Thiazide diuretics enhance nocturnal blood pressure fall and reduce proteinuria in immunoglobulin A nephropathy treated with angiotensin II modulators

Objective We examined whether thiazide diuretics could restore nocturnal blood pressure (BP) decline and reduce urinary protein excretion in patients with glomerulopathy treated with angiotensin II modulators (angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers). Methods Twenty-five Japanese outpatients (11 men, 14 women; mean age 43 +/- 12 years) with biopsy-proven immunoglobulin (Ig)A nephropathy, preserved renal function (serum creatinine concentration <= 1.2 mg/dl), stable non-nephrotic proteinuria (0.5-3 g daily), and treatment with angiotensin II modulators were studied. The patients received a diuretic, trichlormethiazide (2 mg daily) for 4 weeks after a baseline period lasting for 4 weeks. Results Diuretic therapy significantly reduced conventional, 24-h, daytime and night-time blood pressures. Nocturnal blood pressure fall was significantly enhanced by diuretic therapy and a significant interaction existed between diuretic therapy and nocturnal fall in mean arterial pressure, which indicated that the degree of nocturnal blood pressure fall was affected by diuretic therapy. The urinary protein excretion rate was significantly reduced from 1.10 +/- 0.62 to 0.63 +/- 0.39 g/day by diuretic therapy. Diuretic/baseline ratio of urinary protein excretion rate was not correlated with diuretic/baseline ratio of conventional, 24-h and daytime mean arterial pressures, but with diuretic/baseline ratio of night-time mean arterial pressure (r = 0.54, P = 0.006). Conclusions Diuretics enhanced nocturnal BP decline and reduced urinary protein excretion in patients with IgA nephropathy treated with angiotensin II modulators. The combination of angiotensin II modulators and diuretics may have additional therapeutic advantages in relieving the renal and cardiovascular risks by reducing nocturnal high blood pressure.