Schistosomal Glomerulopathy Research Articles

Schistosoma japonicum infection associated with membranous nephropathy: a case report

BackgroundSchistosomiasis is one of the most contagious parasitic diseases affecting humans; however, glomerular injury is a rare complication mainly described with Schistosoma mansoni infection. We report a case of membranous nephropathy associated with Schistosoma japonicum infection in a Chinese man.Case presentationA 51-year-old Chinese male with a long history of S. japonicum infection presented to the hospital with a slowly progressing severe lower limb edema and foaming urine for over 5 months. Serum S. japonicumantigen test was positive and immunohistochemistry showed that the glomeruli were positive for the antigens. The renal pathologic diagnosis was stage III membranous nephropathy. The patient was treated with glucocorticoid, praziquantel, and an angiotensin-converting enzyme inhibitor. The edema in both lower limbs disappeared within 2 weeks, but his renal function declined progressively and proteinuria persisted after 5 months of therapy.ConclusionsDifferent classes of schistosomal glomerulopathy have completely different clinical manifestation and prognosis. Therefore, efforts should focus on alleviating symptoms, prevention, and early detection. S. japonicumassociated with membranous nephropathy may show a good curative effect and prognosis. However, it is necessary to monitor the renal function in such patients.

Urinary schistosomiasis

Schistosomiasis is the second most common socio-economically devastating parasitic disease after malaria, affecting about 240 million residents of developing countries. In Africa, it predominantly manifests as urogenital disease, and the main infective agent is Schistosoma hematobium. Endemicity is propagated by poor socio-economic status and environmental degradation due to rapid urbanization. Recreational swimming is a potent medium for the spread of disease in children and adolescents. Most affected individuals are asymptomatic. The male and female worms are equipped with an extraordinary capacity for immune evasion and are able to co-habit for several decades within the pelvic venous plexus. Eggs deposited in the bladder wall resist elimination by type 1T lymphocytes. Instead, they are sustained by pro-fibrogenic encapsulation (as modulated by type 2 helper cells). Progressive bladder disease results in obstructive uropathy and predisposes to (mostly) squamous cell carcinoma. Schistosomal glomerulopathy manifests as a clinical spectrum of asymptomatic proteinuria, nephrosis and/or nephritic syndrome. Findings on renal biopsy may be influenced by co-morbidity with Salmonella bacteria, amyloidosis and hepatitis C infection. Potentially fatal Katayama fever and spinal radiculopathy may ensue in tourists visiting an endemic zone. Early detection by urine microscopy is hampered by low urinary excretion rates of the parasite eggs. Although useful in travelers with newly acquired disease, the results of the serological antibody assay may be false positive in residents of an endemic zone. Cystoscopy, however, may be invaluable. Due to its safety, effectiveness and once-daily dosing, praziquantel is the drug of choice. An integrated approach that includes mass chemotherapy, environmental health programs and public health education is the most cost-effective preventive strategy.

Chemokine Profile in the Sera and Urine of Patients with Schistosomal Glomerulopathy

We investigated the serum and urine chemokine levels of patients with schistosomal mansoni glomerulonephritis. This cross-sectional study was conducted in the Southeast of Brazil. Overall, 160 subjects were enrolled and divided into five groups: 1) hepatosplenic schistosomiasis with renal disease (N = 12); 2) hepatosplenic schistosomiasis without renal disease (N = 68); 3) hepatointestinal schistosomiasis (N = 27); 4) glomerulopathy caused by other diseases (N = 22); and 5) healthy controls (N = 31). The patients with microalbuminuria > 30 mg in 24 hours were considered to have renal disease. The sera and urine chemokines CCL2, CCL3, CCL5, CCL11, and CXCL8 were measured using an enzyme-linked immunosorbent assay test. A similar profile was observed between the patients with schistosomal glomerulopathy and the patients with glomerulopathy caused by other diseases, with the exception of serum CCL2 ≤ 634.3 pg/mL. In cases with sera CCL2 > 634.3 pg/mL, the diagnosis of schistosomal glomerulopathy should be considered.

Schistosomiasis-associated kidney disease: A review

Schistosomiasis is a parasitic disease caused by organisms from the genus Schistosoma. The disease is endemic in tropical areas, where there are currently millions of people living in areas with transmission risk. Schistosomiasis-associated kidney disease is not frequently described in literature. The disease has a chronic evolution, with variable severity. Glomerulonephritis is described in 10–12% in autopsy studies. Proteinuria is reported in 20% of patients with S. mansoni infection. Schistosomal glomerulopathy generally occur in young patients, male, with hepato-splenomegaly. The glomerular lesion in schistosomiasis has an immunological nature. Antigens from the parasite seem to be related to glomerulopathy and have been found in the sera of humans and animals infected by the S. mansoni. Vesical involvement is common in the infection by S. haematobium, a parasitic disease prevalent in African countries. In the S. haematobium infection, hematuria and dysuria can be observed due to inflammation and ulceration in the bladder mucosa, generaly occuring 3 to 4 months after primary infection. Specific antiparasitic treatment is indicated to all patients infected by Schistosoma. There are 2 drugs available for treatment, praziquantel and oxamniquine. We revise the general aspects of the disease and describe the features of renal involvement in schistosomiasis.

Schistosomal glomerulopathy and changes in the distribution of histological patterns of glomerular diseases in Bahia, Brazil

Distinct patterns of glomerular lesions, including membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis, are associated with infection by Schistosoma mansoni or Schistosoma japonicum. Evidence suggests that immune complex deposition is the main mechanism underlying the different forms of schistosomal glomerulonephritis and that immune complex deposition may be intensified by portal hypertension. The relationship between focal segmental glomerulosclerosis and schistosomiasis remains poorly understood. A clinicopathologic classification of schistosomal glomerulopathies was proposed in 1992 by the African Association of Nephrology. In Brazil, mass treatment with oral medications has led to a decrease in the occurrence of schistosomal glomerulopathy. In a survey of renal biopsies performed in Salvador, Brazil, from 2003-2009, only 24 (4%) patients were identified as positive for S. mansoni infection. Among these patients, only one had the hepatosplenic form of the disease. Focal segmental glomerulosclerosis was found in seven patients and membranoproliferative glomerulonephritis was found in four patients. Although retrospective studies on the prevalence of renal diseases based on kidney biopsies may be influenced by many patient selection biases, a change in the distribution of glomerulopathies associated with nephrotic syndrome was observed along with a decline in the occurrence of severe forms of schistosomiasis.

Glomerulonephritis in schistosomiasis mansoni: a time to reappraise

The current prevalence of glomerulonephritis in patients with hepatosplenic schistosomiasis mansoni in Brazil was evaluated. Sixty three patients (mean age 45.5 ± 11 years) attending the outpatient infectious disease clinic of a University Hospital in Belo Horizonte, Brazil, from 2007 to 2009, were consecutively examined and enrolled in the present investigation. Diagnosis of hepatosplenic schistosomiasis was based on epidemiological, clinical and parasitological data and imaging techniques. Eight patients, who presented >30 mg/day albuminuria, were submitted to percutaneous ultrasound guided renal biopsy. Kidney tissue fragments were examined under light, direct immunofluorescence and electron microscopy. All patients showed mesangial enlargement. In five, mesangial hypercellularity was observed and four presented duplication of the glomerular basement membrane. Areas of glomerular sclerosis were diagnosed in four. Deposits of immunoglobulin M and C3 were present in six samples; deposits of IgG in four, IgA in three and C1q in two samples. In all patients, immunoglobulin A was reported in the lumen of renal tubules. Deposits of kappa and lambda were observed in six samples. Electron microscopy revealed dense deposits in the glomerular tissue of three patients. Arterial hypertension, small esophageal varices, slight increases in serum creatinine and decreases in serum albumin were associated with glomerular disease. Renal disease associated with hepatosplenic schistosomiasis was verified in 12.7% of patients and type I membranoproliferative glomerulonephritis was observed in 50% of them. Schistosomal glomerulopathy still is an important problem in patients with hepatosplenic schistosomiasis in Brazil.

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.

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 glomerular disease (a review).

In this review paper schistosomal glomerulopathy is defined as an immune-complex disease. The disease appears in 12-15 per cent of the individuals with hepatosplenic schistosomiasis. Portal hypertension with collateral circulation helps the by pass of the hepatic clearance process and the parasite antigens can bind to antibodies in the circulation and be trapped in the renal glomerulus. Chronic membranous-proliferative glomerulonephritis is the most common lesion present and the nephrotic syndrome is the usual form of clinical presentation. The disease can be experimentally produced, and schistosomal antigens and antibodies, as well as complement, can be demonstrated in the glomerular lesions. Specific treatment of schistosomiasis does not seem to alter the clinical course of schistosomal nephropathy.

Schistosoma mansoni: Anodic polysaccharide antigen in glomerular immune deposits of mice with unisexual infections

In mice infected with unisexual Schistosoma mansoni, circulating anodic antigen was detected by immunofluorescence in glomeruli of 20 out of 22 animals from 7 to 30 weeks after infection. Circulating anodic antigen was present as finely granular deposits in the mesangium. The amount of circulating anodic antigen in the glomeruli was not clearly related to the worm burden but it increased during the course of the infection. These circulating anodic antigen deposits were accompanied by deposits of immunoglobulins, sometimes found in the same precise localization, and of complement. They probably represent the antigen part of immune complexes. Circulating anodic antigen appears to be a major candidate among the antigens involved in schistosomal glomerulopathy.