Terminal Phase Components of the Clotting Cascade in Patients with End-Stage Renal Disease Undergoing Hemodiafiltration or Hemodialysis Treatment.

Hemostasis disorder in patients with end-stage renal disease (ESRD) is frequently associated with bleeding diathesis but it may also manifest in thrombotic complications. Analysis of individual coagulation and fibrinolytic factors may shed light on the background of this paradox situation. Here we explored components essential for fibrin formation/stabilization in ESRD patients being on maintenance hemodiafiltration (HDF) or hemodialysis (HD). Pre-dialysis fibrinogen, factor XIII (FXIII) antigen concentrations and FXIII activity were elevated, while α2-plasmin inhibitor (α2PI) activity decreased. The inflammatory status, as characterized by C-reactive protein (CRP) was a key determinant of fibrinogen concentration, but not of FXIII and α2PI levels. During a 4-h course of HDF or HD, fibrinogen concentration and FXIII levels gradually elevated. When compensated for the change in plasma water, i.e., normalized for plasma albumin concentration, only FXIII elevation remained significant. There was no difference between HDF and HD treatments. Individual HDF treatment did not influence α2PI activity, however after normalization it decreased significantly. HD treatment had a different effect, α2PI activities became elevated but the elevation disappeared after normalization. Elevated fibrinogen and FXIII levels in ESRD patients might contribute to the increased thrombosis risk, while decreased α2PI activity might be associated with elevated fibrinolytic potential.

Pediatric Kidney Transplantation in Patients With Urologic Anomalies.

INTRODUCTION: and Aim. End-stage renal disease owing to structural urologic anomalies is frequent in the pediatric population. Impaired bladder function is thought to have a negative effect on graft function and survival. The aim of this study was to present our single-center experience and long-term follow-up results in pediatric patients who underwent renal transplantation for urologic reasons and to compare graft survival among patients who underwent transplantation for nonurologic reasons. METHOD: The paper records of renal transplanted children (<18 years of age) held by Ege University Medical Faculty between 1998 and 2018 were evaluated retrospectively. Patients with normal bladder function who underwent transplantation for urologic reasons were defined as group A, whereas patients who had impaired bladder function and underwent transplantation for urologic reasons were defined as group B; a control group was defined as group C. RESULTS: Eighty-three patients were included in the study. The creatinine values of the patients at their last visit were no different between groups (P = .930). One-, 5-, and 10-year graft survival rates were 97%, 89%, and 74%, respectively, in group A; 100% for all years in group B; and 97%, 94%, and 80%, respectively, in group C. There was no statistically significant difference in terms of graft survival between groups (P = .351). CONCLUSION: Children with end-stage renal disease owing to urologic abnormalities may be good candidates for kidney transplantation with a favorable prognosis for graft function and survival.

Combination of the fetal urinary metabolome and peptidome for the prediction of postnatal renal outcome in fetuses with PUV.

Most of biomarker panels, extracted from single omics traits, still need improvement since they display a gray zone where prediction is uncertain. Here we verified whether a combination of omics traits, fetal urinary metabolites and peptides analyzed in the same sample, improved prediction of postnatal renal function in fetuses with posterior urethral valves (PUV) compared to individual omics traits. Using CE-MS, we explored the urinary metabolome of 13 PUV fetuses with end stage renal disease (ESRD) and 12 PUV fetuses without postnatal ESRD at 2 years postnatally. This allowed the selection of 24 differentially abundant metabolite features which were modelled into predictive classifiers, alone or in combination with 12 peptides previously identified as predictive of ESRD. Validation in 35 new fetuses showed that the combination of peptides and metabolites significantly outperformed the 24 metabolite features with increased AUC (0.987 vs 0.905), net reclassification improvement (36%) and better sensitivity accuracy (86% vs 60%). In addition, the two trait combination tended to improve, but without reaching statistical significance, the already high performances of the 12 peptide biomarkers (AUC 0.967, accuracy 80%). In conclusion, this study demonstrates the potential of cumulating different omics traits in biomarker research where single omics traits fall short. SIGNIFICANCE: Although increasingly proposed in disease-diagnosis and -prognosis because of their improved efficacy over single markers, panels of body fluid biomarkers based on single omics analysis still fail to display perfect accuracy, probably due to biological variability. Here, we hypothesized that combination of different omics traits allowed to better capture this biological variability. As proof of concept, we studied the added value of fetal urine metabolites and peptides using CE-MS, starting from the same urine sample, to predict postnatal renal outcome in fetuses with posterior urethral valves. We observed that the prognostic power of combined metabolite and peptide markers was clearly higher than that of metabolites alone and slightly, but non-significantly, improved compared to the peptides alone. To our knowledge, this report is the first to demonstrate that combining multiomics traits extracted from (fetal) urine samples displays clear promise for kidney disease stratification.

Timing and outcome of renal replacement therapy in patients with congenital malformations of the kidney and urinary tract.

BACKGROUND AND OBJECTIVES: Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of ESRD in children, but the proportion of patients with individual CAKUT entities progressing to ESRD during adulthood and their long-term clinical outcomes are unknown. This study assessed the age at onset of renal replacement therapy (RRT) and patient and renal graft survival in patients with CAKUT across the entire age range. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with CAKUT were compared with age-matched patients who were undergoing RRT for other renal disorders on the basis of data from the European Renal Association-European Dialysis and Transplant Association Registry. Competing risk and Cox regression analyses were conducted. RESULTS: Of 212,930 patients commencing RRT from 1990 to 2009, 4765 (2.2%) had renal diagnoses consistent with CAKUT. The proportion of incident RRT patients with CAKUT decreased from infancy to childhood and then increased until age 15-19 years, followed by a gradual decline throughout adulthood. Median age at RRT start was 31 years in the CAKUT cohort and 61 years in the non-CAKUT cohort (P<0.001). RRT was started earlier (median, 16 years) in patients with isolated renal dysplasia than in those with renal hypoplasia and associated urinary tract disorders (median, 29.5-39.5 years). Patients with CAKUT survived longer than age- and sex-matched non-CAKUT controls because of lower cardiovascular mortality (10-year survival rate, 76.4% versus 70.7%; P<0.001). CONCLUSIONS: CAKUT leads to ESRD more often at adult than pediatric age. Treatment outcomes differ from those of acquired kidney diseases and vary within CAKUT subcategories.

Malformaciones urinarias del recién nacido: estudio ECLAMC 1998-2010 / Urinary malformations among newborns: ECLAMC registry, 1998-2010

Introduction: Congenital abnormalities of the Urinary Tract are frequent and prevalence has increased since the introduction of routine prenatal sonogram. Objectives: To determine the prevalence rate of congenital urinary malformations at birth at Hospital Clínico de la Universidad de Chile. These data will be compared to other Chilean hospitals participating in ECLAMC (Estudio Colaborativo Latino Americano de Malformaciones Congénitas - Latin American Collaborative Study of Congenital Malformations). A longitudinal study will serve to evaluate if significant variation has occurred, and risk factors will be investigated. Patients and Methods: All births occurring between January, 1998 and December, 2010 were included. Prevalence rate of urinary malformations were calculated, and compared to those obtained in previous years. Statistical analysis of proportions was calculated through mean and average comparison was made through Student t test. Results: Urinary anomalies appeared at a rate of 64.5 per 10.000 births. This represents a significant increase from previous studies. Highest risk factor seemed to be "other family members with disease". Most frequent anomaly was Hydroureteronphrosis (24,2 percent) followed by Hypospadias (17 percent). The rate of these malformations in ECLAMC participating Chilean hospitales was 23.37/10.000 births. Conclusion: A significant increase in the diagnosis of these anomalies was shown, being the most important risk factor the presence of family members with similar congenital disorders.

Introducción: Las anomalías congénitas del Aparato Urinario son frecuentes y ha aumentado su prevalencia al nacimiento con la introducción rutinaria del estudio prenatal por ultrasonografía. Objetivos: Determinar la Tasa de prevalencia al nacimiento de las malformaciones urinarias en el Hospital Clínico de la Universidad de Chile. Compararlas con las del resto de los hospitales chilenos que participan en el ECLAMC (Estudio Colaborativo Latino Americano de Malformaciones Congénitas). Estudiarlas a lo largo del tiempo para ver si han tenido variaciones significativas. Investigar factores de riesgo que pueden influir en la aparición de ellas. Pacientes y Método: Se estudió todos los nacimientos ocurridos entre Enero de 1998 y Diciembre de 2010 en el Hospital Clínico de la Universidad de Chile. Se calculó las tasas de prevalencia al nacimiento de las malformaciones urinarias y se las comparó con las obtenidas en períodos anteriores. El análisis estadístico de comparación de proporciones se realizó mediante la prueba de c² y las comparaciones entre promedios se hicieron mediante prueba t de Student. Resultados: La tasa de Anomalías urinarias fue 64,5 por 10 000 nacimientos. Ellas aumentaron significativamente al compararlas con los períodos estudiados anteriormente. El factor de riesgo más influyente fue "otros malformados en la familia". La anomalía más frecuente fue Hidroureteronefrosis (24,2 por ciento) seguida por Hipospadias (17 por ciento). La tasa de estas malformaciones en los hospitales chilenos participantes del ECLAMC fue 23,37/10 000 nacimientos. Conclusión: Se demuestra un incremento significativo del diagnóstico de estas anomalías, siendo el factor de riesgo más importante el antecedente de otros malformados en la familia.

HNF1B and PAX2 mutations are a common cause of renal hypodysplasia in the CKiD cohort.

Malformations of the kidney and lower urinary tract are the most frequent cause of end-stage renal disease in children. Mutations in HNF1Β and PAX2 commonly cause syndromic urinary tract malformation. We searched for mutations in HNF1Β and PAX2 in North American children with renal aplasia and hypodysplasia (RHD) enrolled in the Chronic Kidney Disease in Children Cohort Study (CKiD). We identified seven mutations in this multiethnic cohort (10% of patients). In HNF1Β, we identified a nonsense (p.R181X), a missense (p.S148L), and a frameshift (Y352fsX352) mutation, and one whole gene deletion. In PAX2, we identified one splice site (IVS4-1G>T), one missense (p.G24E), and one frameshift (G24fsX28) mutation. All mutations occurred in Caucasians, accounting for 14% of disease in this subgroup. The absence of mutations in other ethnicities is likely due to the limited sample size. There were no differences in clinical parameters (age, baseline eGFR, blood pressure, body mass index, progression) between patients with or without HNF1B and PAX2 mutations. A significant proportion of North American Caucasian patients with RHD carry mutations in HNF1Β or PAX2 genes. These patients should be evaluated for complications (e.g., diabetes for HNF1Β mutations, colobomas for PAX2) and referred for genetic counseling.

Pathogenesis of renal injury in the megabladder mouse: a genetic model of congenital obstructive nephropathy.

Congenital obstructive nephropathy (CON) is the most common cause of chronic renal failure in children often leading to end-stage renal disease. The megabladder (mgb) mouse exhibits signs of urinary tract obstruction in utero resulting in the development of hydroureteronephrosis and progressive renal failure after birth. This study examined the development of progressive renal injury in homozygous mgb mice (mgb-/-). Renal ultrasound was used to stratify the disease state of mgb-/- mice, whereas surgical rescue was performed using vesicostomy. The progression of renal injury was characterized using a series of pathogenic markers including alpha smooth muscle isoactin (α-SMA), TGF-ß1, connective tissue growth factor (CTGF), E-cadherin, F4/80, Wilm's tumor (WT)-1, and paired box gene (Pax) 2. This analysis indicated that mgb-/- mice are born with pathologic changes in kidney development that progressively worsen in direct correlation with the severity of hydronephrosis. The initiation and pattern of fibrotic development observed in mgb-/- kidneys appeared distinctive from previous animal models of obstruction. These observations suggest that the mgb mouse represents a unique small animal model for the study of CON.

Growth and body composition in very young SGA children.

Infants with a very low birth weight are at risk of a reduced number of nephrons predisposing to kidney disorder, hypertension, and metabolic syndrome. Approximately 3% of infants are born small for gestational age (SGA), defined as birth weight and/or length at least 2 SD below the mean for gestational age (GA), independently of whether these children are born prematurely or at term. About 10% of these children do not show postnatal catch-up growth and remain of short stature during childhood. Most of these infants are not growth hormone (GH)-deficient, but may have GH resistance. Although GH-resistant, the majority of patients benefit from GH therapy, normalize height during childhood, maintain a normal growth velocity during puberty, and attain a normal adult height. To date, GH has been shown to be safe and no significant adverse effects have been demonstrated. Children with congenital chronic kidney disease (CKD) are born with subnormal birth weight and length and about 25% are born SGA. Shortness and need for GH treatment is highly correlated with weight at birth and gestational age. Primary renal disorders modify the response to GH treatment. Analysis of whether SGA is an additional risk factor for CKD regarding the development of hypertension, metabolic syndrome and cardiovascular complications is required.

Renal dysplasia and nephrosclerosis in calves.

Renal dysplasia and nephrosclerosis in six calves, which were aged three to six months and from different farms in western Scotland and north-west England, was characterised clinically by stunted growth and renal failure with uraemia. Affected animals were depressed and one case exhibited severe neurological signs. Reduced erythrocyte counts were evident in three of four animals from which blood samples were submitted for haematology. At postmortem examination, the kidneys were bilaterally small, pale and firm, with marked fibrosis and sometimes contraction of the capsule. Histologically, affected calves had disorganised atrophic glomeruli, dilatation of tubules, loss of nephrons, areas of undifferentiated mesenchyme and diffuse interstitial and periglomerular fibrosis. There was minimal inflammation. Renal dysplasia and nephrosclerosis is a form of juvenile nephropathy of unknown aetiology that occurs sporadically in calves in the UK.

What do we know about chronic renal failure in young adults? II. Adult outcome of pediatric renal disease.

Congenital abnormalities of the kidney and urinary tract (CAKUT) account for more than half of all renal failure in children. For young adults with CAKUT two questions are paramount: what is the prognosis and what is the best management to improve outcome? The paediatric literature shows that prognostic factors are glomerular filtration rate (GFR) and the presence of proteinuria. We reviewed data from 101 young adult patients with either primary vesico-ureteric reflux and renal dysplasia or obstructive uropathy. Patients had an estimated GFR (eGFR) of 35 ml/min. The ACEI benefit increased with time. Rate of decline was slower than reported for other diseases and was only -2.4 ml/min per year for those reaching the start of dialysis. Outcome is predictable by the level of residual renal function (GFR). Nevertheless, function remains stable while proteinuria is minimal. Short-term studies overestimate rates of deterioration.

[Congenital and genetic related causes of end-stage renal disease--data from Polish Registry of Renal Rreplacement Therapy in Children 2000-2004]. / Genetycznie uwarunkowane i wrodzone choroby nerek prowadzace do schylkowej niewydolnosci nerek--dane z polskiego rejestru dzieci leczonych nerkozastepczo (2000-2004).

UNLABELLED: One of the objectives of Polish Registry of Renal Replacement Therapy in Children established on 31st Dec. 2000 was to collect complete data on etiology of end stage renal disease (ESRD) in polish children. MATERIAL AND METHODS: Data on 469 patients (251 boys, 218 girls) aged 0-22 years treated with renal replacement therapy (RRT) at 13 pediatric dialysis units in Poland from 2000 to 2004 were analyzed. The mean age at start of dialysis was 10 years and 3 months. Renal diseases were defined according to EDTA coding system. Data is presented for the whole group, in 5-year age groups and separately for both sexes. RESULTS: Congenital and genetic renal diseases were the cause of ESRF in 56% of the polish population of children and adolescents on RRT. 39% of causes were acquired diseases, 5% remained unidentified. Congenital and genetic causes dominated in children < 5 years of age (71%). They accounted for 49%, 61% and 45% of causes in the consecutive 5-year age groups. The most numerous group of congenital diseases leading to ESRF were uropathies 37% and 25% of causes in the consecutive age groups. In boys the most frequent uropathy was obstructive uropathy (25%), the majority caused by posterior urethral valves. In girls the most frequent uropathies were reflux nephropathy (10%) and nephropathy secondary to neurogenic bladder (9%). Uropathies were followed by renal hypo-dysplasia without urinary tract anomalies (11%) and cystic diseases (10%). CONCLUSIONS: Congenital kidney anomalies and genetic diseases are the leading cause of end-stage renal disease in children up to 15 years of age.

[Percutaneus endoscopic gastrostomy (PEG) in an infant with chronic renal failure]. / Przezskórna endoskopowa gastrostomia (PEG) u niemowlecia z przewlekla niewydolnoscia nerek.

Malnutrition is a major problem in patients with chronic renal failure, especially in children in the first three years of life. Meeting high energy needs in these patients may be difficult because of anorexia and vomiting, which are common in predialysis renal failure. Nutritional support for children with chronic renal failure often involves the use of nasogastric tubes or gastrostomy feeding. We describe an infant with pre-dialysis renal failure and severe malnutrition in whom only insertion of percutaneus endoscopic gastrostomy provided adequate caloric intake and satisfactory weight gain.

Nephronophthisis: a variant.

The case report describes a young boy with renal, retinal, hepatic and cerebellar involvement in a rare syndrome. He had polyuria, deranged renal functions and cystic lesions in kidneys, which led to the diagnosis of nephronophthisis (NPH). Extra-renal involvement with night blindness, truncal ataxia, mental retardation and hepatosplenomegaly. Thus, every patient with NPH should be carefully examined for extra-renal involvement.

Lower urinary tract reconstruction is safe and effective in children with end stage renal disease.

PURPOSE: Congenital urinary tract anomalies with bladder dysfunction pose a formidable management challenge in children with end stage renal disease (ESRD). We report a series of patients with ESRD who underwent lower urinary tract reconstruction to assess the results and surgical complications. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients with ESRD who underwent urinary reconstruction. The etiology for renal failure included posterior urethral valves, cloacal anomalies, VATER syndrome and reflux nephropathy. RESULTS: From 1989 to 2000, 20 patients were identified. Median patient age at time of reconstruction was 4.5 years and median followup was 7.3 years. Pre-transplant augmentation cystoplasty was performed in 14 patients (70%) and continent reconstruction without bladder augmentation was performed in 6 patients. Subsequent renal transplant was performed in 19 patients (15 with a living related donor). Overall patient survival was 95%. There was 1 death in the immediate post-transplant period secondary to cerebral edema thought to be due to a precipitous decrease in blood urea nitrogen. The overall graft survival rate is 82%. No patients lost grafts due to infection or technical complications. All patients have stable upper tracts, and mean creatinine is 1.2 mg/dl. Three patients required major surgery due to complications of the reconstruction and 2 treated with gastrocystoplasty had severe hematuria while anuric before transplantation. All patients are continent of urine. CONCLUSIONS: Our long-term data confirm that severe bladder dysfunction can be managed safely and effectively with continent urinary reconstruction in children with ESRD.

Neuropsychological outcome in children with acquired or congenital renal disease.

The neuropsychological abilities of children with congenital ( n=13) or acquired ( n=11) end-stage renal disease (ESRD) were compared. Patients were being treated with or being prepared for dialysis and were awaiting transplantation. None of the children had an identifiable syndrome with associated central nervous system (CNS) dysfunction or had exposure to drugs with known CNS toxicity. There were no group differences in intelligence, academic achievement, behavior, or immediate memory. Children with congenital ESRD had poorer fine motor coordination and more difficulty on tests of verbal and nonverbal long-term memory than children with acquired ESRD. However, the neuropsychological outcome for congenital ESRD is more favorable than previously described. Psychological and education treatment recommendations should be considered.