Chest configuration in children and adolescents with infantile nephropathic cystinosis compared with other chronic kidney disease entities and its clinical determinants.

BACKGROUND: Infantile nephropathic cystinosis (INC) is a systemic lysosomal storage disease causing intracellular cystine accumulation, resulting in renal Fanconi syndrome, progressive kidney disease (CKD), rickets, malnutrition, and myopathy. An INC-specific disproportionately diminished trunk length compared to leg length poses questions regarding the functionality of the trunk. METHODS: Thus, we prospectively investigated thoracic dimensions and proportions, as well as their clinical determinants in 44 pediatric patients with INC with CKD stages 1-5 and 97 age-matched patients with CKD of other etiology between the ages of 2-17 years. A total of 92 and 221 annual measurements of patients with INC and CKD, respectively, were performed, and associations between anthropometric and clinical parameters were assessed using linear mixed-effects models. RESULTS: Patients with INC exhibited altered chest dimensions that were distinct from CKD controls, characterized by markedly increased chest depth to height and chest depth to chest width ratio z-scores (> 1.0), while those of patients with CKD were only mildly affected (z-score within ± 1.0). Ratio z-scores differed significantly between both patient groups from 2-6 years of age onward. The degree of chest disproportion in INC patients was significantly associated with both the degree of CKD and tubular dysfunction (e.g., low serum phosphate and bicarbonate) across three different age groups (2-6, 7-12, and 13-17 years). CONCLUSION: Our data show an INC-specific alteration in thoracic shape from early childhood onward, which is distinct from CKD of other etiologies, suggesting early childhood subclinical changes of the musculoskeletal unit of the thoracic cage, which are associated with kidney function. A higher resolution version of the Graphical abstract is available as Supplementary information.

Body growth, upper arm fat area, and clinical parameters in children with nephropathic cystinosis compared with other pediatric chronic kidney disease entities.

Children with infantile nephropathic cystinosis (INC), an inherited lysosomal storage disease resulting in cystine accumulation in all body cells, are prone to progressive chronic kidney disease (CKD), impaired growth and reduced weight gain; however, systematic anthropometric analyses are lacking. In this prospective multicenter study we investigated linear growth, body proportion, body mass index (BMI), upper arm fat area (UFA) and biochemical parameters in 43 pediatric INC patients with CKD stages 1 to 5 and 49 age-matched CKD controls, with 193 annual measurements. INC patients showed more impaired height than CKD controls (-1.8 vs -0.7 z-score; P < .001), despite adequate cysteamine therapy, treatment for Fanconi syndrome and more frequent use of growth hormone. Only the youngest INC patients shared the same body pattern with CKD controls characterized by preferential impairment of leg length and rather preserved trunk length. In late-prepuberty, body pattern changed only in INC patients due to improved leg growth and more impaired trunk length. Mean UFA z-score in INC patients was slightly reduced in early childhood and progressively decreased thereafter reaching -0.8 z-score in adolescence, while CKD controls showed a steady increase in standardized BMI and UFA especially during adolescent age. Menarche in female INC patients was significantly delayed compared to CKD controls. Our data indicate that with age and progression of disease, pediatric INC patients undergo unique changes of body growth and fat stores that are distinct from those with CKD stemming from other causes, suggesting other factors apart from CKD to contribute to this development. Pediatric patients with infantile nephropathic cystinosis display more severe impaired linear growth than other peer CKD patients, despite of cysteamine treatment, supplementation for Fanconi syndrome, and more frequent use of growth hormone, with a distinct change of body proportions and overall lower body fat.

Growth hormone treatment in the pre-transplant period is associated with superior outcome after pediatric kidney transplantation.

BACKGROUND: Recombinant human growth hormone (rhGH) is frequently used for treatment of short stature in children with chronic kidney disease (CKD) prior to kidney transplantation (KT). To what extent this influences growth and transplant function after KT is yet unknown. METHODS: Post-transplant growth (height, sitting height, leg length) and clinical parameters of 146 CKD patients undergoing KT before the age of 8 years, from two German pediatric nephrology centers, were prospectively investigated with a mean follow-up of 5.56 years. Outcome in patients with (rhGH group) and without (non-prior rhGH group) prior rhGH treatment was assessed by the use of linear mixed-effects models. RESULTS: Patients in the rhGH group spent longer time on dialysis and less frequently underwent living related KT compared to the non-prior rhGH group but showed similar height z-scores at the time of KT. After KT, steroid exposure was lower and increments in anthropometric z-scores were significantly higher in the rhGH group compared to those in the non-prior rhGH group, although 18% of patients in the latter group were started on rhGH after KT. Non-prior rhGH treatment was associated with a faster decline in transplant function, lower hemoglobin, and higher C-reactive protein levels (CRP). After adjustment for these confounders, growth outcome did statistically differ for sitting height z-scores only. CONCLUSIONS: Treatment with rhGH prior to KT was associated with superior growth outcome in prepubertal kidney transplant recipients, which was related to better transplant function, lower CRP, less anemia, lower steroid exposure, and earlier maturation after KT. A higher resolution version of the Graphical abstract is available as Supplementary information.

Determinants of growth after kidney transplantation in prepubertal children.

BACKGROUND: Short stature is a frequent complication after pediatric kidney transplantation (KT). Whether the type of transplantation and prior treatment with recombinant human growth hormone (GH) affects post-transplant growth, is unclear. METHODS: Body height, leg length, sitting height, and sitting height index (as a measure of body proportions) were prospectively investigated in 148 prepubertal patients enrolled in the CKD Growth and Development study with a median follow-up of 5.0 years. We used linear mixed-effects models to identify predictors for body dimensions. RESULTS: Pre-transplant Z scores for height (- 2.18), sitting height (- 1.37), and leg length (- 2.30) were reduced, and sitting height index (1.59) was increased compared to healthy children, indicating disproportionate short stature. Catch-up growth in children aged less than 4 years was mainly due to stimulated trunk length, and in older children to improved leg length, resulting in normalization of body height and proportions before puberty in the majority of patients. Use of GH in the pre-transplant period, congenital CKD, birth parameters, parental height, time after KT, steroid exposure, and transplant function were significantly associated with growth outcome. Although, unadjusted growth data suggested superior post-transplant growth after (pre-emptive) living donor KT, this was no longer true after adjusting for the abovementioned confounders. CONCLUSIONS: Catch-up growth after KT is mainly due to stimulated trunk growth in young children (< 4 years) and improved leg growth in older children. Beside transplant function, steroid exposure and use of GH in the pre-transplant period are the main potentially modifiable factors associated with better growth outcome.

Kidney transplantation fails to provide adequate growth in children with chronic kidney disease born small for gestational age.

BACKGROUND: Children with chronic kidney disease are frequently born small for gestational age (SGA) and prone to disproportionately short stature. It is unclear how SGA affects growth after kidney transplantation (KTx). METHODS: Linear growth (height, sitting height, and leg length) was prospectively investigated in a cohort of 322 pediatric KTx recipients, with a mean follow-up of 4.9 years. Sitting height index (ratio of sitting height to total body height) was used to assess body proportions. Predictors of growth outcome in KTx patients with (n = 94) and without (n = 228) an SGA history were evaluated by the use of linear mixed-effects models. RESULTS: Mean z-scores for all linear body dimensions were lower in SGA compared with non-SGA patients (p < 0.001). SGA patients presented with higher target height deficit and degree of body disproportion (p < 0.001). The latter was mainly due to reduced leg growth during childhood. Pubertal trunk growth was diminished in SGA patients, and the pubertal growth spurt of legs was delayed in both groups, resulting in further impairment of adult height, which was more frequently reduced in SGA than in non-SGA patients (50 % vs 18 %, p < 0.001). Use of growth hormone treatment in the pre-transplant period, preemptive KTx, transplant function, and control of metabolic acidosis were the only potentially modifiable correlates of post-transplant growth in SGA groups. By contrast, living related KTx, steroid exposure, and degree of anemia proved to be correlates in non-SGA only. CONCLUSIONS: In children born SGA, growth outcome after KTx is significantly more impaired and affected by different clinical parameters compared with non-SGA patients.

Patterns of growth after kidney transplantation among children with ESRD.

BACKGROUND AND OBJECTIVES: Poor linear growth is a frequent complication of CKD. This study evaluated the effect of kidney transplantation on age-related growth of linear body segments in pediatric renal transplant recipients who were enrolled from May 1998 until August 2013 in the CKD Growth and Development observational cohort study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Linear growth (height, sitting height, arm and leg lengths) was prospectively investigated during 1639 annual visits in a cohort of 389 pediatric renal transplant recipients ages 2-18 years with a median follow-up of 3.4 years (interquartile range, 1.9-5.9 years). Linear mixed-effects models were used to assess age-related changes and predictors of linear body segments. RESULTS: During early childhood, patients showed lower mean SD scores (SDS) for height (-1.7) and a markedly elevated sitting height index (ratio of sitting height to total body height) compared with healthy children (1.6 SDS), indicating disproportionate stunting (each P<0.001). After early childhood a sustained increase in standardized leg length and a constant decrease in standardized sitting height were noted (each P<0.001), resulting in significant catch-up growth and almost complete normalization of sitting height index by adult age (0.4 SDS; P<0.01 versus age 2-4 years). Time after transplantation, congenital renal disease, bone maturation, steroid exposure, degree of metabolic acidosis and anemia, intrauterine growth restriction, and parental height were significant predictors of linear body dimensions and body proportions (each P<0.05). CONCLUSIONS: Children with ESRD present with disproportionate stunting. In pediatric renal transplant recipients, a sustained increase in standardized leg length and total body height is observed from preschool until adult age, resulting in restoration of body proportions in most patients. Reduction of steroid exposure and optimal metabolic control before and after transplantation are promising measures to further improve growth outcome.

Birth parameters and parental height predict growth outcome in children with chronic kidney disease.

BACKGROUND: We analyzed the impact of birth parameters and parental height on long-term growth outcome in children with chronic kidney disease (CKD) stage 3-5. METHODS: Linear growth was prospectively investigated in 509 children, with a mean follow-up of 4.1 years. Growth outcome was categorized in (i) poor growth (PG): height standard deviation score (SDS) during follow-up < -2.0 and/or actual or previous growth hormone (GH) treatment, and (ii) good growth (GG): height SDS ≥ -2.0 and no need for GH. A multivariate binary logistic regression model was constructed for predictors of PG outcome. RESULTS: PG was observed in 55 % of patients. The rate of pre-term and small for gestational age birth was significantly higher in children with PG compared to GG (43.2 vs. 25.6 % and 36.8 vs. 18.9 %; p < 0.001). Children with PG had significantly lower average values for gestational age, birth weight, length, and head circumference, umbilical cord pH, Apgar scores, and parental height than children with GG. Birth length, umbilical cord pH, and parental height were significant independent predictors of PG outcome (sensitivity 72.8 %, specificity 69.3 %). CONCLUSIONS: Birth parameters and parental height are independent predictors of growth outcome in children with CKD.

Growth and maturation improvement in children on renal replacement therapy over the past 20 years.

BACKGROUND: The attainment of normal growth and maturation remains a major challenge in the management of children and adolescents requiring renal replacement therapy (RRT). METHODS: We compared growth and maturation in 384 German children with RRT who were followed between 1998 and 2009 with 732 children who were enrolled in the European Dialysis and Transplant Association (EDTA) Registry from 1985 to 1988; of these children, 78 and 88 %, respectively, were transplanted. RESULTS: The data on the German patients included in the EDTA registry did not differ significantly from those of the patients from other European countries. Overall, the mean height standard deviation score (SDS) has improved over the past 20 years from -3.03 to -1.80 (p < 0.001). Until the age of 6 years, the difference in height SDS was not significant, whereas it improved significantly in adolescence (-3.40 vs. -1.52; p < 0.001). Significant improvements in the delay of the pubertal growth spurt, age at menarche, bone maturation and body mass index (BMI) were noted in the recent German group compared to the EDTA group (each p < 0.001). CONCLUSIONS: Our findings demonstrate a marked improvement of growth and maturation in paediatric patients on RRT during the past 20 years.

Prematurity, small for gestational age and perinatal parameters in children with congenital, hereditary and acquired chronic kidney disease.

BACKGROUND: Low birth weight has been identified as a risk factor for chronic kidney disease (CKD). METHODS: We analysed perinatal parameters taken from the National Birth Certificates of 435 children with CKD stages 3-5 of different aetiology and time of onset of CKD. Diseases were classified as congenital with onset of renal disease during fetal life (n = 260; 60%), hereditary as genetically determined with onset after 3 months of life (n = 93; 21%) and acquired CKD (n = 82; 19%). RESULTS: The rates of prematurity and small for gestational age (SGA) were elevated in children with congenital (39.3% and 29.2%), hereditary (24.7% and 22.6%) and acquired CKD (15.5% and 29.3%); these compared to 8% (for both) in the normal population. Newborns with congenital CKD had a significantly lower gestational age [median 38 weeks, interquartile range (IQR) 36-40 weeks] than those with hereditary (39.9 weeks, IQR 37.5-40 weeks) or acquired CKD (40 weeks, IQR 38-40 weeks; P < 0.001). Median birth weight and length were lower in newborns with congenital than in hereditary and acquired diseases [2975 g (IQR 2460-3420 g) versus 3250 g (IQR 2740-3580 g) and 3260 g (IQR 2858-3685 g) (P < 0.01); 49 cm (IQR 47-52) versus 50 cm (IQR 48-52.8) and 51 cm (IQR 49-53) (P < 0.01)]. Head circumference was smaller (P < 0.05), and Apgar scores were lower (P < 0.005) in newborns with congenital diseases than in hereditary and acquired diseases. CONCLUSIONS: Children with congenital CKD had the highest rate of prematurity, a significantly lower birth weight, length, head circumference and Apgar score than newborns with hereditary or acquired CKD. Irrespective of the aetiology of CKD, all of the children had a significantly higher rate of SGA and prematurity than the reference population. We conclude that both SGA and prematurity predispose for advanced renal disease in childhood and that fetal kidney disease impairs fetal growth.

Reliability of different expert systems for profiling proteinuria in children with kidney diseases.

This study was designed to compare three urinary protein expert systems for profiling proteinuria in children with kidney diseases. Freshly voided urine specimens were collected from 61 children with glomerular diseases, 19 children with tubular diseases and 25 healthy children aged 3-16 years. The urinary protein expert systems were: (1) albumin/total protein ratio (APR), (2) alpha-1-microglobulin/alpha-1-microglobulin + albumin algorithm (AAA), and (3) the complex urine protein expert system (UPES, PROTIS) algorithm. APR correctly identified glomerular proteinuria in 47/61 children, tubular proteinuria in 16/19 children and normal proteinuria in 23/25 healthy children. AAA correctly identified glomerular proteinuria in 61/61 children and tubular proteinuria in 18/19 children, and 25/25 healthy children were characterized as having no abnormal proteinuria. AAA was not influenced by the stage of chronic kidney disease. UPES differentiated the type of proteinuria in children with glomerular diseases into glomerular (50/61 patients) and mixed glomerulo-tubular (6/61 patients). Tubular proteinuria was identified in 16/19 patients and described as mixed glomerulo-tubular proteinuria in 3/19 patients. Mixed glomerulo-tubular proteinuria was found only in children with chronic kidney disease stages 2-5 of glomerular and tubular diseases. In conclusion, the AAA and UPES had the highest accuracy levels.

Anthropometric changes in elite male water polo players: survey in 1980 and 1995.

AIM: To assess the differences in anthropometric parameters, body fat, body mass index (BMI), and body density induced by sport-specific morphological optimization (adaptation) between two generations (1980 and 1995) of male elite water polo players. METHODS: The survey included a total of 160 elite male water polo players, all members of the top clubs in Croatia. The 1980's generation consisted of 95 players (71.9% of target population) aged between 18 and 32 years, and the 1995's generation included 65 players (50% of target population) aged between 19 and 29 years. Trained and qualified anthropometrists performed the measurements under standardized experimental conditions and in accordance with the procedures described by the International Biological Program. They measured 23 anthropometric variables reflecting basic human body characteristics described by skeletal bone lengths (total leg length, total arm length, hand length, foot length, and height), breadths (hand at proximal phalanges, foot in metatarsal area, biacromial, biiliocristal, biepycondylar femur, biepycondyar humerus, and radio-ulnar wrist breadth), girths (chest, arm, forearm, thigh, and calf girth), skinfold thickness as a measure of subcutaneous adiposity (triceps, subscapular, axillary, calf, and abdominal skinfold thickness), and mass. Additionally, estimates of body mass index (BMI), body density, and percentage of body fat were calculated from the primary measures. RESULTS: Comparison between anthropometric measures of the two generations of water polo players revealed a positive trend in body skeletal measures and negative trend in body adiposity measures. Most noteworthy differences (d) were an increase in height (d=37.3 mm, p

Analysis of indicators of load during the game in activity of the second line attacker in water polo.

Water polo, as an activity, belongs in the category of polystructural complex move sports. The activities of a player's in role of second line attacker is observed on the sample of competitive games in the First national league. The study is aimed to define a set of new measurement variables for the objective recording of amount, intensity and duration of player's activities, and its evaluation by means of factor validity criteria. On the sample of 87 players, 29 variables were applied. Competent, trained officials made measurements. Basic statistics of all measured variables is presented as referent values of various player activities. In the factor analysis, three factors are found to be significant, explaining 84.6% of source variability, which is a subset of multivariate normally, distributed variables. Factors are interpreted as: "quantity of actions", "intensity of activity in the vertical body posture", and "intensity and extensity of activity in horizontal body posture". Of the last two, body posture is found to be specific in water polo, due to specifics of the game that is played in water. It is concluded that the proposed variables and measurement procedures are very well suited and objectively instrument for the purpose of measurement of the energetic aspect of kinesiological activity analysis.