A 46-year-old woman with multi-organ sarcoidosis, type 2 diabetes, subnephrotic-range proteinuria, hypertension and recurrent episodes of hypercalcaemia-induced acute kidney injury was referred for evaluation of worsening renal function and nephrotic range proteinuria. In 1987, the patient presented with an episode of iritis and was found to have hilar adenopathy. A bronchial biopsy was consistent with sarcoidosis. At the time of diagnosis, she did not have any evidence of renal involvement, but she had stage II sarcoidosis and was symptomatic from the pulmonary, ocular and neurologic points of view. Treatment with steroids resulted in multiple side effects including the successive developments of diabetes, hypertension, hyperlipidaemia and obesity. Over the next several years, multiple attempts were made to taper corticosteroid therapy, which resulted in episodes of hypercalcaemia and acute renal failure. Each episode almost completely resolved with the administration of fluids and resumption of steroids with a new baseline creatinine of 141.4 mumol/L (1.6 mg/dL). The administration of methotrexate as a steroid-sparing agent was not only ineffective but also poorly tolerated due to gastrointestinal side effects. In 2002, her proteinuria measured ~2.6 g/24 h and her serum creatinine ranged between 159.2 mumol/L and 176.8 mumol/L (1.8 and 2.0 mg/dL). The diagnosis of multiple myeloma was excluded with a negative urine and serum electrophoresis. In 2007, she was referred to nephrology for evaluation of elevated creatinine and proteinuria in the setting of a corrected calcium level of 2.46 mmol/L (9.84 mg/dL) with an albumin of 36 g/L. At the time of evaluation, her serum creatinine was 212 mumol/L (2.4 mg/dL) and she had ~10 g of protein excretion per day. She had poorly controlled diabetes and was on maximal dosages of an angiotensin receptor blocker but was unable to tolerate an angiotensin converting enzyme inhibitor due to persistent cough. We performed a renal biopsy due to the rapid decline in GFR in a few months and the large increase in proteinuria from baseline. The biopsy consisted of at least seven glomeruli revealing granulomatous interstitial nephritis consistent with renal sarcoidosis with moderate-to-severe chronic tubulointerstitial disease, multiple granulomas along with hypertensive vasculopathy and diabetic glomerulosclerosis with diffuse and nodular lesions (Figure 1A and B). The biopsy was not suggestive of glomerular involvement from sarcoidosis. High-dose steroids were felt to be an inappropriate therapeutic option in the setting of her poor glycaemic control and underlying diabetic nephropathy. Therefore, we chose to initiate a TNF-alpha inhibitor as an alternative therapy. She was evaluated for risk factors for tuberculosis and was found to have a negative tuberculin skin test prior to initiation of therapy. She was initiated on HumiraTM 40 mg/0.8 cc weekly for an arbitrary duration of 6 months after which we performed a follow-up renal biopsy to assess disease resolution. At the initiation of therapy, her serum creatinine was 345 mumol/L (3.9 mg/dL) and she had ~10 g of protein excretion/24 h. After 6 months of therapy her serum creatinine improved
to 159 mumol/L (1.8 mg/dL) and her protein excretion declined to ~3.5 g in 24 h (Figure 2). A repeat biopsy sampled ~17 glomeruli and revealed stable diabetic glomerulosclerosis, moderate chronic tubulointerstitial inflammation with complete resolution of interstitial epitheliod granulomas (Figure 1C and D). This patient tolerated this therapy for 6 months with no adverse events reported.