Evidence that urea is a better surrogate marker of uremic toxicity than creatinine

The protein equivalent of nitrogen appearance normalized to standard weight was determined from urea nitrogen appearance (nPNA U) and from total Kjeldahl nitrogen appearance (nPNA K) in dialysate and/or urine in 45 predialysis patients (pre D) and in 95 patients on continuous ambulatory peritoneal dialysis (CAPD). Correlations with weekly Kt/Vurea and creatinine clearance (Ccr, L/wk/1.73 m2) were determined; renal contributions of CCr in both populations were calculated both as total CCr (A) and as CCr by GFR (CCr [B], mean of renal CCr and Curea). Correlations with weekly Kt/Vurea were significant in individual (pre D:nPNA U 0.57, p < 0.01, and nPNA K 0.37, p < 0.01; CAPD:nPNA U 0.50, p < 0.01, and nPNA K 0.43, p < 0.01) and pooled populations (nPNA U 0.54, p < 0.01 and nPNA K 0.37, p < 0.01). Correlations with neither Ccr (A) nor Ccr (B) were significant. The data also allowed comment on mathematical coupling. Ccr vs nPNA K correlations share even more mathematical couplers than does the nPNA K vs Kt/Vurea correlation, yet the correlation of nPNA K with Ccr is quite low. The authors conclude that urea is a better surrogate marker of small molecular weight toxins that inhibit protein intake in uremia, and correlations of nPNA with Kt/Vurea represent more than simple mathematical coupling.