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Background: Social determinants of health are non-medical factors that impact health. For patients with chronic kidney disease (CKD) progressing to kidney failure, the influence of social determinants of health on dialysis modality selection (haemodialysis vs. peritoneal dialysis (PD)) is incompletely understood., Methods: Retrospective cohort study of 981 consecutive patients with advanced CKD referred to the Ottawa Hospital Multi-Care Kidney Clinic (Canada) who progressed to dialysis from 2010 to 2021. Multivariable logistic regression was used to measure odds ratios (OR) for the associations between social determinants of health (education, employment, marital status and residence) and modality of dialysis initiation., Results: The mean age and estimated glomerular filtration rate were 64 and 18 mL/min/1.73 m 2 , respectively. Not having a high school degree was associated with lower odds of initiating dialysis via PD compared to having a college degree (29% vs. 48%, OR 0.55 (95% confidence interval (CI) 0.34-0.88)). Unemployment was associated with lower odds of initiating dialysis via PD compared to active employment (38% vs. 62%, OR 0.40 (95% CI 0.27-0.60)). Being single was associated with lower odds of initiating dialysis via PD compared to being married (35% vs. 48%, adjusted OR 0.52 (95% CI 0.39-0.70)). Living alone at home was associated with lower odds of initiating dialysis via PD compared to living at home with family (33% vs. 47%, adjusted OR 0.55 (95% CI 0.39-0.78))., Conclusions: Social determinants of health including education, employment, marital status and residence are associated with dialysis modality selection. Addressing these 'upstream' social factors may allow for more equitable outcomes during the transition from advanced CKD to kidney failure., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AA has received speaker fees from AstraZeneca and holds research grants from Otsuka. MMS has received speaker fees from AstraZeneca. All other authors declare no conflicts of interest.

Background: Development of a short timeframe (6-12 months) kidney failure risk prediction model may serve to improve transitions from advanced chronic kidney disease (CKD) to kidney failure and reduce rates of unplanned dialysis. The optimal model for short timeframe kidney failure risk prediction remains unknown., Methods: This retrospective study included 1757 consecutive patients with advanced CKD (mean age 66 years, estimated glomerular filtration rate 18 mL/min/1.73 m2). We compared the performance of Cox regression models using (a) baseline variables alone, (b) time-varying variables and machine learning models, (c) random survival forest, (d) random forest classifier in the prediction of kidney failure over 6/12/24 months. Performance metrics included area under the receiver operating characteristic curve (AUC-ROC) and maximum precision at 70% recall (PrRe70). Top-performing models were applied to 2 independent external cohorts., Results: Compared to the baseline Cox model, the machine learning and time-varying Cox models demonstrated higher 6-month performance [Cox baseline: AUC-ROC 0.85 (95% CI 0.84-0.86), PrRe70 0.53 (95% CI 0.51-0.55); Cox time-varying: AUC-ROC 0.88 (95% CI 0.87-0.89), PrRe70 0.62 (95% CI 0.60-0.64); random survival forest: AUC-ROC 0.87 (95% CI 0.86-0.88), PrRe70 0.61 (95% CI 0.57-0.64); random forest classifier AUC-ROC 0.88 (95% CI 0.87-0.89), PrRe70 0.62 (95% CI 0.59-0.65)]. These trends persisted, but were less pronounced, at 12 months. The random forest classifier was the highest performing model at 6 and 12 months. At 24 months, all models performed similarly. Model performance did not significantly degrade upon external validation., Conclusions: When predicting kidney failure over short timeframes among patients with advanced CKD, machine learning incorporating time-updated data provides enhanced performance compared with traditional Cox models., (© American Association for Clinical Chemistry 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Rationale & Objective: Race-free estimated glomerular filtration rate (eGFR) equations incorporating creatinine with and without cystatin C were recently developed and recommended for routine use. However, the performance of these equations among kidney transplant recipients (KTRs) remains unknown., Study Design: Cross-sectional study to validate the 2021 race-free Chronic Kidney Disease (CKD) Epidemiology Collaboration (CKD-EPI) eGFR equation based on creatinine alone (eGFR cr ) or based on creatinine and cystatin C (eGFR cr-cys ) among KTRs., Setting & Participants: KTRs in stable condition (N = 415) from Canada and New Zealand with same-day measurements of creatinine, cystatin C, and glomerular filtration rate (GFR) using radiolabeled diethylenetriaminepentaacetic acid., Tests Compared: The 2009 CKD-EPI eGFR cr , 2021 CKD-EPI eGFR cr , 2012 CKD-EPI eGFR cr-cys , 2021 CKD-EPI eGFR cr-cys , 2012 CKD-EPI eGFR cys , and Modification of Diet in Renal Disease (MDRD) Study eGFR equations were compared with measured GFR., Outcomes: Bias, precision, accuracy, and correct classification by CKD stage. Bias was defined as the difference between estimated and measured GFR. Precision was represented by the interquartile range. Accuracy was defined as the percentages of participants with eGFRs within 10%/20%/30% (P 10 /P 20 /P 30 ) of measured GFR, root mean square error, and mean absolute error., Results: 87% of patients studied were White, 3% Black, and 10% other races. Mean measured GFR was 53 ± 19 (SD) mL/min/1.73 m 2 . The 2009 and 2021 CKD-EPI eGFR cr equations demonstrated similar median bias (-2.3 vs -0.2 mL/min/1.73 m 2 , respectively), precision (14.5 vs 14.9 mL/min/1.73 m 2 ), and accuracy (P 10 /P 20 /P 30 , 32%/65%/84% vs 33%/63%/84%). The 2012 and 2021 CKD-EPI eGFR cr-cys equations also demonstrated similar median bias (-3.6 vs 0.3 mL/min/1.73 m 2 , respectively), precision (13.3 vs 14.3 mL/min/1.73 m 2 ), and accuracy (P 10 /P 20 /P 30 , 32%/63%/80% vs 32%/67%/83%). No clear difference in performance was detected between the 2021 CKD-EPI eGFR cr and eGFR cr-cys equations among KTRs. The proportion of correct classification by CKD stage was similar across all eGFR equations., Limitations: Moderate sample size, few patients had a GFR <30 mL/min/1.73 m 2 , and the large majority of patients were White., Conclusions: Among KTRs, the 2021 race-free CKD-EPI eGFR equations perform similarly to the previous CKD-EPI equations that included race correction terms. No significant difference in performance was observed between the 2021 CKD-EPI eGFR cr and eGFR cr-cys equations in the kidney transplant population., (Copyright © 2022 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Chronic kidney disease (CKD) results in calcitriol deficiency and altered vitamin D metabolism. The objective of this study was to assess the 24-hydroxylation-mediated metabolism of 25(OH)D 3 and 1,25(OH) 2 D 3 in a cross-sectional analysis of participants with a range of kidney function assessed by precise measured GFR (mGFR) (N = 143) and in rats with the induction and progression of experimental kidney disease. Vitamin D metabolites were assessed with LC-MS/MS. Circulating measures of 24-hydroxylation of 25(OH)D 3 (24,25(OH) 2 D 3 :25(OH)D 3 ) precisely decreased according to mGFR in humans and progressively in rats with developing CKD. In contrast, the 1,24,25(OH)3D3: 1,25(OH) 2 D 3 vitamin D metabolite ratio increased in humans as the mGFR decreased and in rats with the induction and progression of CKD. Human participants taking cholecalciferol had higher circulating 1,24,25(OH) 3 D 3 , despite no increase of 1,25(OH) 2 D 3 . This first report of circulating 1,24,25(OH) 3 D 3 in the setting of CKD provides novel insight into the uniquely altered vitamin D metabolism in this setting. A better understanding of the uniquely dysfunctional catabolic vitamin D profile in CKD may guide more effective treatment strategies. The potential that 24-hydroxylated products have biological activity of is an important area of future research., (© 2022. The Author(s).)

Aims: Individuals with type 1 diabetes (T1D) are at an increased risk of chronic kidney disease making estimation of glomerular filtration rate (eGFR) an important component of diabetes care. Which eGFR equation is most appropriate to use in patients with T1D during the transition to adult care is unclear. We, therefore, sought to evaluate the performance of five eGFR equations in adolescents and young adults with T1D., Methods: Measured iohexol-based glomerular filtration rate was compared to the Chronic Kidney Disease and Epidemiology Collaboration (CKD-EPI) eGFR, Chronic Kidney Disease in Children (CKiD) eGFR, and three recently developed age-adjusted versions of these in 53 patients with T1D and preserved GFR using bias, precision, and accuracy., Results: The best performance was found in the sex-dependent CKiD equation (bias: -0.8, accuracy: 11.8 ml/min/1.73 m 2 ). Bias and accuracy (26.4 and 26.8 ml/min/1.73 m 2 ) were worst in the CKD-EPI equation. Age-dependent adjustment improved performance for this equation (bias: 5.3, accuracy: 13.4 ml/min/1.73 m 2 ), but not for the CKiD equation (bias: 15.5, accuracy: 18.8 ml/min/1.73 m 2 )., Conclusion: Age-adjustment improved performance for the CKD-EPI equation, but not for the CKiD equation. The sex-adjusted CKiD equation performed best out of all equations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Parathyroid hormone (PTH) is measured routinely as part of Chronic Kidney Disease Bone and Mineral Disorders (CKD-MBD) assessment. Multiple PTH assays exist with known differences resulting in CKD-MBD guidelines recommending treatment based on assay-specific thresholds. The study objectives are to assess between manufacturer and within manufacturer variability of PTH assays and the impact of assay variability on the assessment of CKD-BMD using both vendor defined and empirically derived thresholds., Methods: Data were collected from Ontario, Canada's Proficiency Testing Program (24 challenge vials, 115-133 laboratories all using secondary generation PTH assays. Mean PTH and precision by the coefficient of analytical variation (CV a) were calculated. For each vial, whether the manufacturer's mean value exceeded the vendor-defined and empirically-derived upper limit of normal (ULN) was recorded and the concordance between assays was determined., Results: Across all laboratories, the mean PTH range was 12.0 ± 3.9 pmol/L and the mean CV a was 30%. The percent of vials with a mean PTH exceeding manufacturer's specific ULN varied substantially between manufacturers. Only 58% of vials had complete concordance as to whether mean PTH was above assay-specific ULNs. This increased to 83% using the empirically derived ULN., Conclusions: CKD-BMD assessment and management will depend on the PTH assay. The between-assay variability is reduced but not eliminated when empirically derived reference intervals are used. Improvements in PTH measurement are required in order to ensure consistent patient care., (Copyright © 2021 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: The kidney failure risk equation is a clinical tool commonly used for prediction of progression from CKD to kidney failure. The kidney failure risk equation's accuracy in advanced CKD and whether this varies by CKD etiology remains unknown. This study examined the kidney failure risk equation's discrimination and calibration at 2 and 5 years among a large tertiary care population with advanced CKD from heterogeneous etiologies., Design, Setting, Participants, & Measurements: This retrospective cohort study included 1293 patients with advanced CKD (median eGFR 15 ml/min per 1.73 m 2 ) referred to the Ottawa Hospital Multi-Care Kidney Clinic between 2010 and 2016, with follow-up clinical data available through 2018. Four-variable kidney failure risk equation scores for 2- and 5-year risks of progression to kidney failure (defined as dialysis or kidney transplantation) were calculated upon initial referral and correlated with the subsequent observed kidney failure incidence within these time frames. Receiver operating characteristic curves and calibration plots were used to measure the discrimination and calibration of the kidney failure risk equation both in the overall advanced CKD population and by CKD etiology: diabetic kidney disease, hypertensive nephrosclerosis, GN, polycystic kidney disease, and other. Pairwise comparisons of the receiver operating characteristic curves by CKD etiology were performed to compare kidney failure risk equation discrimination., Results: The kidney failure risk equation provided adequate to excellent discrimination in identifying patients with CKD likely to progress to kidney failure at the 2- and 5-year time points both overall (2-year area under the curve, 0.83; 95% confidence interval, 0.81 to 0.85; 5-year area under the curve, 0.81; 95% confidence interval, 0.77 to 0.84) and across CKD etiologies. The kidney failure risk equation displayed adequate calibration at the 2- and 5-year time points both overall and across CKD etiologies (Hosmer-Lemeshow P≥ 0.05); however, the predicted risks of kidney failure were higher than the observed risks across CKD etiologies with the exception of polycystic kidney disease., Conclusions: The kidney failure risk equation provides adequate discrimination and calibration in advanced CKD and across CKD etiologies., (Copyright © 2020 by the American Society of Nephrology.)

Background: The Wnt/β-catenin pathway has been implicated in the development of adynamic bone disease in early-stage chronic kidney disease (CKD). Dickkopf-related protein 1 (DKK1) and sclerostin are antagonists of the Wnt/β-catenin pathway yet have not been widely used as clinical indicators of bone disease. This study characterized levels of DKK1, sclerostin, and other biomarkers of mineral metabolism in participants across a spectrum of inulin-measured glomerular filtration rate (GFR)., Methods: GFR was measured by urinary inulin clearance (mGFR) in 90 participants. Blood samples were obtained for measurement of circulating DKK1, sclerostin, fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), calcium, phosphate, α-klotho, and vitamin D metabolites including 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3. Spearman correlations and linear regressions were used where appropriate to examine the associations between measured values., Results: The median [IQR] age was 64 years [53.0-71.0], and the median [IQR] mGFR was 32.6 [21.7-60.6] mL/min. DKK1 decreased (r = 0.6, p < 0.001) and sclerostin increased (r = -0.4, p < 0.001) as kidney function declined, and both were associated with phosphate, PTH, FGF-23, and 1,25-dihydroxyvitamin D3 in the unadjusted analysis. After adjustment for age and mGFR, DKK1 remained significantly associated with PTH., Conclusion: The results of this study demonstrate opposing trends in Wnt/β-catenin pathway inhibitors, DKK1 and sclerostin, as mGFR declines. Unlike sclerostin, DKK1 levels decreased significantly as mGFR declined and was independently associated with PTH. Future studies should determine whether measurement of Wnt signaling inhibitors may be useful in predicting bone histomorphometric findings and important clinical outcomes in patients with CKD., (© 2020 S. Karger AG, Basel.)

Background: Patients with chronic kidney disease (CKD) have higher levels of coronary artery calcification (CAC) compared with the general population. The role of CAC in renal function decline is not well understood., Methods: In this prospective cohort study of Stages 3-5 CKD patients with CAC scores kidney function decline, development of end-stage kidney disease (ESKD) and all-cause mortality were determined at 5 and 10 years. Baseline variables included markers of CKD and chronic kidney disease mineral and bone disorder (CKD-MBD), demographics and comorbidities. Multivariable analyses identified predictors of outcomes, and survival curves demonstrated the association of CAC score with ESKD and mortality., Results: One hundred and seventy-eight patients were enrolled between 2005 and 2007. Independent predictors of ESKD at 5 years were estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR); at 10 years, eGFR was no longer a predictor, but CAC was now significant. Those who developed ESKD at the fastest rate either had the highest CAC score (≥400 AU) or were youngest and had the lowest calcidiol, and highest serum phosphate, UACR and percentage change in CAC per year. Predictors of eGFR decline over 5 years were UACR, parathyroid hormone and CAC score. Predictors of mortality at 5 years were age, diabetes and eGFR and at 10 years also included CAC score., Conclusions: In Stages 3-5 CKD patients, CAC is an independent predictor of both ESKD and mortality at 10 years. Those who developed ESKD at the fastest rate either had the highest CAC score or the worst CKD-MBD derangements., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Diagnosis, prognostication and treatment in chronic kidney disease is often informed by an estimate of the glomerular filtration rate (GFR). Commonly used GFR estimation (eGFR) equations are based on serum creatinine (Cr) concentrations and display suboptimal precision and accuracy. Newer equations incorporating additional endogenous markers such as β-Trace Protein (BTP), β 2 -Microglobulin (B2M) and cystatin C (cysC) have been developed but require validation., Methods: This prospective cohort study evaluated the performance of 6 eGFR equations developed by the chronic kidney disease - epidemiology collaboration group (CKD-EPI) against urinary inulin clearance GFR in patients recruited from outpatient nephrology clinics., Results: Mean biases were negligible and similar between equations. The eGFR-EPI Cr/cysC had the best precision and accuracy of all the equations and the best agreement with inulin mGFR when classifying participants into GFR categories. The BTP and B2M equations displayed the worst precisions and accuracies and showed the least consistent performance across levels of GFR. Thus, the eGFR-EPI Cr/cysC is the least biased, most precise and has the highest accuracy as compared to other eGFR-EPI equations., Conclusions: The BTP and B2M equations are the worst performing of the eGFR-EPI equations, and no benefit is observed with the addition of BTP or B2M to Cr/cysC., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The Kidney Failure Risk Equation (KFRE) predicts the need for dialysis or transplantation using age, sex, estimated glomerular filtration rate (eGFR), and urine albumin to creatinine ratio (ACR). The eGFR and ACR have known biological and analytical variability. We examined the effect of biological and analytical variability of eGFR and ACR on the 2-year KFRE predicted kidney failure probabilities using single measure and the average of repeat measures of simulated eGFR and ACR. Previously reported values for coefficient of variation (CV) for ACR and eGFR were used to calculate day to day variability. Variation was also examined with outpatient laboratory data from patients with an eGFR between 15 and 50 mL/min/1.72 m2. A web application was developed to calculate and model day to day variation in risk. The biological and analytical variability related to ACR and eGFR lead to variation in the predicted probability of kidney failure. A male patient age 50, ACR 30 mg/mmol and eGFR 25, had a day to day variation in risk of 7% (KFRE point estimate: 17%, variability range 14% to 21%). The addition of inter laboratory variation due to different instrumentation increased the variability to 9% (KFRE point estimate 17%, variability range 13% to 22%). Averaging of repeated measures of eGFR and ACR significantly decreased the variability (KFRE point estimate 17%, variability range 15% to 19%). These findings were consistent when using outpatient laboratory data which showed that most patients had a KFRE 2-year risk variability of ≤ 5% (79% of patients). Approximately 13% of patients had variability from 5-10% and 8% had variability > 10%. The mean age (SD) of this cohort was 64 (15) years, 36% were females, the mean (SD) eGFR was 32 (10) ml/min/1.73m2 and median (IQR) ACR was 22.7 (110). Biological and analytical variation intrinsic to the eGFR and ACR may lead to a substantial degree of variability that decreases with repeat measures. Use of a web application may help physicians and patients understand individual patient's risk variability and communicate risk (https://mccudden.shinyapps.io/kfre&#95;app/). The web application allows the user to alter age, gender, eGFR, ACR, CV (for both eGFR and ACR) as well as units of measurements for ACR (g/mol versus mg/g)., Competing Interests: The authors have declared that no competing interests exist.

Rationale & Objective: The KDIGO (Kidney Disease: Improving Global Outcomes) guideline for chronic kidney disease (CKD) presented an international classification system that ranks patients' risk for CKD progression. Few data for children informed guideline development., Study Design: Observational cohort study., Settings & Participants: Children aged 1 to 18 years enrolled in the North American Chronic Kidney Disease in Children (CKiD) cohort study and the European Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) trial., Predictor: Level of estimated glomerular filtration rate (eGFR) and proteinuria (urine protein-creatinine ratio [UPCR]) at study entry., Outcome: A composite event of renal replacement therapy, 50% reduction in eGFR, or eGFR<15mL/min/1.73m 2 . eGFR was estimated using the CKiD-derived "bedside" equation., Analytical Approach: Accelerated failure time models of the composite outcome using a conventional generalized gamma distribution. Likelihood ratio statistics of nested models were used to amalgamate levels of similar risk., Results: Among 1,232 children, median age was 12 (IQR, 8-15) years, median eGFR was 47 (IQR, 33-62) mL/min/1.73m 2 , 60% were males, and 13% had UPCRs>2.0mg/mg at study entry. 6 ordered stages with varying combinations of eGFR categories (60-89, 45-59, 30-44, and 15-29mL/min/1.73m 2 ) and UPCR categories (<0.5, 0.5-2.0, and >2.0mg/mg) described the risk continuum. Median times to event ranged from longer than 10 years for eGFRs of 45 to 90mL/min/1.73m 2 and UPCRs<0.5mg/mg to 0.8 years for eGFRs of 15 to 30mL/min/1.73m 2 and UPCRs>2mg/mg. Children with glomerular disease were estimated to have a 43% shorter time to event than children with nonglomerular disease. Cross-validation demonstrated risk patterns that were consistent across the 10 subsample validation models., Limitations: Observational study, used cross-validation rather than external validation., Conclusions: CKD staged by level of eGFR and proteinuria characterizes the timeline of progression and can guide management strategies in children., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Endogenous markers of kidney function are insensitive to early declines in glomerular filtration rate (GFR) and in rodent models, validated, practical alternatives are unavailable. In this study, we determined GFR by modeling the plasma clearance of two compounds, iohexol and inulin, and compared the findings to common endogenous markers. All plasma clearance methods of both iohexol and inulin detected a decline in renal function weeks prior to any increase in endogenous marker. Iohexol plasma clearance and inulin plasma clearance had a very high agreement and minimal bias when using 12-sample models. However, only iohexol could be accurately simplified to a two-sample, one-compartment estimation strategy. Following an IV injection of low-dose iohexol and two timed blood samples at 30 and 90 min, one can accurately approximate a complex 12-sample strategy of plasma clearance. This method is simple enough to use in routine, longitudinal analysis of larger cohort animal studies., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Background and Objectives: The tracing of creatinine (Cr) reference materials to isotope dilution mass spectrometry-assigned values was implemented worldwide to reduce interlaboratory variability and improve assay accuracy. The aims of this study were to examine the current extent of interlaboratory variability and its effect on eGFR., Design, Setting, Participants, & Measurements: Leftover plasma from 2-3 consecutive days was obtained from 53 intensive care unit patients with a range of kidney functions. Individual patient samples were pooled and split and sent to 12 different laboratories for Cr measurement. For each patient, the mean Cr and Chronic Kidney Disease Epidemiology Collaboration eGFR (eGFR-EPI), assuming a 65-year-old nonblack woman, were determined. Interlaboratory variability was assessed by the range and SD of Cr and eGFR-EPI. This was repeated after stratifying by assay type and by the median Cr of 1.36 mg/dl. For patients whose eGFR-EPI range included 60 ml/min per 1.73 m 2 , the percentage of laboratories with eGFR-EPI<60 ml/min per 1.73 m 2 was determined., Results: The mean±SD of the Cr and eGFR-EPI ranges were 0.20±0.09 mg/dl and 14±9 ml/min per 1.73 m 2 for Cr<1.36 mg/dl. Jaffe Cr results were an average 0.1 mg/dl (Cr≥1.36 mg/dl) and 0.05 mg/dl (Cr<1.36 mg/dl) higher than enzymatic results (P<0.001 for both). Ten patients had an eGFR-EPI range that included 60 ml/min per 1.73 m 2 . Their median eGFR-EPI range was 15 ml/min per 1.73 m 2 . There was significant discordance in the diagnosis of CKD (eGFR-EPI<60 ml/min per 1.73 m 2 ), with laboratories using Jaffe Cr methods making the diagnosis more frequently than those using enzymatic Cr methods (60% versus 39%)., Conclusions: Significant interlaboratory variability in Cr measurement still exists. Jaffe assays yield higher Cr values than enzymatic assays, leading to lower eGFR-EPIs and more frequent CKD diagnoses. Further improvements in assay performance are required to standardize patient CKD diagnosis and to facilitate longitudinal Cr monitoring across laboratories., (Copyright © 2016 by the American Society of Nephrology.)

Background: As with creatinine, cystatin C can be incorporated into a formula to estimate the glomerular filtration rate (GFR). The overall performance of cystatin C-based equations in kidney transplantation is unclear with conflicting results between studies., Methods: Systematic review of adult kidney transplant recipients. Studies that reported mean bias (mean difference between the measured and estimated GFRs) or accuracy of the cystatin C-based GFR estimation equation (e.g. percentage of estimates within 30% of the measured GFR) against the measured GFR using renal or plasma clearance of contrast agents, radioisotopes or inulin were included., Results: The search identified 10 studies that examined 14 different cystatin C-based estimating equations (n = 5 equations evaluated in more than one study). The Le Bricon equation had the best performance with a bias that ranged from -6.4 to +2.8 mL/min/1.73 m(2); 85% (95% CI, 82-88) of estimates were within 30% of the measured GFR. For the other equations, 66-82% of estimates were within 30% of the measured GFR. For the modification of diet in renal disease (MDRD) equation, 68% (95% CI, 65-72) of estimates were within 30% of the measured GFR., Conclusions: The cystatin C-based Le Bricon equation was the most accurate, and most of the cystatin C-based equations showed improvements in 30% and 50% accuracy compared with the creatinine-based MDRD equation. Cystatin C-based equations may offer an advantage over the MDRD equation in kidney transplant recipients. Estimating equations re-expressed with standardized cystatin C have been developed and their accuracy needs to be tested in the kidney transplant population.