Acute Renal Failure Requiring Renal Replacement Therapy: Unusual Presentation of Multisystem Inflammatory Syndrome in Children

An 18-month-boy presented with fever for 7 days, facial puffiness, periorbital oedema and anuria. He had fever and cough briefly 3 weeks earlier. All family members had a similar illness at that time. Examination showed anasarca, pitting oedema and irritability. Investigations revealed haemoglobin 85 g/L, total leukocyte count 15.5 × 109/L (polymorphs 44%, lymphocytes 46%, monocytes 6% and eosinophils 3%) and platelet count 707 × 109/L with normal peripheral smear. Biochemical investigation showed serum sodium 129 mmol/L, potassium 6.6 mmol/L, blood urea 34.3 mmol/L and serum creatinine 999.9 μmol/L. Blood gas analysis showed pH 7.30, bicarbonate 11.2 mmol/L and serum lactate 1.1 mmol/L (normal: 0.5–1 mmol/L). His total urine output over the last 24 h was only 5 mL. As per Kidney Disease Improving Global Outcomes (KDIGO) classification, he was classified as having acute kidney injury (AKI) stage III. His serum C-reactive protein was 54.6 mg/L, d-dimer 3.8 μg/mL (normal: 0.1–0.5), serum fibrinogen 275.5 mg/dL (normal: 240–355) and serum interleukin-6 level 17.9 pg/mL (normal < 4.4). Aspartate transaminases and alanine transaminase were 32.9 U/L (<40 U/L) and 22.0 U/L (<40 U/L), respectively. Lactate dehydrogenase, serum ferritin, serum triglycerides, troponin and plasma B-type natriuretic peptide were 291.5 U/L (normal < 248), 403.9 ng/mL, 250.2 mg/dL (<150 mg/dL), negative and 11 pg/mL (<29.40 pg/mL), respectively. He was initiated on supportive therapy and peritoneal dialysis (PD) using percutaneously inserted peel-away sheath catheter by Seldinger technique. Urine examination showed proteinuria (+2), no casts or dysmorphic red blood cells. Spot urine protein/creatinine ratio was 1.4 (normal < 0.2). Blood and urine cultures were sterile. Human immunodeficiency virus enzyme-linked immunosorbent assay was non-reactive. Ultrasound of kidney, ureter and bladder (KUB) revealed normal sized kidneys with mildly increased echogenicity bilaterally. Doppler evaluation of the renal vessels was normal. Complement C3, C4, antinuclear antibodies, anticytoplasmic antibodies, serum albumin and cholesterol were normal. In view of his fever, high inflammatory markers, thrombocytosis and the family's febrile respiratory illness 3 weeks prior, the clinical possibility of multisystem inflammatory syndrome in children (MIS-C) was considered. At the time of presentation of this case to hospital, the country was facing the second pandemic wave of COVID-19. The patient fulfilled the Royal College of Paediatrics and Child Health definition of paediatric multisystem inflammatory syndrome temporally associated with COVID-19.1 Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) polymerase chain reaction was negative, while SARS-CoV-2 antibody titres (IgG: 12.56 index; normal < 1 index) were elevated, confirming a diagnosis of MIS-C. The patient was initiated on oral prednisolone (2 mg/kg/day) and subcutaneous low-molecular weight heparin (1 mg/kg/day). Gradually, his urine output improved to 1.3 mL/kg/h, and blood urea (5.95 mmol/L) and serum creatinine (61.88 μmol/L) normalised. PD was stopped on day 7 when his kidney function tests, electrolytes and urine examination were normal. The patient was discharged on tapering doses of oral prednisolone (over 6 weeks). MIS-C is a post-infectious phenomenon usually appearing weeks after COVID-19 infection.2 It is difficult to differentiate recent SARS-CoV-2 infection from an infection several months prior based on just IgG positivity. Studies have shown that antibodies against SARS-CoV-2 may persist for several months after infection but IgG titres decrease significantly during the first 6 months after exposure.3, 4 Anderson et al. have shown that children with MIS-C have higher levels of IgG antibodies that neutralise SARS-CoV-2 more effectively compared to children with severe COVID-19.5 In our case, the history of a recent compatible illness, with multiple family members affected at the same time and high daily caseloads suggest recent infection. Renal involvement in patients with MIS-C can manifest as proteinuria, haematuria and AKI. AKI has been reported in quarter to one-third of patients with MIS-C.6-8 McCulloch et al. have described a 9-year-old boy with MIS-C requiring PD.9 In one of the largest series of AKI in MIS-C (57 children with MIS-C), only 1 required dialysis.10 AKI may occur due to direct viral tropism to renal parenchyma, haemodynamic compromise, cytokine storm and multiorgan dysfunction.4 High levels of ACE2 receptor expression in proximal tubular epithelial cells may be responsible for viral tropism and kidney injury.6 To conclude, AKI requiring renal replacement therapy is an unusual presentation of MIS-C.