Normalized protein nitrogen appearance is correlated with hospitalization and mortality in hemodialysis patients with Kt/V greater than 1.20

Objectives: Normalized protein nitrogen appearance (nPNA), also known as protein catabolic rate (nPCR), reflects the daily protein intake in maintenance hemodialysis (MHD) patients. Several studies indicate that nPNA and Kt/V correlate with clinical outcome and also with each other. Thus, the relationship between low nPNA and poor outcome could be due to uremia, low Kt/V or due to reported mathematical coupling between nPNA and Kt/V. We therefore investigated whether nPNA is associated with outcome in patients who have adequate or high Kt/V.

Design: Prospective cohort.

Settings: Outpatient dialysis unit affiliated with a tertiary-care community medical center.

Patients: From a pool of 135 MHD outpatients in one dialysis unit, 122 patients with a delivered, Kt/V(sp)>1.20, independent of their residual renal function, were evaluated. Patients (61 women, 61 men), aged from 23 to 89 years (53.4+/-14.0 years)(+/-SD), had been undergoing MHD for one month to 17 years.

Intervention: Review of laboratory values and clinical outcome.

Main outcome measures: Twelve-month mortality and hospitalization.

Results: Delivered Kt/V(sp) ranged from 1.23 to 2.71 (1.77+/-0.34), nPNA from 0.5 to 2.15 (1.13+/-0.29 g/kg/day), and serum albumin, from 1.9 to 4.6 (3.76+/-0.37 g/dL). During the 12-month follow-up, 55 patients were hospitalized overnight at least once; 12 patients died; 5 patients underwent renal transplantation, and 6 patients left the study. The nPNA and Kt/V(sp) did not correlate significantly (r=.09) except when analysis was limited to Kt/V values < 1.5 (r=.54). Serum nPNA and albumin were the only variables with statistically significant correlations with both mortality and 3 measures of hospitalization (H): total days of H (H(D)), total number of H (H(F)), and time to first H (H(T)). The case-mix adjusted correlations for serum albumin and nPNA versus total days (r(HD)) and frequency of H (r(HF)) were significant, and Cox analysis based on H(T) and time to death resulted in significant odds ratios for each standard deviation decrement for both serum albumin and nPNA. Serum total iron binding capacity (TIBC) and creatinine concentrations also correlated with some but not all outcome measures: lower serum concentrations of these values were each significantly associated with poor clinical outcomes.

Conclusions: Both nPNA and serum albumin predict prospective hospitalization and mortality in MHD patients with Kt/V > 1.20. Serum TIBC and creatinine concentrations appear to have association with some outcome measures as well. These data are consistent with the possibility that protein intake affects the clinical course even in the setting of an adequate to high hemodialysis dose. Studies based on randomized assignments to different protein intakes would be helpful to confirm these conclusions.