A method for monitoring dietary compliance would be useful in treating patients with chronic renal failure (CRF). Nineteen nitrogen balances were measured while patients were eating unrestricted diets containing 6.4 to 15.1 g of nitrogen per day and 14 while patients consumed a 20 to 25 g mixed-quality protein ketoacid-supplemented diet containing 5.2 to 6.6 g of nitrogen per day. Urea nitrogen appearance (U) calculated as the sum of urinary urea nitrogen plus the variation in the body urea pool (using changes in serum urea nitrogen and either the 14C urea space or 60% body weight) was correlated with nitrogen intake (r = 0.84). Both methods gave indistinguishable values for U. Total non-urea nitrogen excretion (NUN) and its components did not correlate with dietary nitrogen. NUN averaged 31.3 +/- 2.1 mg N/kg/day and was not different between the two groups or in patients in neutral compared to those in mildly negative or positive nitrogen balance. Nitrogen balance calculated using estimated U and 31 mg N/kg/day was indistinguishable statistically from measured nitrogen balance. Thus, U varies directly with dietary protein intake and can be estimated using urinary urea nitrogen, SUN, and body weight. Total nitrogen excretion can be estimated accurately as U + 31 mg N/kg/day. From the estimated total nitrogen excretion, dietary compliance of CRF patients in approximately neutral nitrogen balance could be assessed. Furthermore, if nitrogen intake were known, nitrogen balance could be estimated.

This study confirms that several readily-measured nutritional indicators predict mortality among hemodialysis patients and that changes in indicator values over six months provide additional important prognostic information. Interventions that modify these indicators of nutritional status may have an important impact on the survival of hemodialysis patients.

Current treatment of anemia in chronic kidney disease (CKD) with erythropoiesis-stimulating agents can lead to substantial hemoglobin oscillations above target range and high levels of circulating erythropoietin. Vadadustat (AKB-6548), a novel, titratable, oral hypoxia-inducible factor prolyl hydroxylase inhibitor induces endogenous erythropoietin synthesis and enhances iron mobilization. In this 20-week, double-blind, randomized, placebo-controlled, phase 2b study, we evaluated the efficacy and safety of once-daily vadadustat in patients with stages 3a to 5 non-dialysis-dependent CKD. The primary endpoint was the percentage of patients who, during the last 2 weeks of treatment, achieved or maintained either a mean hemoglobin level of 11.0 g/dl or more or a mean increase in hemoglobin of 1.2 g/dl or more over the predose average. Significantly, the primary endpoint was met in 54.9% of patients on vadadustat and 10.3% of patients on placebo. Significant increases in both reticulocytes and total iron-binding capacity and significant decreases in both serum hepcidin and ferritin levels were observed in patients on vadadustat compared with placebo. The overall incidence of adverse events was comparable between the 2 groups. Serious adverse events occurred in 23.9% and 15.3% of the vadadustat- and placebo-treated patients, respectively. Three deaths occurred in the vadadustat arm. Thus, this phase 2b study demonstrated that vadadustat raised and maintained hemoglobin levels in a predictable and controlled manner while enhancing iron mobilization in patients with nondialysis-dependent CKD.

These cross-sectional findings suggest that in patients with chronic renal disease, dietary protein and energy intakes and serum and anthropometric measures of protein-energy nutritional status progressively decline as the GFR decreases. The reduced protein and energy intakes, as GFR falls, may contribute to the decline in many of the nutritional measures.