Intensive Therapy With Addition Of Spironolactone To Ras Blockers On Hypertensive Diabetic Nephropathy With Proteinuria

Objective: Mineralocorticoid receptor antagonists, when added to a renin-angiotensin system blocker, further reduce proteinuria in patients with chronic kidney disease. To study the effects spironolactone on proteinuria, blood pressure(BP) and renal function in diabetic nephropathy patients with proteinuria who are receiving an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker(ARB) plus loop diuretics furosemide. Design and Method: A case-controlled trial in patients from outpatient clinic with a follow-up of 1 year. Patients were recruited from March 2013 to February 2015 February. Diabetic patients with moderate proteinuria (>1.0g/day), estimated glomerular filtration rate (eGFR, >60 mL/min/1.73 m2), despite long-term use of an ACE inhibitor or ARB were allocated to spironolactone, 25–50 mg once daily (n = 13) or furosemide 40 mg twice daily (n = 15). Urinary protein to creatinine ratio (UPCR), BP, biochemical parameters and eGFR were measured monthly. Results: The patient groups have similar baseline BP (systolic 156.1 ± 1.3 and diastolic 93.7 ± 0.7 mmHg), proteinuria as UPCR 3.61 ± 1.7 (g/g creatinine) and eGFR (67 ± 8.7 ml/min/1.73 m2). Systolic BP was lower with spirolonolactone than furosemide therapy (133.5 ± 1.4 vs 140.7 ± 1.2 mmHg; P > 0.01). Proteinuria decreased by 40.6% [95% confidence interval (CI) 23.4–57.8%] and BP by 5 mmHg (2–9 mmHg)/3 mmHg (1–6 mmHg) with spironolactone group, but did not change with furosemide group. eGFR during the 1-year follow-up declined on average by 4.9 ml/min/1.73 m (2.8–10.2 ml/min/1.73 m2) in the spironolactone and by 9.6 ml/min/1.73 m2 (8.5–14.7 ml/min/1.73 m2) in the furosemide group (P = 0.004). Potassium concentrations (5.1 ± 0.3 versus 4.5 ± 0.2 mEq/l) were elevated (P < 0.001). Two patients of the spironolactone and one of the furosemide group developed hyperkalemia (>6.0 mEq/l) and had to be excluded. Conclusions: Addition of spironolactone to an ACE inhibitor or ARB seems to be associated with a marked antiproteinuric effect, which in part has the more slow-down of renal function in diabetic nephropathy with proteinuria.