Lesley A. Stevens

Background. Proteinuria is a candidate surrogate end point for randomized controlled trials (RCTs) in chronic kidney disease (CKD). There is a reasonably sound biological basis for this hypothesis, but only preliminary empirical evidence currently exists. Methods. A systematic review and creation of a patient-level dataset of randomized controlled trials (RCTs) in CKD that reported changes in proteinuria and assessed progression of kidney disease as defined by dialysis, transplantation, death, or changes in GFR or creatinine were performed. Results.Systematic review. Seventy RCTs met the eligibility criteria; 17 eligible RCTs contained analyses of proteinuria as a predictor of outcomes; 15 RCTs concluded that greater proteinuria was associated with adverse outcomes. A majority were studies of diabetic or hypertensive kidney disease and tested renin–angiotensin system blockade. Definitions of predictor and outcome variables were too variable to conduct a meta-analysis of group data. Database creation. Over 4 years was required to create the patient-level dataset. The final dataset included 34 studies and > 9000 patients with a variety of CKD types and interventions. Conclusions. There are a relatively small number of RCTs designed to rigorously test therapies for kidney disease progression. Current analyses of change in proteinuria as a predictor of CKD progression are heterogeneous and incomplete, indicating further evaluation in a pooled individual patient-level database is necessary to advance knowledge in this field.

Purpose of review Estimated glomerular filtration rate (eGFR) is now commonly reported by clinical laboratories. Here, we review the performance of current creatinine and cystatin C-based estimating equations as well as demonstration of their utility in public health and clinical practice. Recent findings Lower levels of GFR are associated with multiple adverse outcomes, including acute kidney injury and medical errors. The new Chronic Kidney Disease–Epidemiology Collaboration (CKD-EPI) equation improves performance and risk prediction compared with the Modification of Diet in Renal Disease study equation. Current cystatin C-based equations are not accurate in all populations, even in those with reduced muscle mass or chronic illness, in which cystatin C would be expected to outperform creatinine. eGFR reporting has led to a greater number of referrals to nephrologists, but the increased numbers do not appear to be excessive or burdensome. The Modification of Diet in Renal Disease study equation appears to be able to provide drug dosage adjustments similar to the Cockcroft–Gault equation. Summary Estimated GFRs and their reporting can improve and facilitate clinical practice for chronic kidney disease. Understanding strengths and limitations facilitates their optimal use. Endogenous filtration markers, alone or in combination, which are less dependent on non-GFR determinants of the filtration markers, are necessary to lead to more accurate eGFRs.

Clinical assessment of kidney function is central to the practice of medicine. GFR is widely accepted as the best index of kidney function in health and disease, and accurate values are required for optimal decision making. Estimated GFR based on serum creatinine is now widely reported by clinical laboratories, and in most circumstances, estimated GFR is sufficient for clinical decision making. GFR estimates may be inaccurate in the non–steady state and in people in whom non-GFR determinants differ greatly from those in whom the estimating equation was developed. If GFR estimates are likely inaccurate or if decisions based on inaccurate estimates may have adverse consequences, a measured GFR is an important confirmatory test. Endogenous creatinine clearance is the most common method used to measure GFR in clinical practice but may be difficult to obtain or fraught with error. We review methods for GFR measurement using urinary and plasma clearance of exogenous filtration markers and focus on urinary clearance of iothalamate and plasma clearance of iohexol compared with inulin clearance. We suggest plasma clearance of nonradioactive markers be more widely implemented in clinical settings. Further research is necessary on the impact of the use of measured GFR as a confirmatory test.