prednisone plus hGH (n = 8 in each group). Whether protein balance was calculated from the leucine kinetic data or nitrogen balance values, prednisone alone induced protein wasting (P less than 0.001), whereas hGH alone resulted in positive (P less than 0.001) protein balance, when compared to the placebo-treated subjects. When hGH was added to prednisone therapy, the glucocorticoid-induced protein catabolism was prevented. Using leucine kinetic data, negative protein balance during prednisone was due to increased (P less than 0.05) proteolysis, whereas hGH had no effect on proteolysis and increased (P less than 0.01) whole body protein synthesis. During combined treatment, estimates of proteolysis and protein synthesis were similar to those observed in the placebo treated control group. In conclusion, human growth hormone may have a distinct role in preventing the protein losses associated with the administration of pharmacologic doses of glucocorticosteroids in humans.
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Affiliation(s)
- F F Horber
- Department of Pediatrics, Mayo Clinic, Rochester, Minnesota 55905
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Hatton J, Parr MD, Blouin RA. Estimation of creatinine clearance in patients with Cushing's syndrome. DICP : THE ANNALS OF PHARMACOTHERAPY 1989; 23:974-7. [PMID: 2603451 DOI: 10.1177/106002808902301203] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
The predictive value of the Cockcroft-Gault equation in patients with Cushing's syndrome was evaluated in 23 patients. Patients were subdivided based on total body weight into two groups, obese and nonobese. Estimated creatinine clearance (EClcr) values were obtained by the Cockcroft-Gault method using ideal body weight (IBW) and total body weight (TBW). These values were then compared with a 24-hour measured creatinine clearance (MClcr). EClcr values based on TBW consistently overestimated measured values in all patients (p less than 0.05). In obese patients with Cushing's syndrome IBW predictions were not statistically different. However, linear regression analysis revealed a poor correlation (r = 0.32). Daily creatinine production rates (Ucr) were calculated and contrasted with an appropriate historical control for obese and nonobese subjects. Nonobese patients revealed a marked reduction in total Ucr compared with normal-weight controls (p less than 0.05). Obese patients also showed a reduction in Ucr when compared with a normal obese control population (p less than 0.05). Difficulty in predicting creatinine clearance in patients with Cushing's syndrome appears to be related to alterations in Ucr. These data suggest that the pathophysiologic changes that accompany Cushing's syndrome are sufficient to alter Ucr and may limit the usefulness of existing methods to predict creatinine clearance and renal function in these patients.
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Affiliation(s)
- J Hatton
- University of Kentucky Medical Center, Department of Pharmacy, Lexington 40536
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