Hemolytic uremic syndrome in adults.

The long-term clinical course of 11 adults with hemolytic-uremic syndrome (HUS) is reported. All patients were treated with heparin and antiplatelet drugs, and ten required dialysis. One patient died after 38 days; the others recovered from anuria after seven to 400 days. One patient was resubmitted to regular dialysis five years later, and another died because of cerebral hemorrhage. Among the remaining eight patients, four show renal failure and four have normal renal function after one to ten years of observation. All but three require vigorous antihypertensive therapy. It is concluded that in adults with HUS (1) recovery may occur even after a prolonged anuria; (2) severe hypertension and progressive renal failure may appear later in apparently recovered patients; and (3) heparin and antiplatelet drugs seem to be beneficial in reversing acute renal failure.

De novo focal glomerular sclerosis in an identical twin renal transplant recipient.

A patient with end-stage renal failure caused by bilateral kidney stones received a kidney transplant from his identical twin. No immunosuppressive therapy was given. After a few days he developed a urinary fistula from a polar artery section, which spontaneously healed. Renal function remained subnormal, blood pressure and urinalysis were normal. After one year proteinuria appeared, and after about four years it entered a nephrotic range. Renal biopsy showed focal glomerular sclerosis (FGS). In the following years progressive renal insufficiency and arterial hypertension developed, and the patient had to be submitted to regular dialysis about 9 years after transplantation. As far as we know this is the first case of late renal failure in an isograft related to the development of de novo FGS. It is suggested that de novo FGS in this isotransplant was related to the partial loss of renal mass caused by polar necrosis, which caused glomerular hyperfiltration. Another possible contributing factor may be kidney denervation, which removes an important mechanism for adjustment of renal arterial flow.

High levels of tissue factor pathway inhibitor in patients with nephrotic proteinuria.

Acquired deficiency of naturally occurring anticoagulant proteins, due to loss in the urine, has been proposed as one of the major thrombogenic alterations in nephrotic proteinuria. The aim of this study was to investigate if proteinuria may induce deficiency of tissue factor pathway inhibitor (TFPI). TFPI, protein C (PC) and antithrombin (AT) were measured in 31 patients with nephrotic proteinuria, compared with 62 age- and sex-matched controls. Plasma levels of TFPI activity, total TFPI antigen and free TFPI antigen were significantly higher in patients with nephrotic proteinuria than in controls, and none of the patients had TFPI deficiency. Intravenous injection of 7500 IU unfractionated heparin induced a significant further increase of TFPI in two patients with high pre-heparin levels. Also plasma levels of PC were significantly higher in patients than in controls. Mean AT antigen levels were not significantly different between patients and controls, and AT activity was only marginally increased with borderline significance. Three out of 31 patients had substantial acquired AT deficiency. In conclusion, proteinuria is not associated with TFPI deficiency, but with a marked increase of this anticoagulant protein. The acquired thrombophilic diathesis of patients with nephrotic proteinuria can therefore not be attributed to TFPI deficiency.

Ciclosporin in minimal-change glomerulopathy and in focal segmental glomerular sclerosis.

Results of the available literature and preliminary data of an ongoing multicenter, prospective, randomized Italian trial indicate that ciclosporin (CS), at low doses, may maintain remission of the nephrotic syndrome in most steroid-sensitive patients. In steroid-resistant patients CS may cause either complete or partial remission in about 40% of patients with idiopathic nephrotic syndrome. With doses not exceeding 5 mg/kg/day and careful monitoring of renal and liver function, blood pressure and blood levels, severe side effects can be prevented. Although an extensive use of CS in nephrotic syndrome is still premature, cautious trials may be attempted in patients with steroid toxicity and/or devastating nephrotic syndrome.

Glomerulonephritis associated with myasthenia gravis.

In a follow-up study of 128 myasthenic patients from a neurological center in Northern Italy, three were found to have developed glomerulonephritis at variable intervals after the onset of myasthenia gravis, thymoma (two patients), and thymectomy. By renal biopsy, two patients (cases 1 and 3) were found to have membranous nephropathy; and one (case 2), pauciimmune extracapillary glomerulonephritis. At follow-up, patient 1 was persistingly nephrotic and developed renal failure, and patient 3 only had urinary abnormalities. Patient 2 developed end-stage renal disease. The review of the literature showed 10 other cases of glomerulonephritis associated with myasthenia gravis with or without thymoma and thymectomy. Therefore, it is likely that these conditions are pathogenetically linked. The role of autoantibodies, thymoma, and thymectomy in favoring glomerulonephritis in myasthenic patients is discussed.

Asymptomatic parasitic infections in renal transplant recipients and in haemodialysis patients.

One hundred and sixty-seven clinically asymptomatic renal transplant recipients and 119 patients on chronic haemodialysis were studied for the presence of intestinal parasites and for the prevalence of anti-Toxoplasma gondii antibodies. Intestinal parasitic infections were more frequently found in transplant recipients than in haemodialysis patients and in controls. Among transplant recipients, the prevalence rate of T. gondii antibodies at high titres was significantly increased, but in these subjects the positivity rate of specific IgM assays was reduced. This seems to indicate a greater occurrence of asymptomatic reactivated infections. Our findings suggest that parasitologic surveys of immunosuppressed patients should be periodically performed also in temperate climates, in order to prevent the possibility of disseminated infections.

Reversible acute anuric lupus nephritis.

Six cases of acute anuric lupus nephritis are described; renal biopsy showed intracapillary proliferation, epithelial crescents in some glomeruli, wire loops, and intracapillary thrombi. In two patients there were thrombotic occlusions and fibrinoid necrosis of arterioles. The patients were treated by heparin at anticoagulant doses, corticosteroids and dialysis (four). All patients showed improvement of renal function. One died following a gastric haemorrhage - the others were alive and well 64, 61, 40, 40 and 22 months from the onset of renal failure. One patient had a second episode of acute renal failure after 39 months and improved after resumption of heparin and high doses of steroids. It is suggested that heparin and high doses of corticosteroids may be a successful treatment in acute anuric lupus nephritis.

Acute renal failure in systemic lupus erythematosus.

Acute anuric renal failure complicating systemic lupus erythematosus does not usually respond to treatment with corticosteroids and immunosuppressive agents. We describe four cases treated by dialysis, corticosteroids, and heparin in anticoagulant doses in which there was remarkable improvement in renal function after prolonged anuria. One patient died later from a gastric haemorrhage. The other three were alive and well 55, 54, and 30 months from the onset of anuria. In two cases a second renal biopsy showed a striking improvement in the lesions. Large doses of corticosteroid and heparin may be the best treatment in acute anuric lupus nephritis.

Hypertension in man with a kidney transplant: role of familial versus other factors.

Genetic factors are clearly involved in the pathogenesis of essential hypertension in man. In at least three rat models of genetic hypertension it is possible to transplant the hypertension with the kidney. To see whether or not the same is true for humans, we carried out a 2-year retrospective study of 50 selected recipients of a cadaver kidney. We correlated the following factors by multivariate statistical analyses: presence or absence of hypertension in the family of donor and recipients; donor's and recipient's age; mean blood pressure (MBP) and antihypertensive therapy (AHT) score during dialysis; months of dialysis and body surface before transplantation; body weight, plasma creatinine, prednisone dosage and cumulative rejections with MBP and AHT score at various time intervals after transplantation. The results obtained showed that, considering the recipients coming from normotensive families, the AHT score after transplantation was significantly greater (p less than 0.05 1st and p less than 0.01 2nd year) in the patients receiving a kidney removed from donors with hypertensive families than in patients receiving a kidney removed from donors with normotensive families. This difference was not present when the recipients coming from hypertensive parents were considered. AHT score after transplantation is also correlated with AHT score on dialysis (p less than 0.01 1st and 2nd year), body weight (p less than 0.02 1st and p less than 0.01 2nd year), cumulative rejections (p less than 0.025 1st and 2nd year) and inverse MBP after dialysis (p less than 0.025 2nd year).

Controlled trial of two different methylprednisolone doses in cadaveric renal transplantation.

In a controlled trial the effects of two different methylprednisolone (MP) schedules were studied in 100 cadaver kidney adult recipients followed for 18-46 months. Group A patients were given 160 mg/day i.v. for 3 days, then oral MP (0.8 mg/kg/day), which was tapered by 4 mg/week to a maintenance dose of 16 mg/day up to the 6th month. Group B patients were given 80 mg/day i.v. for 3 days followed by 0.4 mg/kg/day oral MP; the dose was reduced by 2 mg/week to 16 mg/day. In both groups, the dose was further reduced bimonthly to a final dose of 8 mg/day. No significant differences were evidenced between the two groups in patients and kidney survival or in the incidence of complications. The number of patients with at least one rejection episode was significantly higher in the lower dose group.

A randomized trial of cyclosporine in steroid-resistant idiopathic nephrotic syndrome.

To compare the efficacy (induction of remission) and safety of cyclosporine (CsA) with those of supportive therapy in patients with steroid-resistant idiopathic nephrotic syndrome (INS), we organized an open, prospective, randomized, multicentric, controlled study for parallel groups, stratified for adults and children. Forty-five patients with steroid-resistant INS were randomly assigned to supportive therapy or CsA (5 mg/kg/day for adults, 6 mg/kg/day for children) for six months, then tapered off by 25% every two months until complete discontinuation. Four patients were lost to follow-up. During the first year 13/22 CsA-treated patients versus three of 19 controls attained remission of the nephrotic syndrome (P < 0.001). A symptom score was assessed at time 0 and at six months. The mean score significantly decreased in the CsA group (P < 0.001), but remained unchanged in the controls. At month 6 the mean urinary protein excretion, the mean serum proteins and plasma cholesterol had significantly improved in the CsA group but were not changed in the controls. There were no significant differences in serum creatinine and creatinine clearance between treatments (interaction time* treatments, P = 0.089 and P = 0.935, respectively) at month 6 versus basal. The CsA-related side-effects were mild; no significant difference in blood pressure between the two groups was seen at any time. This study shows that CsA can bring about remission in some 60% of patients with steroid-resistant INS. In patients with normal renal function and without severe hypertension, CsA at the therapeutic scheme adopted did not produce severe renal or extrarenal toxicity.

Nephrotic syndrome in a mother and her infant: relationship with cytomegalovirus infection.

This case report describes infantile nephrotic syndrome (NS) in a baby girl with a clinically severe cytomegalovirus (CMV) infection. Culture of the baby's urine was positive for CMV and IgM anti-CMV antibodies were detected. After an unsuccessful course of corticosteroids, gancyclovir treatment was started and a remission of cutaneous, pulmonary, and renal symptoms was achieved. As the mother also developed NS at the end of pregnancy, a common etiology could be postulated, although there were no signs of recent CMV infection in the mother, only anti-CMV IgG. The relationship between CMV infection and glomerular disease is still unclear; NS may represent another manifestation of CMV disease.

Multicentre comparative trial of tienilic acid and hydrochlorothiazide in hypertensive patients.

To compare the clinical and metabolic effects of a new diuretic uricosuric agent, tienilic acid, with those of hydrochlorothiazide, a multicentre double-blind trial was performed in 56 hypertensive patients. Twenty-eight patients were randomly assigned to take tienilic acid and 28 to take hydrochlorothiazide. The diuretic and anti-hypertensive actions of the two compounds were similar. No significant differences were observed between tienilic acid and hydrochlorothiazide in their effects on urinary and serum electrolytes, hepatic and renal function tests, and fasting lipids. The patients who received tienilic acid showed a significant fall in serum uric acid, mediated by the uricosuric effect. The availability of an agent combining diuretic, antihypertensive and hypouricemic effects offers promise in the treatment of arterial hypertension.