Effects of angiotensin II blockade on nitric oxide blood levels in IgA nephropathy.

BACKGROUND: The effects of renin-angiotensin system blockade on nitric oxide (NO), especially in pathological conditions, are far from being established. The influence of kinins and angiotensin type 2 receptor are largely speculative and based mainly on animal studies. This study was aimed to address these aspects in humans. METHODS: Eight IgA nephropathy patients with documented clinical and histological indicators of poor prognosis were given 50 mg of losartan, 10 mg of enalapril, and 40 mg of the NO donor isosorbide 5 mononitrate (as a control of NO generation) in randomized order for 7 days each. Treatment periods were separated by washout periods of 7 days each. Laboratory investigations were performed before and after each study period. Seven healthy controls received losartan and enalapril according to the same study design. RESULTS: Glomerular filtration rate remained stable while effective renal plasma flow increased with each treatment (P<0.05). Under losartan and enalapril, filtration fraction fell (P=0.02), plasma renin activity increased (P<0.05) and urinary aldosterone concentration decreased (P=0.02). Angiotensin-converting enzyme activity was reduced to the limit of detection under enalapril (P<0.001). Blood NO, detected as nitrosylhaemoglobin by a recently developed technique of spin-trap electron paramagnetic resonance, increased significantly, as expected, during treatment with isosorbide 5 mononitrate (P=0.01), with enalapril (P<0.05), and also with losartan (P<0.05). Unlike losartan, enalapril significantly reduced albuminuria (P=0.01) in this short-term period. In the seven healthy controls, neither enalapril nor losartan were able to increase blood NO levels significantly. CONCLUSIONS: Blood levels of nitrosylhaemoglobin, a surrogate marker of NO, increased under blockade of the renin-angiotensin system in patients with IgA nephropathy, but not in healthy volunteers. This increase could contribute to changes of effective renal plasma flow in renal disease states.

[Metabolic effects of changes in dietary sodium intake in patients with essential hypertension]. / Effetti metabolici delle variazioni dell'apporto alimentare di sodio in pazienti con ipertensione essenziale.

BACKGROUND: To evaluate the metabolic effects of modification of sodium intake in patients with essential hypertension. METHODS: Thirteen patients with essential hypertension (10 M, median age 51 yrs, range 21-64) followed in random order a low-sodium and a high-sodium diet (50 mmol Na/day vs 250 mmol/day for two weeks each). At the end of each diet an evaluation was made of 24 hour blood pressure (ABPM, Spacelabs 90207) and serum concentration of: glucose, total and HDL cholesterol, uric acid, lipoproteins A, B, Lp(a), total proteins, albumin. RESULTS: Twenty-four hours systolic and diastolic BP were significantly higher at the end of high sodium diet than of low sodium diet [respectively 132 mmHg (120-161) vs 128 mmHg (109-150); p = 0.008 and 84 mmHg (71-99) vs 81 mmHg (70-95); p = 0.008)]. No significant variations were found as regards serum glucose and lipidic parameters between low and high sodium diets. Serum uric acid was significantly higher following low sodium diet [5.9 mg/dl (4.5-8) vs 4.6 mg/dl (3.4-6.5); p = 0.003)], as well as serum total proteins [7.2 g/dl (6.9-8.2) vs 7 g/dl (6.5-7.8); p = 0.027)]. A significant direct correlation was found between changes of uric acid and total proteins from low to high sodium diet (Spearman's rho = 0.57; p = 0.04). CONCLUSIONS: In patients with essential hypertension a moderate dietary sodium restriction, able to reduce significantly 24 hours arterial pressure, does not worsen serum glucose nor lipids concentration.

[Glomerulonephritis in the elderly]. / Le glomerulonefriti nell'anziano.

The authors present a clinical analysis of the literature data regarding aged patients affected with glomerulonephritis (GN) and of 115 GN patients aged more than 65 years, biopsied in their own Center. Complications of renal biopsy, including the subclinical ones, were found in 19.1% of old patients compared to 19.2% of younger patients (p = NS), major complications in 5 and 1.4% respectively (p = NS). The most frequent GN was membranous GN (MGN) (27.8%), followed by IgA-GN (12%) and rapidly progressive GN (RPGN), idiopathic (8.6%) or secondary to vasculitis (8.6%). Eighteen out of 32 old MGN patients treated with alternated courses of steroids and immunosuppressive drugs for 6 months were compared to 32 MGN patients aged < 65 years identically treated. Complete remission was observed in 27.7% of cases and partial remission in 38.8% (p = NS). Complications of treatment were similar in the two groups of patients (p = NS). Patients with RPGN were treated with steroids (17 patients) plus immunosuppressive drugs (15 patients) and plasma exchange (13 patients). Systemic symptoms disappeared in 13/14 patients; ANCA became negative in all the 5 patients in whom they were detected; a 50% reduction of serum creatinine was obtained in 12 patients. These patients were compared to a control group of 26 patients aged < 65 years. Amelioration of renal function was evidenced more frequently among old patients with vasculitis (p < 0.05). Complications of treatment were more frequent among old patients with idiopathic RPGN (p < 0.05), but severe in only 1 case. Our data and data from the literature support the opportunity to perform renal biopsy in aged people, because it is as safe as in the younger population and allows a rational basis for treatment of GN. Clinical responses are similar to those of younger patients. Complications of treatment seem to be more frequent in old patients, but can be limited by some technical precautions and careful clinical monitorization.

Urinary endothelin in glomerulonephritis patients with normal renal function.

The vasoconstrictor peptide endothelin-1 (ET1) has only recently been characterized and its effects are at present largely speculative. It has been hypothesized that ET1 acts on mesangial cells to cause vasoactive changes which might ultimately contribute to the development of glomerulosclerosis. Opposite to ET1, nitric oxide (NO) inhibits mesangial cell contraction and proliferation. NO activates soluble guanylic acid cyclase and the final product, cyclic GMP (cGMP), has been recently used as a marker of NO action. Urinary levels of ET1 and cGMP were detected in 58 patients with biopsy-proven glomerulonephritis (GN), including 36 IgA nephropathy (IgAGN), 30 with normal and 6 with impaired renal function, 10 patients with non-IgA mesangial GN and 12 pts with membranous GN (MGN) with normal renal function. Compared to normal controls (0.019 +/- 0.006 ng/min), urine ET1 levels were significantly higher in patients with normal renal function having IgAGN (0.035 +/- 0.017, p < 0.01), MGN (0.028 +/- 0.013, p < 0.05), non-IgA mesangial GN (0.027 +/- 0.012, p < 0.05) and those with IgAGN and renal failure (0.032 +/- 0.011, p < 0.01). However no difference was found between MGN patients and normals by deleting MGN cases with mild to moderate mesangial proliferation. The mean value of urinary cGMP in IgAGN patients with renal failure (0.186 +/- 0.117 nmol/min) was lower (p < 0.05) than that of each group with normal renal function (IgAGN: 0.378 +/- 0.010 nM/min; MGN: 0.338 +/- 0.064 nmol/min, non-IgAGN: 0.436 +/- 0.168 nmol/min). The same significant differences were obtained by correcting cGMP values for creatinine urinary excretion. Urinary ET/cGMP ratio (assumed as an index of the relative balance between vasoconstrictor and vasorelaxing factors) was found to be higher than normal (0.570 +/- 0.010 ng/nmol) both in IgAGN patients with normal renal function (0.103 +/- 0.064 ng/mol, p < 0.05), and in those with renal failure (0.203 +/- 0.108 ng/nmol, p < 0.02). Urinary cGMP values were not related to plasma levels of atrial natriuretic peptide (ANP). These data show that hyperexcretion of ET1 occurs in a number of patients with mesangial proliferative GN. In some of them, mainly those with established glomerular damage, the local production of ET1 is not counter-balanced by adequate cGMP biosynthesis.

[Course and significance of various biochemical parameters in 1,25-dihydroxyvitamin D3 therapy of uremic osteodystrophy]. / Andamento e significato di alcuni parametri biochimici sotto trattamento con 1,25(OH)2D3 nell'osteodistrofia uremica.

Thirty-seven osteodystrophic and chronically haemodialyzed patients have been treated for 1-22 months by means of 1,25(OH)2D3. Under treatment a marked improvement of symptomatology and radiographic findings has been observed in the majority of cases; from the haematochemical viewpoint a rise of calcemia and phosphoremia, a fall in alkaline phosphatase and a variable course of PTH have been observed. Several episodes of asymptomatic hypercalcemia ceased with posology reduction; only 3 cases needed stopping the treatment for this reason, one of them definitively; 12/37 cases needed hypophosphoric diets and increase in oral aluminium hydroxide doses to control hyperphosphoremia. The Authors conclude that, to achieve a correct management of a 1,25(OH)2D3 therapy for renal osteodystrophy, is mandatory a strict and accurate biochemical control: in this way is possible to obtain an effective modulation of the posology avoiding the appearance of side-effects as hypercalcemia and ectopic calcifications.

[Rosette E and active rosette E tests in the evaluation of cell-mediated immunity in uremic patients]. / Il test delle rosette E e delle rosette E attive nella valutazione dell'immunità cellulo-mediata nell'uremico.

To evaluate cellular immunity in uremia, we studied 235 uremic patients (178 on regular hemodialysis and 57 on medical treatment). E-rosettes were significantly lower (p less than 0.01) in all patients. The active E-rosettes test was found less significant to study T lymphocyte markers. The kind of correlations made with primary disease, small molecule levels, rehabilitation, suggests that cell-mediated immunodeficiency in uremia is a premature phenomenon and scarcely influenced by adequate hemodialysis treatment.