Systemic and rapidly progressive light-chain deposition disease initially presenting as tubulointerstitial nephritis

Abstract

A 42-year-old woman was admitted to a hospital after first-time detection of proteinuria and hematuria during a routine medical check-up. Because her serum creatinine level had rapidly increased from 0.9 to 3.2 mg/dl since measurement 3 months earlier, she was referred to our hospital. Renal biopsy revealed extensive tubular atrophy and interstitial fibrosis with mild leukocyte infiltration. Glomeruli showed minimal changes, and no immunoglobulin or complement deposition was observed by immunofluorescence. Oral prednisolone was commenced under the diagnosis of chronic tubulointerstitial nephritis, and she discharged once. However, its effects were transient; her renal function deteriorated rapidly and hemodialysis was initiated 5 months after her initial check-up. On readmission, urinary Bence-Jones protein κ-type was detected, and examination of bone marrow led to a diagnosis of Bence-Jones κ-type multiple myeloma. Light-chain staining using a renal biopsy specimen obtained 2 months earlier showed κ-light-chain deposition on tubular basement membranes but not glomeruli. Despite undergoing chemotherapy with vincristine, doxirubicin, and dexamethasone, the patient died suddenly from a cardiac arrhythmia. Autopsy showed κ-light-chain deposition in the heart, thyroid, liver, lungs, spleen, and ovaries. Congo red staining yielded negative results. Typical light-chain deposition disease (LCDD) characterized by nodular glomerulosclerosis was observed in the kidneys. This case demonstrates that tubulointerstitial nephritis can be an early pathological variant of LCDD, which may be followed by accelerated and massive light-chain deposition in glomeruli.

Keywords: Cardiac arrhythmia; Cardiac death; Light-chain deposition disease; Monoclonal immunoglobulin deposition disease; Multiple myeloma; Tubulointerstitial nephritis.

Fig. 1

Renal biopsy findings. a No increase in the mesangial matrix or mesangial proliferation was observed. Tubular atrophy and interstitial fibrosis associated with mild mononuclear cell infiltration were evident around the glomerulus. No definite abnormalities of the capillary walls were observed. b Tubular atrophy and increase of the interstitial space were observed in more than half of the tubulointerstitial area, with mild infiltration of mononuclear cells and few casts. Mild dilation of some tubules was also seen. c Atrophic and dilated tubules with simplified flattened epithelium and thickened tubular basement membranes were observed. d Staining for κ-light chains was positive along tubular basement membranes but was negative in glomeruli. e λ-light-chain deposition was not observed. a, c Periodic acid-Schiff stain and b Elastica-Masson stain. a ×200, b ×20, c–e ×100. G glomerulus

Fig. 2

Autopsy findings of the kidneys. a Nodular glomerulosclerosis was clearly visible. The structure of tubules was destroyed, compatible with marked interstitial fibrosis. b Congo red staining on glomeruli, tubules, and vessels yielded negative results. a H&E stain. a, b ×100

Fig. 3

Electron microscopy findings. a Electron-dense deposits in the inner aspect of the glomerular basement membrane and in the mesangial nodule were seen. However, mesangial electron-dense deposits (asterisks) were subtle or finely granular. b Electron-dense deposits were observed along the tubular basement membrane. The highly dense deposits were located on the outer aspect of the basement membrane and were heavily concentrated. N nodular glomerular lesion