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Monoclonal gammopathy of renal significance (MGRS) encompasses a group of kidney disorders in which a monoclonal immunoglobulin secreted by a B cell or plasma cell clone causes renal damage, without meeting hematological criteria for malignancy. The underlying disorder in patients with MGRS is generally consistent with monoclonal gammopathy of undetermined significance (MGUS). Because of the wide spectrum of MGRS-associated diseases, defined through the location and mechanism of renal injury, it is often challenging to establish the right diagnosis. Kidney biopsy must be considered early; hence, close cooperation between hematologist and nephrologists is crucial in diagnosis and treatment from the beginning to prevent irreversible organ damage. Anti B‑cell or plasma-cell clone directed therapy with cytostatic or immunomodulatory agents can save and ameliorate renal function significantly. This is underlined by the fact that, untreated, MGRS-associated disease shows early recurrence in patients after kidney transplantation.