The value of proliferating cell nuclear antigen (PCNA)/cyclin in the assessment of cell proliferation in glomerulonephritis.

Proliferating cell nuclear antigen (PCNA)/cyclin is an acidic nuclear protein increasing from the late G1 to S phases of the cell cycle and whose detection parallels other standard methods for assessing cell proliferation. The aim of this study was to investigate PCNA expression in normal and diseased human kidneys, in order to clarify cell proliferation in renal tissue and to define a possible correlation of its expression with various types of glomerulonephritis (GN). The immunohistochemical avidin-biotin complex (ABC) method was used for the demonstration of PCNA applying the monoclonal antibody PC-10 to paraffin sections from: 10 normal kidneys, 55 renal biopsies with various types of proliferative GN (PGN), 44 renal biopsies with various types of non proliferative GN (NPGN). In PCNA-positive renal biopsies with GN the antigen showed a heterogenous nuclear expression in occasional or few mesangial and glomerular epithelial cells as well as in a greater number of tubular epithelial cells. PCNA was expressed in 20% of normal kidneys and in 38% of renal biopsies with GN. The frequency of PCNA expression was significantly increased in the cases of PGN (47%) compared to that observed in the cases of NPGN (27%) (p = 0.03). PCNA was detected in 10/24 cases of IgA nephropathy, in 3/4 cases of IgM nephropathy, in 5/14 of other types of primary PGN and in 8/13 of secondary PGN. PCNA expression was not correlated with the degree of mesangial cellularity in PGN. Moreover, there was no significant difference in PCNA expression between primary and secondary PGN. PCNA demonstrated an intense expression in the majority of epithelial cells forming cellular crescents in 8/11 cases of PGN. In conclusion, PCNA was observed more frequently in diseased than in normal kidneys. The significant increase in the frequency of PCNA intraglomerular expression in PGN suggests that PCNA has a certain value in the assessment of mesangial proliferation. Moreover, the increased PCNA expression in tubular epithelial cells especially in PGN, indicates their proliferative state and may be correlated with their proposed activation and role in the progression of renal injury.

HLA antigens in microscopic polyarteritis (MP) with renal involvement.

Serological HLA-A, B, C, DR and DQ typing was performed in 23 patients with microscopic polyarteritis and renal involvement and in 405 healthy individuals, all of Greek origin. An increased frequency of HLA-A26 (26% vs. 11.3%, x2 = 4.423, p < 0.05) and HLA-A11 (26% vs. 9.6%, x2 = 6.825, P < 0.02), and a decreased frequency of HLA-DR3 (4.3% vs. 24.1%, x2 = 5.935, p < 0.025) were found. Five out of six patients, who did not respond to treatment possessed HLA-DR5. These observations suggest that HLA gene products may influence the clinical expression, as well as the outcome of this disease.

Lower urinary tract reconstruction in association with renal transplantation.

Congenital or acquired dysfunction of the lower urinary tract may result in renal failure. In this group of patients urinary diversion or lower urinary tract reconstruction is mandatory prior to renal transplantation. Avoiding creation of an external stoma offers far more better quality of life to these unfortunate patients. We present three patients in end-stage renal disease. Two of them presented with dysfunction of the lower urinary tract and the third with absence of the bladder. Reconstruction or substitution of their bladders has been performed prior to kidney transplantation. In one patient an artificial urinary sphincter was implanted simultaneously in order to achieve continence, while all the patients have to empty their neobladders or augmented bladders by clean intermittent self-catheterization. In conclusion, dysfunction or absence of the lower urinary tract does not preclude renal transplantation and however abnormal the urinary tract, transplantation can still be performed if low-pressure, high-compliance reservoir can be achieved by means of augmentation or substitution cystoplasty.

Expression of bcl-2 oncoprotein in various types of glomerulonephritis and renal allografts.

BACKGROUND: Bcl-2 oncogene was identified as a transcript associated with the t (14;18) and exhibits the unique functional role of blocking apoptosis. Apoptosis as a remodelling mechanism has been reported to embryonic and adult kidney. The aim of this study was to investigate the expression of bcl-2 protein in normal and diseased renal tissue and to define any correlation with the type of renal injury. MATERIALS AND METHODS: Our material comprised of 10 normal adult kidneys, 31 renal allografts with acute (22) and chronic (9) rejection, and 70 renal biopsies with various types of primary (49) (31 proliferative and 18 non-proliferative) and secondary (21) glomerulonephritis. The immunohistochemical strept.ABC method was performed on paraffin sections for the detection of bcl-2 protein with a monoclonal antibody after microwave pretreatment. RESULTS: Bcl-2 protein was detected in all the cases of normal and diseased renal tissue, showing an analogous expression. The antigen was expressed in a few parietal epithelial cells, and in the majority of distal and collecting tubular epithelial cells, but not in the glomerular capillary tuft. No difference was found in bcl-2 expression between cases of proliferative and non-proliferative glomerulonephritis as a whole, or between primary and secondary glomerulonephritis. Bcl-2 expression in acute and chronic rejection demonstrated a similar cytoarchitectural expression to the one observed in normal kidneys and glomerulonephritis. Bcl-2 was detected in podocytes near intraglomerular fibrotic lesions and in epithelial cells of early adhesions and cellular crescents, wherever observed in cases of glomerulonephritis. However, bcl-2 expression in proximal tubular epithelial cells was significantly higher in cases of proliferative glomerulonephritis than in non-proliferative glomerulonephritis (P<0.01), while bcl-2 expression in parietal epithelial cells in cases of chronic rejection was higher than in cases of acute rejection (P<0.08). CONCLUSIONS: The absence of bcl-2 expression in normal and diseased glomeruli suggests and supports the reported notion that the mechanism of apoptosis may be available in the injured glomerulus. Moreover, bcl-2 expression in podocytes near intraglomerular fibrotic lesions and in epithelial cells of early adhesions and cellular crescents indicates the deregulation of apoptosis and its possible role in the progression of glomerular scarring. Key words: apoptosis; bcl-2 oncoprotein; glomerulonephritis; immunohistochemical; renal rejection.

The frequency of hepatitis B virus infection in Greek patients with various types of glomerulonephritis.

The frequency of hepatitis B surface antigen (HBsAg) was studied in the sera of 622 patients with glomerulonephritis (GN). The prevalence of HBs-antigenemia was 2.8% (18/622; eleven adults and seven children); the difference from 2.6% in the general population of Central and Southern Greece was not statistically significant (chi 2 = 0.01; p > 0.50). Two of the 11 HBsAg-seropositive adult patients with GN suffered from IgA nephropathy, one from IgA and membranous glomerulonephritis (MGN), four from diffuse proliferative GN, two from membranous GN and one each from crescentic GN and focal segmental glomerulosclerosis. Five children out of 12 with membranous glomerulonephritis, one out of 24 with IgA nephropathy and one out of 16 with focal segmental glomerulosclerosis had HBs-antigenemia. The frequency of HBs-antigenemia in children with MGN was 41.7%, which is significantly higher than in children with other types of GN (0.9%). All seropositive patients were asymptomatic HBsAg carriers, while one seropositive HBsAg child with MGN suffered from chronic persistent hepatitis. HBsAg was detected by the immunoperoxidase-antiperoxidase (PAP) method in the glomeruli of only 3 children with MGN and HBs antigenemia, while HBcAg was not detected in any case. Our study suggests that in the Greek population there is no increased prevalence of HBs-antigenemia in patients with glomerulonephritis. Moreover, HBsAg was not found to contribute in the pathogenesis of GN in adults but it may be associated with the pathogenesis of membranous GN in children.

Immunohistochemical study of epidermal growth factor receptor (EGFR) in various types of renal injury.

Epidermal growth factor (EGF), a polypeptide with a potent mitogen activity, and its receptor [EGFR] have been previously identified in the kidney, but their expression in normal and diseased kidneys has not been fully elucidated. In order to evaluate EGFR in various histological types of renal injury, EGFR expression was studied by the immunohistochemical avidin-biotin complex (ABC) method with a monoclonal antibody EGFR1 on paraffin sections from 10 normal kidneys, 56 renal biopsies with various types of glomerulonephritis (GN), and 20 renal grafts with rejection. EGFR expression was observed in (a) 3 of 10 (30%) normal kidneys, (b) 17 of 39 (43.6%) renal biopsies with various types of GN mainly in membranous GN (57%) and in focal segmental glomerulosclerosis (FSG) (62.5%), (c) 6 of 17 (35.3%) biopsies with various types of systemic lupus erythematosus GN, and (d) 12 of 20 (60%) renal grafts with acute (42.9%) and chronic (69.2%) rejection. EGFR was mainly localized to the epithelial cells of the distal and collecting tubules and extraglomelar vessels, while it was observed less frequently in parietal epithelial cells and along glomerular basement membranes. Notably EGFR was detected in the epithelial cells adjacent to adhesions with Bowman's capsule and in the connective tissue of fibrocellular crescents. In conclusion, EGFR expression was observed more frequently in diseased than in normal kidneys. The increased incidence of EGFR expression in FSG, in chronic rejection, in small adhesions with Bowman's capsule and fibrocellular crescents suggest that EGF/EGFR may be correlated with a disturbed extracellular matrix production resulting in formation of early sclerotic lesions.

Hepatitis C virus infection among Greek renal transplant patients.

In this study, the prevalence of hepatitis C virus (HCV) infection among renal transplant recipients was high, directly proportional to the haemodialysis time before transplant and inversely proportional to the time after this. There was evidence of previous infection with hepatitis B virus (HBV), and a high prevalence of abnormal liver function tests. Virus induced chronic hepatitis lesions were rare, probably as a result of immunosuppression.

Antibodies against hepatitis C virus among renal transplant patients in Greece.

To evaluate the prevalence of hepatitis C virus (HCV) infection in Greek renal transplant (RT) patients and its association with abnormal liver function tests (LFTs), serum anti-HCV was determined (Ortho-ELISA test system) in 206 RT and 245 haemodialysis patients (HD) as controls. The prevalence (10.2%) of anti-HCV in RT patients was significantly higher (P < 0.0001) than in the Greek general population (0.7%) and lower (P < 0.0001) than in the HD patients (23.8%), and was not related to the patients' age, post-transplant time or pre-transplant HD time. None of the anti-HCV RT patients was HBsAg+, whereas 13 (62%) and 12 (57%) of them were anti-HBsAg+ and anti-HBc+, respectively. The incidence of abnormal LFTs in anti-HCV+ HBsAg- and anti-HCV- HBsAg+ RT patients was similar. Our findings indicate that: (a) the prevalence of serum anti-HCV in the Greek RT population is high, although considerably lower than in HD pts; (b) anti-HCV+ RT patients have a high incidence of abnormal LFTs, comparable to that seen in HBsAg+ RT patients; and (c) in a substantial proportion of anti-HCV+ RT patients there is evidence of previous HBV infection.

Multiple hepatocellular tumours in a patient treated with oral contraceptives.

A case of multiple hepatic tumours in a patient treated for four years with high doses of oral contraceptives is described. Solitary hepatocellular lesions associated with conventional doses of oral contraceptives have been reported previously in twenty nine cases. Haemorrhage has been a common mode of presentation and is attributed to the marked vascularity of the lesions, an appearance referred to as peliosis hepatis. Radiographic studies show this term to be inappropriate as the vessels are of arterial origin. Another finding not previously reported is the presence of diffuse hyperplasia in the non-tumourous parts of the liver.