Clarifying the concept of chronic kidney disease for non-nephrologists.

Chronic kidney disease (CKD) expands the prior concept of chronic renal insufficiency by including patients with relatively preserved renal function, as assessed by the estimated glomerular filtration rate (eGFR), as even these early CKD stages are associated with an increased risk for all-cause death and cardiovascular death, CKD progression and acute kidney injury. A decreased eGFR (<60 mL/min/1.73 m2) is by itself diagnostic of CKD when persisting for >3 months. However, when eGFR is ≥60 mL/min/1.73 m2, an additional criterion is required to diagnose CKD. In a recent clinical trial published in The New England Journal of Medicine, all 6190 participants were reported to have CKD: 47% had Stages 1 and 2 CKD and 53% had Stage 3 CKD. This illustrates a widespread misunderstanding of the concept of CKD. Moreover, CKD categories in this study were assigned based on the estimated creatinine clearance. Since both estimated creatinine clearance and creatinine clearance overestimate eGFR, this illustrates another frequent misunderstanding: equating GFR with creatinine clearance. In this commentary, we clarify the concept of CKD and of CKD categories for non-nephrologists. Assigning a diagnosis of CKD to a patient with normal renal function and absence of other evidence of CKD may have negative consequences for the individual (e.g. insurance and others) as well as for the medical community at large by creating confusion about the concept.

Potential Dangers of Serum Urate-Lowering Therapy.

In observational studies, high serum urate levels are associated with adverse outcomes, including mortality. However, the hypothesis that urate-lowering may improve nongout outcomes has not been confirmed by placebo-controlled clinical trials. On the contrary, 7 recent placebo-controlled trials of urate-lowering drugs with different mechanisms of action (uricosuric: lesinurad; xanthine oxidase inhibition: febuxostat; uricase: pegloticase) have observed higher mortality or trends to higher mortality in gout patients, with the largest decreases in serum urate. Because all urate-lowering mechanisms were implicated, this raises safety concerns about urate-lowering itself. Far from unexpected, the higher mortality associated with more intense urate-lowering is in line with the U-shaped association of urate with mortality in some observational studies. Urate accounts for most of the antioxidant capacity of plasma, and strategies to increase urate are undergoing clinical trials in neurological disease. Post hoc analysis of recent trials should explore whether the magnitude of urate-lowering is associated with adverse outcomes, and safety trials are needed before guidelines recommend lowering serum urate below certain thresholds.