Two cases of idiopathic steroid-resistant nephrotic syndrome complicated with thrombotic microangiopathy.

BACKGROUND: Thrombotic microangiopathy (TMA) is a histopathological entity associated with microangiopathic hemolytic anemia, thrombocytopenia, and end-organ ischemic damage. Although TMA is caused by various diseases, there have been few reports regarding children with idiopathic nephrotic syndrome (NS) and TMA. Here we report two 1-year-old infants with steroid-resistant NS (SRNS) who presented with severe hypertension, acute kidney injury (AKI), and TMA.

CASE PRESENTATION: The diagnosis of NS was complicated with anemia, AKI, and hypertension. Maximum blood pressure was 150/70 mmHg in Case 1 and 136/86 mmHg in Case 2. There was no thrombocytopenia during their clinical course in both cases. Renal biopsy showed the features of TMA, including endothelial cell swelling, capillarectasia or marked mesangiolysis, along with mesangial proliferation in Case 1 and TMA with minor glomerular abnormalities in Case 2. Hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and secondary TMA other than that caused by hypertension were excluded. Oral prednisolone therapy, frequent infusion of albumin and diuretics, and multiple anti-hypertensive drugs were initiated. Blood pressure was controlled after 6 and 7 days from initiation of multiple anti-hypertensive drugs and lisinopril was added due to persistent mild proteinuria and mild hypertension after improvement of renal function in both cases. Proteinuria resolved completely 4 months after admission with daily oral prednisolone for 4 weeks followed by alternative daily oral prednisolone for 4 weeks in Case 1. Proteinuria resolved completely 10 months after admission with initial prednisolone treatment for 4 weeks followed by cyclosporine A and intravenous methylprednisolone pulse therapy in Case 2. The follow-up biopsy showed no TMA findings in both patients. Because the patient in Case 1 subsequently developed frequent relapsing NS, cyclosporine A was commenced after the second biopsy and he did not have any flares for 2 years. Renal function was normal in Case 1 and mildly decreased in Case 2 at last follow-up (creatinine-eGFR of 136.2 mL/min/cm2 in Case 1 and 79.5 mL/min/cm2 in Case 2).

CONCLUSION: Severe hypertension and AKI can be signs of TMA in patients with SRNS. Strict anti-hypertensive therapy might improve renal outcomes.