Alba Vangelista

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.

Plasma exchange treatment improves prognosis of antineutrophil cytoplasmic antibody-associated crescentic glomerulonephritis: a case-control study in 26 patients from a single center.

Abstract:  Twenty‐six patients with Antineutrophil cytoplasmic antibody (ANCA)‐associated crescentic glomerulonephritis (GN) were divided into two groups according to the acute phase treatment: drug therapy consisting of steroids and oral cyclophosphamide plus a plasma exchange (PE) course (group A, 13 patients) or drug therapy alone (group B, 13 patients). Group A patients had a more severe clinical picture and higher serum creatinine than group B (12.7 ± 6.9 vs. 8.5 ± 5.3 mg%); nine patients from group A (69%) and five from group B (38%) required dialysis. At follow up (mean 35 months) all patients treated with PE were alive; four of them were in end‐stage renal disease. Among group B patients, three (23%) died in the acute phase; 6 (46%) needed renal replacement therapy at follow up. Of the dialysis‐dependent patients, five out of nine from group A were free of dialysis, while in group B two out of five patients had died, two had entered a regular dialysis treatment and one had received a cadaver graft. These data suggest  that  PE  may  significantly  improve  the  prognosis of patients with ANCA‐associated crescentic GN even if they are  not  dialysis‐dependent  at  the  time  of diagnosis.

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

Idiopathic Membranous Nephropathy in 2 Twin Brothers

Alba Vangelista, MD, Nephrology and Dialysis Department, St. Orsola University Hospital, Via Massarenti 9, I-40138 Bologna (Italy) Dear Sir, In a recent paper published in the June issue of Nephron , Sato et al. [1] described 2 adult brothers with idiopathic membranous nephropathy (IMN) and reviewed the reports on familial IMN published in the literature up until that time. We wish to describe 2 male children, identical twins, with IMN who developed simultaneously signs of renal disease at the age of 5 years. Case Reports Case 1 In September 1981 the child was admitted to the hospital because of the onset of gross hematuria after an attack of influenza. Proteinuria (1.5 g/24 h) and hypercholesterolemia (474 mg/dl) were also discovered. Serum creatinine was 0.4 mg/dl. Therapy with predni-sone 2 mg/kg/day for 4 weeks was followed by complete disappearance of laboratory abnormalities. Regular checks were carried out every 3 months, and everything was found to be normal. In June 1983 he presented a relapse of proteinuria (3.5 g/24 h) associated with peripheral edema. Case 2 This child also had influenza in September 1981, and laboratory examinations were carried out. A slight proteinuria (0.10 g/24 h) and microscopic hematuria were discovered. Serum creatinine was 0.5 mg/dl. Two months later he developed a full nephrotic syndrome which worsened under the same treatment schedule as previously used in his twin brother. After prednisone withdrawal the nephrotic syndrome gradually disappeared within 4 months. A relapse of the nephrotic syndrome occurred in May 1983. A renal biopsy was performed in the 2 children in June 1983. The diagnosis was stage II IMN in both of them (fig. 1). Immunofluorescence showed granular deposition of IgG and C3 along the capillary walls. On light microscopy glomeruli showed slight thickening of the basement membranes. Spikes were seen with silver methenamine stain. Electron microscopy revealed subepithelial deposits. Systemic lupus erythematosus, malignancy, diabetes mellitus, and exposure to glomerulotoxins or drugs were excluded. The HLA typing was A9 (23); 32; B35, blank; DR3, 5. After the pathological diagnosis prednisone was started again only in case 1 and continued for 6 months until the disappearance of proteinuria. Case 2 was treated only with symptomatic therapy. He showed a spontaneous remission of proteinuria within 4 months.

DEFIBROTIDE TREATMENT AND DISEASE PROGRESSION IN PATIENTS WITH IGA NEPHROPATHY AND IMPAIRED RENAL FUNCTION AT DIAGNOSIS

SummaryDefibrotide is an antithrombotic agent that is capable of increasing the synthesis and release of prostaglandin I2 from endothelial cells, and improving fibrinolysis. The aim of this study was to evaluate the effectiveness of defibrotide therapy in slowing down the rate of progression of immunoglobulin (Ig) A nephropathy in patients with impaired renal function at diagnosis. 20 such patients were randomised to receive either prednisolone for 6 months plus defibrotide for 2 years (group A) or a 6-month prednisolone course only (group B). No significant difference was found at baseline between the two groups with regard to renal function, daily protein excretion or renal histological lesions. After 24 months, patients in group A had a mean decrease in serum creatinine level of 14%, compared with a 9% increase observed in group B (p = 0.007). A 14% increase in creatinine clearance occurred in group A patients as opposed to a 12% decrease in group B (p = 0.003). Daily protein excretion was significantly reduced in group A relative to baseline (p = 0.02), while it did not change in group B. These results suggest that nonimmunological factors are important in the progression of IgA nephropathy and that drugs that improve renal haemodynamics can contribute to the maintenance of renal function.

Flow cytometry evaluation of urinary sediment in renal transplantation

The value of exfoliative urinary cytology for the diagnosis of different pathological conditions in renal transplantation is widely recognized. The method, however, has not yet gained full acceptance, mainly because identification of the different cells is not always possible by means of standard staining techniques. In view of its characteristics, flow cytometry (FC) seems to represent a consistently reliable, rapid and innovative approach for differentialing the various cells present in the urinary sediment and assessing their number. This study gives the examination result of 223 urinary specimens from 127 transplanted patients selected according to pathology. Sediment cells, collected from fresh urine samples, were washed, treated with a lysing solution, resuspended in saline solution and directly analysed in a FACSCAN cytometer. Morphological evaluation showed: a small number of cells in patients with stable renal function; a larger number of cells, with predominance of lymphocytes, during acute rejection episodes; an absolute predominance of neutrophils during bacterial infection; large-sized cellular debris in cases of post-transplant tubular necrosis; and small cell debris in cases of cyclosporine cytotoxicity. Lymphocyte surface-marker evaluation made it possible to differentiate lymphocyte populations observed during acute rejection episodes (cytotoxic T-cell, CD8 and HLA class II and NK cells) from those detected during bacterial infection (T-cell CD4 positive). These results suggest that urinary FC may be a reliable diagnostic tool in clinical renal transplantation.

Long Term Clinical and Morphological Evaluation of Acute Renal Failure

Acute Renal Failure(ARF)is a severe clinical event characterized by a sudden reduction in renal function.This apparently well defined condition may be the result of different etiological and pathogenetic mechanims which largely determine the type of renal lesions and influence the immediate outcome and long-term prognosis.

Kidney, Patient and New Millennium Nephrology

The way nephrology develops in the new millennium is bound to be affected by changes in the nephrologist’s clinical environment, as well as by the progress made in basic research which will need to find a clinical application. The nephrologist can expect to be more and more involved in renal substitution therapy, not just providing the treatment, but also managing the cost of the service. In the field of nephropathology, the highest expectations surround molecular biology and its application to both acquired and hereditary renal disease; the goal is to find an outlet for gene therapy in clinical practice. Artificial substitution therapy will focus chiefly on the project of ‘intelligent dialysis’, whereby biological and diagnostic components are combined according the specific needs of the individual patient. The ideal scenario for renal transplantation in the coming millennium would be one where donor supply matches the demand (xenotransplant?), where immunomodulation is perfected, and where diagnoses are based on precise biomolecular events observed in real time.

Vasculitis and the kidney.

The term “vasculitis” denotes a heterogeneous group of diseases characterized by inflammation and necrosis of blood vessels and a variable clinical picture, according to the organs or tissues mainly involved by the vasculitic lesions.