A 2-year-old male born at 37 weeks’ gestation presented to the emergency department for abdominal distension and constipation.
He was discharged from the hospital three days ago after a three-day admission for acute respiratory failure with hypoxia secondary to COVID-19. His last normal bowel movement was four days prior, despite home use of stool softeners and enemas. His mom denied fevers, vomiting, and anorexia, but did report intermittent periorbital edema for an unclear amount of time. During his recent hospitalization, he was not noted to have edema or signs of fluid overload.
The patient’s vital signs in the ED were as follows: HR, 100-128; RR, 22-28; temperature, 37°C; SpO2, 97-98%RA; and weight, 12.7kg (11.3kg at most recent discharge).
Physical exam showed an alert child crying while examined and nontoxic in appearance. The patient’s abdomen was distended and full, but not tense. Bowel sounds were present. Discomfort with palpation, but no focal tenderness/rebound/guarding. No stool in the rectal vault.
Pertinent lab results: (CBC) WBC 25, Platelets 940; (CMP) Potassium 3.0, Albumin 0.7, Alkaline Phosphatase 104; (Urinalysis) Protein 3+, Occult Blood 2+.
Differential Diagnosis, Next Steps
Differential diagnoses: nephrotic syndrome (minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy), glomerulonephritis, liver disease (cirrhosis, Alpha-1 antitrypsin deficiency), protein-losing enteropathy, and malnutrition.
ED workup continued: CT abdomen and pelvis showed small pleural effusions, large amount of ascites, dense liver (consider hepatic etiology for ascites), mildly atrophic left kidney.
The patient was admitted for further management including electrolyte replacement and consultation by pediatric nephrology and gastroenterology. Paracentesis was considered but deemed unnecessary from a therapeutic standpoint due to stable respiratory status. Gastroenterology recommended stool alpha one antitrypsin testing. Nephrology agreed with the suspected diagnosis of nephrotic syndrome versus minimal change disease and recommended a low-sodium diet with fluid restriction and 1mg/kg steroids twice daily. The patient has not yet returned for follow-up.
Nephrotic syndrome (NS) is diagnosed by the presence of proteinuria (protein excretion greater than 50 mg/kg/day or greater than or equal to 3+ proteins on urine dipstick), hypoalbuminemia (less than 2.5 g/dL), and peripheral edema. Hyperlipidemia and thrombotic disease are also frequently observed.1,2
Additional workup should include a lipid panel, ANA, C3, C4, viral hepatitis, and chest x-ray to evaluate for possible pleural effusions if suspected, and renal US if renal vein thrombosis is suspected.2
Most cases of NS in pediatric patients are secondary to minimal change disease (MCD). A presumptive diagnosis of MCD can be made without a renal biopsy based on clinical findings (e.g., age 1-9 years, absence of HTN/hematuria, normal complement levels and renal function). The most common risk factor is recent illness, particularly upper respiratory tract infection. Presenting symptoms commonly include periorbital/genital or, less commonly, lower extremities edema, ascites/pleural effusions, and fatigue with or without weight gain.4
There have been a few recent cases in the pediatric community with COVID-19 infection preceding NS. To date, there has been one published case of new onset NS reported with COVID-19 infection. Recurrence of nephrotic syndrome has also been reported in a pediatric patient ill with COVID-19.5 More than one-third of patients admitted to the hospital for COVID-19 infection also develop acute kidney injury (AKI), with many requiring kidney-replacement therapy.7 Histopathologic kidney findings of patients who died with COVID-19 have been most remarkable for acute tubular injury and are generally lacking classic viral nephropathy, diffuse thrombotic microangiopathy, or glomerulonephritis.8
As a reminder, nephritic syndrome also presents with edema with or without proteinuria, but more often is associated with elevated blood pressure and decreased GFR. The most significant differentiation is that nephritic syndrome manifests with hematuria (either gross or microscopic) while nephrotic syndrome does not.
Hospital admission is necessary for severe edema, symptomatic fluid overload, infection, or thrombosis. Cases of mild to moderate edema can be discharged with outpatient management, including nephrology follow-up.
Mainstay treatment for nephrotic syndrome includes diuresis and a low-salt diet. Intravenous fluids should be administered, even if edema is severe, if the patient is in hypovolemic shock. Furosemide (1-2 mg/kg) is recommended for volume overload. Correct hypoalbuminemia if <2 g/dL with a dose of 0.5-1 g/kg. Finally, the need for immunosuppressive therapy depends on the etiology of the nephrotic syndrome. In pediatrics, 90% of NS cases are due to MCD. In these cases, a six-week course of prednisone (2 mg/kg a day taken BID or TID) should be administered. Despite the known association with thrombotic disease, prophylactic anticoagulation is not recommended unless the patient has a history of known thromboembolism.
- Kidney Disease Improving Global Outcomes. KDIGO clinical practice guideline for glomerulonephritis. Kidney Int Suppl. 2012;2(2):139–274.
- International Study of Kidney Disease in Children. Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. Kidney Int. 1978;13(2):159–165.
- Park SJ, Shin JI. Complications of nephrotic syndrome. Korean J Pediatr. 2011 Aug; 54(8): 322–328.
- Keilman A, Marin JR. Nephrotic Syndrome. Fleisher&Ludwig’s 5-Minute Pediatric Emergency Medicine Consult 2nd Ed. 2020: 596-597.
- Alvarado A, Franceschi G, Resplandor E, Sumba J, Orta N. COVID-19 associated with onset nephrotic syndrome in a pediatric patient: coincidence or related conditions?. Pediatr Nephrol. 2021;36(1):205-207. doi:10.1007/s00467-020-04724-y
- Enya T, Morimoto Y, Oshima R, et al. Nephrotic syndrome relapse in a boy with COVID-19. CEN Case Rep. 2021;10(3):431-434. doi:10.1007/s13730-021-00587-w.
- Silver SA, Beaubien-Souligny W, Shah PS, et al. The Prevalence of Acute Kidney Injury in Patients Hospitalized With COVID-19 Infection: A Systematic Review and Meta-analysis. Kidney Med. 2021 Jan-Feb;3(1):83-98.e1. doi: 10.1016/j.xkme.2020.11.008. Epub 2020 Dec 9. PMID: 33319190; PMCID: PMC7723763.
- Su H, Yang M, Wan C, et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int. 2020; (published online April 6.) DOI:10.1016/j.kint.2020.04.003.