Statin Adverse Effects Revisited: Rosuvastatin-Induced Nephrotoxicity Presenting as Proteinuria and Kidney Failure

Introduction: Rosuvastatin was the thirteenth most prescribed medication in the United States in 2022. As cardiovascular guidelines increasingly recommend high-intensity statins for atherosclerotic cardiovascular disease, adverse effects have been observed. We evaluated several patients in clinic for new or worsening proteinuria and kidney function shortly after initiation or dose escalation of rosuvastatin, without alternative etiologies. Case Description: Case 1: A 61-year-old woman had a rise in creatinine (Cr) from 0.95 to 1.55 mg/dL and worsening proteinuria to 968 mg/day. Her primary workup was unremarkable. Upon switching from rosuvastatin 40 mg to atorvastatin 40 mg, her renal function improved (Cr 1.16 mg/dL, proteinuria 290 mg) 3 months later. We noticed deterioration in both indices when she was rechallenged with rosuvastatin. Case 2: A 66-year-old woman with vasculopathy and stable limited granulomatosis with polyangiitis on rituximab was noted to have worsening renal function and proteinuria (Cr 0.93 to 1.23 mg/dL, proteinuria 161 to 647 mg) after starting rosuvastatin 40 mg. When switched to atorvastatin, without any other intervention, proteinuria improved to 83 mg/day. Case 3: A 54-year-old man referred to our clinic with Cr 2.56 mg/dL and proteinuria of 1520 mg on rosuvastatin 40 mg. His overall workup was unremarkable. When he was switched to atorvastatin 40 mg, we noted improvement in his proteinuria (853 mg) while renal function remained stable. Discussion: The cases above demonstrated a temporal relationship between high-dose rosuvastatin use and worsening proteinuria and/or renal function, which improved when switched to atorvastatin. These findings raise concern for rosuvastatin-induced nephrotoxicity, particularly at higher doses, although the mechanism remains unclear. Multiple prior reports have been made, with a press release by ASN in 2022 highlighting a significant rise in inappropriate rosuvastatin dosages. This adverse effect is underrecognized and should be considered when evaluating patients with unclear etiology of proteinuria or reduced renal function. Further studies are needed to characterize this entity further, raise awareness among clinicians, and ultimately reflect on treatment guidelines.