Effect of urine urea nitrogen and protein intake adjusted by using the estimated urine creatinine excretion rate on the antiproteinuric effect of angiotensin II type I receptor blockers

• This is the first study to try eliminating the error to estimate protein intake.
• The protein intake showed a positive association with the level of albuminuria.
• The increase of protein intake ameliorated the antiproteinuric effect of angiotensin II type I receptor blocker.
• The relation between protein intake and albuminuria was independent from blood pressure.
• The relationship was also independent from urine sodium excretion.

ObjectivesThe aim of this study was to determine the role of protein intake on proteinuria in chronic kidney disease (CKD), as it is presently not conclusive.MethodsThis is a subanalysis of data from an open-label, case-controlled, randomized clinical trial on education about low-salt diets (NCT01552954). We estimated the urine excretion rate of parameters in a day, adjusted by using the equation for estimating urine creatinine excretion, and analyzed the effect of urine urea nitrogen (UUN), as well as estimating protein intake on the level of albuminuria in hypertensive patients with chronic kidney disease.ResultsAmong 174 participants from whom complete 24-h urine specimens were collected, the estimates from the Tanaka equation resulted in the highest accuracy for the urinary excretion rate of creatinine, sodium, albumin, and UUN. Among 227 participants, the baseline value of estimated urine albumin excretion (eUalb) was positively correlated with the estimated UUN (eUUN) or protein intake according to eUUN (P = 0.012 and P = 0.038, respectively). We were able to calculate the ratios of eUalb and eUUN in 221 participants and grouped them according to the ratio of eUUN during 16-wk trial period. The proportion of patients that achieved a decrement of eUalb ≥25% during 16 wk with an angiotensin II type I receptor blocker (ARB) medication was 80% (24 of 30) in group 1, with eUUN ratio ≤−25%; 82.2% (111 of 135) in group 2, with eUUN ratio between −25% and 25%; and 66.1% (37 and 56) in group 3, with eUUN ratio ≥25% (P = 0.048). The probability of a decrease in albuminuria with ARB treatment was lower in patients with an increase of eUUN or protein intake during the 16 wk of ARB treatment, as observed in multiple logistic regression analysis as well.ConclusionsThe estimated urine urea excretion rate showed a positive association with the level of albuminuria in hypertensive patients with chronic kidney disease. The increase of eUUN excretion ameliorated the antiproteinuric effect of ARB.