Acute tubulointerstitial nephritis associated with antineutrophil cytoplasmic antibody following cimetidine treatment: a case report

Abstract

Background Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis usually induces rapidly progressive glomerulonephritis, including pauci-immune necrotizing crescentic glomerulonephritis. Acute tubulointerstitial nephritis (ATIN), which is often drug-induced, is a frequent cause of kidney injury. However, ATIN associated with ANCA without any glomerular lesions has been rarely reported, and drug-induced ATIN associated with ANCA is not well recognized. Here we present a case of an older woman with ATIN associated with myeloperoxidase-ANCA (MPO-ANCA) following cimetidine treatment. Case presentation A 70-year-old woman was admitted to our hospital due to acute kidney injury and mild proteinuria. She had a one-year history of chronic thyroiditis and dyslipidemia, for which she was taking levothyroxine sodium and atorvastatin, respectively. Two weeks before admission she had started cimetidine, methylmethionine sulfonium chloride, and itopride hydrochloride for gastric discomfort persistent since a month. She had experienced fatigue for two weeks and later appetite loss. The patient demonstrated a positive titer for MPO-ANCA (192 IU/mL) and a positive drug-induced lymphocyte stimulation test for cimetidine. She underwent two kidney biopsies that revealed ATIN without any glomerular lesions. Despite discontinuation of cimetidine on admission, renal injury continued with the presence of high MPO-ANCA titer. Oral steroid treatment was closely related with the recovery of her renal function and disappearance of MPO-ANCA. Conclusions In this case, ATIN presented as sustained renal insufficiency and high MPO-ANCA titer despite withdrawal of cimetidine. Therefore, we reason that the development of ANCA-associated ATIN was caused by cimetidine. Serologic follow-up with measurement of MPO-ANCA titers and renal biopsy are recommended when the clinical history is inconsistent with the relatively benign course of drug-induced ATIN.

Implication of platelets and complement C3 as link between innate immunity and tubulointerstitial injury in renal vasculitis with MPO-ANCA seropositivity

“…In this context, experimental studies have already shown that platelets are main contributors to microvascular injury and rarefaction of tubulointerstitial capillaries (49). In ANCA-associated renal vasculitis, the occurrence of tubulointerstitial injury independent of glomerular lesions has already been described (50)(51)(52)(53). Our observations might indicate that the tubulointerstitial compartment is particularly susceptible to a hypercoagulable state mediated by platelets.…”

Interstitial nephritis without glomerulonephritis in ANCA-associated vasculitis: a case series and literature review

“…A detailed mechanism for AAV-associated interstitial nephritis remains unknown [ 19 ], with limited clues from the literature. Peritubular capillaritis is common in AAV with glomerular capillaritis, vasculitis in vessels, and extravascular granuloma formation [ 18 ]. This result indicated that the loss of CD34 vascular endothelial markers occurs in the early phase of the disease [ 19 ] with infiltration of neutrophils and mononuclear cells into tubular epithelial cells, which was associated with tubular basement membrane lysis.…”

“…A few AAV patients with acute interstitial nephritis progressed to crescentic glomerulonephritis. Their confounding factors were cimetidine treatment and other unknown mechanisms [ 10 , 18 , 22 ]. Further research is required to reveal the exact pathogenesis of AAV-associated interstitial nephritis.…”

Tocilizumab Attenuates Anti-neutrophil Cytoplasmic Antibody-associated Nephritis Occurring during Abatacept and Adalimumab Therapy for Rheumatoid Arthritis

“…It was suggested that the extensive tubulointerstitial lesions were related to renal dysfunction rather than the glomerular lesions in our case. Most reports of AAV have focused on glomerular lesions due to crescent formation (12), but there have been reports of AAV with tubulointerstitial nephritis as the predominant lesion (14,15). As described in the reported case, it is essential to consider drug-induced tubulointerstitial nephritis in our case as well, although eosinophil infiltration is scant.…”