Background: High phosphate levels attenuate nephroprotection through angiotensin-converting enzyme inhibition in patients with proteinuric chronic kidney disease (CKD). Whether this phenomenon holds true for other nephroprotective interventions like very-low-protein diet (VLPD) is unknown.
Methods: We tested the hypothesis that phosphate interferes with the anti-proteinuric response to VLPD in a non-randomized, sequential study in 99 proteinuric CKD patients who sequentially underwent low-protein diet (LPD; 0.6 g/kg) and VLPD (0.3 g/kg) supplemented with keto-analogues, each for periods longer than 1 year.
Results: Serum phosphate significantly reduced during VLPD (3.2 ± 0.6 mg/dL) when compared with LPD (3.7 ± 0.6 mg/dL, P < 0.001), an effect paralleled by a substantial decline in phosphate excretion (LPD, 649 ± 180 mg/day; VLPD, 462 ± 97 mg/day; P < 0.001). The median proteinuria during LPD was 1910 mg/24 h (interquartile range: 1445-2376 mg/24 h) and reduced to 987 mg/24 h (656-1300 mg/24 h) during VLPD (P < 0.001). No significant change in the estimated glomerular filtration rate (eGFR) was observed during the two diet periods. In linear mixed models including the diagnosis of renal disease, eGFR, 24-h urine sodium and urea and other potential confounders, there was a strong interaction between serum phosphate (P = 0.04) and phosphaturia (P < 0.001) with the anti-proteinuric response to VLPD. Accordingly, 24-h proteinuria reduced modestly in patients who maintained relatively higher serum phosphate levels or relatively higher phosphaturia to be maximal in those who achieved the lowest level of serum and urine phosphate.
Conclusion: Phosphate is an important modifier of the anti-proteinuric response to VLPD. Reducing phosphate burden may decrease proteinuria and slow the progression of renal disease in CKD patients, an issue that remains to be tested in specific clinical trials.