Act Before It's Too Late: Avoid Mixed Connective Tissue Disease's Rare Renal Fate

Introduction: Scleroderma renal crisis (SRC) is a rare and life-threatening complication of mixed connective tissue disease (MCTD). We report a case with a challenging presentation. Case Description: A 42-year-old male developed Raynaud’s phenomenon and progressive dyspnea. Serologic evaluation revealed positive ANA (1:2560, speckled), anti-U1 RNP and smith antibodies, hypocomplementemia (C3 60 mg/dL, C4 <2 mg/dL), autoimmune hemolytic anemia, and negative RNA polymerase III antibody. Further workup demonstrated a mild pericardial effusion and pulmonary arterial hypertension (PAH) by right heart catheterization (RHC). He started prednisone, hydroxychloroquine (HCQ) and dual vasodilators for MCTD with PAH. Three months before Nephrology involvement, a contrast-enhanced CT scan was done to evaluate unintentional weight loss and he was admitted a few weeks later with dyspnea. A cardiac workup demonstrated an ejection fraction of 35% on echocardiogram, dilated cardiomyopathy on cardiac MRI, and a normal coronary angiogram. He was discharged home after IV diuresis, but was soon readmitted with pulmonary edema and worsening creatinine for which Nephrology was consulted. He was hypervolemic on examination, supported by point-of-care ultrasound. His urine studies were significant for a protein-to-creatinine ratio of 0.4 g/g but otherwise bland sediment. A diagnosis of cardiorenal syndrome was favored and he underwent aggressive diuresis. SRC was considered, but was discounted in the absence of hypertension and hemolysis. A repeat RHC demonstrated improved pulmonary vascular resistance while off vasodilators and normalized ejection fraction. After just a few days in the outpatient setting he quickly developed recurrent dyspnea, so Nephrology coordinated prompt readmission. He was severely hypertensive, had worsening kidney function, and active hemolysis. Captopril was initiated, but he ultimately required hemodialysis. Kidney biopsy demonstrated acute thrombotic microangiopathy with negative immunofluorescence, best representative of SRC. Discussion: This case highlights an insidious presentation of SRC in MCTD, which could represent its own distinct syndrome separate from SRC. We hypothesize that in the context of corticosteroids, the pathogenesis was hastened by radiocontrast exposure, aggressive diuresis, and removal of endothelin-receptor antagonism that may have been masking early signs of SRC.