Chronic Renal Failure In Children Research Articles

Renin gene rs1464816 polymorphism contributes to chronic kidney disease progression in ADPKD.

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is a monogenic disorder and is a common genetic cause of chronic renal failure in children and adults. The enzyme renin plays a key role in the RAAS cascade and an important role in the development of hypertension and progression of renal disease in ADPKD. The present study is aimed to investigate the potential modifier effect of REN gene polymorphisms on the progression of chronic kidney disease (CKD) in ADPKD.MethodsWe analyzed 102 ADPKD patients and 106 healthy controls from the same geographic area. FRET-based KASPar single-nucleotide polymorphism (SNP) genotyping assays for REN gene tag-SNPs (rs2887284, rs2368564, rs1464816, rs7521667, rs10900555, rs6693954, rs6676670 and rs11571078) were performed. Cochran-Armitage trend test was used to assess the potential associations between these polymorphisms and CKD stages. Haplotype frequencies and LD measures were estimated by using the software Haploview. Mantel-Haenszel stratified analysis was used to explore confounding and interaction effects of these polymorphisms.ResultsOf the eight tag-SNPs genotyped, the rs10900555 polymorphism deviated from the Hardy-Weinberg equilibrium in controls. The presence of ADPKD in general was not significantly associated with the REN tag-SNPs included in this study. Linkage disequilibrium analysis yielded three haplotype blocks and the haplotypes of the respective blocks are not statistically different between ADPKD and controls. In multivariate analysis, the rs1464816 TG genotype showed a significant association with the advancement of CKD in ADPKD (OR = 4.80; 95 % CI = 1.30–17.82; p = 0.019).ConclusionsThe present study provides evidence that the rs1464816 polymorphism in REN is associated with CKD progression in ADPKD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12929-015-0217-0) contains supplementary material, which is available to authorized users.

Genetics of Vesicoureteral Reflux.

Vesicoureteral reflux (VUR) is the retrograde passage of urine from the bladder to the upper urinary tract. It is the most common congenital urological anomaly affecting 1-2% of children and 30-40% of patients with urinary tract infections. VUR is a major risk factor for pyelonephritic scarring and chronic renal failure in children. It is the result of a shortened intravesical ureter with an enlarged or malpositioned ureteric orifice. An ectopic embryonal ureteric budding development is implicated in the pathogenesis of VUR, which is a complex genetic developmental disorder. Many genes are involved in the ureteric budding formation and subsequently in the urinary tract and kidney development. Previous studies demonstrate an heterogeneous genetic pattern of VUR. In fact no single major locus or gene for primary VUR has been identified. It is likely that different forms of VUR with different genetic determinantes are present. Moreover genetic studies of syndromes with associated VUR have revealed several possible candidate genes involved in the pathogenesis of VUR and related urinary tract malformations. Mutations in genes essential for urinary tract morphogenesis are linked to numerous congenital syndromes, and in most of those VUR is a feature. The Authors provide an overview of the developmental processes leading to the VUR. The different genes and signaling pathways controlling the embryonal urinary tract development are analyzed. A better understanding of VUR genetic bases could improve the management of this condition in children.

CHRONICKIDNEYDISEASE IN CHILDREN AND RENAL REPLACEMENT THERAPYIN UKRAINE

Classification of Chronic Kidney Disease and stages of Chronic Renal Failure in children were compared. There was presented adapted Schwartz formula for estimated Glomerular Filtration Rate. Prevalence of the genitourinary system diseases in Ukrainian children was considered. There was first time systematized data on Chronic Kidney Disease in children and renal replacement therapy in the years 2009-2014.

Commentary to ‘Multidisciplinary consensus on the classification of prenatal and postnatal urinary tract dilation (UTD classification system)’

[65] Ulman I, Jayanthi VR, Koff SA. The long-term followup of newborns with severe unilateral hydronephrosis initially treated nonoperatively. J Urol 2000;164:1101e5. [66] Braga LH, Mijovic H, Farrokhyar F, Pemberton J, DeMaria J, Lorenzo AJ. Antibiotic prophylaxis for urinary tract infections in antenatal hydronephrosis. Pediatrics 2013;131:e251e61. [67] Gimpel C, Masioniene L, Djakovic N, Schenk JP, Haberkorn U, Tonshoff B, et al. Complications and long-term outcome of primary obstructive megaureter in childhood. Pediatr Nephrol 2010;25:1679e86. [68] Davenport MT, Merguerian PA, Koyle M. Antenatally diagnosed hydronephrosis: current postnatal management. Pediatr Surg Int 2013;29:207e14. [69] Kose E, Yavascan O, Turan O, Kangin M, Bal A, Alparslan C, et al. The effect of circumcision on the frequency of urinary tract infection, growth and nutrition status in infants with antenatal hydronephrosis. Ren Fail 2013;35:1365e9. [70] Wong CJ, Moxey-Mims M, Jerry-Fluker J, Warady BA, Furth SL. CKiD (CKD in children) prospective cohort study: a review of current findings. Am J Kidney Dis 2012;60:1002e11. [71] Nyengaard JR, Bendtsen TF. Glomerular number and size in relation to age, kidney weight, and body surface in normal man. Anat Rec 1992;232:194e201. [72] Hostetter TH, Olson JL, Rennke HG, Venkatachalam MA, Brenner BM. Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am J Physiol 1981; 241:F85e93. [73] Remuzzi G, Ruggenenti P, Perico N. Chronic renal diseases: renoprotective benefits of renin-angiotensin system inhibition. Ann Int Med 2002;136:604e15. [74] Ardissino G, Dacco V, Testa S, Bonaudo R, Claris-Appiani A, Taioli E, et al. Epidemiology of chronic renal failure in children: data from the ItalKid project. Pediatrics 2003;111: e382e7. [75] Quirino IG, Diniz JS, Bouzada MC, Pereira AK, Lopes TJ, Paixao GM, et al. Clinical course of 822 children with prenatally detected nephrouropathies. Clin J Am Soc Nephrol 2012;7:444e51. [76] Carlstrom M. Causal link between neonatal hydronephrosis and later development of hypertension. Clin Exp Pharmacol Physiol 2010;37:e14e23. [77] Jodal U. The natural history of bacteriuria in childhood. Infect Dis Clin North Am 1987;1:713e29. [78] Kogon AJ, Pierce CB, Cox C, Brady TM, Mitsnefes MM, Warady BA, et al. Nephrotic-range proteinuria is strongly associated with poor blood pressure control in pediatric chronic kidney disease. Kidney Int 2014;85:938e44. [79] Navis G, Faber HJ, de Zeeuw D, de Jong PE. ACE inhibitors and the kidney. A risk-benefit assessment. Drug Saf 1996;15: 200e11. [80] Ruster C, Wolf G. Renin-angiotensin-aldosterone system and progression of renal disease. J Am Soc Nephrol 2006;17: 2985e91. [81] Martens DH, Rake JP, Navis G, Fidler V, van Dael CM, Smit GP. Renal function in glycogen storage disease type I, natural course, and renopreservative effects of ACE inhibition. Clin J Am Soc Nephrol 2009;4:1741e6. [82] Reddy UM, Abuhamad AZ, Levine D, Saade GR, Fetal Imaging Workshop Invited P. Fetal imaging: executive summary of a joint Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, American Institute of Ultrasound in Medicine, American College of Obstetricians and Gynecologists, American College of Radiology, Society for Pediatric Radiology, and Society of Radiologists in Ultrasound Fetal Imaging Workshop. J Ultrasound Med 2014;33:745e57.

Seguridad de la diálisis peritoneal automatizada-DPA en niños por cuidadores primarios en casa

Introduction: Chronic renal failure in children is considered high-cost disease, causing great emotional impact, family and society on the child and the primary caregiver. Most of the processes of care in this group of patients are complex, requiring renal replacement therapy. Objective: Evaluate the Safety of DPA children at home, through training for nursing primary caregivers. Material and Mhetods: Cross-sectional study using convenience sampling included 12 primary caregivers of children in DPA urban and rural area of Valle del Cauca department belonging to the Renal Unit of Cali-Colombia, was assessed through home visits: socio-demographic profile, environmental conditions, treatment adherence, and risk factors in two time periods. Results: We evaluated 12 children between 5-18 years, 60% with 10-15 years, at ambient conditions, 83% lived in houses completed, 17% in construction, 50% belonged to socioeconomic status 2. In relation to the educational level of the caregiver, 58% attended elementary, 58.3% had a caregiver to mother, father 8.3% and 25% the same patient. Conclusion: Children with APD are vulnerable to multiple risk factors, being strategies necessary for evaluation. The interdisciplinary team and especially addressed nurse care guidelines for DPA, becoming an effective way to minimize risks and complications triggers to develop skills to guide DPA security at home.

Megabladder mouse model of congenital obstructive nephropathy: genetic etiology and renal adaptation

Congenital obstructive nephropathy remains one of the leading causes of chronic renal failure in children. The direct link between obstructed urine flow and abnormal renal development and subsequent dysfunction represents a central paradigm of urogenital pathogenesis that has far-reaching clinical implications. Even so, a number of diagnostic, prognostic, and therapeutic quandaries still exist in the management of congenital obstructive nephropathy. Studies in our laboratory have characterized a unique mutant mouse line that develops in utero megabladder, variable hydronephrosis, and progressive renal failure. Megabladder mice represent a valuable functional model for the study of congenital obstructive nephropathy. Recent studies have begun to shed light on the genetic etiology of mgb −/− mice as well as the molecular pathways controlling disease progression in these animals.

Urinary angiotensinogen as a novel marker of obstructive nephropathy in children

Obstructive nephropathy due to congenital or acquired urinary tract obstruction is one of the most important causes of chronic renal failure in children. There is a need for identification of new noninvasive urinary biomarkers to provide the clinician with fast, specific and reliable diagnostic and prognostic tool. The aim of the study was to determine whether urinary angiotensinogen (uAGT) may be a useful marker of obstruction in children with hydronephrosis (HN) caused by ureteropelvic junction obstruction (UPJO). The study cohort consisted of surgical group (SG): 31 children with severe HN who required surgery; nonsurgical group (NSG): 20 patients with mild HN, and reference group (RG): 19 healthy children. Urinary concentrations of angiotensinogen were measured using immunoenzymatic ELISA commercial kit and were expressed in ng/mg Cre (uAGT/uCre). uAGT/uCre level was higher in SG when compared to NSG (p < 0.01) and healthy participants (SG vs. RG: p < 0.01). The difference between the uAGT/uCre in NSG and RG was not statistically significant (p > 0.05). uAGT/uCre was correlated negatively with differential renal function (r = -0.46; p < 0.01). The present pilot study has clearly demonstrated that children with UPJO showed increased uAGT levels, which correlated negatively with differential renal function in radionuclide scan.

Dehydration upon admission is a risk factor for incomplete recovery of renal function in children with haemolytic uremic syndrome.

Haemolytic uremic syndrome (HUS) is the most common cause of acute renal failure and the second leading cause of chronic renal failure in children. The factors that affect incomplete renal function recovery prior to hospital admission are poorly understood. To analyse the risk factors that determine incomplete recovery of renal function prior to hospitalisation in children with HUS. A retrospective case-control study. age, sex, duration of diarrhoea, bloody stools, vomiting, fever, dehydration, previous use of antibiotics, and incomplete recovery of renal function (proteinuria, hypertension, reduced creatinine clearance, and chronic renal failure during follow-up). Patients of both sexes under 15 years of age were included. Of 36 patients, 23 were males (65.3%; 95%CI: 45.8 to 80.9), with an average age of 2.5 ± 1.4 years. Twenty-one patients required dialysis (58%; 95% CI: 40.8 to 75.8), and 13 (36.1%; 95% CI: 19.0 to 53.1) did not recover renal function. In the bivariate model, the only significant risk factor was dehydration (defined as weight loss >5%) [(OR: 5.3; 95% CI: 1.4 to 12.3; P=.0220]. In the multivariate analysis (Cox multiple regression), only dehydration was marginally significant (HR: 95.823; 95% CI: 93.175 to 109.948; P=.085). Our data suggest that dehydration prior to admission may be a factor that increases the risk of incomplete recovery of renal function during long-term follow-up in children who develop HUS D+. Consequently, in patients with diarrhoea who are at risk of HUS, dehydration should be strongly avoided during outpatient care to preserve long-term renal function. These results must be confirmed by larger prospective studies.

Primary Hyperoxaluria is the Main Cause of Chronic Renal Failure in Children under 15 Years Old in Jenin District (Palestine)

Background: This was the first study which has been conducted on chronic renal failure children under 15 years old in Jenin District to know the underlying etiology of the disease. The study was conducted on all patients who are treated by medications or hemodialysis in the dialysis unit of The Martyr Dr. Khalil Sulaiman Hospital in Jenin city which is the only dialysis unit in Jenin District where all the patients in Jenin District are treated. The study was conducted in the period 1/8/2005 to 1/8/2006. Materials and methods: The subjects were nine patients. The information was taken from files of the patients in the kidney unit. The diagnosis was based on family history, medical history, laboratory tests, X-rays, CT scans, ultrasound and renal biopsies. Results: The results showed that the causes of chronic renal failure were primary hyperoxaluria (66.7%) and congenital abnormalities of the kidney (33.3%). Conclusion: It is obvious from the results that the most common cause of CRF in children under 15 years old in Jenin District was primary hyperoxaluria which is an inherited disorder. These results differ from what is found in many countries around the world including Arab and Islamic countries where the most common causes of chronic renal failure in children are urological abnormalities and malformations (congenital anomalies) and not primary hyperoxaluria. The primary inherited nephropathy in Jenin District was primary hyperoxaluria with a percentage much higher than that found in many countries around the world. This seems to be due to the very high prevalence of parental consanguinity (especially among cousins) in some families in Jenin District, a practice that is repeated through generations.

Quality of life in a cohort of patients diagnosed with renal failure in childhood and who received renal transplant

Studies on HRQOL on kidney-transplanted young adults who had a diagnosis of chronic renal failure (CRF) in the pediatric age are uncommon. We studied HRQOL and its predictors in a sample of young adults with CRF in childhood who underwent a renal transplant. We recruited patients ≥18 yr old with renal transplant. We measured HRQOL by a standardized questionnaire on lifestyle, Short Form-36 (SF-36; including a PCS and a MCS; scale: 0-100), the GHQ (for short-term changes in mental health; scale: 0-36), and the MSPSS (with scales for family, friends, and significant others; scale: 0-100). We assessed the association of potential predictors of HRQOL through multiple linear regression models. We studied 66 patients aged 18-34 yr. The average PCS score was 76.4, and the average MCS score was 73.9. The mean GHQ total score was 14.8, and the total scale MSPSS mean score was 70. Severe comorbidities significantly affected the PCS score. Individuals with severe comorbidities had lower PCS scores.

Adult Care of Children From Pediatric Urology

In this article we highlight the difference, from established adult urology, in required approach to the care of adolescents and young adults presenting with the long-term consequences of the major congenital anomalies of the genitourinary tract. We review some abnormalities of the kidneys, progressive renal failure and disorders of bladder function from which general conclusions can be drawn. The published literature was reviewed and augmented with material from our institutional databases. For renal function the CAKUT (congenital abnormalities of the kidney and urinary tract) database at University College London Hospitals was used, which includes 101 young adult patients with CAKUT in whom the urinary tract has not been diverted or augmented. For bladder function some data are from patient records at Boston Children's Hospital. Adolescents who grow up with the burden of a major congenital anomaly have an overwhelming desire to be normal. Many achieve high levels of education and occupy a wide range of employment scenarios. Babies born with damaged kidneys will usually experience improvement in renal function in the first 3 years of life. Approximately 50% of these cases will remain stable until puberty, after which half of them will experience deterioration. Any urologist who treats such patients needs to test for proteinuria as this is a significant indicator of such deterioration. In its absence, the urologist must have a reasonable strategy for seeking a urological cause. The most effective management for nephrological renal deterioration is with angiotensin converting enzyme inhibitors, which slow but do not prevent end stage renal failure. Renal deterioration is generally slower in these patients than in those with other forms of progressive renal disease. The bladder is damaged by obstruction or by functional abnormalities such as myelomeningocele. Every effort should be made to stabilize or reconstruct the bladder in childhood. A dysfunctional bladder is associated with or causes renal damage in utero, but continued dysfunction will cause further renal damage. Bladder function often changes in puberty, especially in boys with posterior urethral valves who may experience high pressure chronic retention. Dysfunction is managed with antimuscarinic drugs, clean intermittent self-catheterization and intestinal augmentation. Adult urologists must be able to manage the long-term problems associated with these treatments. Pediatric conditions requiring management in adolescence are rare but have major, lifelong implications. Their management requires a broad knowledge of pediatric and adult urology, and could well be a specialty in its own right. Therefore, adult urologists must remain aware of the conditions, the problems that they may encounter and the special management required for these patients to live normal lives.

Urological Disorders in Chronic Kidney Disease in Children Cohort: Clinical Characteristics and Estimation of Glomerular Filtration Rate

Urological disorders are the most common cause of pediatric chronic kidney disease. We determined the characteristics of children with urological disorders and assessed the agreement between the newly developed bedside glomerular filtration rate estimating formula with measured glomerular filtration rate in 586 patients in the Chronic Kidney Disease in Children study. The Chronic Kidney Disease in Children study is a prospective, observational cohort of children recruited from 48 sites in the United States and Canada. Eligibility requirements include age 1 to 16 years and estimated glomerular filtration rate by original Schwartz formula 30 to 90 ml/min/1.73 m(2). Baseline demographics, clinical variables and glomerular filtration rate were assessed. Bland-Altman analysis was conducted to assess agreement between estimated and measured glomerular filtration rates. Of the 586 participants with at least 1 glomerular filtration rate measurement 348 (59%) had an underlying urological diagnosis (obstructive uropathy in 118, aplastic/hypoplastic/dysplastic kidneys in 104, reflux in 87 and other condition in 39). Among these patients median age was 9 years, duration of chronic kidney disease was 7 years and age at first visit with a urologist was less than 1 year. Of the patients 67% were male, 67% were white and 21% had a low birth weight. Median height was in the 24th percentile. Median glomerular filtration rate as measured by iohexol plasma disappearance was 44.8 ml/min/1.73 m(2). Median glomerular filtration rate as estimated by the Chronic Kidney Disease in Children bedside equation was 44.3 ml/min/1.73 m(2) (bias = -0.5, 95% CI -1.7 to 0.7, p = 0.44). Underlying urological causes of chronic kidney disease were present in 59% of study participants. These children were diagnosed early in life, and many had low birth weight and growth delay. There is good agreement between the newly developed Chronic Kidney Disease in Children estimating equations and measured glomerular filtration rate in this population.

The BMP-7–Smad1/5/8 Pathway Promotes Kidney Repair After Obstruction Induced Renal Injury

Urinary tract obstruction causes hydroureteronephrosis and requires surgical intervention to prevent permanent renal injury. While many studies have focused on the development of renal injury, we examined the molecular mechanisms that promote renal recovery after correcting obstruction. A reversible murine model of ureteral obstruction was used to examine the bone morphogenic protein-7 and transforming growth factor-β signaling pathways during renal recovery after obstruction induced injury. Analysis was done using standard molecular techniques, including reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, immunoblotting and co-immunoprecipitation. After correcting obstruction the up-regulation of bone morphogenic protein-7 inhibited the transforming growth factor-β dependent profibrotic pathways that are central to renal injury pathogenesis. The inhibitory effects of bone morphogenic protein-7 were mediated in part by the activation of its downstream target proteins, SMA and MAD related proteins 1, 5 and 8, which suppress the activity of transforming growth factor-β dependent Smad proteins and in turn inhibit the expression of transforming growth factor-β dependent genes. Activation of the bone morphogenic protein-7-Smad related protein 1/5/8 pathway during renal recovery promoted renal architecture restoration and fibrosis resolution in the kidney after correcting obstruction. Together these findings show that the bone morphogenic protein-7-Smad1/5/8 pathway promotes kidney repair after obstruction induced injury. Accordingly the pathway represents an important therapeutic target to stimulate this innate repair mechanisms of the kidney during treatment for obstruction induced renal injury.

KIM-1 and NGAL: new markers of obstructive nephropathy.

Congenital obstructive nephropathy is the primary cause of chronic renal failure in children. Rapid diagnosis and initiation of the treatment are vital to preserve function and/or to slow down renal injury. The aim of our study was to determine whether urinary (u) kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) may be useful non-invasive biomarkers in children with congenital hydronephrosis (HN) caused by ureteropelvic junction obstruction. The study cohort consisted of 20 children with severe HN who required surgery (median age 2.16 years) and two control groups (control group 1: 20 patients with mild, non-obstructive HN; control group 2: 25 healthy children). All of the children had normal renal function. Immunoenzymatic ELISA commercial kits were used to measure uKIM-1 and uNGAL concentrations. The preoperative median uKIM-1/creatinine (cr.) and uNGAL levels were significantly greater in the children with severe HN than in both control groups. Three months after surgery, uNGAL had decreased significantly (p < 0.05) in the children with severe HN, but was still higher than that in control group 2 children (p < 0.05). Receiver operator characteristic analyses revealed a good diagnostic profile for uKIM-1 and uNGAL in terms of identifying a differential renal function of <40% in HN patients (area under the curve (AUC) 0.8 and 0.814, respectively) and <45% in all examined children (AUC 0.779 and 0.868, respectively). Based on these results, we suggest that increasing uNGAL and uKIM-1 levels are associated with worsening obstruction. Further studies are required to confirm a potential application of uKIM-1 and uNGAL as useful biomarkers for the diagnosis and progression of chronic kidney disease.

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-β1, 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.

The Pattern of Ocular Abnormalities in Childhood Chronic Renal Failure

Background: Few literatures reported the pattern of ocular abnormalities in chronic renal failure (CRF). The aim of this paper is to determine the pattern of ocular abnormalities in childhood CRF. Patients and Methods: From January 1993 to July 2007, 80 patients with a diagnosis of chronic renal failure (CRF) were observed at the University Hospital in Al Kadhimiyia. They were examined to determine the presence of ocular abnormalities. Fifty one patients were males (63.75%) and 29 (36.25%) were females. The male-female ratio was 1.75, and the age at referral ranged from 2 months to 18 years (mean 9 years). Results: Corneal cystine crystals were the most common ocular abnormalities associated with childhood CRF observed in 6 patients with Nephropathic cystinosis (7.5%). Congenital cataract and glaucoma were the second most common ocular abnormality; observed in 3 patients (3.75%) with Oculo-cerebro-renal syndrome (OCRS). Conclusions: Ocular abnormalities are relatively common in childhood CRF occurring in approximately 19%.

Major complication after intrauterine vesico-amniotic shunting

Bilateral foetal uropathy is the leading cause of chronic renal failure in childhood. Vesico-amniotic shunting (VAS) is a simple, feasible, and widely used procedure for decompressing the foetal urinary system. We report a case of a boy with bilateral foetal uropathy who underwent VAS at a gestational age of 29 weeks. Vesico-abdominal shunt dislodgement occurred and led to urinary ascites and anhydramnios. Postpartal laparotomy showed a shunt perforation between the urinary bladder and the peritoneal cavity.

Expression profiling of the AT2R mRNA in affected tissue from children with CAKUT

Objectives: Congenital anomalies of the kidney and urinary tract (CAKUT) are common causes of chronic renal failure in children. The angiotensin II receptor type 2 (AT2R) is one of proposed candidate genes for CAKUT, but the expression was never explored in humans. The aim was to establish the AT2R gene expression in human CAKUT concerning -1332A/G polymorphism, which might affect alternative splicing. Design and methods: Forty-eight patients with CAKUT constitute the basis of this study. Genotyping for -1332A/G, RT-PCR for AT2R gene expression and confirmation sequencing were performed. Results: The expression of Ex 1/2/3 and Ex 1/3 transcript splice variants of the AT2R mRNA were detected in human CAKUT tissue. The pattern was observed independently of A to G transition. Conclusions: The expression of AT2R mRNA in human CAKUT was established for the first time and was not affected by -1332A/G polymorphism in children with CAKUT.

Hypomorphic mutations in meckelin (MKS3/TMEM67) cause nephronophthisis with liver fibrosis (NPHP11)

Background:Nephronophthisis (NPHP), a rare recessive cystic kidney disease, is the most frequent genetic cause of chronic renal failure in children and young adults. Mutations in nine genes (NPHP1-9) have been...

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC): Compound heterozygous mutation in the claudin 16 (CLDN16) gene

BackgroundFamilial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal recessive disorder of renal calcium and magnesium wasting frequently complicated by progressive chronic renal failure in childhood or adolescence.MethodsA 7 year old boy was investigated following the findings of marked renal insufficiency and nephrocalcinosis in his 18-month old sister. He too was found to have extensive nephrocalcinosis with increased fractional excretion of magnesium: 12.4% (<4%) and hypercalciuria: 5.7 mmol (< 2.5/24 hours). He had renal impairment, partial distal renal tubular acidosis and defective urinary concentrating ability. Therapy with thiazide diuretics and magnesium supplements failed to halt the progression of the disorder. Both children subsequently underwent renal transplantation. Both children's parents are unaffected and there is one unaffected sibling.ResultsMutation analysis revealed 2 heterozygous mutations in the claudin 16 gene (CLDN16) in both affected siblings; one missense mutation in exon 4: C646T which results in an amino acid change Arg216Cys in the second extracellular loop of CLDN16 and loss of function of the protein and a donor splice site mutation which changes intron 4 consensus splice site from 'GT' to 'TT' resulting in decreased splice efficiency and the formation of a truncated protein with loss of 64 amino acids in the second extracellular loop.ConclusionThe mutations in CLDN16 in this kindred affect the second extra-cellular loop of claudin 16. The clinical course and molecular findings suggest complete loss of function of the protein in the 2 affected cases and highlight the case for molecular diagnosis in individuals with FHHNC.