Pediatr Nephrol DOI 10.1007/s00467-014-2773-z
ORIGINAL ARTICLE
Is oxidative stress related to childhood urolithiasis? Nilufer Göknar & Faruk Oktem & Engin Arı & Aysegul Doğan Demir & Emel Torun
Received: 1 October 2013 / Revised: 10 January 2014 / Accepted: 22 January 2014 # IPNA 2014
Abstract Background Urolithiasis is a common condition in pediatric populations in Turkey. The role of oxidative stress in renal stone formation in pediatric patients has not been reported to date. The aim of this study was to assess oxidative stress in childhood urolithiasis. Methods Seventy-four children diagnosed with urolithiasis and 72 healthy control subjects were enrolled in the study. Kidney stone formers were evaluated by analysis of metabolic conditions related to urolithiasis, such as hypercalciuria, hyperoxaluria, hypocitraturia and hyperuricosuria. Urine total antioxidant status (TAS), and total oxidant status (TOS) were measured, and oxidative stress index (OSI) was calculated as an indicator of the degree of oxidative stress. Results Among the stone formers, metabolic analyses revealed that 30 % had hypercalciuria, 45 % had hypocitraturia, 6 % had hyperoxaluria and 40 % had hyperuricosuria. Elevated levels of the renal tubular damage marker urinary N-acetylbeta-D-glucosaminidase (NAG) was elevated in 25 % of the patient group, but microalbuminuria was not detected. Total oxidant status and total antioxidant status were significantly higher in stone formers than in the controls (p=0.023 and 0.004, respectively). In addition, urinary NAG was significantly correlated with TOS (r=0.427, p=0.019). Conclusions The results of this study show that oxidative stress may play an important role in the pathogenesis of pediatric stone formers.
N. Göknar : F. Oktem Department of Pediatric Nephrology, Bezmialem Vakif University Medical Faculty, Istanbul, Turkey E. Arı : A. D. Demir : E. Torun (*) Department of Pediatrics, Bezmialem Vakif University Hospital, Adnan Menderes Avenue P.K, 34093 Fatih, Istanbul, Turkey e-mail: [email protected]
Keywords Urolithiasis . Oxidative stress . Children . Metabolic conditions
Introduction Urolithiasis is a common condition that affects 11 % of the population in Turkey with considerable morbidity and recurrence [1]. Genetic, metabolic, anatomic, dietary and environmental factors are common contributing factors to urolithiasis. Pediatric urolithiasis has different characteristics compared to that in adults. Unlike adults, metabolic risk factors, such as hypercalciuria, hyperoxaluria and cystinuria, are well described in 33–95 % of all urolithiasis cases in childhood [2]. Humans excrete millions of urinary crystals every day, yet few people develop kidney stones. Kidney stones can only form in the presence of urine supersaturation, crystal formation and renal tubular damage. Supersaturation, although necessary for crystal formation, is by itself not sufficient for stone formation [3]. Within the urinary tract, crystal formation, particularly of calcium phosphate and calcium oxalate (CaOx), is widespread. Persistent mild hyperoxaluria and CaOx crystals are not only injurious to the renal epithelium but can result in its death and degradation [4, 5]. Hydroxyl radicals (OH−) and their subsequent products are the most harmful reactive oxygen species (ROS) and are the main factors responsible for the oxidative injury of biomolecules; however, they are neutralized by antioxidants. Exposure to excessive Ox and CaOx crystals produces more ROS that can be compensated for by endogenous antioxidants; consequently, the formation of these crystals also results in renal injury. Cellular damage promotes crystal retention through the promotion of nucleation, aggregation and attachment of crystals to the renal epithelium. In addition to all of these factors, an inflammatory response is mandatory for stone formation [3].
Pediatr Nephrol
Oxidant status can be assessed by determining the total oxidant status (TOS). The antioxidant status of individuals depends on multiple factors, such as systemic antioxidants, antioxidant enzymes and dietary composition. The effects of these factors, which are additive, are termed the total antioxidant status (TAS). Oxidative stress occurs when there is an imbalance between pro-oxidants and antioxidants in favor of oxidants, which can lead to inflammation and injury [6, 7]. Published studies have addressed both oxidative stress in renal stone patients and the use of antioxidants to treat adults, but to our knowledge no data have been published on pediatric stone formers who exhibit properties different from those of adult ones. Oxidant and antioxidant parameters have been measured individually in recent studies [8–12]. Measurements of single oxidant or antioxidant parameters are complex and expensive and are not a practical means by which to accurately determine the free radical burden among those in the pediatric age group. Neither TOS nor TAS has yet been investigated in pediatric urolithiasis, and with Erel’s method, both can be measured easily and inexpensively. This method can also be used to determine the overall oxidative stress index (OSI), which may include those antioxidants or oxidants not yet recognized or not easily measured [6, 7]. The aim of our study was to define the total oxidative and antioxidative status of children with renal stone disease by measuring TAS, TOS and OSI. We were also interested in the results of the metabolic analysis related to urolithiasis in children.
laboratory. Urinary NAG was analyzed using a photometric method (Cobbas 8000 autoanalyzer, Diazyme Labsoratories, Poway, CA). Hypercalciuria, hyperoxaluria and hyperuricosuria were defined as calcium, oxalate and uric acid excretion of >4 mg/kg/day, >40 mg/1.73 m2/day and >10.7 mg/kg/day, respectively. Hypocitraturia was defined as urinary citrate excretion of
ORIGINAL ARTICLE
Is oxidative stress related to childhood urolithiasis? Nilufer Göknar & Faruk Oktem & Engin Arı & Aysegul Doğan Demir & Emel Torun
Received: 1 October 2013 / Revised: 10 January 2014 / Accepted: 22 January 2014 # IPNA 2014
Abstract Background Urolithiasis is a common condition in pediatric populations in Turkey. The role of oxidative stress in renal stone formation in pediatric patients has not been reported to date. The aim of this study was to assess oxidative stress in childhood urolithiasis. Methods Seventy-four children diagnosed with urolithiasis and 72 healthy control subjects were enrolled in the study. Kidney stone formers were evaluated by analysis of metabolic conditions related to urolithiasis, such as hypercalciuria, hyperoxaluria, hypocitraturia and hyperuricosuria. Urine total antioxidant status (TAS), and total oxidant status (TOS) were measured, and oxidative stress index (OSI) was calculated as an indicator of the degree of oxidative stress. Results Among the stone formers, metabolic analyses revealed that 30 % had hypercalciuria, 45 % had hypocitraturia, 6 % had hyperoxaluria and 40 % had hyperuricosuria. Elevated levels of the renal tubular damage marker urinary N-acetylbeta-D-glucosaminidase (NAG) was elevated in 25 % of the patient group, but microalbuminuria was not detected. Total oxidant status and total antioxidant status were significantly higher in stone formers than in the controls (p=0.023 and 0.004, respectively). In addition, urinary NAG was significantly correlated with TOS (r=0.427, p=0.019). Conclusions The results of this study show that oxidative stress may play an important role in the pathogenesis of pediatric stone formers.
N. Göknar : F. Oktem Department of Pediatric Nephrology, Bezmialem Vakif University Medical Faculty, Istanbul, Turkey E. Arı : A. D. Demir : E. Torun (*) Department of Pediatrics, Bezmialem Vakif University Hospital, Adnan Menderes Avenue P.K, 34093 Fatih, Istanbul, Turkey e-mail: [email protected]
Keywords Urolithiasis . Oxidative stress . Children . Metabolic conditions
Introduction Urolithiasis is a common condition that affects 11 % of the population in Turkey with considerable morbidity and recurrence [1]. Genetic, metabolic, anatomic, dietary and environmental factors are common contributing factors to urolithiasis. Pediatric urolithiasis has different characteristics compared to that in adults. Unlike adults, metabolic risk factors, such as hypercalciuria, hyperoxaluria and cystinuria, are well described in 33–95 % of all urolithiasis cases in childhood [2]. Humans excrete millions of urinary crystals every day, yet few people develop kidney stones. Kidney stones can only form in the presence of urine supersaturation, crystal formation and renal tubular damage. Supersaturation, although necessary for crystal formation, is by itself not sufficient for stone formation [3]. Within the urinary tract, crystal formation, particularly of calcium phosphate and calcium oxalate (CaOx), is widespread. Persistent mild hyperoxaluria and CaOx crystals are not only injurious to the renal epithelium but can result in its death and degradation [4, 5]. Hydroxyl radicals (OH−) and their subsequent products are the most harmful reactive oxygen species (ROS) and are the main factors responsible for the oxidative injury of biomolecules; however, they are neutralized by antioxidants. Exposure to excessive Ox and CaOx crystals produces more ROS that can be compensated for by endogenous antioxidants; consequently, the formation of these crystals also results in renal injury. Cellular damage promotes crystal retention through the promotion of nucleation, aggregation and attachment of crystals to the renal epithelium. In addition to all of these factors, an inflammatory response is mandatory for stone formation [3].
Pediatr Nephrol
Oxidant status can be assessed by determining the total oxidant status (TOS). The antioxidant status of individuals depends on multiple factors, such as systemic antioxidants, antioxidant enzymes and dietary composition. The effects of these factors, which are additive, are termed the total antioxidant status (TAS). Oxidative stress occurs when there is an imbalance between pro-oxidants and antioxidants in favor of oxidants, which can lead to inflammation and injury [6, 7]. Published studies have addressed both oxidative stress in renal stone patients and the use of antioxidants to treat adults, but to our knowledge no data have been published on pediatric stone formers who exhibit properties different from those of adult ones. Oxidant and antioxidant parameters have been measured individually in recent studies [8–12]. Measurements of single oxidant or antioxidant parameters are complex and expensive and are not a practical means by which to accurately determine the free radical burden among those in the pediatric age group. Neither TOS nor TAS has yet been investigated in pediatric urolithiasis, and with Erel’s method, both can be measured easily and inexpensively. This method can also be used to determine the overall oxidative stress index (OSI), which may include those antioxidants or oxidants not yet recognized or not easily measured [6, 7]. The aim of our study was to define the total oxidative and antioxidative status of children with renal stone disease by measuring TAS, TOS and OSI. We were also interested in the results of the metabolic analysis related to urolithiasis in children.
laboratory. Urinary NAG was analyzed using a photometric method (Cobbas 8000 autoanalyzer, Diazyme Labsoratories, Poway, CA). Hypercalciuria, hyperoxaluria and hyperuricosuria were defined as calcium, oxalate and uric acid excretion of >4 mg/kg/day, >40 mg/1.73 m2/day and >10.7 mg/kg/day, respectively. Hypocitraturia was defined as urinary citrate excretion of
