Dietary protein restriction, blood pressure control, and the progression of polycystic kidney disease. Modification of Diet in Renal Disease Study Group.

Abstract

In the Modification of Diet in Renal Disease Study, a follow-up (mean, 2.2 yr) of 200 study participants with autosomal dominant polycystic kidney disease (ADPKD) was conducted to determine the effect of lowering protein intake and blood pressure on the rate of decline in GFR. The rate of decline was faster in participants with ADPKD than in persons with other diagnoses, reflecting, in part, faster disease progression in the ADPKD group. Baseline characteristics that predicted a faster rate of decline in GFR in persons with ADPKD were greater serum creatinine (independent of GFR), greater urinary protein excretion, higher mean arterial pressure (MAP), and younger age. In patients with initial GFR values between 25 and 55 mL/min per 1.73 m2, neither assignment to a low-protein diet group nor assignment to a low blood pressure group significantly reduced the rate of decline of GFR in ADPKD participants. Similarly, the decline in GFR was not related to achieved protein intake or MAP. In participants with GFR values between 13 and 24 mL/min per 1.73 m2, assignment to the low MAP group led to a somewhat more rapid decline in GFR. However, the more rapid decline in GFR did not appear to be due to a detrimental effect of low blood pressure or the antihypertensive agents used to reach the low blood pressure goal. Lower protein intake, but not prescription of the keto acid-amino acid supplement, was marginally associated with a slower progression of renal disease.

Tolvaptan in ADPKD Patients With Very Low Kidney Function

“…The observation that annualized eGFR slopes were similar in magnitude during REPRISE and OLE trials in subjects receiving tolvaptan in both trials suggested that reduced decline of eGFR among subjects in the REPRISE placebo data set in the OLE period (tolvaptan-treated) as compared with that in the REPRISE period (placebo-treated) was not a consequence of an unrelated slower pace of eGFR decline as suggested by data in the Modification of Diet in Renal Disease study. 8 Finally, changes from the REPRISE baseline during the OLE trial were larger in the REPRISE placebo subjects compared with the matched REPRISE tolvaptan subjects owing to the shorter duration of tolvaptan treatment in the former group, yet the change from REPRISE baseline slopes was comparable and parallel for the 1-year period regardless of previous treatment in REPRISE, indicating tolvaptan treatment effects were maintained in advanced CKD G4 (eGFR 15–29).…”

“…The control analysis was performed to reveal whether observed differences in eGFR decline in REPRISE compared with OLE for the REPRISE placebo subset were attributable to a tolvaptan treatment effect or alternatively to a plateau in eGFR decline in the OLE trial associated with late-stage kidney disease, as suggested by data from the Modification of Diet in Renal Disease. 8 …”

Insights Into the Molecular Mechanisms of Polycystic Kidney Diseases

“…Several studies highlighted that animal protein intake can affect early kidney failure during ADPKD (Klahr et al, 1995;Ogborn and Sareen, 1995). A very interesting trial conducted from 2012 to 2014 (ClinicalTrials.gov NCT01810614) explored the correlation between diet and markers of ADPKD.…”

New Trends in the Diagnosis and Management of Hypertension

“…The KDIGO guidelines emphasize that the advantage of intensive BP lowering (SBP <120 mm Hg) is less certain in those with A3 albuminuria (>300 mg/g, or >30 mg/mmol), stage 5 CKD, or diabetics with CKD [12]. This statement is based on the results of several landmark clinical trials ( [13]; AASK: The African American Study of Kidney Disease and Hypertension [14]; REIN-2: Ramipril in non-diabetic renal failure Study-2 [15]; ACCORD: Action to Control Cardiovascular Risk in Diabetes Study [16]; BP: blood pressure; SBP: systolic blood pressure; MAP: mean arterial pressure; CKD: chronic kidney disease; GFR: Glomerular filtration rate; ESRD: end-stage renal disease.…”