The Case

A 5-year-old previously healthy female presented from her pediatrician’s clinic to the emergency department for a complaint of whole body swelling. Her parents reported approximately one week ago they noticed intermittent periorbital swelling to their child. Over the last several days, her parents then noticed that her whole body appeared to be swelling, most prominently in hands and feet; her pediatrician noted on day of presentations that she had gained ten pounds during this time. Of note, she had been previously treated for strep throat with amoxicillin approximately one month prior.  The patient and parents denied fevers, abdominal pain or urinary symptoms.

Lab work and urinalysis were obtained and relevant findings are listed below:

Discussion

This patient’s presentation and labwork are consistent with nephrotic syndrome, a condition caused by a variety of renal diseases that increase membrane permeability across the glomerular filtration barrier. Four clinical features are used to aid in diagnosis: High proteinuria, hypoalbuminemia (<3g/dl), edema, and hyperlipidemia. [1]

A urine protein/creatinine ratio greater than or equal to 2 is also suggestive of nephrotic syndrome.  A small amount of blood may be seen in the urine, but if >5 RBCs are found, you should consider nephritic syndrome as an underlying cause of symptoms.

Nephritic syndrome is also characterized by findings of proteinuria and edema, however it can be distinguished from nephrotic syndrome in that it also presents classically with hematuria and hypertension. [2]  There are a variety of nephritic syndromes which are typically thought to be due to an underlying immune response.

Post-streptococcal glomerulonephritis (PSGN) is the most common cause of nephritic syndrome in children. [3] PSGN occurs after an infection by Group A beta-hemolytic streptococcus (GAS), causing circulating immune complexes which then are thought to damage glomeruli of kidneys. Most commonly, PSGN will occur 1-3 weeks after GAS pharyngitis and 3-6 weeks after a GAS skin infection. [4] Urinalysis will typically demonstrate hematuria with RBC casts, proteinuria (however lower levels than found in nephrotic syndrome) and pyuria. [5] In PSGN, complement levels will be low as this immune process is activated after the infection. Additionally, antibodies to GAS are commonly tested to determine if there was recent GAS infection. As seen in the table above, these antibodies were negative (ASO titer and anti-DNase-B antibody) pointing away from a diagnosis of nephritic syndrome. 

Given this patient’s age, lab work (particularly the level of proteinuria and lack of hematuria) and clinical presentation, the most likely diagnosis was minimal change disease as this is the most common cause of nephrotic syndrome in children. Nephrology recommended starting a course of prednisolone. Given that she was otherwise well appearing and without other complaints, she was discharged home with close nephrology follow up.  She was recommended to use home urine dipsticks to monitor for protein levels, which helps to determine responsiveness to treatment.  

Treatment

The mainstay of treatment for nephrotic syndrome is steroids. [6] In minimal change disease, nearly all children respond and enter remission by eight weeks of steroid therapy. If patients are not responsive to steroid therapy, the patient should be considered for a renal biopsy as an alternative diagnosis may be found such as amyloidosis or lupus-induced nephropathy that may influence management. [7] The patient was started on a course of twice-daily steroids for twelve weeks. [8]  She was also screened for tuberculosis given that immunosuppression was being initiated. Patients who develop severe edema can also be treated with a sodium-restricted diet and diuretics. [9]

It is important to note that children with nephrotic syndrome are at increased risk infection for a variety of reasons including reduced concentrations of IgG, impaired production of antibodies, decreased complement levels, and immunosuppressive therapy with steroids. [10] Thus, patients with nephrotic syndrome who present with infectious symptoms should be comprehensively evaluated. A diagnosis of spontaneous bacterial peritonitis (SBP) should also be strongly considered in these patients, especially if they have abdominal pain. SBP is an ascitic fluid infection typically diagnosed by a positive bacterial culture and/or polymorphonuclear leukoctye count >250 cells. Paracentesis must be performed to obtain ascitic fluid for analysis.

Case Resolution

The following week, the patient returned to the emergency department for severe abdominal pain and fever. An abdominal ultrasound was performed and notable for ascites. Given concern for SBP, a paracentesis was performed by interventional radiology after which the patient was started on ceftriaxone and admitted to the hospital. A rapid viral panel was sent and patient was ultimately found to be positive for norovirus. Her clinical status improved with continued IV fluids and steroid treatment and she was discharged home the following day. Ultimately, the patient had a positive response to steroid treatment after her edema and proteinuria resolved and is currently doing well.

Faculty Reviewer: Dr. Jane Preotle

References

[1] Gipson DS, Massengill SF, Yao L, et al. Management of childhood onset nephrotic syndrome. Pediatrics 2009; 124:747.

[2] 2.Rodriguez-Iturbe B, Musser JM. The current state of poststreptococcal glomerulonephritis. J Am Soc Nephrol 2008; 19:1855.

[3] Rodriguez-Iturbe B. Postinfectious glomerulonephritis. Am J Kidney Dis 2000; 35:XLVI.

[4] Nissenson AR, Baraff LJ, Fine RN, Knutson DW. Poststreptococcal acute glomerulonephritis: fact and controversy. Ann Intern Med 1979; 91:76.

[5] Baldwin DS, Gluck MC, Schacht RG, Gallo G. The long-term course of poststreptococcal glomerulonephritis. Ann Intern Med 1974; 80:342.

[6] The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. A report of the International Study of Kidney Disease in Children. J Pediatr 1981; 98:561.

[7] Richards NT, Darby S, Howie AJ, et al. Knowledge of renal histology alters patient management in over 40% of cases. Nephrol Dial Transplant 1994; 9:1255.

[8] Arbeitsgemeinschaft fur Padiatrische Nephrologie. Short versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children. Lancet. 1988;1:380-383.

[9] Hogg RJ, Portman RJ, Milliner D, et al. Evaluation and management of proteinuria and nephrotic syndrome in children: recommendations from a pediatric nephrology panel established at the National Kidney Foundation conference on proteinuria, albuminuria, risk, assessment, detection, and elimination (PARADE). Pediatrics 2000; 105:1242.

[10] Alwadhi RK, Mathew JL, Rath B. Clinical profile of children with nephrotic syndrome not on glucorticoid therapy, but presenting with infection. J Paediatr Child Health 2004; 40:28.