Light chain deposition disease (monoclonal immunoglobulin deposition disease)

Cast nephropathy (myeloma kidney) is acute or subacute kidney injury caused by intratubular obstruction from free light chain and Tamm-Horsfall protein casts, occurring almost exclusively in multiple myeloma with markedly elevated serum free light chains. Treatment is emergency chemotherapy to rapidly lower free light chain production, combined with aggressive isotonic hydration and avoidance of nephrotoxins.

Amyloidosis is extracellular deposition of misfolded protein fibrils that stain apple-green with Congo red under polarized light, most often AL (clonal light chains, linked to plasma cell dyscrasias), AA (chronic inflammation), or ATTR (transthyretin, hereditary or wild-type). Diagnosis requires tissue biopsy for Congo red birefringence plus typing of the amyloid protein, and treatment targets the underlying source, plasma-cell-directed therapy for AL, inflammatory disease control for AA, and transthyretin stabilizers or silencers for ATTR.

Multiple myeloma is a clonal plasma cell neoplasm that produces a monoclonal immunoglobulin and end-organ damage summarized by CRAB (hypercalcemia, renal failure, anemia, bone lesions), diagnosed by marrow clonal plasma cells of 10% or more plus a CRAB or SLiM myeloma-defining event. Treatment combines a proteasome inhibitor, an immunomodulatory drug, and dexamethasone, followed by autologous stem cell transplant and maintenance in eligible patients.

Monoclonal gammopathy of unknown significance (MGUS) is an asymptomatic, premalignant plasma cell disorder defined by a serum monoclonal protein under 3 g/dL, clonal marrow plasma cells under 10%, and no myeloma-defining end-organ damage. It is the most common plasma cell dyscrasia, progresses to multiple myeloma or a related malignancy at about 1% per year, and requires no treatment, only periodic surveillance.

Diabetic kidney disease is the leading cause of chronic kidney disease and end-stage kidney disease worldwide, driven by chronic hyperglycemia acting through advanced glycation end products on the glomerulus. It is diagnosed clinically from progressive albuminuria and falling eGFR in a patient with long-standing diabetes and other microvascular disease, and treatment centers on RAS blockade, SGLT2 inhibition, and glycemic and blood pressure control.

Cryoglobulinemia is the presence of immunoglobulins that precipitate below 37 degrees Celsius, classified as type I (monoclonal, driven by a lymphoproliferative disorder, causing hyperviscosity) or mixed types II/III (immune-complex, driven mainly by hepatitis C virus infection, causing small-vessel vasculitis). Type I is treated by targeting the underlying clonal disorder; mixed disease is treated with direct-acting antiviral therapy for hepatitis C, escalating to glucocorticoids plus rituximab for organ-threatening vasculitis.

Membranoproliferative glomerulonephritis is a rare chronic glomerulonephritis divided into immune-complex forms, most often driven by hepatitis C virus infection, and complement-mediated C3 glomerulopathies from alternative-pathway dysregulation, diagnosed by kidney biopsy with immunofluorescence. Treatment targets the underlying cause plus immunosuppression for nephrotic-range proteinuria or kidney dysfunction, and more than half of patients progress to end-stage kidney disease within 15 years.

Waldenstrom macroglobulinemia is an indolent B-cell lymphoma of clonal lymphoplasmacytic cells that secrete monoclonal IgM, causing anemia, lymphadenopathy, and hyperviscosity syndrome without the lytic bone disease of myeloma. Diagnosis rests on serum IgM electrophoresis plus a bone marrow lymphoplasmacytic infiltrate, and symptomatic hyperviscosity is a hematologic emergency treated with emergent plasmapheresis alongside rituximab-based or BTK-inhibitor therapy.

Chronic kidney disease is abnormal kidney structure or function present for more than 3 months, staged by the Kidney Disease: Improving Global Outcomes (KDIGO) system using estimated glomerular filtration rate and albuminuria, and managed with blood pressure control, renin-angiotensin blockade, an SGLT2 inhibitor, and correction of its metabolic complications.