Assessment of detached podocytes in the Bowman's space as a marker of disease activity in lupus nephritis.

Podocyte damage is an important pathogenic component of glomerular disease progression. This study is a trial to clarify the value of counting and scoring the number of shed Bowman's space podocytes as an activity parameter of lupus nephritis, a trial that has not been conducted before. This study was performed on 42 female patients with the clinical diagnosis of lupus nephritis. Beside the routine stains tissue sections were stained by colloidal iron and anti podocalyxin for sialomucin. Podocytes in the Bowman's space were counted and scored. Thorough statistical work was carried out to correlate the podocyte scores with the morphological lesions of lupus nephritis. This study revealed significant association and correlation of shed Bowman's space podocytes with histopathological parameters of activity in different classes of lupus nephritis. We concluded that counting and scoring shed Bowman's space podocytes is statistically significant as a marker of disease activity in lupus nephritis. It can be one of the parameters of activity index but not of chronicity index.

Impact of clinical and histopathological factors on outcome of Egyptian patients with crescentic glomerulonephritis.

This study included 128 patients with crescentic glomerulonephritis (CGN) having sufficient clinical and histopathological data and were followed up in our institute for a mean period of 34 +/- 28 months. There were 49 males and 79 females with mean age 22.7 +/- 14 years. We studied the effect of clinical, laboratory and histopathological parameters on kidney function and patient survival at the end point of the study. The multivariate analysis revealed that serum creatinine at presentation, nephrotic range proteinuria during the follow up period, percentage of glomeruli affected by crescents, percentage of fibrous crescents and absence of cellular infiltration were significant risk factors affecting the kidney function at termination of the study. The only risk factor which correlated significantly with the patient mortality was the serum creatinine at last follows up.

Clinical significance and long-term evolution of minimal change histopathologic variants and of IGM nephropathy among Egyptians.

In children, the most frequent idiopathic nephrotic syndrome is minimal change nephrotic syndrome (MCNS). Typically, MCNS shows no abnormalities by light microscopy: "nil disease". Beside this classic picture, there are other minor light microscopic abnormalities which are considered as MCNS variants. Our 172 MCNS patients were divided into a nil disease group, two groups of MCNS variants (mild mesangial hypercellularity and mild mesangial thickening) and a fourth group with normal light microscopy and diffuse IgM deposition (IgM nephropathy group). The relation of this fourth group to MCNS is controversial in the literature. Age and serum creatinine were significantly different in the four histologic groups (P=0.03 for age and 0.047 for serum creatinine). Comparing the groups in pairs, it appeared that these significant differences were due to significantly higher age and serum creatinine in the mild mesangial hypercellularity group than in the IgM nephropathy group (P = 0.02 for age and 0.01 for serum creatinine). The groups were similar as regards follow-up creatinine clearance and early and late steroid response. We concluded that mild mesangial hypercellularity may differ from other MCNS forms as regards age at presentation and renal function. We also suggest that IgM nephropathy with normal light microscopy is similar to MCNS.

Helicobacter pylori and uremic gastritis: a histopathologic study and a correlation with endoscopic and bacteriologic findings.

In this work 70 asymptomatic uremic patients under maintenance hemodialysis in our institution underwent upper-gastrointestinal endoscopy as part of a routine investigation prior to kidney transplantation. Their endoscopic findings were scored and antral mucosal biopsies were obtained and subjected to histopathologic and bacteriologic assessment. Bacteriologic examination included culture, rapid urease test, and microscopic examination for detection of Helicobacter pylori. Histopathologic examination of the gastric mucosa showed chronic superficial gastritis in 52%, atrophic gastritis in 5.7% and intestinal metaplasia in 37% of the cases. Of the cases with superficial gastritis, 5 showed in addition gastric mucosal dysplastic changes. There was no correlation between the histopathologic and endoscopic findings. Nevertheless, there was a significant association between histopathologic changes and H. pylori infection (p = 0.0001). All cases with atrophic gastritis showed H. pylori, and of 24 cases with chronic active superficial gastritis. H. pylori was detected in 18, while it was detected in only 2 of 13 cases with chronic inactive superficial gastritis and in 4 of 29 cases with normal antral mucosal biopsies. Among different variables in dialysis patients, only patients' ages were found to have significant association with H. pylori infection (p < 0.03). We have concluded that in asymptomatic uremic patients under maintenance hemodialysis, relying only on endoscopy for critical assessment of the upper gastrointestinal tract is unsatisfactory and histopathologic examination of the antral mucosal biopsies is mandatory. Chronic superficial gastritis and atrophic gastritis should be expected in up to 60% of the patients, and there is a strong association between H. pylori infection and gastritis.

Schistosoma mansoni hepatic fibrosis in Syrian golden hamsters: effect of dose and duration of infection as shown by immunohistopathological studies.

In this work, 180 Syrian golden hamsters were infected with Schistosoma mansoni and 30 cross matched for age and sex served as control. Infected hamsters were divided into six main groups according to the number of infected cercariae (20, 50, 100, 150, 200 and 250 cercariae). Each group was sub-divided into 5 subgroups, according to the duration of infection after which animals were sacrificed (4, 6, 8, 12 and 24 weeks). Control and infected hamsters were subjected to laboratory evaluation of serum albumin, S. globulin and A/G ratio and histopathological examination of the liver and splenic tissues. A significant reduction of albumin was observed in Schistosma infected hamster (50 cercariae or more) but not in the control ones and those infected with 20 cercariae. There was a significant correlation between these changes and the duration of infection and the number of adult worms recovered from the mesenteric circulation at the end of the experiments. Histopathologic evaluation showed appearance of the circulating schistosome antigens, circulating anodic antigen (CAA), and circulating cathodic antigen (CCA) deposits in the liver by the 14th week after infection; liver granuloma, amyloid deposits, fibrosis, Schistosma pigments as well as inflammatory infiltration was observed at 8-12th week and amyloid deposits, CAA & CCA in the spleen was observed nearly at the same time.

Effect of anti-schistosomal treatment on schistosomal hepatic pathology: an experimental study in Syrian golden hamsters.

Thirty Syrian golden hamsters were infected with Schistosoma mansoni and 10 were used as negative controls. Hamsters were infected by 100 cercariae; 15 were treated by praziquantel in doses of 100 mg/kg at 12, 13, 14 and 15 weeks postinfection, and 15 hamsters were left as positive control. Five from each subgroup were sacrificed at 24, 28 and 32 weeks after infection. Animals were subjected to weekly analysis for total plasma protein, serum albumin and urinary total protein excretion. At the end point, animals were sacrificed and the mesenteric venous plexus was explored for adult worms. Liver and splenic specimens were examined by light microscopy, and immunofluorescence microscopy. Complete parasite eradication was achieved in the treated animals. Although, there were significantly higher plasma total protein and albumin in the treated group, there was no significant differences in proteinuria. Histopathological examination of liver specimens showed highly significant reduction of granulomas, CAA and CCA, while amyeloid deposition showed minimal reduction in treated animals. Histopathological examination of splenic specimens showed highly significant reduction of fibrosis, granulomas, CAA and CCA, while follicular hyperplasia and amyeloid deposition showed non significant reduction.

Infectious glomerulopathy induced by a defined agent (Schistosoma mansoni): progression despite early elimination of the causal agent.

Thirty Syrian golden hamsters were infected with Schistosoma mansoni and 10 were used as negative controls. Hamsters were infected by 50 cercaria; 15 were treated by praziquantil in doses of 100 mg/kg at 12, 13, 14 and 15 weeks postinfection, and 15 hamsters were left as positive control. Five from each subgroup were sacrificed at 24, 28 and 32 weeks postinfection. Animals were subjected to weekly analysis for total plasma protein, serum creatinine, albumin, cholesterol, 24-hour urine volume, and urinary total protein excretion. At the end point, animals were sacrificed and the mesenteric venous plexus was explored for adult worms. Kidney and liver specimens were examined by light microscopy, immunofluorescence microscopy, and electron microscopy. Complete parasite eradication was achieved in treated animals. Although there were significantly higher plasma total protein, albumin, and lower cholesterol in the treated group, there were no significant differences in proteinuria or renal histopathologic changes between treated and untreated animals. We conclude that in golden hamsters, with complete and early parasite eradication no regression occurs in S. mansoni-related nephropathy. Moreover, we suggest that in this glomerulopathy, short exposure to an antigen may be sufficient to set in motion a cascade of events which is irreversible and which leads to permanent glomerular damage.

Study of asymptomatic microscopic hematuria in potential living related kidney donors.

Thirty potential living related kidney donors with asymptomatic microscopic hematuria of nonsurgical causes were entered in this study. They underwent thorough history taking, medical and ENT examination, laboratory and radiologic assessment and pure-tone audiometry. Family members were also subjected to urine analysis and audiometry. Moreover, the 30 donors were subjected to kidney biopsies which were examined by light microscopy, direct and indirect immunofluorescent microscopy, and electron microscopy. Hereditary nephritis (with or without sensorineural deafness) was found to be the most common cause of asymptomatic microscopic hematuria (25/30), followed by isolated C3 deposits disease (3/30), IgA nephropathy (1/30) and IgM nephropathy (1/30). Since these disease conditions are of a progressive nature, we have concluded that relatives of uremic patients with asymptomatic microscopic hematuria should not be considered for kidney donation even if they are strongly motivated.

Urological complications following live donor kidney transplantation: effect of urinary schistosomiasis.

Urological complications were studied in 310 live donor kidney transplants. All recipients and donors were investigated for urinary schistosomiasis by examining tissue obtained intra-operatively from the donor's ureter or the patient's bladder. Schistosomiasis was histologically documented in 76 cases (patient's bladder (46), donor's ureter (9), both (21)). The incidence of urological complications was 11/76 (15%) in the schistosomal group and 14/234 (6%) in the non-schistosomal group; this was statistically significant. Among the schistosomal patients, the site of infestation had no statistically significant effect on the incidence of urological complications. No deaths or graft losses were directly attributable either to these complications or to their surgical correction.

Effects of schistosomiasis on living kidney donors.

Twenty living kidney donors with schistosomiasis were compared with 20 uninfected donors for a mean follow-up period of 42 months (range 12-62). All patients with schistosomiasis had been treated preoperatively with antischistosomal chemotherapy. None of the donors developed any appreciable change in mean systolic or diastolic blood pressure during the follow-up period, though one infected and two uninfected donors had traces of protein in the urine. One uninfected donor developed microscopic haematuria. The two groups has similar reductions in renal function after unilateral nephrectomy. The response of the remaining kidneys to a combined infusion of dopamine and an amino acid preparation was similar in both groups. One infected and two uninfected donors were found to have developed mild hydroureter and hydronephrosis on excretory urography. Schistosomiasis did not significantly affect compensatory hypertrophy of the remaining kidney. We conclude that uncomplicated schistosomiasis in living kidney donors does not adversely affect either the function or the morphology of the remaining kidney, at least during an observation period of up to five years. Schistosomal infection does not seem to alter the adaptive changes in the remaining kidney, provided that the donor had functionally and morphologically intact kidneys and that the schistosomiasis was treated before kidney donation. Longer term evaluation is recommended, however, to confirm the validity of these observations.

Impact of schistosomiasis on patient and graft outcome after kidney transplantation.

In this work the impact of schistosomiasis on kidney transplantation was investigated by comparing two groups of patients, group 1 (Schistosoma-infected cases) and group 2 (control cases). In group 1, schistosomiasis was diagnosed in both donor and recipient in 63 cases, in recipient only in 65 cases, and in donor only in eight cases. Schistosomal infection among kidney transplant recipients was S. haematobium in 17 cases, S. mansoni in 58 cases, and mixed in 53 cases. Schistosomiasis was diagnosed by finding Schistosoma eggs in urine, stools, rectal mucosal biopsy, recipient bladder mucosal biopsy, or in the donor ureter obtained during surgery. Patients and donors with active lesions were treated at least 3 weeks before transplantation by the antischistosomal drugs praziquantel and oxamniquine. Follow-up after kidney transplantation showed no significant difference between the two groups regarding the incidence of acute and chronic rejection. Nevertheless, dose of cyclosporin, HBs antigenaemia, incidence of urinary tract infection, renal stones, ureteric stricture, and urinary leakage were significantly greater among schistosomal patients when compared to control cases. Schistosomal reinfection was observed in 23% of cases at high risk. Antischistosomal treatment did not affect the graft function. We have concluded that schistosomiasis may affect the outcome of kidney transplantation.

Schistosoma haematobium-induced glomerular disease: an experimental study in the golden hamster.

Information regarding glomerular lesions related to Schistosoma haematobium infection in man or animal are extremely lacking and disputed. The objective of this experimental study was to investigate glomerular lesions in S. haematobium-infected golden hamsters. In this work, 53 hamsters were infected with S. haematobium cercariae and 18 animals of similar age and sex served as controls. Hamsters were infected either with 50, 200, 300, 400 or 600 cercariae and sacrified after 8, 9, 10, 14, 18, 24 or 32 weeks. Infected and control hamsters were subjected to laboratory examinations including serum creatinine, serum albumin, total protein, serum cholesterol, total urine protein as well as histopathologic evaluations. Kidney biopsies were examined by light microscopy, indirect immunofluorescence and by electron microscopy. Significant proteinuria, hypoalbuminaemia and hypercholesterolaemia were observed in all but 5 S. haematobium-infected, but in none of the control hamsters. Renal impairment was observed in 5 hamsters. Histopathologic evaluations showed IgG, circulating anodic antigen and circulating cathodic antigen deposits in the renal glomeruli. By electron-microscopic examination, these deposits were seen mainly in the subendothelial, mesangial and paramesangial areas. Amyloid deposits were also seen in the renal glomeruli, tubular basement membrane and in the interstitium. A correlation was found between the extent of amyloid deposition and the duration but not the intensity of schistosomal infection. We have concluded that S. haematobium infection can lead to glomerulopathy in golden hamsters.

A prospective, randomized therapeutic trial for schistosomal specific nephropathy.

In this work 26 patients with schistosomal specific nephropathy were randomly distributed among three groups. Group I cases were given anti-schistosomal drugs (oxamniquine and praziquantel), group II cases were given anti-schistosomal drugs plus prednisolone, and group III cases were given anti-schistosomal drugs plus cyclosporine. The schistosomal specificity of kidney lesions was assessed by detecting the schistosomal specific antigens (CAA and CCA) and antibodies deposited in the renal glomeruli of these patients. Patients who had another etiologic cause which may explain their kidney disease were not admitted to this study. After initiation of the treatment, patients were followed up every other week in the outpatient clinic for 12 months. Follow-up showed complete remission of proteinuria in two cases in group II (duration of remission was 4 and 8 months) and in one case in group III (duration of remission was 6 months) but in none in group I. Partial remission was observed in one case in group I, in three cases in group II and in one case in group III. During the observation period, improvement in kidney function was observed in two cases in group II but deterioration in kidney function was observed in one case in group I and in one other case in group III. We conclude that in patients with schistosomal nephropathy, none of the tried therapeutic regimens produce regression of the disease if given to patients with established disease.

Peripheral blood morphology: could it be of value in prediction and diagnosis of renal allograft rejection?

Forty kidney transplant recipients were examined twice weekly during the first postoperative month and once weekly during the second month and whenever graft rejection was suspected. Fine-needle aspiration biopsies (FNAB) of the graft and examination of the peripheral blood for changes in different cell population were performed. Furthermore, to study the predictive value of peripheral blood examination for diagnosis of graft rejection another 30 patients were subjected to daily peripheral blood examination after transplantation during the first postoperative month. The sensitivity of peripheral blood examination to diagnose rejection was found to be 53.8% and the specificity was 81% while the predictive value was 75%. We conclude that peripheral blood examination is an additional beneficial test for diagnosis of graft rejection.

Effect of anti-schistosomal treatment on schistosomal-specific nephropathy.

Twenty-one patients with schistosomal-specific nephropathy (18 nephrotics and three with non-nephrotic proteinuria) were given anti-schistosomal treatment (oxamniquine and praziquantel). The schistosomal specificity of the kidney lesions was assessed by the detection of schistosomal-specific antigens (CAA and CCA) and antibodies deposited in the renal glomeruli of these patients. After anti-schistosomal treatment, the patients were followed for clinical and laboratory changes occurring within 12 months. In addition, 15 patients had a second kidney biopsy and the histopathological and the immunopathological findings were compared with those observed in the first biopsy. Based on clinical, laboratory and histopathological evaluations, none of the patients subjected to the study showed regression of the kidney lesion following antischistosomal treatment; in fact three patients showed progression in their lesions, one of them reaching end-stage renal failure. The histopathology of these three cases was focal segmental glomerulosclerosis. Our data suggest that anti-schistosomal treatment in an established disease state, will not produce remission.

Characterisation of kidney lesions in early schistosomal-specific nephropathy.

In this work 42 patients with active Schistosoma mansoni infection and renal involvement were examined. Of these, 16 had asymptomatic proteinuria (group I) and 26 had the nephrotic syndrome (group II). Fifteen nonschistosomal patients with idiopathic nephrotic syndrome were included as control cases (group III). Renal biopsy specimens were obtained from all patients and controls. These were examined by light microscopy (LM), by direct immunofluorescence microscopy using antisera against human IgG, IgM, IgA, C3, C4, C1q, and fibrinogen, and by indirect immunofluorescence microscopy using monoclonal antibodies directed against the circulating schistosome antigens, circulating anodic antigen (CCA) and circulating cathodic antigen (CCA). Schistosomal-specific deposits were seen in the renal glomeruli in 24 of the 42 schistosomal patients but in none of the 15 control patients. Although schistosomal-specific deposits were seen in seven of the 16 patients presenting with asymptomatic proteinuria, no morphological changes could be seen by LM. On the other hand, schistosomal-specific deposits could be seen in the kidneys of 17 of the 26 patients presenting with the nephrotic syndrome. All but one specimen showed morphological changes when examined by LM. These were consistent with mesangioproliferative glomerulonephritis in seven, focal segmental glomerulosclerosis in five, mesangiocapillary glomerulonephritis in two, membranous glomerulonephritis in one, and focal segmental hyalinosis in one patient. The present study clearly suggests that (a) schistosomal-specific nephropathy does exist in human settings, (b) it is an immune complex disease, and (c) CAA and CCA are major responsible antigens.

Schistosomal specific nephropathy leading to end-stage renal failure.

In this study 17 patients, 11 with end-stage renal failure and six with nephrotic syndrome were selected. The selection criteria were presence of active intestinal schistosomiasis and absence of any surgical or other medical disease which could explain the renal disease. When examined by light microscopy, kidney biopsies showed membranoproliferative glomerulonephritis in nine, membranous in four, focal segmental glomerulosclerosis in two, sclerosing glomerulonephritis in one case, and no changes in another case. Direct immunofluorescence showed IgG deposits in 13 cases, IgM in 10 and different complement components (C3, C1q) in eight cases. Eluates from the kidney biopsies of the 17 schistosomal as well as six control cases were examined by ELISA against schistosoma mansoni adult worm antigen (AWA). This test showed the presence of antibodies against the AWA in 12 out of 17 of the schistosomal cases, and zero out of six of the controls. When examined by direct IFA using sheep anti-circulating anodic antigen/FITC and by indirect IFA using monoclonal antischistosomal CAA IgG3, kidney biopsies of the ELISA positive cases showed granular deposits of circulating anodic antigen (CAA). We conclude that schistosomal specific nephropathy does exist in the clinical settings and can lead to end-stage renal disease, with CAA probably being a major responsible antigen.