KIDNEY, RIGHT, PERCUTANEOUS RENAL BIOPSY -
In summary this 74 year old man with a history of previously treated scleroderma with renal involvement, ? penicillamine induced proteinuria and recent rapidly progressive renal insufficiency has on biopsy 1.) diffuse type I membranoproliferative glomerulonephritis secondary to immunotactoid deposition and 2.) severe arterial and arteriolar chronic vascular disease. No necrotizing lesions/crescents or significant interstitial nephritis are present.
Immunotactoid glomerulonephritis has been reported in the setting of both autoimmune (most frequently rheumatoid arthritis and mixed connective tissue disease) and lymphoproliferative disorders. Typical presentation includes proteinuria (nephrotic range in 60-70%), renal dysfunction (>50%), hypertension (70%) and microscopic (occasionally gross) hematuria. ANA is only rarely elevated and serum complements are infrequently depressed. Immunotactoid deposits have not been identified in an extrarenal site. Half of the reported patients have progressed to renal failure, with no effective therapy available. Recurrence has been reported in at least two transplanted patients, however insufficient numbers of patients have been transplanted to determine an overall frequency of recurrence.
The diagnosis of immunotactoid GN can be made after excluding systemic diseases known to be associated with organized glomerular immune deposits on the basis of clinical and/or serologic findings. On renal biopsy, typical histologic features are described as mesangial prominence with mild hypercellularity. Less frequently, other glomerular patterns of injury, including more extensive mesangial cell proliferation, focal or diffuse mesangiocapillary proliferation (membranoproliferative), and crescent formation may be seen. The deposits are PAS and silver positive, but negative with amyloid stains (Congo-red, thioflavin-T, etc.) Large microtubular deposits are confined to the glomerulus, specifically in the mesangium and/or glomerular capillary wall. On silver stain, capillary walls show variable features depending on location of deposits and surrounding reaction to the deposits, eg. spike-like projections with subepithelial deposits. Ultrastructurally, the morphology of the deposits may range from highly organized parallel bundles of microtubules to randomly arranged microtubules in a loose fibrillar arrangement. Fibrils range from 18-22nm in about half of the patients, the remaining half being either smaller than 18nm or larger than 22nm, up to 50 nm. The pathogenesis of immunotactoid GN is yet unknown, as is the precise composition of the microfibrils. The microfibrils have been shown to contain intact immunoglobulins, both heavy and light chains, and amyloid P component. All cases contain intact IgG and C3, with 75% containing polyclonal IgG; however, 25% of cases contain a light chain restricted form of IgG, usually kappa. In one study, subclass IgG4 monoclonality was demonstrated in all cases studied.
The glomerular pathologic changes in this biopsy are characteristic of immunotactoid GN except for the lambda light chain restriction noted on the immunofluorescence, prompting SPEP, UPEP and cryoglobulin screen, all of which were negative. As noted above, though most reports indicate polyclonal immunoglobulin (usually IgG) and C3, there are a few reports of kappa or lambda light chain restriction by immunofluorescence. The overall significance of this isolated finding and the relationship of the immunotactoid GN to the patient's scleroderma are not clear.
The chronic vascular disease with secondary tubulointerstitial chronicity change is probably related to the patient's prior scleroderma renal involvement. The glomerulosclerosis, as noted above, though increased (26%) relative to the patient's age is not randomly distributed, but rather, is concentrated in a subcapsular distribution on one core suggesting the possibility of a focal ischemic etiology. The baseline renal insufficiency in this patient's biopsy is explainable on the basis of chronic vascular and secondary tubulointerstitial changes. The recent deterioration in renal function with depressed serum complements appears to be due to the development of the acute immunotactoid glomerular disease.
Contributed by Lina Perry, M.D. and Sheldon Bastacky, M.D.