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The technique of immunofluorescence in fresh renal tissue, without fixation and frozen (IF-F), has been the gold standard for over 60 years for histological studies to detect immune complexes. However, there is a complementary technique known as immunofluorescence in fixed and paraffin-embedded sections (IF-P), which has shown greater sensitivity than IF-F in detecting immunoglobulin deposits. IF-P proves useful when the sample for IF-F is inadequate or unavailable. We report a case where the use of IF-P was crucial for diagnosing renal significant monoclonal gammopathy (RSMG).
A 72-year-old male admitted for complete A-V block requiring permanent pacemaker placement. Admitted alert, BP 140/70 mmHg, HR 35 bpm, good peripheral tissue perfusion, no edema. Laboratory: Hct 38%, Hb 11 g/dl, urea 105 mg/dl, creatinine 6.4 mg/dl, albumin 2.7 g/dl, Cl creatinine 16 ml/min, proteinuria 23 g/24h. Sediment: WBC 0-1/hpf, RBC 20-40/hpf, non-dysmorphic. Ultrasound: both kidneys orthotopic, preserved shape, size, and echostructure. Lab from the past 6 months: creatinine 4.21 mg/dl. Serum protein electrophoresis and immunofixation: IgG-Kappa monoclonal component. Urine immunofixation: higher concentration in IgG and Kappa zone. C3 149 mg/dl, C4 26 mg/dl. Renal biopsy: membranoproliferative pattern, global glomerulosclerosis, tubular atrophy, and interstitial fibrosis 35-40% of cortical area. Direct IF: IgG + and C3 positive in glomerular capillary walls, negative for IgA, IgM, C1q, Kappa, and lambda. Re-evaluation requested with IF-P.
IF-P revealed kappa chain deposits (++/4+) in glomerular basement membranes, and to a lesser extent, in tubular membranes, with no lambda chains. Additionally, electron microscopy (2 glomeruli) showed slightly enlarged mesangium with electrodense deposits, capillary loops with electrodense deposits in subepithelial and subendothelial aspects, extensive retraction of podocyte foot processes with cytoplasmic vacuolization. Clinical/histological diagnosis: proliferative glomerulonephritis with monoclonal immunoglobulin deposits.
While IF-P does not replace IF-F, there are specific indications where it acts as a alternativa technique for renal biopsies. IF-P unmasks immunoglobulin deposits in cases with negative IF-F, becoming a necessary resource for diagnosing certain expressions of RSMG. Its use is suggested in cases of suspected proximal tubulopathy due to light chains, C3 glomerulonephritis associated with monoclonal gammopathy, membranous nephropathy without IgG deposits, and membranoproliferative glomerulonephritis without Ig or complement deposits in IF-F. In the presented case, suspicion of RSMG, membranoproliferative pattern in light microscopy, and negative IF-F prompted additional IF-P, revealing IgG Kappa deposits, confirming the diagnosis. The significance lies in recognizing the implementation and usefulness of IF-P in renal pathology diagnosis, influencing prognosis and disease progression.