Timing of onset of CKD-related metabolic 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.

Figure 1.

Prevalence of metabolic complications according to GFR. Hyperparathyroidism was defined as PTH >60 pg/ml or active vitamin D treatment; anemia was defined as Hb <110 g/L according to K/DOQI-based criteria or erythropoiesis-stimulating agent treatment; acidosis was defined as a tCO₂ <22 mmol/L or bicarbonate treatment; hyperkalemia was defined as a plasma potassium concentration >5 mmol/L or ion exchange resin treatment; hyperphosphatemia was defined as a plasma phosphate concentration >4.3 mg/dl (>1.38 mmol/L) or phosphate binder treatment. mGFR, measured glomerular filtration rate; eGFRcl, estimated glomerular filtration rate, using the MDRD Study equation with serum creatinine values calibrated by the Cleveland Clinic Laboratory; eGFRms, eGFR using the MDRD equation with serum creatinine values standardized to mass spectrometry.