Predictive performance of the modification of diet in renal disease and Cockcroft-Gault equations for estimating renal function.

Recent recommendations emphasize the need to assess kidney function using creatinine-based predictive equations to optimize the care of patients with chronic kidney disease. The most widely used equations are the Cockcroft-Gault (CG) and the simplified Modification of Diet in Renal Disease (MDRD) formulas. However, they still need to be validated in large samples of subjects, including large non-U.S. cohorts. Renal clearance of (51)Cr-EDTA was compared with GFR estimated using either the CG equation or the MDRD formula in a cohort of 2095 adult Europeans (863 female and 1232 male; median age, 53.2 yr; median measured GFR, 59.8 ml/min per 1.73 m(2)). When the entire study population was considered, the CG and MDRD equations showed very limited bias. They overestimated measured GFR by 1.94 ml/min per 1.73 m(2) and underestimated it by 0.99 ml/min per 1.73 m(2), respectively. However, analysis of subgroups defined by age, gender, body mass index, and GFR level showed that the biases of the two formulas could be much larger in selected populations. Furthermore, analysis of the SD of the mean difference between estimated and measured GFR showed that both formulas lacked precision; the CG formula was less precise than the MDRD one in most cases. In the whole study population, the SD was 15.1 and 13.5 ml/min per 1.73 m(2) for the CG and MDRD formulas, respectively. Finally, 29.2 and 32.4% of subjects were misclassified when the CG and MDRD formulas were used to categorize subjects according to the Kidney Disease Outcomes Quality Initiative chronic kidney disease classification, respectively

Chronic neutral phosphate supplementation induces sustained, renal metabolic alkalosis

Chronic neutral phosphate supplementation induces sustained, renal metabolic alkalosis. The aim of the present study was to test whether intravenous neutral phosphate supplementation, recently shown in our laboratory to acutely stimulate proton secretion in the distal nephron, was able to induce a sustained metabolic alkalosis. Neutral Na and K phosphate supplementation for seven days, with equivalent reduction in chloride supply and unchanged intake of sodium and potassium, in ADX rats receiving fixed physiological doses of aldosterone and dexa-methasone (group 1, N = 7), was responsible for a severe metabolic alkalosis (MA; Δ [HCO3] 11 ± 1.3mM, and Δ pH 0.11 ± 0.06 unit). Metabolic alkalosis was at least in part of renal origin, since net acid excretion (NAE) transiently increased, principally due to an increment in titratable acid excretion rate. Balances were equilibrated for sodium and negative for chloride and potassium, which may have contributed to the severity of the MA. Chronic i.v. neutral Na phosphate, without change in potassium and chloride supply, in ADX rats receiving the same doses of steroids (group 2, N = 5), was responsible for a less severe MA (Δ [HCO3] 7.5 ± 0.9mM, and Δ pH 0.07 ± 0.01 unit), also of renal origin. In this group, balances were positive for chloride and sodium and equilibrated for potassium. Finally, neutral Na and K phosphate supplementation with reduction in chloride supply in intact rats (group 3, N = 4) was also able to induce a MA (Δ [HCO3] 5.5 ± 1.8mM, and Δ pH 0.06 ± 0.01 unit) of renal origin, with balances negative for chloride and equilibrated for potassium and sodium. In all groups, the generation and maintenance of MA probably resulted from stimulated proton secretion in the distal nephron, as suggested by the observed increase of PCO2 over HCO3 concentration ratio in the urine and a fall in urine pH despite augmented urinary buffer content throughout the phosphate infusion period. Glomerular filtration rate did not significantly vary in any group. In conclusion, chronic supplementation of neutral phosphate appears to stimulate per se proton secretion in the distal nephron, independently of sodium, chloride, and potassium balances, and adrenal steroid secretion. Thus neutral phosphate supplementation should be added to the previously known factors able to induce MA