Timing of Onset of CKD-Related Metabolic Complications

TLDR

CKD guidelines recommend screening patients with GFR < 60 ml/min/1.73 m² for metabolic complications, yet evidence supporting a universal GFR cutoff is limited. The study analyzed 1,038 non‑dialysis CKD stage 2–5 adults from the NephroTest cohort, measuring mGFR by 51Cr‑EDTA clearance and estimating GFR with MDRD equations. Lower mGFR was associated with progressively higher prevalence of hyperparathyroidism, anemia, hyperphosphatemia, metabolic acidosis, and hyperkalemia, with 90 % sensitivity thresholds ranging from 50 to 37 ml/min/1.73 m², and anemia and hyperparathyroidism appeared earlier than the other complications.

Abstract

Chronic kidney disease (CKD) guidelines recommend evaluating patients with GFR <60 ml/min per 1.73 m(2) for complications, but little evidence supports the use of a single GFR threshold for all metabolic disorders. We used data from the NephroTest cohort, including 1038 adult patients who had stages 2 through 5 CKD and were not on dialysis, to study the occurrence of metabolic complications. GFR was measured using renal clearance of (51)Cr-EDTA (mGFR) and estimated using two equations derived from the Modification of Diet in Renal Disease study. As mGFR decreased from 60 to 90 to <20 ml/min per 1.73 m(2), the prevalence of hyperparathyroidism increased from 17 to 85%, anemia from 8 to 41%, hyperphosphatemia from 1 to 30%, metabolic acidosis from 2 to 39%, and hyperkalemia from 2 to 42%. Factors most strongly associated with metabolic complications, independent of mGFR, were younger age for acidosis and hyperphosphatemia, presence of diabetes for acidosis, diabetic kidney disease for anemia, and both male gender and the use of inhibitors of the renin-angiotensin system for hyperkalemia. mGFR thresholds for detecting complications with 90% sensitivity were 50, 44, 40, 39, and 37 ml/min per 1.73 m(2) for hyperparathyroidism, anemia, acidosis, hyperkalemia, and hyperphosphatemia, respectively. Analysis using estimated GFR produced similar results. In summary, this study describes the onset of CKD-related complications at different levels of GFR; anemia and hyperparathyroidism occur earlier than acidosis, hyperkalemia, and hyperphosphatemia.