Enrico Valvo

Captopril in Patients with Type II Diabetes and Renal Insufficiency: Systemic and Renal Hemodynamic Alterations

PURPOSE To our knowledge, clinical studies on the long-term use of angiotensin converting enzyme inhibitors in patients with type II diabetes mellitus and nephropathy with incipient renal failure are nonexistent. We therefore assessed the effects of long-term treatment with captopril on systemic and renal hemodynamics and urinary protein excretion in patients with type II diabetes mellitus and the clinical syndrome of diabetic nephropathy. PATIENTS AND METHODS Twelve patients, 10 men and two women, with an average age of 52 years (range, 40 to 66), participated in the study. After the basal hemodynamic evaluation, the patients received captopril in two daily doses. The dosage was adjusted at weekly intervals in order to obtain normalization of blood pressure without exceeding the maximum allowable dosage. Four patients also received furosemide (20 to 40 mg/day). RESULTS After six months of treatment, the intra-arterial blood pressure fell (from 162 +/- 17/103 +/- 5 to 139 +/- 26/89 +/- 10 mm Hg) due to the reduction in total peripheral vascular resistance index (from 3,720 +/- 658 to 3,190 +/- 762 dynes/second/cm-5/m2), with no change in cardiac index (2.78 +/- 0.36 to 2.79 +/- 0.47 liters/minute/m2). No significant change was seen in renal vascular resistance (from 30,175 +/- 5,371 to 30,173 +/- 5,372 dynes/second/cm-5/1.73 m2) and in filtration fraction (from 26 +/- 8 to 27 +/- 10 percent). A slight, not significant, decrease in renal plasma flow (from 243 +/- 97 to 217 +/- 108 ml/minute/1.73 m2), in glomerular filtration rate (from 57 +/- 17 to 51 +/- 19 ml/minute/1.73 m2), and in proteinuria (from 4.50 +/- 3.10 to 3.40 +/- 2.31 g/day) was also observed. CONCLUSION Our findings suggest that captopril is an effective antihypertensive agent in patients with diabetic nephropathy, but the renal beneficial effects seem to be limited when this syndrome is complicated by renal insufficiency.

Clinical Features of Patients with Solitary Kidneys

A clinical study was performed in 2 groups of patients with solitary kidneys, followed for 11-146 months. Group 1 had 9 patients (7 males and 2 females, aged between 23 and 68 years) with unilateral renal agenesis. Group 2 had 13 patients (9 females and 4 males, aged between 27 and 70 years) who underwent unilateral nephrectomy for the following reasons: hydronephrosis secondary to ureteropelvic junction stenosis, 7 patients; renal trauma, 4 patients; benign neoplasia, 2 patients. During the follow up, urinary protein excretion of more than 300 mg/day was observed in 9 patients, 3 in group 1 and 6 in group 2. Eleven patients, 8 in group 1 and 3 in group 2, were hypertensive (diastolic blood pressure higher than 95 mm Hg). Hyperuricemia was observed in 14 patients, 10 in group 1 and 4 in group 2. Seven patients, 4 in group 1 and 3 in group 2, had a significant deterioration of renal function. Neither proteinuria nor renal failure were observed before at least 10 years had elapsed since the anatomic condition of solitary kidney had been established. A surgical renal biopsy was performed in 1 patient with unilateral renal agenesis and showed focal glomerular sclerosis. This study adds support to the view that the reduction of 50% of the renal tissue may be a risky situation in humans as well as in animals.

Bone Histology and Calcium Metabolism in Patients with Nephrotic Syndrome and Normal or Reduced Renal Function

Bone histology and its relationship with calcium metabolism was evaluated in adult patients with nephrotic syndrome: 29 had normal renal function (GFR 103 +/- 4 ml/min/1.73 m2) (group 1) and 20 had renal insufficiency (GFR 31 +/- 4 ml/min/1.73 m2) (group 2). In group 1, serum PTH, 1.25-HCC and 24.25-HCC levels were normal, while 25-HCC values were reduced. Bone histology was normal in 76% of the patients, while 17% had isolated osteomalacia and 7% an associated bone resorption. Group 2 showed a higher incidence of bone resorption when compared with a matched group of patients with renal failure and no proteinuria (40% vs. 13%) and a comparable frequency of isolated mineralization defect (25% vs. 34%). PTH levels were definitely increased and serum total calcium and all the vitamin D metabolites were reduced. A significant correlation between the apparent duration of the disease and the severity of osteodystrophy was found only in group 2. In conclusion, no constant derangement of calcium metabolism and bone histology is evident in patients with nephrotic syndrome and normal renal function, while patients with persistent proteinuria are at high risk of osteodystrophy even in the early phases of renal failure.

Angiotensin converting enzyme inhibition with a low dose of enalapril in normotensive diabetics with persistent proteinuria.

Angiotensin II is the main regulator of both glomerular haemodynamics and glomerular capillary permeability. An alteration in the function of intrarenal angiotensin II seems to be the cause of diabetic glomerulopathy in animals and humans. In order to investigate the renal effects of the angiotensin converting enzyme (ACE) inhibitor enalapril (5 mg once a day), 24 normotensive diabetic patients with persistent proteinuria, after a 3-month run-in period, were randomly allocated to receive the active drug (12 patients) or the corresponding placebo, for the 6 months. Effective renal plasma flow, glomerular filtration rate, renal vascular resistance and filtration fraction were measured at the end of the run-in and the treatment periods. Blood pressure, heart rate, urinary albumin excretion, plasma renin activity and aldosterone, blood glucose, serum fructosamine and body weight were checked monthly during the run-in and every 2 months during the treatment period. Enalapril decreased urinary albumin excretion in the normotensive diabetic patients without any changes in systemic blood pressure or glomerular haemodynamics. These results indicate that ACE inhibition interferes with the glomerular capillary permeability induced by angiotensin II.

Systemic and renal effects of chronic angiotensin converting enzyme inhibition with captopril in hypertensive diabetic patients.

Nine outpatients with mild to moderate arterial hypertension, type 2 diabetes mellitus and persistent macroalbuminuria were studied. After 1 month of placebo, the patients were treated with 50 mg captopril twice a day for the following 6 months. Blood pressure and urinary albumin excretion were significantly reduced but no relationship was found between these two variables. No changes were detected in the renal plasma flow, glomerular filtration rate, filtration fraction, renal vascular resistance or metabolic pattern. Captopril significantly reduced blood pressure and albuminuria without any change in the renal function. The decrease in albuminuria may be related to the reduction in blood pressure as well as to a direct effect of captopril on glomerular haemodynamics.

Medullary Sponge Kidney and Hyperparathyroidism -a Puzzling Association

28 adult patients with radiological evidence of medullary sponge kidney (MSK) were studied. Hypercalcemia and increased serum parathyroid hormone (PTH) values were found in 10 patients (36%). In 7 of them, parathyroid surgery was performed: a single adenoma was found in 6 cases and multiple-gland hyperplasia in 1 case. After surgery, 3 patients had normalization of calcium metabolism; 4 patients had persistence of hypercalciuria with progressive increase in serum PTH values (and recurrence of the adenoma in 1 case). Of the remaining patients, 10 (36%) had definite or marginal hypercalciuria, resulting from renal calcium leak in 8 and from intestinal calcium hyperabsorption in 2 of them. In 8 patients (28%), no evidence of disordered calcium metabolism was found. The association of MSK and hyperparathyroidism is not a chance occurrence. MSK might be a renal anatomical complication of primary hyperparathyroidism, or it might be regarded as an anatomic substrate--or rather as a consequence--of prolonged hypercalciuria, regardless of its pathogenesis. The lack of disordered calcium metabolism in a considerable number of patients, however, shows that the enigma of MSK is still far from being solved.

Angiotensin converting enzyme inhibition in normotensive type II diabetics with persistent mild proteinuria

To evaluate the effect of enalapril on proteinuria, 16 normotensive type II diabetics with persistent proteinuria were studied. At random, the patients were allocated to enalapril (5 mg once a day) or placebo, in a double-blind fashion, for 12 months. Blood pressure, heart rate, urinary albumin excretion, plasma renin activity and aldosterone, blood glucose, serum fructosamine, urine urea and body weight were checked monthly during the run-in period and every 2 months during the treatment period. The kidney function was studied at the beginning of the study and during the sixth and 12th months. Enalapril decreased urinary albumin excretion in our patients in the absence of any effect on blood pressure and kidney function. Our data may be interpreted on the basis of a direct vascular effect of enalapril that is probably related to a tissue mechanism consisting of reduced angiotensin formation, increased kinins, or both, or of other unknown factors.

Biochemical and Morphological Aspects of Bone Tissue in Chronic Renal Failure

A biochemical and bone biopsy investigation was made in 30 patients with chronic renal failure. Osteomalacia was the main pathological feature in 60% of the patients. Both optical and electron microsc

Systemic and renal effects of a new angiotensin converting enzyme inhibitor, benazepril, in essential hypertension.

Seventeen essential hypertensive patients with normal renal function were treated with a new non-sulphydryl orally active angiotensin converting enzyme (ACE) inhibitor, benazepril, 10 mg given once or twice daily, according to diastolic blood pressure levels, for 6 weeks. In all patients, changes in blood pressure, systemic and renal hemodynamics, plasma renin activity and urinary aldosterone and albumin excretions were assessed at the end of a 2-week placebo run-in period and at the end of the study. Benazepril monotherapy controlled blood pressure well. No changes in cardiac output, heart rate or stroke volume were observed, while peripheral vascular resistance was significantly decreased (-11%, P less than 0.05). Plasma volume was unaltered. The glomerular filtration rate was stable, but effective renal plasma flow was increased because of the marked reduction in renal vascular resistance (-35%) and, therefore, the filtration fraction was decreased. Urinary albumin excretion remained unchanged. A significant increase in plasma renin activity (P less than 0.001) and a decrease in urinary aldosterone excretion were seen. No side effects were observed during the treatment period. In conclusion, our results suggest that benazepril alone is an effective antihypertensive agent in patients with essential hypertension. The blood pressure lowering effect is due mainly to systemic vasodilation and is observed up to 24 h after administration of the drug. The vasodilation appears to be more consistent in the renal than in the systemic circulation.

Invasive assessment of renal artery atherosclerotic disease and resistant hypertension before renal sympathetic denervation.

BACKGROUND Renal sympathetic denervation (RSD) is emerging as a new therapeutic option for patients with severe hypertension refractory to medical therapy. The presence of a renal artery stenosis may be both a cause of secondary hypertension and a contraindication to RSD if a renal artery stent is implanted; therefore, the definition of the functional importance of a renal artery stenosis in a patient with refractory hypertension is crucial. METHODS We describe the imaging and functional intravascular assessment of an angiographically severe stenosis of the renal artery in a patient with severe refractory hypertension, by means of intravascular ultrasound (IVUS), and measurement of the translesional pressure gradient with a pressure wire. RESULTS Pressure wire examination excluded any severity of the stenosis, and IVUS showed the presence of a dissected plaque that resolved spontaneously after 3 months of intensive medical therapy and high-dose statin. Subsequently the patient was treated with RSD, achieving a significant effect on blood pressure control. CONCLUSIONS Intravascular imaging and functional assessment of renal artery anatomy in patients with atherosclerotic disease may prove particularly suited to patients with refractory hypertension and multilevel vascular disease who are considered for endovascular therapies, either renal artery stenting or RSD.