Orthostatic proteinuria and the spectrum of diurnal variability of urinary protein excretion in healthy children

Brandt, John R.; Jacobs, Aaron; Raissy, Hengameh H.; Kelly, Franceska; Staples, Amy; Kaufman, Ellen; Wong, Craig S.

doi:10.1007/s00467-010-1451-z

Cited by 61 publications

(49 citation statements)

References 25 publications

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“…Such screening is already standard of care in certain other high-risk groups, such as children with type 1 diabetes mellitus 91 and sickle cell disease. 92 Unfortunately, the utility of microalbuminuria as a screening tool may be hampered by a high false-positive rate due to the prevalence of benign proteinurias (such as orthostatic proteinuria 93 or exercise-induced proteinuria 94 ) in the pediatric population. For example, in the NHANES, 8.9% of adolescents had microalbuminuria, although the majority of these had no other risk factors for cardiovascular or renal disease.…”

Section: Figurementioning

confidence: 99%

Short-Term Gestation, Long-Term Risk: Prematurity and Chronic Kidney Disease

2013

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Thanks to remarkable advances in neonatal intensive care, infants who once had little chance for survival can now enter adulthood. Yet the consequences of premature birth or low birth weight (LBW) on nephrogenesis, final nephron number, and long-term kidney function are unclear. This review focuses on the theory, experimental evidence, and observational data that suggest an increased risk of chronic kidney disease (CKD) for infants born prematurely. Many premature and LBW infants begin life with an incomplete complement of immature nephrons. They are then exposed to a variety of external stressors that can hinder ongoing kidney development or cause additional nephron loss such as hemodynamic alterations, nephrotoxic medications, infections, and suboptimal nutrition. Acute kidney injury, in particular, may be a significant risk factor for the development of CKD. According to Brenner' s hypothesis, patients with decreased nephron number develop hyperfiltration that results in sodium retention, hypertension, nephron loss, and CKD due to secondary focal segmental glomerulosclerosis. Because the risk of CKD in premature and LBW infants has not been accurately determined, there are no evidence-based recommendations for screening or management. Yet with the first generation of infants from the surfactant era only now reaching adulthood, it is possible that there is already an unrecognized epidemic of CKD. We suggest individualized, risk-based assessments of premature and LBW infants due to the increased risk of CKD and call for additional research into the long-term risk for CKD these infants face.

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Section: Figurementioning

confidence: 99%

Short-Term Gestation, Long-Term Risk: Prematurity and Chronic Kidney Disease

2013

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“…It was almost twofold prevalent among 6 -19-year-old than in 20 -39-year-old, increasing continuously starting at 40-year-old [33]. Possible explanation for high prevalence in adolescents might be the influence of orthostatic proteinuria [34]. A positive association was found between albumin excretion rate and pubertal developmental stage [35].…”

Section: Microalbuminuria In Healthy Childrenmentioning

confidence: 88%

“…Microalbuminuria has also been investigated in numerous nephrologic and other diseases, such as microhaematuria [56], sickle cell anemia [30,57], low-birth weight [58], congenital solitary kidneys [59], orthostatic proteinuria [34], metabolic syndrome [28].…”

Section: Microalbuminuria In Different Childhood Diseasesmentioning

confidence: 99%

Microalbuminuria in pediatric patients with hypertension

Varda¹

2013

Health

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Microalbuminuria in adults has been found to be an early indicator of both renal and systemic vascular disease, as well as significant cardiovascular risk predictor and therapeutic marker. Its role in essential hypertension in adults has also been well established. As diseases like hypertension and obesity have their roots in childhood and are already present in children, influencing the morbidity in adulthood, the role of microalbuminuria has been extensively investigated in children as well. Most investigations have been performed in diabetic children, confirming its clinical significance. There is also enough evidence to suggest that microalbuminuria in obese children should be taken as seriously as in children with diabetes. In children with hypertension rare studies also indicate that its presence identifies hypertensive children with higher risk, although the exact role has to be confirmed in prospective and larger studies. The mechanisms of microalbuminuria onset could be the result of renal damage secondary to hypertension or underlying renal and systemic endothelial dysfunction. Evidence from small intervention studies in children with microalbuminuria also suggests that early intervention with antihypertensive drugs is likely to be beneficial, pointing out the role of microalbuminuria as a therapeutic marker in children too. In addition, we have to stress the importance of follow-up of children with microalbuminuria, confirmation of its persistence and identification of progression. However, longitudinal prospective studies in children, investigating its future cardiovascular risk, are still lacking.

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“…This raises the question of whether these children have orthostatic proteinuria. Orthostatic proteinuria is a benign increase in daytime urine protein excretion without renal pathology and has been described in 4% -20% of healthy children [16,24]. In a previous study by our group, orthostatic proteinuria was associated with a proportional change in creatinine clearance, suggesting that changes in GFR mediate the variation in protein excretion [24].…”

Section: Discussionmentioning

confidence: 99%

“…In a previous study on orthostatic proteinuria [24] in this cohort of subjects we found that measured CrCl was higher during the daytime compared to the night and a higher CrCl was associated with an increased risk of orthostatic proteinuria. Our finding of a correlation between total urine creatinine and albumin excretion suggests that the difference in albumin excretion between day and night may be mediated by changes in glomerular filtration rate.…”

Section: Discussionmentioning

confidence: 99%

Urine albumin excretion: Characterization of normal variability in healthy children

Brandt¹,

Wong²,

Jacobs³

et al. 2013

OJPed

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Objective: Elevated urine albumin to creatinine ratio (ACR) of >30 mg/gm is a widely agreed upon indicator of pathologic albuminuria in children. However, the most reliable specimen to measure ACR in children remains undefined. We assess the range and limits of upright and supine total albumin and ACR in healthy children. Methods: Healthy children age 6 -18 years completed 24-hour and split upright and supine urine collections. Upright, supine and 24-hour protein, albumin and creatinine were measured. Primary outcomes are range and variation in urine albumin by diurnal status, age, gender, BMI percentile and Tanner stage. Results: In healthy children, with mean age 12.9 year (sd 3.2), upright ACR was 2-fold greater than supine (13.9 vs 6.8 mg/gm, p = 0.02). The range of ACR was much greater in the upright (2 -323 mg/gm) compared to the supine (1.7 -76 mg/gm) samples. The average total 24-hour urine albumin was 8.4 mg (sd 9.8) and the mean ACR was 8.9 mg/gm (sd 11.7). The 24-hour albumin increased with age and Tanner stage, but this relationship was not significant after adjusting for BSA or urine creatinine. A supine or upright ACR of >30 mg/gm was found in 5.4% of each group. However, in all subjects with an elevated ACR on an individual upright or supine sample, a second 1st am ACR sample was normal. Conclusions: In healthy children there is a marked diurnal variability in ACR with a higher value from a daytime sample compared to 1st morning specimen. Screening for pathologic albuminuria should always use a first morning urine specimen.

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Orthostatic proteinuria and the spectrum of diurnal variability of urinary protein excretion in healthy children

Cited by 61 publications

References 25 publications

Short-Term Gestation, Long-Term Risk: Prematurity and Chronic Kidney Disease

Short-Term Gestation, Long-Term Risk: Prematurity and Chronic Kidney Disease

Microalbuminuria in pediatric patients with hypertension

Urine albumin excretion: Characterization of normal variability in healthy children

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