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Suspicious Findings

GN. Suspicious Findings. History: Gross hematuria Frothy urine HTN Recent/chronic illness (URI, Hep C, HIV, etc.) History of rheum disease or + ROS History of Cancer or + ROS Family history Increased edema. Suspicious Findings. Active urine sediment: Granular/muddy brown casts

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Suspicious Findings

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  1. GN

  2. Suspicious Findings • History: • Gross hematuria • Frothy urine • HTN • Recent/chronic illness (URI, Hep C, HIV, etc.) • History of rheum disease or + ROS • History of Cancer or + ROS • Family history • Increased edema

  3. Suspicious Findings • Active urine sediment: • Granular/muddy brown casts • Sterile pyuria vs. WBC casts • Dysmorphic RBCs vs. RBC casts • Proteinuria • Nephrotic range proteinuria • Non-nephrotic range proteinuria • Paraproteinemia • Progressive unexplained decline in GFR

  4. Nephrotic vs. Nephritic • Nephrotic syndrome: • NRP: > 3.5 gm • Low Albumin • High cholesterol • Lipiduria • Edema • More bland urine sediment • Decreased change of HTN • Pro-thrombotic state

  5. Nephrotic Differential • MCD • Membranous GN: primary and secondary • FSGS: primary and secondary • IGM nephropathy • DM • Fibrillary GN • C1q nephropathy • Amyloidosis • IgA nephropathy • PSGN, Lupus etc

  6. Nephrotic vs. Nephritic • Nephritic • HTN • Active urine sediment (Dysmorphic RBC/RBC cast) • NNRP or NRP • Edema with volume overload • Oliguric • Reduced GFR

  7. Nephritic Differential • Lupus • IgA nephropathy • PSGN • Vasculitis (Wegener’s, MPA, CS) • Anti-GBM disease • MPGN and Cryoglobulinemia • Malignant HTN • TTP/HUS • Embolic/immune complex deposition disease

  8. Syndromes • Nephrotic Syndrome • As previous • Acute Glomerulonephritis • As previous • Chronic Glomerulonephritis • Insidious/smoldering/slow progressive GN

  9. Syndromes • Rapidly progressive glomerulonephritis • Focal proliferative/necrotizing/Crescents • Rapid decline in renal function (days/weeks) • Vasculitis vs. Anti-GBM dz vs. TMA/TTP vs. IgA nephropathy vs. DPLN vs. PSGN vs. MPGN • Asymptomatic Urinary Abnormalities • Recurrent/persistent non-GU hematuria • TBMD; Alport’s syndrome, IgA • Isolated NNR proteinuria or sterile pyuria • Same differential of NRP or TI dz • Only one finding with no HTN, GFR decline abnormal exam findings

  10. Syndrome Classification Issues • Each disease not limited to one classification • IgA can present with all five • Lupus can present with all five • Disease continuum • AUA to NRP to Acute GN to RPGN (Lupus) • The neurology game of “guess the lesion” while awaiting renal biopsy (our MRI) • Biopsy gold standard, but: • Sample variation: may miss FSGS; Lupus IV/V • Each histopathology diagnosis likely represents multiple pathophysiology mechanisms

  11. FSGS • ‘Permeability factor’ (evident post transplant) • Genetic (nephrin, podocin, alpha-actin IV) • ESRD common endpoint (hyperfiltration) • Viral infection (Parvovirus, HIV) • Elevated GH levels • Obesity • Reflux nephropathy • Drugs (palmidronate, heroin)

  12. Serology Diagnosis Help • Membranous GN • mesangial involvement suggests secondary cause: • CA screening • ANA; //DNA • Hepatitis panel • FSGS • HIV • Genetic testing • MPGN • Hepatitis panel • Cryoglobulins • C3/C4

  13. Serology Diagnosis Help • Lupus Nephritis • ANA • // DNA • C3/C4/C50 • Vasculitis • P-ANCA; C-ANCA • CRP • Anti-GBM disease • Anti-GBM antibody • Acute interstitial nephritis • Serum/urine eosinophils

  14. Serology Diagnosis Help • TMA/TTP • Platelets • Hgb • Haptoglobin, LDH, indirect bilirubin • Peripheral smear • PSGN • ASO • Anti-DNAase • Cryoglobulinemia • Serum cryoglobulins

  15. Serology Diagnosis Help • Paraproteinemia • SPEP, UPEP, Kappa/Lambda light chain ratio • IgA nephropathy • IgA levels NOT diagnostic • Galactose deficient IgA1 associated with disease • IgM nephropathy • IgM levels NOT diagnostic • IgM to IgG ratio could be diagnostic • Minimal Change Disease • none • Fibrillary GN • none

  16. Low C3/C4 • Lupus Nephritis • MPGN • PSGN • Cryoglobulinemia • Embolic/Immune Complex deposition disease

  17. Diagnosis: Renal Biopsy • Light Microscopy • Numerous stains: Silver stain GBM/matrix • Hypercellular (proliferative) mesangial/endothelial • Hypercellular (Exudative): Inflammatory leukocytes • Glomerular necrosis : RPGN • Crescents: Collection of inflammatory cells in Bowman’s space • Capillary loop collapse; attachment to Bowman’s • Thickening/division of capillary loops • Tublules: Cells; cell inclusions, lumen contents • Interstitium: Edema, infiltration, fibrosis

  18. Acute Disease • Interstitial Edema • Interstitial inflammatory infiltrate • Glomerular hypercellularity • Glomerular Necrosis • Increased mesangial matrix • Congested tubules • Cellular crescents

  19. Chronic Disease • Interstitial Fibrosis • Tubular Atrophy • Glomerular sclerosis (obsolescence) • Dilated tubules • Results in broad waxy casts on urine microscopy

  20. Diagnosis: Renal Biopsy • Immunofluorescence • Evaluation for immune deposits • Detect IgA, IgM, IgG, C3, C4, and C1q • Also Fibrin (Crescents; capillaries in thrombotic dz) • Linear (continuous) or granular (discontinuous) • Anti-GBM: Linear GBM deposits • Membranous GN: Granular GBM deposits • Capillary walls or mesangium • Vasculitis has a ‘pauci-immune’ IF • Lupus has a ‘full house’ IF

  21. Diagnosis: Renal Biopsy • Electron Microscopy • Anatomy of GBM (Alport’s, TBMD, MPGN II) • Localization of deposits: • Subepithelial (nephrotic) • Subendothelial (nephritic) • Mesangial (nephritic); secondary membranous • Foot process fusion (nephrotic) • Special deposits (Fibrillary, amyloidosis, LCDD)

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