Distribution of alpha-chains of type IV collagen in glomerular basement membranes with ultrastructural alterations suggestive of Alport syndrome.

BACKGROUND: In Alport syndrome (AS) impaired production and/or assembly of col IV alpha-chain isoforms results in abnormal structure of glomerular basement membrane (GBM), haematuria and, frequently, progressive renal disease. We investigated the relationship between col IV alpha-chains expression and morphology of GBM, as a possible key to the better understanding of the pathogenesis of renal disease in AS. METHODS: GBM distribution of col IV alpha1-, alpha3-, and alpha5-chain was investigated by immunohistochemistry in 32 patients (21 males and 11 females, mean age at biopsy of 11.5 years) with ultrastructural findings suggestive of AS. Ten patients had a proven COL4A5 mutation. Based on the severity of ultrastructural findings, the biopsies were grouped in three (I-III) electron microscopy (EM) classes. Significant EM changes of GBM (thinning, thickening, splitting, basket weaving of the lamina densa) were singularly evaluated using a semiquantitative scale (0-3). RESULTS: Col IV alpha1-chain was demonstrated in GBM of all patients. Three patterns of staining for col IValpha3- and alpha5-chains were observed: positive, negative, and alpha3(IV)-positive/alpha5(IV)-negative. By chi(2)-test, EM class III lesions and complete loss of alpha3(IV)- and alpha5(IV)-antigen were significantly more frequent (P<0.05 and P<0.01) in male patients, but no significant relation was observed between EM classes and immunohistochemical patterns. GBM alterations did not correlate with staining for alpha5(IV)-chain. Intensity of alpha3(IV)-chain staining, however, had a negative correlation (P<0.05) with the severity of GBM basket weaving. CONCLUSIONS: Our results suggest that the alpha3(IV)-chain-containing col IV-network plays a fundamental role in structural and, possibly, functional organization of GBM. Absence of alpha3(IV)-chain in GBM could indicate a more severe renal disease in AS.

IgA serology in recurrent and non-recurrent IgA nephropathy after renal transplantation.

BACKGROUND: This study investigated whether abnormal circulation of macromolecular IgA and IgA with altered glycosylation or electrical charge plays a role in the recurrence of IgA nephropathy (IgAN) after transplantation. STUDY DESIGN: A total of 92 renal transplant patients were enrolled; 52 IgAN patients and 40 with other non-IgAN. The IgAN group included 10 patients showing IgA mesangial deposits in the grafted kidneys (recurrent group) and 10 who did not (immunohistochemically proven non-recurrent group). In addition another 22 IgAN transplant patients were clinically free of recurrent disease. METHODS: The analyses included macromolecular IgA (IgAIC) detected by the conglutinin assay (K), heavy IgA precipitated in 2.5% polyethylene glycol (PEG), IgA-fibronectin aggregates (IgA/F Aggr), mixed IgA/IgGIC, IgA binding to mesangial matrix components (fibronectin, laminin, type IV collagen) or polycations (poly-L-lysine) and IgA with altered glycosylation (Jacalin-binding assay). RESULTS: After transplantation, IgAN patients displayed significantly higher mean levels for each variable measured than non-IgAN (ANOVA, P < 0.05). By stepwise regression analysis, the binding of IgA to fibronectin had the highest coefficient. By comparing data in recurrent and clinically non-recurrent IgAN, we observed that two groups could be distinguished by the results of the two assays for macromolecular IgA (conglutinin IgAIC and IgA-fibronectin aggregates) and IgA with increased affinity for type IV collagen (P < 0.05). When the selected group of immunohistochemically proven non-recurrent IgAN was compared to the recurrent one, a statistically significant difference was found only for the binding of IgA to type IV collagen (P < 0.05). Data from this test were significantly related with proteinuria (P < 0.05) and microscopic haematuria (P < 0.04). CONCLUSIONS: Even though the IgA serology of renal transplant IgAN patients shows peculiar features and recurrent and non-recurrent IgAN differ in many aspects, the prevalence of positive data in the two groups had no predictive value. This suggests that the recurrence of IgAN is modulated by factors affecting the interaction between circulating abnormal IgA and mesangial cells and/or matrix.

[Dialysis treatments outside the hospital]. / I trattamenti dialitici extra-ospedalieri.

In the early sixties a dramatic lack of hospital dialysis facilities prompted the development of home dialysis programs. The same reasons favoured in Turin, several years later, the start of a home-dialysis program and of the first European self dialysis program in an out-of-hospital setting. In the following years continuous ambulatory peritoneal dialysis was begun. In the last few years we are experiencing a new shortening of in-hospital dialysis facilities; moreover, special attention is devoted to the costs of dialysis treatment, often overlooked in the past. It is likely that self-care and home dialysis will again aid us to solve these problems, as in the past. In this paper we report on the clinical, rehabilitative and socioeconomic results of out-of-hospital dialysis treatments, and on the possible future development of home-hemodialysis and CAPD in Piedmont.

[Informatics support and teledialysis]. / Supporto informatico e teledialisis.

Computer-assisted medical activity is increasing in several fields, with wide perspectives in nephrology and dialysis accounting for the peculiar characteristics of this population such as number, complexity, follow-up length and economic costs. Since 1980 we have been studying a computerized organization of our Region's departments in order to achieve 3 main results: 1) a registry of all patients undergoing dialysis in the area, with a one- a-year complete clinical update; 2) a computerized medical chart, which could gather all the clinical, technical and managerial aspects of the treatment; 3) a teledialysis program, to follow every session in local and remote stations. The first aim has been reached with useful information for the dialytic policy in the area. The second objective is ongoing with straight evidence of easy, speedy procedures, and accurate data collection. The third goal is on a preliminary phase looking at the safety, reliability and precision of the treatments. Informatic procedures seem to be quite advisable in improving as clinical surveillance of the patients, as technical and managerial aspects of dialysis units.

Colour-coded Doppler sonography in monitoring native kidney biopsies.

Two hundred and one patients had biopsies of their native kidneys with ultrasound-guided needle technique. They were evaluated on the second post-biopsy day with colour-coded Doppler sonography. Ten patients out of these 201 were found to have an arteriovenous fistula, which remained asymptomatic for the whole follow-up period (follow-ups ranged from 2 to 31 months). Four of these 10 patients developed a perirenal haematoma as well and five macroscopic haematuria. Our study shows that the systematic use of colour-coded Doppler sonography after renal biopsy facilitates diagnosis of arteriovenous renal fistula.

Membranous glomerulonephritis (MGN) in transplanted kidneys: morphologic investigation on 256 renal allografts.

Twenty-two cases of membraneous glomerulonephritis (MGN) were identified among 256 bioptically investigated transplanted patients. MGN was defined as de novo in 15 patients and recurrent in three. The type of MGN could not be ascertained with certainty in the other four. Several morphologic features unusual for the idiopathic form of MGN were found. Most cases disclosed focal segmental distribution of subepithelial deposits and showed the contemporaneous presence of different stages of the disease according to Ehrenreich and Churg classification. In addition mild-to-moderate mesangial cell proliferation was found in about one third of de novo MGN biopsies. Endocapillary hypercellularity was observed in 14 specimens and held to be due to an excess of mononuclear blood cells, related to a concomitant episode of rejection. Chronic transplant glomerulopathy was found in 47% of patients with de novo MGN and in 66% of those with recurrent MGN, being more frequently observed in specimens with diffuse distribution of deposits. Repeated biopsies showed progression of the stage and extension of deposits to a large number of capillary loops in four out of six patients. De novo MGN was documented 1 to 54 mo (mean value 20.2 mo) after transplantation, and the recurrence was observed after 12, 15, and 42 mo. All but two patients (who were anuric) complained of proteinuria, which was in the nephrotic range in 12. Apart from the significantly higher frequency in de novo MGN patients of DR4 antigen, whose significance must in any case be re-evaluated in a larger series, none of the factors so far suggested to be linked to the onset of de novo MGN has found further support in our study. On the contrary, relevance in favoring the appearance and the evolution of MGN has to be attributed to transplant glomerulopathy, which, moreover, seems to be more important than MGN itself in causing the unfavorable outcome of the graft.

Soluble interleukin-2 receptors and beta 2-microglobulin in patients with primary glomerulonephritis.

Serum levels of soluble interleukin-2 receptors (IL2R) and of beta 2-microglobulin (beta 2M) were studied with the immunoenzymatic technique in 38 patients with primary glomerulonephritis (GN), in 10 patients with essential hypertension (EH) and in 30 healthy subjects. IL2R correlated with beta 2M (p < 0.05). IL2R and beta 2M were higher in patients with GN (p < 0.003, p < 0.001, respectively) and in patients with EH (p < 0.003, p < 0.01, respectively) than in healthy subjects. IL2R and beta 2M correlated with serum creatinine, but not with proteinuria. Our data would suggest the existence of lymphocyte activation in patients with GN. Only speculations can be advanced with regard to the observed increase in these parameters in EH patients.

[Changes in cellular ion transport and arterial pressure in renal transplant recipients undergoing cyclosporin treatment]. / Alterazioni del trasporto ionico cellulare e pressione arteriosa nei portatori di trapianto renale in trattamento con ciclosporina.

Arterial hypertension is a common side effect of cyclosporine A (CyA). Aim of the study was to evaluate the activity of erythrocyte (RBC) Na transport in two groups of patients with a well functioning renal graft (Crs less than 1.7 mg/dl) treated by prednisone+azathioprine (10 pts), or prednisone+CyA (21 pts), in relationship with blood pressure status. Twenty-one age matched healthy subjects were studied as a control group. Na,K pump and Na,K cotransport were significantly lower in CyA than in AZA patients (2,184 +/- 106 vs 3,089 +/- 162 and 58 +/- 8 vs 187 +/- 28 mumol/l RBC/h: p less than 0.01), without differences between normotensive and hypertensive patients. Na,K pump efflux in normal subjects was 2334 +/- 66 mumol/l RBC/h (p less than 0.01 vs AZA), NA,K cotransport was 205 +/- 18 mumol/l RBC/h (p less than 0.01 vs CyA). Significant correlations were found between RBC Na,K pump activity and trough plasma CyA levels (p less than 0.02) and between systolic pressure and plasma creatinine in CyA patients (p less than 0.01). Trough plasma CyA levels were higher in hypertensive than in normotensive CyA patients (64 +/- 5 vs 46 +/- 4 ng/ml; p less than 0.01).

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 Wegener's 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.