Vittorio Bonomini

Residual Renal Function and Effective Rehabilitation in Chronic Dialysis

The results of a 1-7 years follow-up of multiple processed and recorded semiquantitative parameters in 148 cases of chronic uremia on regular dialysis treatment (RDT) are reported. Patients were grouped according to different levels of residual creatinine clearance (CCr) at the beginning of treatment (0-5, 5-15, and 15-21 ml/min). Regardless of a possible return to work and reasonable quality of life, patients on RDT with 0-5 ml/min CCr invariably present a worsening in various subclinical parameters semiquantitatively evaluated (bone biopsies; nerve conduction velocity; glucose A-V, etc.). In patients with 5-15 ml/min CCr better results are found. In patients with residual CCr above 15 ml/min, impairment in several parameters is hardly evident and even after several years of dialysis may still remain minimal. These results seem of importance as far as the effective and not the apparent dialysis rehabilitation is concerned.

Long-Term Patient and Renal Prognosis in Acute Renal Failure

A long-term clinicomorphological study in 227 patients with acute renal failure due to intrinsic renal damage shows the clinical value of renal biopsy for assessing treatment and predicting prognosis. Early morphological diagnosis enables appropriate therapeutic measures, which play their part in patient survival and renal survival. Present long-term results show that 5 years after the acute episode, chronic renal failure may be expected to occur in about 50% of cases with acute renal failure due to glomerular and vascular injuries. Tubulointerstitial lesions are associated with definitely better long-term prognosis.

Efficacy and safety of tacrolimus compared with ciclosporin A in renal transplantation: three-year observational results.

BACKGROUND The European tacrolimus versus ciclosporin A microemulsion (CsA-ME) renal transplantation study showed that tacrolimus was significantly more effective in preventing acute rejection and had a superior cardiovascular risk profile at 6 months. METHODS The endpoints of this investigator-initiated, observational, 36-month follow-up were acute rejection incidence rates, rates of patient and graft survival and renal function. An additional analysis was performed using the combined endpoints BPAR, graft loss and patient death. Data available from the original ITT population (557 patients; 286 tacrolimus and 271 CsA-ME) were analysed. RESULTS A total of 231 tacrolimus and 217 CsA-ME patients participated. At 36 months, Kaplan-Meier-estimated BPAR-free survival rates were 78.8% in the tacrolimus group and 60.6% in the CsA-ME group, graft survival rates were 88.0% and 86.9% and patient survival rates were 96.6% and 96.7%, respectively. The estimated combined endpoint-free survival rate was 71.4% with tacrolimus and 55.4% with CsA-ME (P <or= 0.001, chi-square test). Significantly more CsA-ME patients crossed over to tacrolimus during the 3-year follow-up: 21.2% versus 2.6%, P <or= 0.0001, chi-square test. Most patients in the tacrolimus arm discontinued steroids and received monotherapy and fewer tacrolimus patients remained on a triple regimen. Mean serum creatinine concentration was 145.4 +/- 90.9 micromol/L with tacrolimus and 149.0 +/- 92.1 micromol/L with CsA-ME. Significantly more CsA-ME patients had a classified cholesterol value >6 mmol/L (26.3% versus 12.6%, P <or= 0.0003, chi-square test). CONCLUSIONS Patients treated with tacrolimus had significantly higher combined endpoint-free survival rates and lower acute rejection rates with less immunosuppressive medication at 36 months.

Effect of a New Antithrombotic Agent (Defibrotide) in Acute Renal Failure Due to Thrombotic Microangiopathy

8 patients with thrombotic microangiopathy were treated with a new antithrombotic agent, defibrotide. This drug displays considerable fibrinolytic and antithrombotic activity, and induces generation and release of a prostacyclin-like substance from vascular tissue. At admission all patients presented severe renal involvement and coagulation abnormalities. Neurological manifestations were present in 6. Defibrotide administration was followed by recovery of renal function in 6, disappearance of neurological symptoms and coagulation abnormalities in all patients. The use of defibrotide was not associated with side effects. On the basis of the results obtained in these patients, we suggest that defibrotide might be considered as a valuable drug in the management of patients with thrombotic microangiopathy.

A new antithrombotic agent in the treatment of acute renal failure due to hemolytic-uremic syndrome and thrombotic thrombocytopenic purpura

Prof. Vittorio Bonomini, Department of Nephrology, St Orsola University Hospital, Via Massarenti 9, I-40138 Bologna (Italy) Dear Sir, The hemolytic-uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) share many common features including microangiopathic hemolytic anemia, thrombocytopenia, and renal involvement. Prolonged anuria, severe hypertension and marked neurological manifestations are signs of poor prognosis for both the recovery of renal function and patient’s survival. The etiology and pathogenesis of the two conditions are still unclear. It has been suggested [1] that a process of intravascular coagulation plays a role in the development of renal lesions, and thrombotic lesions are seen in the glomeruli and vessels up to the arcuate arteries. These findings have prompted numerous therapeutic attempts using heparin, urokinase, streptokinase, and platelet aggregation inhibitors, but the efficacy of these approaches is difficult to assess. On the other hand such therapies are not without considerable morbidity and mortality. Recent studies [2] suggest the hypothesis that a deficiency of plasma factor(s), which normally modulate vascular PGL· synthesis and release, have some role in the pathogenesis of HUS and TTP. In the last year we treated 5 patients (3 children and 2 adults) affected by HUS or TTP with a new antithrombotic agent (Defibrotide). This drug is a polydeoxyribonu-cleotide [3], extracted from mammalian organs, which has been demonstrated to increase the generation of PGI, from vascular tissue, and displays considerable fibrino-lytic and antithrombotic activity. Clotting investigations did not indicate that Defibrotide has any significant heparin-like activity. All patients were anuric on admission. Serum creati-nine ranged from 5.3 to 8.7 mg/dl; platelet count was low (from 11,000/mm3 to 35,000/mm3); circulating fibrin degradation products (FDP) were found to be raised in all patients. Severe neurological involvement was present in 3 of them. All patients required dialysis treatment. Defibrotide was administered by intravenous infusion at a dosage of 10 mg/kg/day. Treatment was started 16–28 h after admission, and was continued for an average of 14 days (range from 9 to 21). All patients showed a rapid decrease of circulating FDP associated with an increase in platelet count. Diuresis increased and serum creati-nine concentration decreased in 4 patients, with a complete recovery of renal function within 12–47 days. In the 5th patient, who presented severe neurological involvement and hypertension at the admission, Defibrotide administration was followed by a rapid disappearance of neurological manifestations, and normalization of

Renal Transplantation in Patients with Microscopic Polyarteritis and Antimyeloperoxidase Antibodies: Report of Three Cases

This paper reports on 3 patients on renal dialysis for crescentic glomerulonephritis associated with microscopic polyarteritis (MPA) and antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase (MPO-ANCAs). They successfully underwent renal transplantation from a cadaver donor 6-63 months after the onset of the disease, despite the persistence of antibodies at high titer. A triple immunosuppressive regimen including steroids, cyclosporin and azathioprine was used. One patient underwent transplantectomy for surgical complications 3 months later, while the serum creatinine was 2.0 mg/dl (178 mu mol/l): the remainder have a well-functioning graft after 21 and 38 months, no clinical sign of disease recurrence, and a MPO titer within the normal range. We conclude that MPA patients can undergo renal transplantation even if ANCAs persist at a high titer in the circulation.

Posttraumatic Chyluria Due to Lymphorenal Fistula Regressed after Somatostatin Therapy

A sudden-onset chyluria after trauma was evaluated giving evidence of a lymphatic-urinary fistula in the right kidney. Treatment with somatostatin normalized the urinary pattern and the result was maintained even after the discontinuation of the therapy.

Epidemiology of Hepatitis C in a Population of Hemodialysis Patients

A search for antibodies against hepatitis C virus (HCV) was performed in 185 patients on chronic hemodialysis by means of 1st and 2nd generation ELISA tests. Immunoblot assays were performed on positive sera. This study shows a 38% prevalence of HCV-positive patients in our dialysis population according to the 2nd generation ELISA test which shows a higher specificity and sensitivity when compared to the 1st generation one (38 vs. 20%). A correlation was found between the prevalence of HCV-positive patients and how long they had been on dialysis and how many blood transfusions they had received.

Validity of flow cytometry for cross-match evaluation in clinical renal transplantation.

This paper reports a 2-year experience of more than 5,000 cross-match tests for renal transplantation. Tests were performed by means of both standard light microscopy and an innovatory method based on flow cytometry, an up-to-date investigative technique for computerized analysis of individual cell characteristics. Flow cytometry allowed a better detection of weak positive reactions (false-negative cross-matches) than light microscopy, thus reducing the risk of selecting candidates with donor presensitization. Transplant clinical outcome supported the value of this original and advanced technological method.

Bone Remodelling after Renal Transplantation (RT)

With the recovery of the excretory and endocrine renal functions after successful Renal Transplantation (RT), renal bone disease also tends to disappear. Nonetheless, several new biochemical changes to the calcium-phosphorus metabolism (e.g. hypercalcemia, hypophosphatemia) may appear while bone histology may remain altered or show new lesions. Apart from scattered reports in the literature, the new bone remodelling that invariably occurs after RT has not been sufficiently investigated, above all as a possible source of overt clinical bone disease.