When should a kidney biopsy be carried out in monoclonal gammopathy?

Monoclonal gammopathy of renal significance (MGRS) defines paraprotein-induced renal injury that can occur during the course of monoclonal gammopathy of undetermined significance (MGUS). The diagnosis of MGRS needs to be ultimately confirmed by kidney biopsy. In the case of detection of MGRS, the MGUS is no longer considered as monoclonal gammopathy of undetermined significance, since MGRS obviously defines an organ manifestation of the disease. The MGRS fulfills all definition criteria of MGUS, except for the fact of renal end-organ damage but is, however, associated with a worse prognosis in contrast to MGUS. If the renal damage is caused by light chain cast nephropathy, by definition a multiple myeloma is present. The possible spectrum of renal damage in MGRS is very broad and requires clarification by kidney biopsy. Light chain (AL) amyloidosis, light chain deposition disease and various forms of glomerulonephritis (GN), e.g. membranoproliferative GN, represent possible entities of early light chain damage. A kidney biopsy to clarify a suspected MGRS is indicated when there is coexistence of monoclonal gammopathy and progressive signs of renal damage. Therefore, in the follow-up of MGUS it is important to regularly screen for signs of renal damage, e.g. the course of the glomerular filtration rate (GFR), proteinuria and hematuria, which if present should lead to extended diagnostics with determination of immunofixation and free light chains in serum and immunofixation in urine. In the case of pathological findings, especially during the course, a renal biopsy should be performed by a relatively low threshold of indication, since an early diagnosis of MGRS is accompanied by a better prognosis. Conversely, MGRS should always be included in the differential diagnostic considerations of unclear proteinuria, renal failure, and renal pathologies, especially in older patients.