Risk Factors For Renal Involvement In Dysproteinemias

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Acute deterioration of renal function (5-10%) Dehydration Hypercalcemia Cast nephropathy Crescentic glomerulonephritis Chronic renal insufficiency (45-75%) Myeloma cast nephropathy Light chain (AL) amyloidosis Interstitial plasma cell infiltration (rare) Proteinuria-nephrotic syndrome (50-80%) Light chain (AL) amyloidosis Light chain deposition disease Heavy chain deposition disease Cryoglobulinemic glomerular lesions Fanconi's syndrome (1%) Secondary lesions (20-30%) Pyelonephritis Nephrocalcinosis Hyperuricemic nephropathy

Factors enhancing amyloid formation Unfolding of paraprotein X Light chain Factors enhancing cast nephropathy High urinary excretion of light chains Binding of light chain to Tamm-Horsfall protein (THP) Iso-electric point of light chain >5.1 ? (enhances binding to anionic THP (pI:3.2) Tendency to self-aggregation of light chains k Light chain

High levels of acute-phase proteins

Resistance of light chain to urinary or macrophage-derived proteases Factors enhancing monoclonal immunoglobulin deposition k Light chain

Presence of hydrophobic aminoacids in CDR1 or CDR2 of VL-chain Deletion of CH1 domain Fc part immunoglobulin Factors enhancing acute renal failure Hypercalcemia (19-44%)* Dehydration (10-65%) Urinary tract infection (8-44%)

Nephrotoxic drugs (aminoglycosides; nonsteroidal anti-inflammatory drugs) (0-26%) Intravenous radio contrast media (0-11%) Loop diuretics

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