Search

Background: Several studies have demonstrated a short-term antiproteinuric effect of mineralocorticoid receptor blockers (MRB) on proteinuric kidney diseases, but no information is available about the long-term persistence (>1 year) of such reduction in proteinuria and the long-term effects of MRB on renal function., Methods: We prospectively studied the effects of adding spironolactone (25 mg/day) to 87 patients who maintained proteinuria higher than 1 g/day in spite of renin-angiotensin system blockade. The mean follow-up was 25 ± 15 (1-84) months., Results: Estimated glomerular filtration rate (eGFR) showed an acute fall in the first month of treatment (5.1 ± 9.4 mL/min/1.73 m(2)), but it remained stable thereafter (+0.04 ± 0.7 mL/min/1.73 m(2)/month), with a significant difference with respect to the eGFR slope during the 12-month pre-treatment period. The initial eGFR fall predicted a more stable course of renal function, the higher the eGFR initial fall, the better the long-term evolution of eGFR. Proteinuria showed an important and sustained reduction since the first month of treatment. At the end of follow-up, it had decreased by 61% (43-77%) with respect to baseline values. The antiproteinuric and renoprotective influence of spironolactone was also observed in diabetic patients and in patients with renal function impairment, although tolerance was poorer among the latter., Conclusions: Spironolactone induces an initial acute fall in eGFR that predicts a later favourable influence on the course of renal function and a remarkable and sustained reduction in proteinuria.

The participation of renal prostaglandins in the nephrotic syndrome has been investigated by the measurement of the urinary excretion of prostaglandin E2 (PGE2), renal function and the renin-angiotensin-aldosterone system before, during and after the administration of indomethacin in a group of patients diagnosed as having chronic idiopathic glomerulonephritis with and without nephrotic syndrome. Our results indicate increased renal production of PGE2 in nephrotic patients. This contributes to the maintenance of renal function, probably by counteracting an activated renin-angiotensin system and could be accompanied by a simultaneous and deleterious enhancement of the degree of proteinuria. Nevertheless, the participation of angiotensin II in this last even cannot be excluded.

The combination of hydrochlorothiazide and amiloride has been used in a group of patients diagnosed as having essential hypertension. Sixty-five percent of the patients for whom dietary restrictions did not achieve a reduction in blood pressure were initially controlled with this combination; the addition of a second or third drug was required by the remaining patients. During the six-month follow-up, the control of blood pressure was satisfactory with increased drug requirements, but the diuretic had to be discontinued in 12 patients because of side effects.

In a retrospective study we have examined 20 liver specimens from haemodialysis patients with a mean time on treatment of 27 months. Thirteen specimens were biopsies, the remaining came from autopsies. The presence of refractile particles was found in 55 per cent of biopsies and 100 per cent of autopsies. Its presence was not constantly associated with morphological lesions of the liver. We believe that the deposition of this material could be a fortuitous finding with uncertain clinical implications.

A 12-year-old boy presented with acute renal failure (ARF) accompanied by a disproportionate increase of serum uric acid level and massive uric acid crystalluria. After alkalinization and allopurinol therapy, serum uric acid and renal function returned to normal values. A further enzymatic study showed the existence of a partial hypoxanthine-guanine phosphoribosyl transferase (HPRT) deficit (less than 1% of HPRT normal activity). Although ARF is an exceptional form of presentation of HPRT deficiency, this possibility should be considered whenever an ARF is accompanied by disproportionate high levels of serum uric acid.

In a group of 26 patients diagnosed as essential hypertensive (EH) and in a control group (CG) of 27 normotensive volunteers the urinary excretion of PGE2, plasma renin activity (PRA) and plasma aldosterone were measured. EH patients were classified into normoreninemic (NREH) (n = 21) and hyporeninemic (LREH) (n = 5) by the response of PRA to the combined stimuli of ambulation and furosemide. Urinary PGE2 excretion was higher in NREH than in CG (p less than 0.05) while LREH showed values lower than in CG (p less than 0.001). Plasma aldosterone levels were similar in the three groups. In CG and EH patients PRA and urinary PGE2 were closely related (CG r = 0.516, p less than 0.05, EH patients r = 0.674, p less than 0.001). Indomethacin administration induced a decrease of PGE2 in both CG (n = 8) and NREH (n = 8) (p less than 0.01). In contrast, indomethacin induced no changes in PGE2 excretion of LREH (n = 5). Furthermore in the group of patients with NREH indomethacin induced a significant increase in blood pressure (p less than 0.01) and body weight (p less than 0.01) while glomerular filtration rate, 24 hour natriuresis PRA and plasma aldosterone decreased (p less than 0.01). On the contrary, in LREH indomethacin did not alter any of the parameters measured. These results indicate that LREH and NREH may be regarded as two different populations distinguishable not only by different secretion of PRA but also by different excretion of PGE2 in urine and by their characteristic response to indomethacin.

We have prospectively investigated the effect of desferrioxamine (DFO) administration (2 gi.v. after every haemodialysis session for 6 months) on the normocytic and normochromic anaemia of seven haemodialysis patients. None had either clinical or analytical data characteristic of chronic aluminium intoxication. At the end of DFO therapy, the haematocrit had increased from 20.5 +/- 2.7% to 30.4 +/- 7.7% (P less than 0.005), and the transfusional requirements decreased from 3.5 +/- 2.2 units (range 1-8 units) in the 6 months prior to DFO, to 0.7 +/- 0.9 units (range 0-2 units) during DFO administration (P less than 0.01). No transfusion was required during the second half of the DFO therapy period. Serum ferritin decreased from 105g +/- 532 nmol/l (2649 +/- 1331 ng/ml) to 507 +/- 403 nmol/l (1268 +/- 1008 ng/ml) (P less than 0.025). Two months after DFO withdrawal the haematocrit value fell significantly to 22.2 +/- 1.6% (P less than 0.01). DFO therapy was restarted in one patient at a lower dose (1 gi.v. after every haemodialysis session) and an increase of haematocrit from 23.8% to 40.2% was again observed after 3 months of treatment. The tolerance to DFO was excellent. We conclude that DFO therapy should be considered in haemodialysis patients with severe anaemia and increased blood transfusion requirements.

Recent experimental and clinical data have suggested that angiotension converting enzyme (ACE) inhibitors may decrease glomerular proteinuria by specific effects on the glomerulus. We studied a group of 15 adult patients with chronic renal failure and proteinuria due to various glomerulopathies. These patients had mild to moderate hypertension which was effectively controlled with conventional antihypertensive therapy. We then treated the patients with captopril, maintaining a similar dietary protein and salt intake. After 6 months of study, proteinuria was reduced significantly without reduction in inulin or para-aminohippurate clearance. This supports the concept that captopril may have salutary effects on the glomerulus, independently of its effect on systemic blood pressure.