Lupus Nephritis Emily Chang April 13, 2010

The “Glom”

Classification Based exclusively on glomerular pathology WHO classification last revised in 2004 Definitions Diffuse: involving >50% glomeruli Focal: involving <50% glomeruli Global: involving more than half of the glomerular tuft Segmental: involving less than half of the glomerular tuft

Lab findingsHistologyTreatmentPrognosis Class I minimal mesangial normal UA normal Cr minimal mesangial by IF +/- EM no specific therapy follow excellent Class II mesangial proliferative microscopic hematuria and/or proteinuria htn & renal insufficiency rare mesangial hypercellularity in association with mesangial immune deposits treat proteinuria (ACE-I) steroids excellent Class III focal (<50%) variable - hematuria, proteinuria, renal insufficiency, htn global or segmental, endocapillary, extracapillary, mesangial proliferation, wireloops, subendothelial deposits, crescents IV cyclophosphamide (lupron for ovaries), maintenance MMF azathioprine 2nd line variable, depending on # of gloms involved Class IV diffuse (>50%) hematuria, proteinuria htn, renal insufficiency frequent hypocomplementemia and anti-dsDNA global or segmental, endocapillary, extracapillary, mesangial proliferation, wireloops, subendothelial deposits, crescents as above (for class III) fair Class V membranous nephrotic range proteinuria, microscopic hematuria, htn, may have renal insufficiency granular subepithelial immue deposits, mesangial hypercellularity treat proteinuria (ACE-I) prednisone fair Class VI advanced stage slowly progressive renal dysfunction, bland urine sediment >90% global glomerulosclerosis hemodialysis kidney transplantation poor

Other forms of Lupus Renal Disease Tubulointerstitial nephritis: Severity of involvement is an important prognosticator. Almost always seen with concurrent glomerular disease. Sometimes it is the only manifestation of lupus nephritis. Vascular disease: Presence can adversely affect prognosis of renal disease. Most frequently seen is immune complex deposition leading to vascular narrowing, immunoglobulin microvascular casts, TMA and vasculitis. Drug-induced lupus: Hydralazine, procainamide, isoniazid.

MKSAP A 29 yo black woman comes for a routine exam. She has a 3-yr h/o SLE. She recently was diagnosed with a progressive kidney disease characterized by glomerular hematuria with dysmorphic erythrocytes and proteinuria. Over the past 3 weeks, her Cr has risen from 0.9 to 1.4. Lab studies: C3 60, C4 8, ANA +, anti-ds-DNA + Kidney biopsy reveals diffuse proliferative immune complex- laden glomerulonephritis with endothelial tubular reticular inclusion bodies.

MKSAP, cont’d. In addition to corticosteroid therapy, which of the following is the most appropriate treatment for this patient? A. IV cyclophosphamide followed by maintenance IV cyclophosphamide. B. IV cyclophosphamide followed by maintenance MMF. C. Oral cyclophosphamide. D. IV cyclophosphamide.

References Weening, Jan J. et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney International, Vol. 65 (2004), pp Cotran, Ramzi S., Kumar, Vinay, Robbins, Stanley L. Robbins Basic Pathology, 7th edition. Saunders MKSAP 14. Nephrology. utdol.com. Types of renal disease in systemic lupus erythematosus.