Bruno Basolo

Hepatitis C virus infection and membranous glomerulonephritis.

Cristiana Rollino, MD, Divisione di Nefrologia e Dialisi, Ospedale Giovanni Bosco, Piazza del Donatore di Sangue 3, I-10154 Torino (Italy) Dear Sir, Chronic hepatitis B virus (HBV) infection is known to be associated with membranous glomerulonephritis (MGN), where it represents one of the etiologic factors identified up to now [1]. The frequency of association varies according to different authors and is particularly high in childhood [2]. HBs, HBe and HBc antigens have been identified in subepithelial deposits [3–5]. Whether other forms of hepatitis can also be associated with this nephropathy is still unknown. As new tests for the detection of anti-hepatitis C virus antibodies (HCV-Abs) have become available recently, we looked for a possible association between HCV and MGN. We tested sera of 27 adult patients (16 males, 11 females; mean age 49.8 ± 12.2 years) with biopsy-proven MGN. None of them exhibited systemic lupus erythe-matosus, diabetes mellitus, syphilis, malignancy or exposure to heavy metals or drugs known to induce MGN. HBV antigen and antibody were negative in all the patients. The presence of HCV-Abs was evaluated by the enzyme-linked immunosorbent assay ‘Abbott HCV EIA’, which employs a recombinant antigen of HCV. The neutralizing confirmatory Abbott test was used to bear out the positive results. Only 1 of 27 patients showed the presence of HCV-Abs in several sera; this result was corroborated by the confirmatory test. The onset of MGN in this patient occurred in July 1989. At the time of the admittance to our nephrology department (April 1990), laboratory investigations showed slight elevation of serum transaminases; alkaline phosphatase and prothrombin time were within the normal range, proteinuria was 4,400 mg/24 h, and renal function was normal. The patient was given a treatment with 3 × 1 g methylprednisolone pulses followed by oral prednisone 25 mg daily for 1 month and by chlorambucil 10 mg daily for the next month. The treatment was repeated 3 times and lasted on the whole 6 months [6]. At the end of the therapy, complete remission of the nephropathy (proteinuria 0.2 g/day) was achieved and transaminases were within the normal range. The relationship between hepatitis and occurrence of the nephrotic syndrome is not simply defined. At the time of the admittance to our department, we probably might have observed a late

Plasmapheresis in a Patient with Rapidly Progressive Idiopathic IgA Nephropathy: Removal of IgA-Containing Circulating Immune Complexes and Clinical Recovery

Primary IgA nephropathy is generally considered a benign disease, but progression to renal failure is not uncommon and a rapidly progressive course is observed in some cases, especially when extensive epithelial crescents are present. Circulating IgA-containing immune complexes (IgAIC) seem to play the most important pathogenetical role, hence the authors adopted plasmapheretic treatment in association with immunosuppressive drugs for 1 patient affected by primary IgA nephritis, with florid crescents and progressive renal failure. IgAIC decreased significantly after each plasma exchange and finally returned to normal values; over the same period urinary protein loss and heavy microscopic hematuria gradually disappeared and renal function was completely recovered.

Monoclonal Gammopathy and Glomerulonephritis With Organized Microtubular Deposits

We report a case with IgG-kappa monoclonal gammopathy of unidentified significance (MGUS) and glomerulonephritis (GN) with organized microtubular deposits on electron microscopy (EM). Light microscopy (LM) examination showed exudative features and moderate extracapillary proliferation. An acute nephritic syndrome with a rapidly progressive renal failure was clinically manifest at the onset and during each relapse. The patient was treated with methylprednisolone pulses followed by oral prednisone, cyclophosphamide, plasmapheresis, and maintenance courses of chemotherapy. The response to treatment was good, with a temporary improvement of renal function and control of the downhill course over a 3-year follow-up.

A Case of Recurrent Proliferative Glomerulonephritis with Monoclonal IgG Deposits after Kidney Transplant Treated with Plasmapheresis

Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a rare and recently identified disease with a poor prognosis irrespective of the treatment. Recently, the possibility of recurrent or de novo PGNMID after kidney transplantation has been reported, which is associated with a better prognosis compared to PGNMID on native kidneys. Nevertheless, at present, due to the very few cases of recurrent PGNMID diagnosed, there is no proven effective treatment. Here, we report a case of recurrent PGNMID successfully treated with plasmapheresis, steroids and mycophenolate mofetil. Our report suggests that plasmapheresis might be a valid therapeutic option to treat recurrent PGNMID.

Single kidney function: Effect of acute protein and water loading on microalbuminuria

The hyperfiltration induced by an acute response to an oral protein and water load was investigated to ascertain whether it can modify the urinary albumin excretion (UAE) in the microalbuminuric range by further increasing the glomerular filter permeability. To this end, six patients with a single kidney selected as having microalbuminuria on a regular diet without the clinical or laboratory data of overt renal disease and eight healthy subjects received a short-term protein and water load (150 g of meat-derived protein and 1 liter of water). In patients with one kidney, mean basal UAE values were significantly higher than in control subjects (p less than 0.006), whereas endogenous creatinine clearance values were only slightly lower (p greater than 0.05). One hour after the protein and water load, an abrupt increase in microalbuminuria levels was found in patients with one kidney and mean UAE values were significantly higher than in control subjects (p less than 0.002), whereas mean creatinine clearance values were significantly lower in patients than in control subjects (p less than 0.01). High UAE (p less than 0.002) and low creatinine clearance (p less than 0.002) values were maintained over the following four hours in patients with one kidney. These data suggest that in the single kidney with reduced renal functional reserve, an oral protein and water load magnifies the pre-existing loss of glomerular permselective properties due to chronic hyperfiltration as manifested by a further increase in microalbuminuria.

Rituximab therapy for IgA-vasculitis with nephritis: a case series and review of the literature.

Henoch–Schonlein purpura, also called IgA-vasculitis, is a systemic small vessels vasculitis with immunoglobulin A1-dominant immune deposits. The optimal treatment remains controversial. Because IgA-vasculitis is characterized by leukocyte infiltration of the blood vessel walls along with immunoglobulin A deposition, and because glucocorticosteroids inhibit inflammatory processes, early administration of glucocorticosteroids has been postulated to be effective, but this indication remains controversial. Immunosuppressive agents (azathioprine, cyclophosphamide, cyclosporine, mycophenolate) have been used in combination with glucocorticosteroids without definitive evidence of effectiveness. The efficacy of rituximab in adult IgA-vasculitis has been reported in few cases. We described a monocentric experience on the use of rituximab in adult IgA-vasculitis with biopsy-proven nephritis. The patients achieved a complete remission of nephritis and syndromic manifestations, and no patients experienced adverse reactions. These data have been compared with the limited literature nowadays available.

Small frameshift deletions within the COL4A5 gene in juvenile-onset Alport syndrome.

Small frameshift deletions within the COL4A5 gene were identified in three Alport syndrome Italian families by non-isotopic single-strand conformation polymorphism (SSCP) screening: in family RMA, a 7-bp deletion (GGGTGAA) in exon 39; in family DGR, a 4-bp deletion (TGGA) in exon 41; in family MIB, deletion of a G in exon 50. The phenotype was characterized by juvenile-onset renal failure with sensorineural hearing loss in males, and a milder clinical pattern in heterozygous females.

Failure to Relate Mononuclear Phagocyte System Function to HLA-A, B, C, DR, DQ Antigens in Membranous Nephropathy

Nineteen patients with idiopathic membranous nephropathy were typed for HLA pattern and analyzed for the Fc receptor function of splenic macrophages by detecting in vivo the clearance of IgG-sensitized 51Cr-labelled autologous erythrocytes. Seven out of 19 patients were found to have a macrophage dysfunction. This defect was not related to any HLA-A, B, C, DR, DQ antigen tested nor to the levels of IgG-containing immune complexes, as detected by a Clq solid phase test, nor to the magnitude of proteinuria. Since HLA-B8 and HLA-DR3 antigens were significantly more frequent in patients than in the control group, the factors that may impair the macrophage system in individuals predisposed to this nephropathy are discussed.

Classic and Perinuclear Anti-Neutrophil Cytoplasm Antibodies and Antimyeloperoxidase Antibodies in Rapidly Progressive Glomerulonephritis

Classic anti-neutrophil cytoplasm antibodies (cANCA), perinuclear ANCA (pANCA) and antibodies directed against myeloperoxidase (MPO-Ab) were evaluated in 25 patients with either idiopathic or secondary rapidly progressive glomerulonephritis (RPGN). While cANCA were found almost exclusively in Wegeners granulomatosis, pANCA were detectable in several disorders, including microscopic polyarteritis (mPA), but also idiopathic RPGN. MPO-Ab were frequently found in sera from patients with all types of idiopathic but not of secondary RPGN. These results support the hypothesis that some cases of RPGN are early or limited forms of systematic vasculitis. We then looked for the presence of IgA-ANCA in Henoch-Schoenlein purpura (HSP): we found IgA-ANCA with immunoenzymatic assay but not with immunofluorescence in HSP, in primary IgA-GN and in membranous GN as well, thus suggesting the poor specificity of this type of ANCA. The possible pathologic implications of ANCA were examined in vitro. Serum samples from several patients with ANCA were assessed for their capacity to enhance chemiluminescence generation from resting or PMA-stimulated macrophages. Sera from RPGN and mPA patients displaying anti-MPO activity induced granulocytes to enhance the production of oxygen free radicals, thus suggesting a phlogistic effect of MPO-Ab positive sera.

Ineffectiveness of phenytoin treatment on IgA-containing circulating immune complexes in IgA nephropathy.

Ineffectiveness of Phenytoin Treatment on IgA-Containing Circulating Immune Complexes in IgA Nephropathy R. Coppo B. Basolo M.R. Bulzomi G. Piccoli R. Coppo, B. Basolo, M. R. Bulzomi, G. Piccoli, Cattedra di Nefrologia Medica, dell’Università di Torino, Divisione di Nefrologia e Dialisi, Nuova Astanteria Martini, Largo Gottardo 143, I-10153 Torino (Italy) Dear Sir, After the first report [1] indicating that in patients affected with IgA nephropathy, phenytoin selectively decreases serum IgA – especially polymeric IgA – levels, leading to a reduction in the number of episodes of macroscopic hematuria and in some cases a decrease in the amount of IgA deposits, a recent trial reported by Clarkson et al. [2] failed to find any significant influence of this treatment on the clinical and histological course of this nephropathy. Since immunological studies from our group [3] and others [4] in agreement with recent experimental models [5, 6] suggest a primary role for IgA-containing circulating immune complexes (IgAIC) in Berger’s and Henoch-Schönlein’s glomerulonephritis (GN), we would like to comment the data we obtained by monitoring IgAIC detected by a modified conglutinin solidphase assay [3], in two groups of patients: one (3 Berger’s GN and 2 Henoch-Schönlein’s GN) treated with phenytoin (300 mg/day for 8–14 months), and the other (3 Berger’s GN and 2 Henoch-Schönlein’s GN) without any treatment (control group). In the group of patients treated with phenytoin, we observed (table I), as early as 3 months after treatment was started, a significant reduction in mean serum IgA levels (p < 0.05). The IgA concentration decreased by 24.8% after 3 months and by 31.4% at the end of the follow-up. No significant fluctuations were observed in the control group. A slight reduction in mean polymeric IgA values -detected by the reduction-alkylation test [7] – was observed from the beginning to the end of the follow-up (p < O.l), and was particularly evident in 3 of 5 cases who initially showed high values of polymeric IgA. The IgA-containing immune complex levels showed a slight, although not significant (p > O.l), decrease from the beginning to the end of the follow-up in both groups of patients, with and without treatment (table I). No correlation was found between IgA levels and IgAIC values (r0.17, p > O.l). Fig. 1. G.B. ♂ 23 year old, affected with Berger’s GN ( ). After 3 months of phenytoin treatment, total IgA and polymeric IgA decreased, whereas IgAIC increased concomitantly with the appearance of gross hematuria. Z.V. ♂ 19 year old, affected with Henoch-Schönlein’s GN ( ). During phenytoin treatment, IgAIC initially decreased, but rose again concomitantly with gross hematuria even though a decrease in total IgA and polymeric IgA had been obtained. In 2 cases on phenytoin (1 Berger’s GN and 1 Henoch-Schönlein’s GN) gross hematuria was observed: the IgAIC levels were very high, albeit a decrease in total IgA and polymeric IgA was