Proteinuria in Children: Evaluation and Differential Diagnosis

 

Am Fam Physician. 2017 Feb 15;95(4):248-254.

  Patient information: See related handout on proteinuria in children.

Author disclosure: No relevant financial affiliations.

Although proteinuria is usually benign in the form of transient or orthostatic proteinuria, persistent proteinuria may be associated with more serious renal diseases. Proteinuria may be an independent risk factor for the progression of chronic kidney disease in children. Mechanisms of proteinuria can be categorized as glomerular, tubular, secretory, or overflow. A history, a physical examination, and laboratory tests help determine the cause. Transient (functional) proteinuria is temporary. It can occur with fever, exercise, stress, or cold exposure, and it resolves when the inciting factor is removed. Orthostatic proteinuria is the most common type in children, especially in adolescent males. It is a benign condition without clinical significance. Persistent proteinuria can be glomerular or tubulointerstitial in origin. The urine dipstick test is the most widely used screening method. Although a 24-hour urine protein excretion test is usually recommended for quantitation of the amount of protein excreted in the urine, it may be impractical in children. A spot, first-morning urine test for a protein-to-creatinine or protein-to-osmolality ratio is a reliable substitute. Treatment of proteinuria should be directed at the underlying cause. Patients with active urinary sediments, hematuria, hypertension, hypocomplementemia, renal insufficiency with depressed glomerular filtration rate, or signs and symptoms suggestive of vasculitic disease may require referral to a pediatric nephrologist and a renal biopsy.

The presence of protein in urine is a common laboratory finding in children. Although proteinuria is usually benign, it can be a marker of a serious underlying renal disease or systemic disorder.13 When proteinuria coexists with hematuria, the likelihood of clinically significant renal disease is higher.1,2 Further, proteinuria represents an independent risk factor for the progression of nonglomerular or glomerular chronic kidney disease in children.49 The Chronic Kidney Disease in Children study demonstrated that persistent proteinuria with a high urine protein-to-creatinine (UPr/Cr) ratio (more than 2 in patients with nonglomerular disease and more than 0.5 in patients with glomerular disease) predicts significant chronic kidney disease progression.7 The challenge for the primary care physician is to separate benign forms of proteinuria from those with clinical significance.

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SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferences

When proteinuria is present, physicians should monitor children with nonglomerular or glomerular chronic kidney disease for disease progression.

C

4, 7, 9

When a child's UPr/Cr ratio is more than 0.2 (more than 0.5 for children six to 24 months of age) or urinalysis results are abnormal, further evaluation with history, physical examination, and additional blood work is recommended to rule out significant renal disease.

C

3

A 24-hour urine protein excretion test is often difficult in children. Spot, first-morning urine testing for determining UPr-to-osmolality ratio is more useful and correlates well with the 24-hour urine collection; it should be used in children if the urine dipstick test result is 1 or more.

C

3, 16, 19

There is no evidence that early treatment with prednisone reduces the prevalence of persistent proteinuria 12 months after onset of Henoch-Schönlein purpura.

B

11

For the treatment of idiopathic nephrotic syndrome, the duration of prednisone should not be increased beyond two to three months.

A

22

In patients with renal dysfunction, treatment with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker appears to decrease proteinuria.

C

5, 26, 27

Patients with active urinary sediments, hematuria, hypertension, hypocomplementemia, renal insufficiency with depressed glomerular filtration rate, or signs and symptoms suggestive of vasculitic disease may require referral to a pediatric nephrologist and renal biopsy.

C

3, 28


UPr/Cr = urine protein-to-creatinine.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferences

When proteinuria is present, physicians should monitor children with nonglomerular or glomerular chronic kidney disease for disease progression.

C

4, 7, 9

When a child's UPr/Cr ratio is more than 0.2 (more than 0.5 for children six to 24 months of age) or urinalysis results are abnormal, further evaluation with history, physical examination, and additional blood work is recommended to rule out significant renal disease.

C

3

A 24-hour urine protein excretion test is often difficult in children. Spot, first-morning urine testing for determining UPr-to-osmolality ratio is more useful and correlates

The Authors

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ALEXANDER K.C. LEUNG, MD, is a clinical professor of pediatrics at the University of Calgary and a pediatric consultant at Alberta Children's Hospital in Alberta, Canada....

ALEX H.C. WONG, MD, MPH, is a clinical assistant professor of family medicine at the University of Calgary.

STEFANI S.N. BARG, MD, is a clinical lecturer of family medicine at the University of Calgary.

Address correspondence to Alexander K.C. Leung, MD, University of Calgary, Suite 200 Plaza 162 233, 16th Ave., NW, Calgary, Alberta, Canada T2M OH5 (e-mail: aleung@ucalgary.ca). Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.

REFERENCES

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