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/V(urea) 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.