Malignancies and glomerulonephritis: when to suspect and when to screen?

Abstract

Glomerular diseases may occur secondary to malignancies. Age-specific cancer screening is recommended for patients with glomerular diseases and may be extended based on the specific risk associated with the detected histopathologic pattern. Membranous nephropathy is the prototype of cancer-associated glomerulonephritis, with 10% of cases presenting with malignancy within a year from diagnosis. Among antigens that are expressed in patients with membranous nephropathy thrombospondin type 1 domain-containing 7A and neural epidermal growth factor-like-1 are often reported in patients with underlying malignancies. However, the risk of having a concurrent malignancy does not exceed 25%-30% when these antigens are expressed. While less frequent in other glomerulonephritides, co-occurrence of malignancy is reported in a substantial proportion of glomerular diseases including IgA nephropathy, podocytopathies with prominent podocyte foot process effacement such as minimal change disease as glomerular lesion pattern, amyloidosis, C3 glomerulopathy, monoclonal immunoglobulin deposition disease, or immune-complex-mediated glomerulonephritis. Treatment of malignancy-associated glomerulonephritis is usually directed toward treatment of the underlying malignancy with combinations of surgery, chemotherapy, and/or radiotherapy. Moreover, relapse of the malignancy may result in recurrence of glomerulonephritis. Refractoriness of glomerulonephritis to initial therapy may be due to an occult primary malignancy that was not diagnosed during initial cancer screening. In such a scenario a step-up diagnostic approach is recommended. In addition, re-screening may be sensible for relapsing patients who carry higher risks for cancer including patients of older age and those with a smoking history. This review focuses on the description of malignancies in the context of glomerular diseases and provides practical guidance on screening.

Keywords: cancer; glomerulonephritis; malignancy; membranous nephropathy; paraneoplastic syndrome.

Graphical Abstract

Figure 1:

A proposed algorithm for cancer screening, surveillance for underlying or concomitant malignancies, and treatment of glomerular diseases. Screening for underlying malignancy should be based on individual risk factors and presenting features of the patients, i.e. the presence of constitutional symptoms. Some glomerular diseases tend to occur more frequent as a paraneoplastic syndrome, especially patients with MN or those within the monoclonal gammopathy of renal significance spectrum. Constitutional symptoms are common for severe systemic autoimmunity and should not trigger intensified screening; only if the symptoms are persisting or part of a renal-limited disease such as a podocytopathy. If patients are resistant to treatment measures or relapse early in the disease course, consider a more intensified search for occult malignancies.