Glomerulonephritis in disadvantaged populations.

Glomerulonephritis (GN) still enjoys a high rank as a cause of chronic kidney disease (CKD) worldwide. Its burden is particularly manifest in disadvantaged populations, with a proportional contribution up to 6-folds compared to that in the USA. There are several overlapping risk factors that render a particular population "disadvantaged" in this respect. It is envisaged that these may be categorized into a triad of genetic, climatic and socioeconomic factors. An attempt is made to dissect the impact of each of these factors, which combine in different proportions in different populations thereby explaining regional disparity in the epidemiology, clinical manifestations and outcomes of CKD. The genetic impact is manifest in racial variations in the incidence of GN as a whole, the predominance of FSGS mainly in blacks and IgA nephropathy in Asians, the increased susceptibility to SLE and decreased incidence of IgAN and vasculitis in blacks, with similar trends in other "subraces" as Indians, Afro-Caribbean's, Martinique and other indigenous populations. The climatic impact is mainly displayed in the tropics, where the "rich bioecological environment" increases the incidence of infection-associated GN, usually proliferative with a few exceptions. The socioeconomic impact, reflecting low national economy in the developing world, modifies the two other arms of the triad according to the level of primary care, efficiency of the referral system and adequate management of primary infections as well as associated glomerular injury.

Health-related quality of life in emotionally related kidney transplantation: deductions from a comparative study.

The health related quality of life (HRQOL) has not been compared between live related and un-related donations. We set out to assess the HRQOL in 52 recipients and compare them to 68 HD patients using the Karnofsky performance status scale. Statistical package for social sciences (SPSS) was used for data analysis. The duration of end-stage renal disease was 7.14 + 3.8 years and 5.30 + 4.15 years for transplant and HD patients respectively. The HRQOL was similar in both living and emotionally related recipients but both were significantly better than that of HD patients (P < 0.0001). There was significant negative correlation between HRQOL and age (r = -0.363, P < 0.0001), serum creatinine (r = -0.502, P = 0.0001), serum urea (r = -0.493, P < 0.0001), serum phosphate (r = -0.363, P = 0.003) and calcium-phosphate product (r = -0.305, P < 0.0001). There was significant positive correlation between HRQOL and haemoglobin (r = +0.495, P < 0.0001) and serum calcium (r = +0.247, P = 0.017). Age of the patients appears to be the most important determinant of HRQOL in the studied population. HRQOL was similar in the related and unrelated donors and was better than in hemodialysis patients.

Spectrum of glomerulonephritis in egypt.

Identification of the profile of glomerular disease in a particular geographical region is of fundamental academic, clinical and epidemiological importance. It helps in the recognition of specific risk factors and subsequent planning for adequate prevention. In the present study, 1234 consecutive renal biopsies referred to the nephropathology team of Cairo University over two years were retrospectively analyzed. The main indications for biopsy included nephrotic syndrome, persistent sub-nephrotic proteinuria, recurrent hematuria, suspected secondary hypertension, lupus nephritis and acute and chronic renal failure of undetermined etiology. Proliferative forms of glomerulonephritis [GN] (32.1%) and focal and segmental glomerulosclerosis [FSGS] were the most prevalent lesions among patients with the nephrotic syndrome (22.6%). In subjects with sub-nephrotic proteinuria, FSGS was the principal lesion followed by proliferative lesions. Although all forms of GN were encountered in those presenting with recurrent hematuria, mesangioproliferative GN and FSGS were significantly more frequent. IgA glomerular deposits were detected in 9.8% of all GNs and 15% of those presenting with hematuria. One half of the biopsies obtained for the assessment of suspected secondary hypertension showed only changes compatible with the effect of hypertension per se, i.e. nephroangiosclerosis. On the other hand, a parenchymal renal lesion was found in 52.9% of biopsies. The common glomerular pathologies in patients with lupus nephritis were Classes III and IV. Among patients with chronic renal failure, the predominant lesion was chronic interstitial nephritis (32.6%). An acute interstitial inflammatory element was also detected in 8.4% of cases. About one third of the biopsies obtained for acute renal failure showed acute tubular (11%) or cortical (13.2%) necrosis. Another third showed vasculitis (17.6%) or acute interstitial nephritis (14.3%), and the remaining showed chronic lesions in which the rapid deterioration was probably functional.

The acute effect of intravenously administered recombinant human erythropoietin on the immune response of uremic patients maintained on regular hemodialysis.

The uremic patient on regular hemodialysis (RHD) is subjected to a wide range of immune modulators including the uremic state per se, multiple transfusions and exposure to bioincompatible materials and endotoxins. Erythropoietin (EPO) therapy may raise concern about its potential influence on this complex scenario. To envisage this issue, 15 adequately selected patients, stable on RHD, were randomly assigned in a 2:1 ratio into EPO and placebo groups. After initial assessment and determination of baseline values, they received, in a double-blind manner, either EPO or normal saline as an intravenous bolus immediately after termination of dialysis for 30 successive sessions. Thirty minutes later, following sessions 1, 10, 20, and 30, samples were obtained for determination of blood counts, red cell indices, peripheral lymphocyte counts (PLC), CD4/CD8 ratios, blood EPO levels, and serum concentrations of interleukins (IL) IL-2r, IL-3, and IL-6, tumor necrosis factor (TNFs and TNFalpha), and neopterin (NPT). Blood EPO levels displayed the predicted rise in the EPO group, which correlated with partial improvement of red cell parameters. The mean total leukocyte count and PLCs was significantly increased in the EPO group (p < 0.05) but not in the placebo group. CD4/CD8 ratios were not significantly changed in either group. The serum concentrations of IL-2r, IL-3, and NPT remained fairly stable while that of IL-6 was widely variable in both study groups. The mean serum concentrations of TNF and particularly TNFalpha showed a steady and statistically significant increment in the EPO group from 6 to 41 pg/ml (p < 0.05) and 93 to 128 pg/ml (p < 0.03), respectively. No significant change was noticed in the control group. It is concluded that intravenous administration of EPO under the conditions of this study may have an immune stimulating effect. This is shown by the release of TNFs, which in turn may be responsible, through different potential mechanisms, for the increase in the mean peripheral neutrophil count and the blunting of erythroid responsiveness to EPO therapy.

Immunoglobulin-A and the pathogenesis of schistosomal glomerulopathy.

Several observations suggest that the evolution of schistosomal glomerulopathy into clinically overt and progressive disease may involve pathogenetic mechanisms other than simple glomerular deposition of parasitic antigens. In a previous study, IgA was suggested to be a mediator of late glomerular lesions in this disease. This issue is further addressed in this work. The study includes 32 patients with hepatosplenic schistosomiasis, of whom 16 had overt glomerular involvement, along with four control groups: (a) 15 healthy volunteers; (b) 15 patients with simple intestinal mansoniasis; (c) 17 patients with non-schistosomal chronic liver disease; and (d) 21 subjects with primary nephrotic syndrome not associated with schistosomiasis. Routine assessment was done for all subjects including confirmatory tests for schistosomal infection, liver and renal function tests, hepatitis viral markers and abdominal ultrasonography. The total serum concentrations of IgG, IgM, IgA were measured, as well as their respective circulating immune complexes, rheumatoid factors, anti-gliadin- and anti-DNA-antibodies. Liver and renal biopsies were obtained from the relevant groups and studied by light microscopy. Renal biopsies were also examined by immunofluorescence. Patients with simple intestinal schistosomiasis had a significant increase in IgM antigliadin antibodies. Those complicated with hepatosplenic involvement also had a significant increase in the mean IgG anti-gliadin antibodies, IgG rheumatoid factor and IgM anti-DNA activity. Cases further complicated by overt glomerular disease showed a distinct IgA predominance, mainly expressed in the serum anti-gliadin antibody pool and anti-DNA activity. This profile was essentially similar to that observed in control cirrhotics. There was a significant increase in the frequency of IgA glomerular deposits in renal biopsies obtained from patients with overt schistosomal glomerulopathy, in contrast to control nephrotics. The deposits were mainly mesangial, but were also encountered in subendothelial, subepithelial and peritubular locations. Their frequency was significantly higher with more advanced lesions as seen by light microscopy. The relevance of these data is discussed, leading to the following conclusions: (a) serum IgA-anti-gliadin and -anti-DNA antibodies, and glomerular IgA deposits are markers of significant renal involvement in patients with hepatosplenic schistosomiasis. (b) IgA may be involved in the pathogenesis of advanced glomerular pathology when superimposed on parasite-induced lesions. (c) There is a significant increase in serum auto-reactivity in hepatosplenic schistosomiasis, which may also have pathogentic implications. (d) Increased production by the inflammatory bowel lesions, impaired clearance by the fibrotic livers and probable switching of immunoglobulin synthesis are suggested to explain the observed IgA predominance in those who develop renal complications.

Use of the low-dose desferrioxamine test to diagnose and differentiate between patients with aluminium-related bone disease, increased risk for aluminium toxicity, or aluminium overload.

BACKGROUND: Aiming at a safe method in the diagnosis of aluminium-related bone disease (ARBD)/aluminium overload the low-dose desferrioxamine (DFO) test was developed. In a multicentre study histological and histochemical data and aluminium bulk analysis of bone biopsies of 77 dialysis patients were correlated with the results of both the 5 mg/kg and 10 mg/kg DFO tests. METHODS: ARBD was considered to be present when > 15% of the bone surface was positively stained for aluminium and the bone formation rate was below 220 microns 2/mm2/day. Patients in which the Aluminon staining was positive (> 0%) were considered at an increased risk for aluminium toxicity independent of the type of renal osteodystrophy. Patients were considered aluminium overloaded when the bone aluminium content was > 15 micrograms/g wet weight and/or the Aluminon staining was positive (> 0%). RESULTS: Using the proposed criteria 15 patients were found to have ARBD; 13 of them presenting with a serum iPTH below 150 ng/l. In conjunction with an iPTH measurement the DFO test had a more than acceptable sensitivity and specificity in the diagnosis of ARBD. The test was considered positive when a post-DFO serum aluminium increment (delta sA1) above 50 micrograms/l (5 mg/kg) or 70 micrograms/l (10 mg/kg) together with a serum iPTH below 150 ng/l was found. Using these cut-off levels the 5 and 10 mg/kg tests in the diagnosis of ARBD had a sensitivity of 87% and a specificity of 95% and 92% respectively whereas the predictive value for a positive test for the population under study was 80% (5 mg/kg). Not a single patient with a serum iPTH > 650 ng/l had a positive staining (> 0%) even when the bone aluminium level was elevated (> 15 micrograms/g wet weight). In the detection of patients at risk for aluminium toxicity delta sA1 thresholds of 50 micrograms/l (5 mg/kg) and 70 micrograms/l (10 mg/kg) in combination with a serum iPTH < 650 ng/l had a sensitivity of 92% and specificity of 86% and 84% respectively. In the clinical setting of aluminium overload, threshold delta sA1 levels of 50 micrograms/l (5 mg/kg) and 70 micrograms/l (10 mg/kg) had a sensitivity of 91% and a specificity of 95% and 90% respectively. CONCLUSIONS: The low-dose DFO test is a reliable test for the detection of aluminium overload; however, it is not specific enough to differentiate between ARBD, increased risk of aluminium toxicity, and aluminium overload unless it is used in combination with a serum iPTH measurement. In conjunction with a serum iPTH measurement it is an important tool in the differential diagnosis and may avoid the necessity of a bone biopsy in the majority of patients. Data obtained in the present study have allowed us to update the strategies for monitoring, diagnosis and patient follow-up proposed at the Consensus Conference on Diagnosis and Treatment of Aluminium Overload in End-Stage Renal Failure; Paris, 1992.

Renal transplantation in a developing country: the Egyptian 17 year experience

This article addresses some of the major epidemiological; clinical; financial and social issues related to the practice of renal transplantation in Egypt. It highlights the limited availability facing the tremendous need for this line of treatment. It provides an overview of the transplant activity in the country; with a brief description of the medical and surgical protocols generally adopted by most groups. As a representative sample; the results of treatment of the Cairo Kidney Centre are given; emphasising the importance of local ecological factors in modifying the outcome; expressed as short and long term patient and graft survival. The effects of the high prevalence of 6 infective agents are described; including cytomegalovirus (CMV); Hepatitis B and C viruses; salmonellosis; tuberculosis and schistosomiasis. [abstract terminated]

Hepatic macrophage function in schistosomal glomerulopathy.

Hepatic fibrosis in the pathogenesis of schistosomal glomerulopathy cannot be explained by any positive influence of hepatocellular injury. In order to examine the potential role of impairment of hepatic macrophage function, the t1/2 plasma clearance of 99mTc-sulphur colloid was studied in 30 patients with schistosomal glomerulopathy, ten normal volunteers, ten cases of uncomplicated intestinal schistosomiasis, ten non-schistosomal cirrhotic patients and ten non-schistosomal nephrotic patients. Liver and renal biopsies were obtained from appropriate groups and examined by light microscopy and glomerular immunofluorescence. There was a significant correlation between t1/2 of sulphur colloid clearance and proteinuria, mesangial hypercellularity, and predominance of IgA glomerular deposits. These data indicate that hepatic macrophage dysfunction is an important factor in the pathogenesis of schistosomal glomerulopathy, and that IgA plays a major role in advanced glomerular lesions. The degree of impairment of hepatic macrophage function may influence the pattern and severity of glomerular lesions depending upon the affection of IgA clearance mechanisms.

Schistosomal glomerulopathy: selection factors.

Of several hundreds of millions of people infested with schistosomiasis, only a few hundreds have, so far, been documented to have one or other of the three schistosoma-associated immune-mediated glomerulopathies, namely proliferative glomerulonephritis, focal and segmental sclerosis, and amyloidosis. Regardless of undoubted under-reporting, some factors must be involved in the selection of those who develop such glomerulopathies. On the basis of experimental and clinical evidence, this review highlights the importance of parasitic species, associated salmonellosis, genetic predisposition and impaired hepatic macrophage activity. It also discusses the potential pathogenic role of the prevailing parasite 'strains', intensity of infestation, associated infections with hepatitis B, and common urinary pathogens and impairment of hepatocellular function. Selection ultimately seems to be multifactorial, but there is evidence that inefficiency of the hepatic macrophage system plays a key role by allowing both schistosomal antigens and IgA polymers to escape hepatic clearance and/or modulation.

Serum gastrin in chronic renal failure: morphological and physiological correlations.

Elevated serum gastrin (SG) has been reported in chronic renal failure (CRF). We studied SG levels in relation to various humoral and gastroduodenal histopathologic findings in 20 controls, 12 uremics under conservative therapy (CT), 27 patients on regular dialysis (RDT) and 8 transplanted patients (Tx). SG and parathyroid hormone (PTH) levels were estimated by radioimmunoassay (RIA), in addition serum BUN, creatinine, Ca++PO4---and alkaline phosphatase (predialysis in RDT) were determined. 20 patients (12 on CT and 8 on RDT) underwent pentagastrin (PG) stimulation test and upper gastrointestinal endoscopy with biopsy of gastric and duodenal mucosa. The mucosal samples were stained for mucopolysaccharides (MPS), nucleic acid (NA) and alkaline phosphatase (AP), and divided into intense, normal or faint staining. Mean SG was 688.71 pg/ml (CT cases), 636.2 pg/ml (RDT cases) and 280.6 pg/ml (Tx cases), all values being significantly higher than controls (118.46 pg/ml). SG level had a linear correlation with serum creatinine in CT patients and predialysis creatinine in RDT patients, but not with other parameters studied (BUN, Ca++,PTH,PO4---AP). The incidence of gastroduodenal erosions (40%) had a significant negative correlation with SG. They were more frequent with normal MPS stain (p = 0.01) and NA staining (p less than 0.001) than faint staining of gastric mucosa biopsy. The acid response to PG stimulation was inversely correlated with SG. We believe that elevated SG is compensatory to a decreased response of the gastroduodenal mucosa to PG. Mere retention of SG does not explain its elevation as its correlation with serum creatinine existed not only in patients on CT, but also in RDT patients.(ABSTRACT TRUNCATED AT 250 WORDS)