Purpose: To assess the associations between effects of low salt, low protein diet supplemented with keto-analogues (sLPD)-on salt intake, blood pressure (BP) and cardiovascular events (CVEs) in patients with advanced diabetic kidney disease (DKD) and heavy proteinuria.
Methods: Prospective, single-center study (total duration of 15 months), enrolling 92 patients with advanced DKD (median eGFR 11.7 ml/min) and heavy proteinuria (median 4.8 g/g creatininuria). The intervention consisted in a low salt-low protein (0.6 g/kg-day) diet (sLPD) under intensive nutritional counselling, and adjustment of antihypertensive therapy. The endpoints of this sub-analysis were a salt intake ≤ 5 g/day, a mean blood pressure (MAP) ≤ 97 mmHg, corresponding to KDIGO target of 130/80 mmHg, and the rate of CVEs.
Results: Salt intake decreased with 2.5 g/day and the proportion of patients reaching the salt intake endpoint increased with 58%. A salt intake ≤ 5 g/day was associated with a reduced MAP, BMI, proteinuria, fractional excretion of sodium, and eGFR, suggesting a salt-related volume contraction but was not related to protein intake. Mean arterial pressure decreased with 13 mmHg. MAP ≤ 97 mmHg was associated with lower proteinuria, salt, and protein intake, but the contribution of salt intake cannot be differentiated from that of protein intake. CVEs occurred in 20% of patients and were independently related to a lower age and MAP, and increased comorbidities. eGFR only minimally declined and no renal adverse events were noted. sLPD was nutritionally safe.
Conclusions: The multifactorial personalized intervention allowed a stable MAP reduction to KDIGO recommended levels (≤ 97 mmHg), related to the decrease in salt and protein intake. However, BP lower than 130/80 mmHg increased the cardiovascular but not the renal risk in heavy proteinuric patients with advanced DKD.
Trial registration number: 0341507433: NCT03415074. Registered 02/02/2015 in US National Library of Medicine, ClinicalTrials.gov (NCT).
Keywords: Blood pressure; Chronic kidney disease; Diabetic kidney disease; Keto amino acids; Low protein diet; Natriuresis.