An association between membranoproliferative glomerulonephritis and metastatic colorectal carcinoma: a case report

This case highlights that MPGN can be associated with malignancy, although the mechanism underpinning this association has not been completely elucidated.

Little is known about the association between MPGN and malignancy, although there is a wealth of published information regarding nephrotic syndrome and malignancy. As early as the 1960s, there were suggestions that nephrotic syndrome may be related to thyroid cancers, Hodgkin’s lymphoma, or chronic lymphocytic leukemia [1]. Further, a more recent study analyzed approximately 8 million people in the Danish National Registry of Patients, estimating that that 4.7 % of patients who had nephrotic syndrome (from a total of 4293 patients) had underlying malignancy with lung cancer, multiple myeloma, and prostate cancer being most likely [10].

There are two main hypotheses which have been proposed to explain the pathogenesis of the association between MPGN and malignancy. First, an undiagnosed malignancy associated with immune complex deposition may cause a glomerular disease-like paraneoplastic syndrome. While data are limited in MPGN, studies have shown that paraneoplastic membranous nephropathy is characterized by an increased number of inflammatory cells in the glomeruli compared with that of idiopathic membranous nephropathy [4, 11]. There is a greater prominence of the subtypes of IgG1 and IgG2 in the renal biopsy samples of patients with paraneoplastic membranous nephropathy compared with idiopathic membranous nephropathy [12]. Second, viral infection may have induced both glomerulopathy and cancer by intrinsic viral oncogenic activity. It is possible that disrupted renal clearance of biological mediators may be associated with oncogenesis [13]. However, the most likely explanation for the connection between virus latency and tumorigenesis is that replicating viruses may initiate cell death [14]. When latent viruses produce virions, virus replication generates pathogen-associated molecular patterns from partially synthesized viral chromosomes, double-stranded ribonucleic acid (RNAs) and empty capsids that trigger cellular DNA damage responses and innate immune signaling. Toll-like receptor and interferon signaling by virus infection is subsequently activated, amplifying the innate response [14].

Remission of cancer has led to subsequent remission of nephrotic syndrome. Reports have shown that patients who have paraneoplastic glomerulopathy secondary to renal cell carcinoma have undergone remission or a reduction of proteinuria through either radical nephrectomy, nephron-sparing, partial nephrectomy, or laparoscopic nephrectomy [15]. There are, however, no reports that have specifically looked at the remission of cancer in patients with MPGN. There is some evidence for the use of prednisolone when cure of the cancer is not an option. One case of MPGN developed after surgical removal of a bronchial carcinoid tumor, but responded to prednisolone therapy [16]. Furthermore, there has been a case showing use of prednisolone for paraneoplastic MPGN without ablation in a patient with metastatic prostate cancer [7]. Moreover, paraneoplastic glomerulopathy developed in a patient with minimal change disease, who had retroperitoneal sarcoma, probably secondary to a T-cell-mediated response to malignancy, which went into remission with corticosteroid therapy [17]. Administration of corticosteroids was considered in this setting primarily because of the patient’s high performance status.

The prognosis of MPGN in the setting of malignancy is uncertain [18]. The presence of hypertension at presentation, severe nephrotic syndrome, and renal insufficiency are known poor prognostic factors among non-malignancy-associated nephrotic syndrome [18].