National Kidney Foundation Laboratory Engagement Working Group Recommendations for Implementing the CKD-EPI 2021 Race-Free Equations for Estimated Glomerular Filtration Rate: Practical Guidance for Clinical Laboratories.

Recognizing that race is a social and not a biological construct, healthcare professionals and the public have called for removal of race in clinical algorithms. In response, the National Kidney Foundation and the American Society of Nephrology created the Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Diseases to examine the issue and provide recommendations. The final report from the Task Force recommends calculating estimated glomerular filtration rate (eGFR) without a race coefficient using the recently published CKD-EPI 2021 creatinine (cr) and creatinine-cystatin C (cr-cys) equations. The Task Force recommends immediately replacing older eGFRcr equations (MDRD Study and CKD-EPI 2009) with the new CKD-EPI 2021 equation. In a 2019 survey by the College of American Pathologists, 23% of 6200 laboratories reporting eGFRcr used an incorrect equation that is not suitable for use with standardized creatinine measurements, 34% used the CKD-EPI 2009 equation and 43% used the MDRD Study 2006 equation re-expressed for standardized creatinine measurement. Rapid transition to using the CKD-EPI 2021 equation is an opportunity for laboratories to standardize to a single equation to eliminate differences in eGFRcr due to different equations used by different laboratories, and to report eGFR without use of race. We provide guidance to laboratories for implementing the CKD-EPI 2021 equations for both eGFRcr and eGFRcr-cys.

Utilization of Cystatin C in the Outpatient Setting.

INTRODUCTION: Serum creatinine is the traditional biomarker for estimating glomerular filtration rate (eGFR). Cystatin C is an alternative biomarker for which estimating equations exist. The use of cystatin C testing, and the interrelationships among the recently revised Chronic Kidney Disease Epidemiology (CKD-EPI) 2021 estimating equations, was evaluated in a national outpatient laboratory dataset. METHODS: Cystatin C results reported on adults between November 2011 and June 2018 by Laboratory Corporation of America Holdings were examined, with classification of ordering providers and diagnostic codes. Updated eGFR results were calculated using the CKD-EPI 2021 equations for each sample with both cystatin C and creatinine values available. The Spearman correlation coefficients were calculated. Reclassification at clinically relevant cut-off values was examined. RESULTS: There were 87,803 serum cystatin C levels among 55,360 patients; mean age 58 ± 17 years; 50% women. Cystatin C usage increased over time and was ordered for many indications. Among 73,367 samples with simultaneous creatinine and cystatin C, r = 0.84 between eGFR-creatinine and eGFR-cystatin. Correlations of eGFR-creatinine, eGFR-cystatin, and the averaged result of the two equations to the new combined equation were r = 0.94, r = 0.97, and r = 0.998, respectively (p < 0.001 for all). Use of combined/averaged equations tended to result in a higher eGFR and upclassification, compared to eGFR-creatinine. CONCLUSION/DISCUSSION: Use of Cystatin C is increasing and has moved beyond the nephrology community and the original indications from the 2012 KDIGO guidelines. Community utilization of cystatin C measurement is likely to expand, and understanding of the relationships between estimating equations will help clinicians optimize their use in the outpatient setting.

The Epidemiologic Burden of Tacrolimus Variability among Kidney Transplant Recipients in the United States.

BACKGROUND: Within-patient tacrolimus level variability >30% has been shown to be a risk factor for de novo donor-specific antibody formation and death-censored graft failure among kidney transplant recipients. The burden of tacrolimus variability and the correlation between variability and subtherapeutic tacrolimus levels were examined in a large national data set. METHODS: All tacrolimus levels drawn at LabCorp® facilities in the United States with a diagnosis code for kidney transplant between November 2011 and September 2017 were examined, excluding values that could represent new allografts. Tacrolimus variability was calculated if at least 3 levels were available. The percentage of subtherapeutic (<4.0 ng/dL) tacrolimus levels (%subT) was also calculated. Interdependence between %subT and tacrolimus variability was assessed with correlation analysis and linear regression. RESULTS: There were 410,257 tacrolimus levels among 27,375 patients, who had 11 (interquartile range [IQR] 6-20) tacrolimus levels over a median follow-up of 26.5 (IQR 12.8-46.1) months. Median tacrolimus variability was 30.6%, and 51.6% of patients exceeded 30% variability. Median %subT was 11.1% (IQR 0-30.8%), and 34.3% of patients had no subtherapeutic levels. The correlation coefficient between tacrolimus variability and %subT was 0.253 (p< 0.001). In linear regression, tacrolimus variability increased 1.86% for each 10% increase in %subT (p < 0.001), but R-squared for this model was only 0.06. CONCLUSION: More than half of established kidney transplant patients from a large national sample exhibited levels of tacrolimus variability that have been associated with inferior transplant outcomes. Tacrolimus variability has a weak association with subtherapeutic levels, but represents a more complicated constellation of clinical factors.

A laboratory-based algorithm to predict future kidney function decline in older adults with reduced estimated glomerular filtration rate
.

BACKGROUND: Reduced estimated glomerular filtration rate (eGFR) in older adults is common and may reflect normal aging or significant kidney disease. Our objective was to develop a predictive model to better triage these individuals using routine laboratory data. MATERIALS AND METHODS: Using a large US laboratory data set, we calculated individual eGFR regression slopes for 43,523 individuals aged 60 - 75 years with baseline eGFRs between 30 and 59 mL/min/1.73m2. We developed general linear models to predict the eGFR regression slope using urine protein measurements and other routinely available laboratory data as dependent variables. We validated these models on a similar data set comprised of 11,979 individuals. RESULTS: In a model utilizing log10 urine albumin/creatinine (UACR), the variables that significantly predicted the eGFR regression slope were log10 UACR, initial eGFR, serum albumin, chloride, glucose, and aspartate aminotransferase (AST). In an otherwise identical model substituting log10 urine protein/creatinine (UPCR) for UACR, results were similar except that serum calcium was significant and AST was not. We analyzed the correspondence between actual eGFR regression slopes and those predicted by our models using receiver operator characteristic (ROC) statistics to calculate areas under the curves (AUC) for four eGFR slope cut points: -2, -3, -4, and -5 mL/min/year. AUCs using the UACR and UPCR models ranged from 0.716 to 0.900 and 0.751 to 0.868, respectively, for the training data set. Results were nearly identical for the validation data set. CONCLUSION: Use of a laboratory-based predictive model of eGFR decline for older adults with eGFR 30 - 59 mL/min/1.73m2 may help distinguish between individuals with and without risk for further decline in kidney function.

The role of the 24-h urine collection in the management of nephrolithiasis.

Recurrent nephrolithiasis is a common chronic condition that is often preventable with dietary modification and pharmacologic therapy. Patients with recurrent kidney stones should have a metabolic evaluation, consisting of radiologic studies to assess stone burden, crystallographic stone analysis, and laboratory studies including standard serum chemistries and 24 h urine collection(s). This article focuses on the interpretation of urine chemistries to identify lithogenic risk factors and assess the contribution of diet to the formation of kidney stones.

Current recommended 25-hydroxyvitamin D targets for chronic kidney disease management may be too low.

OBJECTIVE: It is uncertain whether increasing 25-hydroxyvitamin D (25-D) levels in chronic kidney disease (CKD) patients above those recommended by current guidelines result in progressive amelioration of secondary hyperparathyroidism. Our objective was to identify a potential therapeutic 25-D target which optimally lowers plasma parathyroid hormone (PTH) without producing excessive hypercalcemia or hyperphosphatemia in CKD. METHODS: We performed a cross-sectional analysis of 14,289 unselected stage 1-5 CKD patients from US primary care and nephrology practices utilizing a laboratory-based CKD clinical decision support service between September 2008 and May 2012. Estimated glomerular filtration rate (eGFR), plasma PTH, and serum 25-D, calcium, and phosphorus results were analyzed. RESULTS: In CKD stages 3-5, progressively higher 25-D pentiles contained progressively lower mean PTH levels. Regression analysis of log PTH on 25-D was significant in all CKD stages with no evidence of a decreasing effect of 25-D to lower PTH until 25-D levels of 42-48 ng/ml. Progressively higher 25-D concentrations were not associated with increased rates of hypercalcemia or hyperphosphatemia. CONCLUSIONS: We found evidence for an optimal level of 25-D above which suppression of PTH progressively diminishes. This level is more than twice that currently recommended for the general population. We found no association between these higher 25-D levels and hyperphosphatemia or hypercalcemia. Additional prospective trials seem appropriate to test the idea that 25-D levels around 40-50 ng/ml could be a safe and effective treatment target for secondary hyperparathyroidism in CKD.