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Biomedical subjects

G Fuiano

Publications and source records attributed to G Fuiano.

At least 37 records · Page 2Linked to original sources

Effects of a two-month treatment with low oral doses of cyclosporin on renal function.

To test the effects of short-term therapy with low doses (LD) of cyclosporin A (CsA) in subjects with normal renal function, seven patients receiving CsA to treat psoriasis were studied. Clearances in maximal H2O diuresis were performed to evaluate changes in GFR (CIn), RPF (CPAH) and tubular function before starting CsA (BAS), after 2 days (S1) and 1 month (S2) of oral therapy with 5 mg/kg per day CsA. The study was repeated at the withdrawal of CsA after tapering (S3) and 2 months after the withdrawal (S4). The studies were performed 12 h after the evening dose of CsA. RPF was significantly less than in BAS throughout the therapy and returned almost to basal values in S4. GFR was significantly less than in BAS both in S2 and in S3. In S4, in spite of an increase, GFR was still significantly less than in BAS. Both in S2 and in S3 proximal tubular fractional sodium reabsorption was significantly less than in BAS and, consequently, both sodium delivery to diluting segments and sodium reabsorption in diluting segments increased. Moreover, both in S2 and in S3 fractional sodium reabsorption in diluting segments and free-water generation were greater than in BAS. In S4 tubular function returned almost to basal values. Our data suggest that short-term therapy with low dose CsA impairs renal function; this impairment is not completely reversed after drug withdrawal.

Administration, Oral↗

Medium-term cyclosporin renal dysfunction and its reversibility in rats.

Renal dynamics and morphology were investigated by metabolic, renal micropuncture (RM), and electron microscopy (EM) studies in 50 female rats treated with cyclosporin A (CsA, 40 mg.kg body wt-1.48 h-1) for either 10, 20, or 30 days (groups CsA 10, CsA 20, and CsA 30, respectively); control rats received olive oil (group N). Body weight gain, sodium metabolism, and plasma volume were not altered by CsA administration in any group. GFR was decreased in group CsA 10 vs. group N (-10%, P less than 0.05) and was further impaired in groups CsA 20 and CsA 30 (-45%, P less than 0.01 vs. group N). RM studies showed a significant decrease of single-nephron glomerular filtration rate (SNGFR) in group CsA 30 vs. group N (-26%, P less than 0.01) after the fall of glomerular capillary pressure (Pgc;-8%, P less than 0.05), the increase of afferent arteriole resistance (Ra; +40%, P less than 0.05), and the consequent decrease of glomerular plasma flow (GPF; -28%, P less than 0.05). Thirty days after CsA withdrawal, SNGFR returned to normal values (P less than 0.01 vs. group CsA) as a result of the normalization of Pgc, Ra, and GPF.EM showed only a progressive vacuolation of proximal and distal tubular cells. These data suggest that medium-term administration of CsA is associated with reversible changes in glomerular dynamics and only mild histological lesions.

Animals↗

Acute effects of ciclosporin on renal hemodynamics and urinary protein excretion in patients with the nephrotic syndrome.

The possibility that the renal hemodynamic abnormalities associated with ciclosporin (CS) administration are enhanced in nephrotic patients (NP), leading to severe impairment of renal function and/or to modifications in proteinuria, has not hitherto been tested. Ten NP and 8 healthy subjects (NC) were examined before and after oral CS administration (10 mg/kg body weight in NP and 12 mg/kg body weight in NC: a lower dosage was adopted in NP because of edema overestimating the actual body weight) under water diuresis by standard renal clearance methods. Basal blood volume was lower in NP. Blood CS levels were not significantly different in the two groups. Basal glomerular filtration rate (GFR) was similar in NP and NC, while renal plasma flow (RPF) was lower in NP. After CS, both GFR and RPF significantly decreased in the two groups, but the percent decrease in inulin clearance was greater in NP. Filtration fraction increased only in NC. Basal renal vascular resistances were greater in NP, and significantly increased after CS in both groups. Basal fractional sodium excretion (FENa) was lower in NP: after CS FENa decreased only in NC. Neither plasma renin activity, nor plasma aldosterone changed after CS. When urinary protein excretion (UP) was corrected by GFR, no change was observed after CS; by contrast, selectivity of proteinuria (as assessed by the CIgG/CTransferrin ratio) markedly increased. Our data indicate that CS induces a greater fall in the GFR in hypovolemic NP than in healthy subjects, probably because in the former GFR becomes extremely plasma flow dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Acute increase in plasma osmolality as a cause of hyperkalemia in patients with renal failure.

These studies were performed in patients with chronic renal failure to understand the mechanism(s) of hyperkalemia secondary to hypertonic NaCl infusion. In 10 patients, after intravenous infusion of either 5% or 2.5% NaCl (6 mEq per kg body wt for 120 minutes in both solutions), the maximum increase in plasma potassium averaged 0.6 (range 0.3 to 1.3) mmol/liter (P less than 0.01) or 0.3 (range 0.2 to 0.6) mmol/liter (P less than 0.01), respectively. The rise of both plasma potassium and osmolality was significantly higher during 5% NaCl than during 2.5% NaCl infusion (P less than 0.01). A significant linear correlation (P less than 0.01) between plasma potassium and osmolality was observed. Urinary potassium excretion was increased to a similar extent by 5% NaCl and 2.5% NaCl infusion. The observed hyperkalemia, secondary to NaCl infusion, was independent of venous pH, plasma bicarbonate, anion gap, insulin levels, and urinary norepinephrine and epinephrine excretion, and was associated with a fall in plasma aldosterone concentration. In separate studies, nine patients were treated with desoxycorticosterone acetate (DOCA; 20 mg i.m. for three days) before receiving saline (5%) infusion. DOCA did not prevent the level increase in plasma potassium that remained significantly correlated with plasma osmolality (P less than 0.01). In conclusion, hypertonic NaCl infusion in patients with renal failure causes a clinically relevant hyperkalemia despite increased renal excretion of potassium. This hyperkalemia is independent of acid-base or hormonal mechanisms known to regulate extrarenal homeostasis of potassium, and is strictly correlated with a rise in plasma osmolality.

Acid-Base Equilibrium↗

Acute cyclosporine renal dysfunction reversed by dopamine infusion in healthy subjects.

Up to now, no studies have been performed in normal humans to investigate the role of renal hemodynamic abnormalities in relation to acute-cyclosporin A (CsA) renal dysfunction and to verify whether the specific renal vasodilator, dopamine, can counteract these abnormalities. Eight normal subjects were examined both (A) after oral CsA (12 mg/kg body wt) and (B) after oral CsA + dopamine infusion (2 mg/kg body wt/min), under water diuresis. Both in protocols A and in B, four basal renal clearances were performed before CsA and every twenty minutes for four hours after CsA administration. In protocol A, after CsA, inulin (GFR) and PAH clearance (RPF) fell by up to 27% and to 41%, respectively, so that filtration fraction (FF) increased (P less than 0.01). A slight (not significant) hypertension occurred while renal resistances were markedly raised (P less than 0.001). Fractional urine and Na+ excretion as well as CH2O decreased, while UOsm increased (P less than 0.01). In protocol B, dopamine was infused from 120 to 180 minutes after CsA (that is, when the maximal adverse effects of CsA on renal hemodynamics had been observed in A). Dopamine infusion could reverse completely the effects of CsA on RPF, GFR, fractional urine output and CH2O; only UOsm remained higher than normal in conclusion with an increased fractional excretion of sodium (P less than 0.01). No changes were observed in plasma renin activity, aldosterone and in urinary epinephrine and norepinephrine excretion both in protocols.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Glomerular dynamics and salt balance in pregnant rats with renal hypertension.

These studies were aimed at investigating whether chronic hypertension in pregnancy causes changes both in salt excretion (NaE) and in glomerular hemodynamics. Metabolic and renal micropuncture studies were performed in pregnant (P) and Virgin (V) Munich-Wistar rats with normal blood pressure (N) and two-kidney Goldblatt hypertension (H). Mean NaE was higher in PN than VN (2.7 vs. 1.7 meq/day, P less than 0.01). Hypertension raised NaE both in P and V rats: in P and V rats with "benign" hypertension (blood pressure less than 180 mmHg) NaE averaged 3.2 and 2.6 meq/day, respectively (P less than 0.05); mean NaE was 5.9 and 3.8 meq/day, respectively (P less than 0.01), in P and V rats with "malignant" hypertension (blood pressure greater than or equal to 180 mmHg). Afferent arteriole resistance (Ra) averaged 1.73 and 3.50 10 dyn.s-1.cm5 in PN and VN, respectively (P less than 0.01). Hypertension raised Ra in V, but not in P rats (4.47 vs. 2.14 10 dyn.s-1.cm5, P less than 0.01). Thus glomerular plasma flow, glomerular capillary hydrostatic pressure, and single-nephron glomerular filtration rate were markedly higher in PH than VH rats: in PH rats single-nephron filtration fraction was significantly lower than in VH. These results show that in PH rats a marked rise in NaE is associated with glomerular vasodilation.

Animals↗

Effects of uremia, acetate and bicarbonate dialysis on beta-adrenergic responsiveness as assessed by epinephrine-stimulated adenylate cyclase.

This study was designed to evaluate beta-adrenergic responsiveness as assessed by the generation of cyclic AMP after the subcutaneous administration of epinephrine in 31 subjects: normal controls, patients with chronic renal insufficiency, hemodynamically stable patients on chronic acetate dialysis and hemodynamically unstable patients with acetate intolerance on chronic bicarbonate dialysis. As compared with controls, only unstable patients on bicarbonate dialysis presented impaired beta-responsiveness, which, in turn, was acutely reduced only after acetate but not bicarbonate dialysis. Our results show that acetate dialysis impairs the beta-adrenergic responsiveness and that the observed beta-hyporesponsiveness in unstable patients with acetate intolerance may represent part of a broader spectrum of autonomic dysfunction which may develop in some patients on chronic hemodialysis.

Acetates↗

Effectiveness of single daily intraperitoneal administration of aztreonam and cefuroxime in the treatment of peritonitis in continuous ambulatory peritoneal dialysis (CAPD).

To discover if the management of peritonitis in continuous ambulatory peritoneal dialysis (CAPD) may be effectively simplified by single daily i.p. administration of aztreonam (A) and cefuroxime (C), 10 adult CAPD patients (pts) with peritonitis were trained to start the following treatment procedure: a) sterile collection of dialysate effluent for cultures; b) 4 rapid in-and-out exchanges with antibiotic free dialysate; c) addition of 2 g C and 2 g A to a 2-L exchange for 6-h dwell time (the same dosage was repeated once a day in the overnight exchange); d) routine CAPD exchanges. Concentrations of C and A were measured in dialysate and serum of the patients 2, 12, 18, and 21-23 h after the i.p. administration: C remained within therapeutic range in all samples, while serum and dialysate A levels fell below such range 16 h after the i.p. administration. Seventeen peritonitis episodes occurred during the observation period (12 months): initial dialysate cultures grew Staph. aureus in 6 episodes, Staph epidermidis in 6, Pseudomonas aer. in 2, Streptococcus faecalis in 1, Citrobacter in 1, and Candida in 1. All patients but 1 (with Candida-positive culture) responded to this treatment with no relapse in 2 months. We conclude that once a day i.p. administration of 2 g aztreonam plus 2 g of cefuroxime is an effective and simple way of treating CAPD pts with gram-positive and gram-negative peritonitis.

Aztreonam↗

Effectiveness of steroid therapy in different stages of membranous nephropathy.

The published studies on histological staging and response to steroid therapy of membranous glomerulonephritis are not consistent. We analysed data from 25 adult patients with stage I (group 1, n = 7) and stage II (group 2, n = 18) disease. The interval between clinical onset and admission was similar in the two groups. At admission all patients had normal creatinine clearance; proteinuria averaged 5.4 +/- 4.0 in group 1 and 9.0 +/- 4.0 in group 2 (g/day per 100 ml GFR). All patients received 6 months steroid therapy (months 1-2, 1 mg/kg b.w. per day; month 3-5: 0.65 mg/kg b.w. e.o.d.; month 6, tapering). After this cycle of steroid therapy, proteinuria declined by 84% in group 1 (five patients being in partial remission, i.e. 0.4-2 g/day, and two patients in complete remission, i.e. less than or equal to 0.3 g/day) and by 47% in group 2 (two patients being in complete remission and six in partial remission). Only 1 patient in group 1 relapsed with nephrotic proteinuria after 36 months, and renal function was still normal in all patients at the most recent follow-up (59 +/- 32 months). In contrast, 14 patients in group 2 had nephrotic syndrome and seven renal insufficiency at the most recent follow-up. We conclude that short-term steroid therapy is effective only in patients with early membranous changes.

Adolescent↗

Improved prognosis of renal microscopic polyarteritis in recent years.

To determine if the short- and long-term prognosis of renal micropolyarteritis (including Wegener's granulomatosis) had improved in our Unit in the last 5 years compared to our previous series from 1965 to 1980, we examined data from 26 recent patients, 1981-1986. Twenty were admitted during acute phase and six after a mean of 7.1 months of disease. The acute phase showed mild to severe impairment of renal function, and renal biopsies showed necrotising glomerulitis in all acute patients with extensive crescents in 67%. Acute patients (20) were treated with 'aggressive' immunosuppression including i.v. methylprednisolone (15), plasmapheresis (seven) and cyclophosphamide (ten). Chronic immunosuppressive treatment was continued in most patients. In the 20 acute-onset patients, life survival at 2 and 5 years was 77%; four of five deaths occurred during the acute phase in aged patients with severe renal failure. The notable improvement in life and kidney survival (only one patient underwent chronic dialysis) probably resulted from greater awareness of vasculitis in general practice with early referral of patients to specialised units, and to more aggressive treatment.

Acute Disease↗

Effects of furosemide therapy on free-water excretion in uremic patients.

To assess the intrinsic effects of treatment with furosemide on free-water excretion in patients with chronic renal failure, two groups of patients with and without replacement of diuretic-induced salt losses have been studied. Furosemide therapy was administered for 1 week during constant sodium intake (100 mEq/day). In neither of the groups did furosemide cause hyponatremia, while it did decrease the urine to plasma osmolality ratio, an effect lasting even when the diuretic effect was exhausted. During water diuresis, furosemide decreased the fractional sodium reabsorption in diluting segments but not the absolute rate of the free-water generation (CH2O). Presumably the expected decrease of CH2O was masked by the increased distal delivery of tubular fluid mainly due to an additional effect of the diuretic on the proximal tubule. The hypotonicity of urine after furosemide treatment may be secondary to the dissipation of medullary hypertonicity, caused by furosemide, in the condition of decreased water permeability of the collecting duct due to uremic disease.

Furosemide↗

Treatment of severe renovascular hypertension by percutaneous transluminal renal angioplasty in patients with solitary functioning kidney. Effects on blood pressure and renal function.

In this study the effects of percutaneous transluminal renal angioplasty on blood pressure and renal function were studied in 9 hypertensive patients with stenosis of the main artery of a solitary functioning kidney. The outcome of the percutaneous dilatation of the renal artery stenosis, and the effects on blood pressure and renal function were evaluated for a mean period of 16.4 +/- 2.13 (SE) months (ranging from 3 to 65 months). A successful dilatation of the renal artery stenosis was shown in all the patients by the aortography performed 1 h after the procedure. At the discharge (7.8 +/- 0.9 days after dilatation), blood pressure was 'cured' in 2 patients and 'improved' in the remaining patients; renal function was improved in all patients who had reduced renal function. At the last follow-up, no restenosis was found in patients who repeated the follow-up angiography; blood pressure was 'cured' in 3 patients and 'improved' in 6 patients, and renal function appeared steadly improved. In contrast with other reports, our results demonstrate that percutaneous renal angioplasty is a safe and effective procedure and should be attempted before considering surgical intervention in patients with artery stenosis of a solitary functioning kidney.

Adult↗