Xu, et al. [4] described a novel substance called renalase, and its possible role in the pathogenesis of cardiovascular complications. Renalase is a monoamine oxidase of renal origin responsible for the degradation of catecholamines. Renalase lowers blood pressure by decreasing cardiac contractility and heart rate and by preventing the expected compensatory increase in peripheral vascular tone. Abnormalities in the renalase pathway are described in animal models of hypertension and chronic kidney disease [5].

This study was performed to measure serum and urine renalase levels in children with a solitary functioning kidney, and compare these with healthy children.

Inclusion criteria for cases were: age <18 years, and a solitary functioning kidney (congenital or acquired) demonstrated by ultrasonography and renal scintigraphy. Exclusion criteria were: clinical and laboratory signs of infection, history of urinary tract infection, use of medications that might influence renal function or any kidney abnormalities detectable by ultrasonography. The reference group was recruited from participants of the OLAF study [6], whose physical examination, urine and blood tests, and renal ultrasonography were normal. The study was approved by the Medical University Ethics Committee.

Research methodology involved recording clinical history, demographic data, and physical examination. Hypertension was defined as blood pressure >95th percentile for age, sex, and height. Venous peripheral blood after overnight fasting, and morning urine samples were collected. Serum and urine samples were frozen and stored at –80°C. Laboratory tests included: serum creatinine, urea, uric acid and urinalysis. Glomerular filtration rate was assessed by an updated Schwartz formula. Microalbuminuria was defined as urinary albumin/creatinine ratio of 30-300 µg/mg.

Using a commercial enzyme-linked immunosorbent assay kit (USCN Life Science Inc., China), serum and urine renalase levels were measured and expressed as micrograms per milliliter (µg/mL) in the serum, and nanograms per milliliter (ng/mL) in the urine. The intra- and inter-assay coefficients of variance were 10% and 12%, respectively. Detection range was 3.12-200 ng/mL.

The data were analyzed using Statistica 10.0 software (StatSoft, Tulsa, OK, USA).

Serum renalase positively correlated with urine renalase (r=0.35, P<0.05). The urine renalase/creatinine values were negatively related to serum creatinine (r=-0.35; P<0.05), and positively to glomerular filtration rate (r=0.37; P<0.05). Kidney overgrowth did not correlate with serum and urinary renalase, glomerular filtration rate, and urinary albumin/creatinine ratio.

Our study, designed to explore serum and urine renalase levels and their relation to kidney function in children with a single kidney, reported that serum and urine renalase levels were significantly lower in single kidney patients. We did not find significant differences in urine renalase/creatinine levels between children with a solitary functioning kidney and the reference groups. Moreover, urine renalase/creatinine values in single kidney patients was related to parameters of kidney function: negatively with serum creatinine and positively with glomerular filtration rate. Neither serum nor urine renalase correlated with age, gender, or blood pressure.

The limitations of the study are: small sample size, single center, and cross-sectional. Additionally, an appropriate measurement of blood pressure in small children is difficult because of "white coat" anxiety and poor cooperation. Furthermore, in prepubertal and younger children no formula of glomerular filtration rate estimation gives acceptable results.

Recent experimental data in animal models support the hypothesis that renalase is an important marker of chronic kidney disease [5]. In humans, several studies have examined the likelihood that the presence of a solitary functioning kidney increases the risk of hypertension, proteinuria, and renal failure during childhood [8]. It has been shown that an apparently normal kidney is usually associated with hypertrophy of the surviving nephrons and accompanied by renal hyperfiltration which may contribute to albuminuria and a decline in glomerular filtration rate.

Patients with chronic kidney disease demonstrate markedly reduced levels of plasma renalase [9]. Based on our findings, significant reductions in serum and urine renalase levels dependent on kidney function were reported in single kidney patients compared with healthy volunteers. Our finding of no significant relationships between serum or urine renalase levels with age, gender, or blood pressure is in agreement with studies in dialyzed adult patients [10].

Based upon these results, a decrease in renalase levels may be related to early renal damage. However, these findings should be interpreted with caution because data from our ROC analyses did not show good diagnostic profiles for renalase in detection of renal dysfunction.

We conclude that renalase levels are altered but are unlikely to be suitable for the detection of early renal damage. Prognostic importance of reduced levels of renalase in children with a solitary functioning kidney to detect early deterioration of kidney functions before hypertension develops should be quantified by further longitudinal studies.

Contributors: KT-J: patient screening, enrollment, outcome assesement, data analysis, writing manuscript; RR: patient screening, data analysis, writing manuscript; AW: final data analyses, writing manuscript, critical revision.

Funding: Supported by a grant from the Medical University of Bialystok, Poland. Competing interests: None stated.