Section 7 -

Light Chain Fanconi Syndrome Donna J. Lager, M.D. Matthew Lewin, M.D.

Case 6: Light Chain Fanconi Syndrome A 79 year old man with history of monoclonal gammopathy and hypertension presents with progressive renal insufficiency and low grade proteinuria. Serum creatinine was 4.1mg/dl (baseline 1.9 mg/dl). Light chain Fanconi Syndrome (LCFS) is a clinical-pathologic entity characterized by proximal tubule injury secondary to monoclonal light chain crystalline deposits. LCFS is a unique pattern of renal disease seen in association with dysproteinemias (abnormal/excessive synthesis of Ig molecules or subunints). The individual properties of the monoclonal proteins are the primary determinants of the pattern of renal parenchymal disease. Patterns of renal diseases associated with dysproteinemia Light Chain Cast Nephropathy (myeloma kidney) Light Chain Fanconi Syndrome Amyloidosis Monoclonal Ig Deposition Disease (LCDD, LHCDD, and HCDD) Cryoglobulinemic Glomerulonephritis Immunotactoid Glomerulonephritis Waldenstrom's Macroglobulinemic Glomerulonephrits Clinical Presentation and Diagnosis: LCFS is a rare entity seen in adults who present with renal insufficiency, Fanconi syndrome, low-grade proteinuria, and/or osteomalacia. At the time of diagnosis most, if not all, patients have evidence of a monoclonal protein and about half of the patients meet the criteria for multiple myeloma. Fanconi syndrome is defined by evidence of proximal tubule dysfunction which includes: glycosuria (with normal serum glucose) aminoaciduria uricosuria hypercitraturia hyperphosphaturia proximal (type II) renal tubular acidosis Morphologic Findings: Light microscopy shows proximal tubular injury associated with intracytoplasmic clear, needle-shaped, nonpolarizable crystals. Tubular atrophy, interstitial fibrosis, and interstitial inflammation may be seen. Crystals may also be found in interstitial macrophages. The Trichrome stain tends to highlight the crystals. Immunofluorescence and immunohistochemistry demonstrate light chain restriction (usually kappa light chain). Ultrastructural evaluation demonstrates rectangular/rod shaped crystals within the cytoplasm of the proximal tubules. The crystals are often located within membrane bound structures. References: Markowitz GS: Dysproteinemia and the kidney. Adv Anat Path 11(1): 49-63. Renal Biopsy Interpretation, Ed. FG Silva, VD D'Agati, T Nadasdy, Churchill Livingstone, 1996. Furness P: Paraproteinaemia and renal disease. Current Diagnostic 10: 52-60.