ALEXANDER Ok.C. LEUNG, MD; ALEX H.C. WONG, MD, MPH; and STEFANI S.N. BARG, MD, College of Calgary, Calgary, Alberta, Canada
Affected person info: See associated handout on proteinuria in kids.
This medical content material conforms to AAFP standards for persevering with medical training (CME). See the CME Quiz Questions.
The presence of protein in urine is a standard laboratory discovering in kids. Though proteinuria is often benign, it may be a marker of a critical underlying renal illness or systemic dysfunction.1–3 When proteinuria coexists with hematuria, the probability of clinically important renal illness is greater.1,2 Additional, proteinuria represents an unbiased threat issue for the development of nonglomerular or glomerular continual kidney illness in kids.4–9 The Persistent Kidney Illness in Kids examine demonstrated that persistent proteinuria with a excessive urine protein-to-creatinine (UPr/Cr) ratio (greater than 2 in sufferers with nonglomerular illness and greater than 0.5 in sufferers with glomerular illness) predicts important continual kidney illness development.7 The problem for the first care doctor is to separate benign types of proteinuria from these with medical significance.
Though proteinuria is often benign within the type of transient or orthostatic proteinuria, persistent proteinuria could also be related to extra critical renal illnesses. Proteinuria could also be an unbiased threat issue for the development of continual kidney illness in kids. Mechanisms of proteinuria may be categorized as glomerular, tubular, secretory, or overflow. A historical past, a bodily examination, and laboratory exams assist decide the trigger. Transient (practical) proteinuria is short-term. It may happen with fever, train, stress, or chilly publicity, and it resolves when the inciting issue is eliminated. Orthostatic proteinuria is the most typical kind in kids, particularly in adolescent males. It’s a benign situation with out medical significance. Persistent proteinuria may be glomerular or tubulointerstitial in origin. The urine dipstick check is essentially the most broadly used screening technique. Though a 24-hour urine protein excretion check is often beneficial for quantitation of the quantity of protein excreted within the urine, it might be impractical in kids. A spot, first-morning urine check for a protein-to-creatinine or protein-to-osmolality ratio is a dependable substitute. Remedy of proteinuria needs to be directed on the underlying trigger. Sufferers with lively urinary sediments, hematuria, hypertension, hypocomplementemia, renal insufficiency with depressed glomerular filtration charge, or indicators and signs suggestive of vasculitic illness might require referral to a pediatric nephrologist and a renal biopsy.
Enlarge
Print
A = constant, good-quality patient-oriented proof; B = inconsistent or limited-quality patient-oriented proof; C = consensus, disease-oriented proof, standard observe, skilled opinion, or case sequence. For details about the SORT proof score system, go to https://www.aafp.org/afpsort.
A = constant, good-quality patient-oriented proof; B = inconsistent or limited-quality patient-oriented proof; C = consensus, disease-oriented proof, standard observe, skilled opinion, or case sequence. For details about the SORT proof score system, go to https://www.aafp.org/afpsort.
Epidemiology
Proteinuria is current in as much as 10% of routine urine testing in school-aged kids, though this decreases to 0.1% with repeated testing.10 The prevalence will increase with age, peaks throughout adolescence, and is greater in women.11
Mechanisms of Proteinuria
Mechanisms of proteinuria may be categorized as glomerular, tubular, secretory, or overflow.1,2,12,13 Glomerular proteinuria is because of elevated filtration of macromolecules, notably albumin, throughout the glomerular capillary wall. This can be a results of elevated permeability of the glomerular basement membrane due to structural defects of the membrane, lack of its adverse expenses, or direct harm by immune complexes.1,2,12 Glomerular proteinuria can even happen when a lowered variety of functioning nephrons results in elevated diffusion of protein throughout the remaining glomeruli. Tubular proteinuria happens when there’s an elevated excretion of usually filtered low-molecular-weight proteins due to impaired reabsorption by the proximal tubules.12 Secretory proteinuria outcomes from oversecretion of sure proteins within the tubules, most notably the Tamm-Horsfall proteins in interstitial nephritis. Overflow proteinuria happens when the plasma concentrations of low-molecular-weight proteins exceed the capability of the tubules to reabsorb the filtered protein.
Etiology
Desk 1 summarizes the various etiologies of proteinuria in kids.1
TRANSIENT PROTEINURIA
Transient (practical) proteinuria is short-term and resolves when the inciting issue remits or is eliminated. Transient proteinuria can happen with a medical situation (e.g., fever, seizure) or one other set off, reminiscent of train, stress, dehydration, or chilly publicity. It can be idiopathic.
ORTHOSTATIC PROTEINURIA
Orthostatic proteinuria is the most typical explanation for proteinuria in kids, particularly in adolescent males.1,14,15 It’s a benign situation with out medical significance.1,15 The analysis is usually recommended with regular protein excretion (i.e., adverse urine dipstick check consequence, or a UPr/Cr ratio of 0.2 or much less) in a spot, first-morning urine pattern after the affected person has been supine for all the evening, however elevated protein excretion (i.e., optimistic urine dipstick check consequence, or a UPr/Cr ratio of greater than 0.2) at the very least 4 to 6 hours after the affected person has been upright.1–3 The reason for orthostatic proteinuria isn’t clear; nonetheless, the anatomic compression of the left renal vein has been urged.
PERSISTENT PROTEINURIA
Persistent proteinuria may be tubulointerstitial or extra generally glomerular in origin.1–3 Albumin and immunoglobulin G within the urine are the same old indicators for glomerular illnesses. Glomerular illnesses can have nephrotic and/or nephritic options, and distinguishing these options might help slim the differential analysis. Nephrotic syndrome is characterised by heavy proteinuria (greater than 1,000 mg per m2 per day or a UPr/Cr ratio of greater than 2), edema, hypoalbuminemia (lower than 2.5 g per dL [25 g per L]), and hyperlipidemia.16 Nephritic options embrace hematuria; hypertension; oliguria; and lively urinary sediments, reminiscent of purple blood cells, white blood cells, and mobile casts.
Tubulointerstitial illnesses often contain low-molecular-weight proteins. Proteinuria related to renal tubular issues is usually gentle. Tubular proteinuria hardly ever presents a diagnostic dilemma as a result of the underlying illness is often detected earlier than the proteinuria.17
Scientific Analysis
Desk 2 lists medical clues to the underlying explanation for persistent proteinuria.1
Diagnostic Analysis – “proteinuria in children”
Proteinuria is usually an incidental discovering on urine dip-stick testing or urinalysis. Kids with asymptomatic proteinuria often have the transient or orthostatic type. Determine 1 is an algorithm for the analysis of asymptomatic proteinuria in kids.1–3
If a urine dipstick check reveals hint quantities of protein, the check needs to be repeated with first-morning urine. If the first-morning check reveals a hint or adverse quantity of protein, it needs to be repeated in a single 12 months to make sure that the proteinuria doesn’t recur.1–3 In kids with a urine dipstick check exhibiting a results of 1 or extra, a first-morning urine dipstick check for UPr/Cr ratio and a urinalysis needs to be carried out (urine bag assortment is appropriate in youthful kids). If the UPr/Cr ratio is 0.2 or much less (0.5 or much less for youngsters six to 24 months of age) and urinalysis outcomes are regular, transient or orthostatic proteinuria is probably going.2 A repeat first-morning urine dipstick check in a single 12 months needs to be thought-about. If the UPr/Cr ratio is greater than 0.2 (greater than 0.5 for youngsters six to 24 months of age) or urinalysis outcomes are irregular (e.g., hematuria, leukocyturia, lively urinary sediments), persistent proteinuria or proteinuria of medical significance is extra seemingly,2 and additional analysis with historical past, bodily examination, and extra laboratory testing is beneficial to rule out important renal illness.1–3
Measurement of Proteinuria
OFFICE TESTING
The urine dipstick check makes use of the tetrabromophenol blue colorimetric technique and is essentially the most broadly used screening check.1,2,17 The check primarily detects albuminuria, with a specificity and sensitivity of greater than 99%, however it isn’t delicate for different proteins.18 The depth of colour modifications from yellow to blue correlates with the quantity of protein within the urine: hint (15 mg per dL), 1+ (30 mg per dL), 2+ (100 mg per dL), 3+ (300 mg per dL), and 4+ (1,000 mg per dL or extra).18 A studying of 1+ or extra is taken into account irregular. The dipstick urine check might yield false-positive outcomes with alkaline urine (pH larger than 8); concentrated urine (particular gravity larger than 1.030); gross hematuria; pyuria; bacteriuria; extended immersion of reagent strip within the urine or placement of reagent strip straight within the urine stream; and presence of phenazopyridine (Pyridium), chlorhexidine (Peridex), benzalkonium, or an iodinated radiocontrast agent within the urine.9,17 False-negative outcomes might happen with acidic urine (pH lower than 4.5), dilute urine (particular gravity lower than 1.010), and presence of proteins apart from albumin within the urine.9,17
The sulfosalicylic acid check detects all types of protein and is usually used as a supplementary check when the presence of a low-molecular-weight or different protein is suspected however not detected by the dipstick urine check. Within the sulfosalicylic acid technique, three drops of a sulfosalicylic acid 20% answer are added to five mL of urine. Relying on the quantity of protein precipitated, varied grades of turbidity, from minimal (hint) to heavy flocculation (4+), are famous.9,17
QUANTITATIVE LABORATORY TESTING
The primary-line check is a 24-hour urine protein excretion. In kids, the traditional quantity of protein is lower than 100 mg per m2 per day.3 Nonetheless, this quantitative measurement is usually troublesome in kids, notably in those that are incontinent.3 Additionally, the check has an inherent time delay, is usually troublesome to acquire in an outpatient setting, and is topic to assortment errors.
A spot, first-morning urine pattern is perfect for figuring out UPr/Cr ratio or UPr-to-osmolality ratio as a result of it excludes any postural impact on the protein part. The spot UPr/Cr or UPr-to-osmolality ratio is a handy and dependable technique for estimating urine protein excretion with no 24-hour urine assortment.16,19–21 To estimate the entire quantity of protein (g per m2 per day) within the urine, the UPr/Cr ratio may be multiplied by 0.63.16
OTHER LABORATORY TESTS
A whole blood rely and measurements of serum electrolytes, blood urea nitrogen, and serum creatinine needs to be thought-about if renal illness is suspected. An elevation in blood urea nitrogen or serum creatinine stage suggests impaired renal operate. Extra blood work needs to be ordered when indicated by historical past, bodily examination, or preliminary laboratory outcomes.1–3,19
IMAGING STUDIES
Ultrasonography of the urinary tract is an applicable, noninvasive screening check for anatomic abnormalities and needs to be thought-about in sufferers with continual kidney illness.1–3 A dimercaptosuccinic acid scan is the popular examine to detect renal scars.
RENAL BIOPSY
Renal biopsy isn’t routinely indicated within the workup of kids with proteinuria.1,2 A biopsy needs to be thought-about when proteinuria is accompanied by lively urinary sediments, persistent and gross hematuria, hypertension, hypocomplementemia, renal insufficiency with depressed glomerular filtration charge (lower than 60 mL per minute per 1.73 m2 for greater than three months), or indicators and signs suggestive of vasculitic illness.3
Administration
The household may be reassured if the proteinuria is transient or orthostatic, and the kid is asymptomatic, has no related hematuria, and has regular blood stress and glomerular filtration charge. Nonetheless, common follow-up is necessary so long as important proteinuria persists. Though there are not any formal tips for monitoring, a baby with persistent proteinuria ought to initially obtain a bodily examination, together with blood stress measurement, urinalysis, and blood exams for creatinine and urea nitrogen ranges, each six to 12 months.1,2 There isn’t a particular limitation on weight loss plan or bodily exercise. As soon as the kid is steady, follow-up may be annual.
Remedy of persistent proteinuria needs to be directed on the underlying trigger.1–3 There isn’t a proof that early remedy with prednisone reduces the prevalence of persistent proteinuria 12 months after onset of Henoch-Schönlein purpura.11 The usual remedy of idiopathic nephrotic syndrome includes 4 weeks of prednisone at a dosage of 60 mg per m2 per day (most, 80 mg per day), adopted by 4 weeks at a dosage of 40 mg per m2 per day (most, 60 mg per day) taken each different day.22 There isn’t a profit of accelerating the period of prednisone past two to a few months.22 If steroid remedy is ineffective or opposed results are insupportable, second-line remedy (e.g., cyclophosphamide, chlorambucil [Leukeran], cyclosporine [Sandimmune]) could also be required.23 In steroid- and cyclosporine-dependent nephrotic syndrome, biologic modifiers, reminiscent of rituximab (Rituxan), could also be tried.23–25 In sufferers with renal dysfunction, renoprotection with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker might lower proteinuria and gradual development of renal illness.5,26,27 Sufferers with lively urinary sediments, hematuria, hypertension, hypocomplementemia, renal insufficiency with depressed glomerular filtration charge, or indicators and signs suggestive of vasculitic illness might require referral to a pediatric nephrologist and renal biopsy.3,28
This text updates earlier articles on this matter by Leung and Wong,1 and Longhman-Adham.29
Knowledge Sources: A PubMed search was accomplished in Scientific Queries utilizing the important thing time period childhood proteinuria. The search included meta-analyses, randomized managed trials, medical trials, and opinions. Search date: June 1, 2016.
editor’s notice: This text relies partly on content material from the e-book chapter in reference 2, which was written by Dr. Leung.
“proteinuria in children”