Long-term antihypertensive treatment inhibiting progression of diabetic nephropathy

Abstract

Six men aged 26-35 years with proteinuria due to insulindependent juvenile-onset diabetes were treated for moderate hypertension (mean blood pressure 162/103 mm Hg) and studied for a mean of 73 months for the effect on the progression of nephropathy. All patients were of normal weight. During a mean control period of 28 months before treatment the mean glomerular filtration rate (three or four measurements) was 86-1 ml/ min and mean 24-hour urinary albumin excretion (also three or four measurements) 3 9 g (range 0-5-8-8 g).During antihypertensive treatment the mean systolic blood pressure fell to 144 mm Hg and mean diastolic pressure to 95 mm Hg. In the control period five patients had shown a mean monthly decline in glomerular filtration rate of 1-23 ml/min; with antihypertensive treatment, however, this decline fell to 0 49 ml/min (2p=0 042). In the remaining patient the glomerular filtration rate was 137 ml/min before treatment and 135 ml/min at the end of the treatment period. In all patients the mean yearly increase in albumin clearance (expressed as a percentage of the glomerular filtration rate) fell from 107% before treatment to 5% during treatment (2p =0-0099).This small study indicates that antihypertensive treatment slows the decline in renal function in diabetic nephropathy. Clinical trials beginning treatment in the incipient phase of diabetic nephropathy will define the optimal modality of treatment in this large patient population.Introduction Diabetic nephropathy is a major medical problem, yet we still do not know why some patients develop proteinuria and renal failure and others not despite a long history of diabetes.1 2 Characteristically diabetics without perceptible renal disease have normal blood pressure,3 whereas patients with nephropathy are hypertensive.4 Only in the past few years,5 however, has the possible role of high blood pressure in the progression of diabetic nephropathy and other vascular lesions attracted interest. In a previous study I identified high blood pressure as a possible factor in the rapid deterioration of kidney function seen in some patients.5I now report a study in which the rate of progression of nephropathy was measured by serial determination of glomerular filtration rate, renal plasma flow, and urinary albumin excretion before and during long-term antihypertensive treatment in six juvenile-onset diabetics with established nephropathy. The results show that the rate of progression can be impeded, thus postponing renal insufficiency in these patients.

Comparison of the renal effects of angiotensin converting enzyme inhibitor and calcium antagonist in hypertensive Type 2 (non-insulin-dependent) diabetic patients with microalbuminuria: a randomised controlled trial

“…Second, Parving et al showed that effective antihypertensive treatment with metoprolol, hydralazin and furosemide could slow the progression of nephropathy [5,40]. The rate of decline in GFR with those drugs (0.37ml.min-a.month -1 [401, 0.22ml.min -1 9 month -t [5], 0.49ml-min-l-month -1 [3]) appears to be comparable to the rate with enalapril (0.40 ml. min-l-month -a [411, 0.20ml-min-l.month -1 [71).…”

“…Hypertension is often associated with diabetic nephropathy [2], and effective antihypertensive treatment has proven to be effective in slowing the progression rate of nephropathy [3][4][5]. Recent studies in patients with diabetic nephropathy suggest that the use of angiotensin converting enzyme (ACE) inhibitors may possess specific advantages in decreasing proteinuria and slowing progression of nephropathy [6][7][8][9].…”

The changing epidemiology of diabetic microangiopathy in type 1 diabetes

“…Two decades ago, it was demonstrated that antihypertensive treatment could delay the development of end-stage renal failure by reducing the rate of decline of the GFR [21,22], a finding that has subsequently been confirmed in randomised controlled trials (see below). Observational studies indicate a decline in the GFR of 3.7 ml min −1 year −1 in patients on antihypertensive therapy [23].…”

Therapeutic Modalities in Diabetic Nephropathy: Standard and Emerging Approaches

“…Normotensive patients with advanced DN show slower progression compared with hypertensive patients. [33][34][35][36][37][38][39][40][41][42] Non-pharmacologic approaches (dietary modifications especially and increased physical activity) are effective in reducing BP in non-diabetic individuals 43 and may have similar benefits for diabetic patients. However, pharmacologic approaches remain the mainstay for controlling BP in patients with DM.…”