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.

Microalbuminuria in single kidney patients: relationship with protein intake.

Experimental models have shown that the reduction in renal mass induces an increase in glomerular filtration rate of the remnant nephrons, leading to proteinuria and glomerular sclerosis. Since the presence of microalbuminuria - increased urinary albumin excretion (UAE) undetectable by routine assays - can be an early sign of this phenomenon, UAE in the normo- and microalbuminuric range was measured in 24 single kidney patients with negative Albustix. Nephrectomy had been performed in 22 cases 1 to 28 years before, mostly because of renal lithiasis. Patients were selected as being normotensive, normoglycemic and free of recurrent urinary infections or stones. On regular diet (mean protein intake 1.2 g/kg/day), UAE mean values were significantly higher in single kidney patients than in 20 controls both in supine position during overnight rest (clinostatism) (37.71 +/- 56.32 vs 2.56 +/- 2.27 micrograms/min, p less than 0.001) and in erect position during moderate physical effort (orthostatism) (67.31 +/- 86.12 vs 4.59 +/- 5.73 micrograms/min, p less than 0.004). Microalbuminuria was observed in 18/24 single kidney patients in clinostatism and 15/24 in orthostatism. A subgroup of 14 patients was also studied on different protein dietetic regimens. After one month on a 0.6 g/kg/day protein containing diet, UAE mean levels significantly decreased in comparison to those found on regular diet (clinostatism: 26.15 +/- 35.93 vs 49.24 +/- 70.29 micrograms/min, p less than 0.02; orthostatism: 31.73 +/- 46.97 vs 68.92 +/- 83.53 micrograms/min, p less than 0.001). One month after a 1.6 g/kg/day protein diet UAE mean values significantly increased (clinostatism 83.99 +/- 88.04 micrograms/min, p less than 0.001; orthostatism: 117.19 +/- 116.12 micrograms/min, p less than 0.001). Our data indicate that microalbuminuria, detectable in the majority of patients with a single kidney, can be modulated by different protein intakes.

Mediterranean diet and primary IgA nephropathy.

Since IgA nephropathy can be experimentally induced by alimentary antigens, mechanisms of oral immunization might be supposed also in human primary IgA nephropathy (PIgAGN). IgA immune complexes (IgAIC) are thought to play a major role in PIgAGN, hence this parameter was monitored in six PIgAGN patients subjected to diets excluding gluten, meat or eggs respectively and selected as having persistent urinary activity and high IgAIC levels. On gluten-free diet IgAIC significantly decreased over 3 different periods of 10 days (Student's t-test p 1 less than 0.03, Rank-Signed test p 2 less than 0.02), 1 month (p 1 less than 0.007, p 2 less than 0.02) and 6 months (p 1 less than 0.05, p 2 less than 0.02). IgAIC significantly increased again on a gluten containing diet over 1 month (p 1 less than 0.008, p 2 less than 0.04) and 3 months (p 1 less than 0.02, p 2 less than 0.04). After 6 months on a gluten-free diet, all patients had normal IgAIC values and decreased IgA2 subclass-IgAIC, in agreement with the hypothesis of withdrawal of an antigen challenging the mucosal immune system. These data indicate a relationship between a gluten-containing diet and high levels of IgAIC in PIgAGN patients, suggesting that dietetic factors might play a role in the different geographical distribution of this nephropathy.

Circulating immune complexes containing IgA, IgG and IgM in patients with primary IgA nephropathy and with Henoch-Schoenlein nephritis. Correlation with clinical and histologic signs of activity.

A new conglutinin solid phase assay for the detection of immune complexes containing IgA (IgAIC) and other conglutinin tests for immune complexes containing IgG and IgM (IgGIC and IgMIC) were used in studies on 34 patients affected by Berger's GN (92 sera) and 12 affected by Henoch-Schoenlein GN (61 sera). Thirty-six patients were observed over follow-up periods of 2-43 months. Levels of IgAIC in both groups of patients were significantly higher than those in healthy people. The values obtained in patients with Henoch-Schoenlein GN were statistically higher than those obtained in patients with Berger's GN. Moreover, IgAIC were frequently found to be associated with IgGIC and/or IgMIC. In both groups of patients, the IgAIC levels were significantly correlated with the presence of signs of clinical and histological activity such as the magnitude of microscopic hematuria, a past history of macroscopic hematuria and the percentage of glomeruli with florid epithelial crescents.

The use of Mallory's phosphotungstic acid-hematoxilin (PTAH) stain in renal pathology.

High quality histology is needed in renal biopsy examination, especially when material for immunofluorescence and/or electron microscopy is not available. For these purposes Mallory PTAH stain was tried on 34 renal biopsies and the results were compared with the immunofluorescent and ultrastructural findings (used as a control of the reliability of the method). PTAH, besides showing extracellular structures, cytological details and rather subtle abnormalities, was able to detect the presence and the site of deposits. PTAH stains the material which appears as electron dense deposits in electron microscopy and as granular deposits in immunofluorescence, whereas it fails to stain linear deposits in immunofluorescence (which are not electron dense). Moreover, a good correspondence between PTAH and electron microscopic data was detected as far as the location of deposits is concerned.

Plasma exchange in progressive primary IgA nephropathy.

Five patients with progressive primary IgA nephropathy (PIgAGN) were treated by plasma-exchange (PE) combined with immunosuppressive drugs. Circulating IgA-containing immune complexes (IgAIC), detected by a specific conglutinin solid phase assay, were monitored. Two patients with acute nephritic syndrome and rapidly progressing course, crescent formations and high levels of IgAIC had substantial lasting clinical improvement after several PE, with a fall in IgAIC levels. Another rapidly progressive case with marked sclerotic changes and a longer history of nephritic syndrome, but with normal levels of IgAIC, did not show any clinical improvement after PE. Two patients with a PIgAGN diagnosed several years before and presenting slowly evolutive course had no substantial clinical benefit from PE treatment. IgAIC levels, very high before PE temporarily decreased, but returned to the previous values after the end of the treatment. We conclude that PE combined with immunosuppressive treatment may be of clinical benefit for cases with acute nephritic syndrome of recent onset who still have high levels of IgAIC, even when important crescent formations are present.

[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).

[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.

Correlation of paramesangial deposits and glomerular sclerosis and/or hyalinosis in patients with IgA nephropathy.

Correlation of paramesangial deposits ("hemispherical body") and glomerular sclerosis and/or hyalinosis was examined by light microscopical analysis in 40 patients of IgA nephropathy. Correlation of paramesangial deposits and intensity of IgA or C3 deposition in glomeruli was also evaluated in these patients. The number of paramesangial deposits was markedly increased in patients with moderate and advanced stages of IgA nephropathy who showed marked glomerular sclerosis and/or hyalinosis. There was a significant correlation between the number of paramesangial deposits and the intensity of IgA deposits in glomeruli. It is suggested that the accumulation of paramesangial deposits might induce severe glomerular injuries such as glomerular sclerosis and/or hyalinosis.

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.

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.

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.

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.

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.

Quantitative and functional analysis of IgG Fc receptor molecules in polymorphonuclear leukocytes and monocyte macrophages in patients with essential mixed cryoglobulinaemia.

In order to gain insight into the role of IgG Fc receptors in essential mixed cryoglobulinaemia (EMC), we analyzed quantitatively the expression of such molecules on polymorphonuclear leukocytes (PMN) and assessed them, functionally, on PMN, tissue macrophages and circulating monocytes in 6 HLA-B8-, DR3-negative patients with EMC and glomerulonephritis. The Fc receptors expressed on PMN surface, as estimated by using AB 8.28 monoclonal antibody to PMN Fc receptor and 125I-labelled rabbit F(ab')2 fragments to mouse IgG as detecting system, were found to be quantitatively normal in EMC patients, whereas PMN Fc- receptor-mediated phagocytosis was reduced. Moreover, the patients were found to have prolonged macrophage clearance of IgG-sensitized autologous erythrocytes and reduced kinetics of ingestion of IgG-coated material by circulating monocytes. This impairment of Fc receptor function may play a remarkable role in the tissue localization of immune material in this disease.

IgA1 and IgA2 immune complexes in primary IgA nephropathy and Henoch-Schönlein nephritis.

The distribution of IgA subclasses in IgA immune complexes (IgA IC) in sera of patients with primary IgA glomerulonephritis and Henoch-Schönlein purpura nephritis was analysed. High levels of IgA IC containing both IgA1 and IgA2 subclasses were present in correlation with the phases of clinical activity. In these nephropathies the finding of IgA subclass distribution in IgA IC similar to that found in secretions may add further support to the hypothesis that IgA IC are of mucosal origin, albeit a primary derangement of the humoral immune system in these patients cannot be disregarded.