A dramatic reduction of normalized protein catabolic rate occurs late in the course of progressive renal insufficiency

Background. Spontaneous reduction in dietary protein intake is a recognized feature of severe renal failure, and previous studies have suggested that this may occur at an early stage of renal functional decline.

Methods. We examined the effects of progressive renal insufficiency on the normalized protein catabolic rate (nPCR) in 1282 patients (mean age 55.8±15.5 years; 60.4% male) over a 7 year period. All values of nPCR (n = 5082) obtained before commencement of dialysis were included. A total of 361 (28.2%) patients later developed end-stage renal failure and were started on dialysis.

Results. Cross-sectional analysis showed nPCR being significantly less at lower creatinine clearance. Mean nPCR was 1.17±0.31 at a clearance >50, 1.04±0.27 at 25–50, 0.93±0.21 at 10–25 and 0.74±0.18 at <10 ml/min. Mean nPCR in each clearance group was different from that in all other groups (P<0.001 in all cases). When nPCR was studied longitudinally in relation to time of initiation of dialysis, the fall in nPCR only became significant in the 3 months preceding initiation. Curve fitting suggested a two-phase exponential association between nPCR and renal function, a gentle decline of nPCR in mild and moderate renal failure culminating in a dramatic decline when CrCl reached 15 ml/min and weekly Kt/Vurea 2.5. nPCR at dialysis initiation predicted survival on dialysis even when corrected for age, diabetes and non-renal co-morbid load. However, it was no longer significant when residual renal function was included in the model. The group initiating dialysis with a normal nPCR maintained this throughout the first 3 years on dialysis whilst the group initiating with a low nPCR, though improving initially, continued to have significantly lower nPCR levels throughout follow-up than their normal nPCR counterparts.

Conclusion. A significant reduction of nPCR occurs late in progressive renal insufficiency and may predict the need for dialysis initiation. nPCR levels <0.8 at initiation predict future low nPCR levels and mortality on dialysis. The correlation between nPCR and CrCl in early renal insufficiency may be partly artefactual.