PMC5109568_01
Light microscopy of the first renal biopsy specimen revealed rare global glomerular sclerosis and tubulointerstitial fibrosis. (A) periodic acid-silver methenamine (PAM) staining shows massive mesangial expansion with the accumulation of the mesangial matrix and a double contour of the glomerular basement membrane (GBM). (B) Immunofluorescence for the kappa light chain. This glomerulus shows mesangial and peripheral (presumably subendothelial) kappa light chain deposits. Light chain deposition is also observed along the tubular basement membrane adjacent to the glomerulus. (C) At the first renal biopsy, electron microscopy (EM) showed a prominent mesangial matrix accumulation and subendothelial dense deposits.
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Mild to moderate expansion of the mesangial matrix and marked thickening of the glomerular basement membrane (GBM) with a double contour were noted evenly on almost all non-sclerotic glomeruli in sections with periodic acid-Shiff (PAS) and periodic acid-silver methenamine (PAM) staining (Fig. 1A). Immunofluorescence microscopy (IF) showed strong staining for kappa light chain in the mesangial region and along the GBM, but weakly and partially along the tubular basement membrane (TBM) (Fig. 1B). Electron microscopy (EM) revealed massive subendothelial dense deposits and edema of the GBM and dense deposits on inner zone of TBM, as well as mesangial dense deposits (Fig. 1C).
Light microscopy of the second renal biopsy revealed no global glomerular sclerosis. Interstitial fibrosis and tubular atrophy were observed in 10% of the renal cortex. (A) A PAM-stained section from the second biopsy reveals marked mesangial expansion associated with glomerular lobulation and typical mesangial nodular lesions. (B) EM shows severe thickening of the GBM with dense subendothelial/mesangial deposits and mesangial interposition. (C) IF showed strong staining for the kappa light chain also along the TBM in addition to the glomeruli.
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TBM (Fig. 3B), and IF showed strong staining for the kappa light chain along TBM in addition to glomeruli (Fig. 3C). Tubulointerstitium and the small arteries showed findings similar to the LM findings identified at the 1st biopsy.
Light microscopy of the third renal biopsy revealed significant chronic ischemic change due to long-term systemic hypertension. Only 14 of 82 glomeruli were preserved and all other glomeruli showed segmental or global sclerosis. Interstitial fibrosis and tubular atrophy involved about 50% of the renal cortex and moderate arteriosclerosis with intimal hyalinosis. (A) A PAM-stained section from the third biopsy shows a marked reduction of nodular lesions. The remnant glomerulus displays slight mesangial expansion with an accumulation of the matrix. (B) EM reveals that mesangial, subendothelial, and intramembranous deposits have become electron-lucent and the GBM is thinner than in the earlier biopsy specimens.
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Each of the non-sclerotic 14 glomeruli demonstrated a marked reduction of the mesangial nodules and thinning of the GBM (Fig. 4A). EM also revealed a marked reduction of the subendothelial lesions of GBM, mesangial lesions and inner zone lesion of GBM, with an appearance of new electron-lucent areas (Fig. 4B).
Light microscopy of the fourth renal biopsy, 26 of 34 glomeruli showed global sclerosis. Interstitial fibrosis and tubular atrophy involved about 70% of the renal cortex and severe arteriosclerosis. (A) A PAM-stained section from the fourth biopsy showed that the glomerulus is almost normal in appearance. (B) EM also demonstrates normal glomerular architecture with normalization of the mesangial area without excess matrix accumulation, and normal thickness of GBM, consistent with the LM findings. (C) Immunofluorescence for the kappa light chain in the fourth biopsy specimen. Despite the improvement in the light microscopic findings, kappa light chain deposits still exist.
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Each of non-sclerotic 8 glomeruli revealed a complete resolution of the nodular lesions, and had a nearly normal appearance by LM (Fig. 5A) as well as EM (Fig. 5B). However, strong staining for kappa light chain was still detected along the GBM, although the staining of the kappa light chain along TBM had become obscure (Fig. 5C).
(A) Surgical specimen of the resected kidney revealed severe tubular atrophy and interstitial fibrosis which involved around 90% of the renal cortex. The majority of the glomeruli demonstrated global sclerosis. (B) Interlobular artery disclosed severe arthrosclerosis with medial thickening. (C) Small arterioles showed severe intimal thickening with subendothelial hyalinosis.
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The accumulation of the meningeal matrix and thickening of the GBM on non-sclerotic glomeruli had both slightly increased (Fig. 6), presumably because of the termination of the MP therapy.