Abstract

Abstract Background and Aims Recent data suggest the possibility to optimize blood pressure control by low protein diet (LPD) in patients with diabetic kidney disease (DKD). We aimed to assess the effects of a low protein diet (LPD) supplemented with keto-analogues on urinary sodium excretion and blood pressure control. Method Prospective, uni-center study with a total duration of 15 months.The study was conducted in a tertiary Nephrology Clinic and included a total of 92 diabetic patients with advanced CKD (eGFR < 30 mL/min) and heavy proteinuria (> 3 g/g creatininuria). Intervention consisted in a LPD (0.6 g/kg-day) supplemented with keto-analogues of essential amino acids with nutritional counselling and adjustment of antihypertensive therapy. The primary efficacy parameter was proteinuria during intervention as compared to pre-enrolment. Blood pressure (BP), urinary sodium excretion, eGFR and blood glucose control were secondary end-points. Results Mean arterial pressure (MAP) decreased from baseline (Bs) to end of study (EOS) with -11 (-17 to -7) mmHg despite a reduction with 22% of patients needing antihypertensive medication. Independent predictors of a lower than median MAP (90mmHg) were a lower protein intake (HR 0.00 (0.00; 0.04; p=0.002), treatment with furosemide (HR 1.06 [1.06; 3.85]; p=0.03) but not with angiotensin-aldosterone system inhibitors (RAASi) [HR 0.17 (0.17; 0.90); p=0.03)] and was not influenced by natriuresis. Natriuresis decreased from 130 (121-135) to 80 (71-86) mmol/day (p<0.0001). A lower than median natriuresis (100mmol/day) was directly related to proteinuria [HR 0.0003 (0.00; 0.004); p=<0.0001], eGFR [HR 0.0001 (0.00; 0.14); p=0.01] and to diuretic therapy [0.21 (0.05; 0.83); p=0.03] but not to protein intake. Cardiovascular events were observed in 20% of patients and their occurrence was related to a lower MAP [0.97 (0.95; 0.99}; p=0.001]. No renal adverse were noted and the diet was nutritionally safe. Conclusion A low protein diet supplemented with ketoanalogues of essential amino acids on top of anti-hypertensive therapy (mostly loop diuretics) allows for a good control of blood pressure, unrelated to natriuresis in heavy proteinuric patients with advanced DKD.

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