Idiopathic Hypocomplementemia and Interstitial Nephritis: A Case Report

Introduction: Interstitial nephritis is a significant cause of renal failure in patients with autoimmune disease. Typically, this condition is associated with IgG4-related disease or systemic lupus erythematosus, often presenting with low complement levels. Here, we present a case of idiopathic hypocomplementemia with interstitial nephritis without evidence of IgG4-related disease. Case Description: A 64-year-old woman with a history of right-sided pulmonary embolism, a large exudative pleural effusion in October 2023, moderate pulmonary hypertension, hypertension, and sarcoidosis presented in November 2023 with elevated creatinine levels of 2.8 mg/dL. On exam, she exhibited severe edema. During her hospitalization, her creatinine subsequently rose to 5.4 mg/dL. She was given pulse-dose steroids for three days, without improvement in the acute kidney injury. Her C3 was 30 mg/dL; her C4 was 3 mg/dL. ANA and dsDNA were positive. The renal biopsy showed immune complex-mediated glomerulonephritis with mesangial deposits immunoreactive for C3 and C1q, with weak reactivity for polyclonal IgG and IgA. Immunofluorescence revealed extensive, diffuse immune complexes within the tubular basement membranes, interstitium, and vasculature. There were no cellular crescents, fibrinoid necrosis, or endocapillary hypercellularity observed. Additionally, no plasma cells were identified, making IgG4-related disease less likely. Importantly, there was severe acute interstitial nephritis with associated acute tubular injury, likely a response to the numerous tubulointerstitial deposits. Frequent finely granular electron-dense deposits were present in the mesangium. The patient eventually succumbed to acute kidney injury, complicated by septic shock in the setting of immunosuppression and extent of illness. Autopsy reaffirmed the diagnosis of an autoimmune process most consistent with idiopathic hypocomplementemia and interstitial nephritis. Discussion: Idiopathic hypocomplementemia and interstitial nephritis is a rare entity that can cause renal failure and death if not identified promptly. Over the past few decades, many cases initially considered idiopathic have been recategorized under IgG4-related disease. This case illustrates the continued utility of renal biopsy in diagnosing undifferentiated renal failure and identifying the underlying disease process.