Glomerular hypertension as one cause of albuminuria in Type II diabetic patients

Abstract

Glomerular capillary hypertension may cause albuminuria and nephropathy in diabetes mellitus, according to animal studies [1±5]. This hypothesis has been supported by the results of many clinical studies showing that antihypertensive drugs, especially angiotensin-converting enzyme (ACE) inhibitors, can reduce albuminuria and slow the progression of diabetic nephropathy [6±8]. Direct measurement of glomerular capillary hydraulic pressure (PGC) by the micropuncture method in diabetic rats given an ACE inhibitor showed that in this animal model, glomerular hypertension is one cause of albuminuria and diabetic nephropathy [9,10]. In humans, PGC cannot, however, be measured directly, so changes in glomerular haemodynamics in diabetic patients have not been reported. Recently, a method for the clinical assessment of glomerular haemodynamics was published [11±13]. Here, using this method, we investi- Diabetologia (1999) Abstract Aims/hypothesis. Results from animal models of glomerular hypertension have suggested that this disorder is one cause of albuminuria in diabetic nephropathy. We evaluated this hypothesis clinically. Methods. The subjects were 20 patients with Type II (non-insulin-dependent) diabetes mellitus but without uraemia or hypertension: 8 had normoalbuminuria and 12 had albuminuria ( ³ 20 mg/min). In the 2-week study, patients were on a diet with ordinary amounts of sodium for 1 week and on a sodium-restricted diet for 1 week. Urinary excretion of sodium and albumin and the systemic blood pressure were measured daily. Intrarenal haemodynamics, in terms of the glomerular pressure and resistance of afferent and efferent arterioles, were calculated from renal clearance, the plasma total protein concentration, and the pressure-natriuresis relation. In 8 of the 12 patients with albuminuria, an angiotensin-converting enzyme inhibitor, cilazapril, was given orally (2 mg/ day) and the 2-week study was repeated.Results. In patients with albuminuria, resistance of efferent arterioles and the glomerular pressure were higher than in patients with normoalbuminuria (glomerular pressure, 53 ± 5 vs 43 ± 5 mmHg, means ± SD, p < 0.001). Urinary excretion of albumin correlated (n = 20, r = 0.675, p < 0.001) with the glomerular pressure but not with systemic pressure. The increased glomerular pressure and the albuminuria were decreased by cilazapril but systemic pressure was not. Conclusion/interpretation. These findings are consistent with the hypothesis that glomerular hypertension is present in Type II diabetic patients with early nephropathy and can cause albuminuria. [Diabetologia (1999

Effect of sodium intake on blood pressure and albuminuria in Type 2 diabetic patients: the role of insulin resistance

“…This is of clinical relevance, as the increase in filtration fraction and in albuminuria after high-sodium diet suggests that dietary sodium has a detrimental effect on the kidney susceptible to development of diabetic nephropathy. Although PGC was only calculated, our results, which are similar to those found in Japanese Type 2 diabetic patients [5], reinforce the evidence that systemic hypertension is transmitted to the single glomerulus in such a way as to lead to hyperperfusion and increased capillary pressure.…”

“…The intraglomerular pressure (PGC) was estimated indirectly from the relationship between pressure and natriuresis, as described [5].…”

Effects of Benidipine on Glomerular Hemodynamics and Proteinuria in Patients with Nondiabetic Nephropathy.

“…Using this method, we earlier investigated the intraglomerular hemodynamics, including PGC, in patients with diabetic nephropathy (5,15) or immunoglobulin A nephropathy (9). The method has been criticized; we gave further details about its utility at that time (17).…”

“…If so, the lack of a decrease in the proteinuria despite the decrease in PGC can be explained. However, in patients with diabetic nephropathy, one cause of proteinuria is an increase in the PGC (in other words, glomerular hypertension): a decrease in the PGC decreases the proteinuria (15). The diabetic nephropathy progresses to glomerulosclerosis.…”

“…PGC can be represented as the sum of the mean oncotic pressure within glomerular capillaries, the effective filtration pressure, and the hydrostatic pressure in Bowman's space. The same method was used for calculation of the resistance of both efferent and afferent arterioles (5,15).…”