Schistosoma japonicum infection associated with membranous nephropathy: a case report - BMC Infectious Diseases - BMC Infectious Diseases

This is the first case report of membranous nephropathy associated with S. japonicum infection in a Chinese man.

Schistosoma infection may be underdiagnosed in endemic areas with high schistosomiasis prevalence due to a lack of comprehensive screening. Furthermore, in 10–15% of patients with S. mansoni infection, glomerular damage related to schistosomiasis has been documented, with MPGN being the most frequent histological type [7,8,9]. Direct deposition of schistosomal antigens causes glomerular damage in most cases. Moreover, immune complex (IC) deposition is the main mechanism underlying the different forms of schistosomal glomerulonephritis [10], which is associated with IC deposition in the sub-endothelial, sub-epithelial, and mesangial regions of the glomerulus, together with lgA aggregates and parasite antigens, as shown in the glomeruli of both experimental animals and people with membranoproliferative and mesangioproliferative glomerulonephritis [11]. Schistosomal glomerulopathy is a distinct disease entity, which has been identified with experimental [12], epidemiologic [13], post-mortem [14], and clinical evidence [4]. The AFRAN endorsed a clinicopathologic classification for schistosomal glomerulopathy in 1992, wherein 5 classes of schistosomal glomerulopathy were recognized. Class I is mesangial proliferative glomerulonephritis. Class II is an exudative glomerulonephritis; patients with this form are concomitantly infected by Salmonella and Schistosoma [4]. Class III is MPGN usually reported in Caucasian individuals, and Class IV is a focal proliferative/sclerosing lesion typically seen in African-origin individuals. Class V is renal amyloidosis of the AA type. Recently, The inclusion of Class VI to the AFRAN classification of schistosomal glomerulopathy has been recommended. Class VI is cryoglobulinemic glomerulonephritis associated with the hepatitis C virus infection.

Approximately, 10–15% of patients with the hepatosplenic form of the disease have renal involvement. Individuals with hepatosplenic schistosomiasis have greater laboratory and clinical indicators of renal impairment than patients with other clinical forms of S. mansoni infection or non-infected controls [15]. Although the present case of membranous nephropathy caused by S. japonicum infection was rare, the mechanism of glomerular damage may have been comparable to that caused by S. mansoni infection. Between 2003 and 2009, the Renal Pathology Services at the Goncalo Moniz Research Centre-Fiocruz conducted a study that indicated a decrease in the number of reports of S. mansoni infection in biopsy specimens. Positive results for S. mansoni was reported for 24 out of 689 patients, and 4 out of the 24 had membranous glomerulonephritis. The prevalence of schistosomal glomerulopathy has decreased as a result of widespread treatment with oral medicines [16]. Compared with the study between 2003 and 2006, a study reported by Queiroz between 1970 and 1973 revealed that positive results for S. mansoni infection were reported for 38 out of 100 individuals, and 2 of these 38 had membranous glomerulonephritis [11]. So far, one case of membranous nephropathy associated with S. mansoni infection has been reported by Neves et al. [6]; the renal biopsy results in this case supported the diagnosis of an organic renal lesion caused by S. mansoni infection.

Altogether, S. japonicum infection leading to membranous nephropathy appears to be unique and previously unreported. While anthelminthic and immunosuppressive drugs can relieve renal injury caused by schistosomiasis, the disease finally evolves to chronic end-stage renal disease (ESRD) [17]. Medical history, physical examination, laboratory examination, and renal pathology results in this report were consistent with a diagnosis of S. japonicum associated with membranous nephropathy. In this case, S. japonicum infection was induced by the patient's contact with infected water, as evidenced by the presence of Schistosomiasis eggs in the feces. Immunohistochemistry showed that the glomeruli were positive for parasitic antigens; treatment using praziquantel was effective. Moreover, since membranous nephropathy caused by other secondary factors was excluded, it can be inferred that the kidney injury was secondary to S. japonicum infection. Renal manifestations of glomerular disease caused by S. mansoni infection can range from asymptomatic albuminuria and normal renal function to chronic ESRD [7], although most patients have nephrotic syndrome and a plasma creatinine concentration between 88 and 176 µmol/l [8]. In individuals with class I–II disease, complete recovery can occur spontaneously or after therapy, while in cases with classes III–V, treatment with anthelmintic drugs and immunosuppressive agents is usually not effective to arrest the progression to ESRD. However, our patient's case differed from all the above classes. During the 10-month follow-up, his plasma creatinine level progressively increased between March 2018 and July 2018 and thereafter remained stagnant between 110 and 120 µmol/l between July 2018 and December 2018; the proteinuria was persistent and showed no decline.

In summary, membranous nephropathy is a rare complication associated with S. japonicum infection. Following treatment with praziquantel, ACEI, and glucocorticoid, our patient's symptoms were rapidly resolved. However, the renal function declined progressively, creatinine and urea nitrogen levels increased, and proteinuria persisted. Therefore, efforts should be focused on alleviating symptoms, prevention, early detection, and treatment of Schistosoma infection among at-risk groups rather than eliminating urinary protein. Moreover, it is necessary to monitor the renal function in such cases.

Our research has several limitations, firstly, no attempt was made to give the patient the immunosuppressive therapy recommended for membranous nephropathy, such as rituximab, tacrolimus (FK506), because the patient did not have regular follow-up appointments. Secondly, it is not known whether the patient has progressed to end-stage renal disease because the follow-up period is not long enough.