Practical Considerations for APOL1 Genotyping in the Living Kidney Donor Evaluation.

BACKGROUND: Association between the apolipoprotein L1 gene (APOL1) and nephropathy has altered the epidemiology of chronic kidney disease. In addition, donor APOL1 genotypes play important roles in the time to allograft failure in kidneys transplanted from deceased donors and the safety of living kidney donation. METHODS: This article reviews genetic testing for inherited kidney disease in living kidney donors to improve donor safety. APOL1 genotyping in donors with recent African ancestry is considered. RESULTS: Based on current data, transplant physicians should discuss APOL1 genotyping with potential living kidney donors self-reporting recent African ancestry. Until results from APOL1 Long-term Kidney Transplant Outcomes Network ancillary studies are available, we present practical approaches from our experience for considering APOL1 genotyping in the living donor evaluation. CONCLUSIONS: Transplant physicians should inform potential living kidney donors at risk for APOL1-associated nephropathy about the gene and possibility of genetic testing early in the donor evaluation, well before scheduling the donor nephrectomy. Transplant programs must weigh risks of performing a donor nephrectomy in those with 2 APOL1 renal risk variants (high-risk genotypes), particularly younger individuals. Our program counsels kidney donors with APOL1 high-risk genotypes in the same fashion as with risk genotypes in other nephropathy genes. Because most African American kidney donor candidates lacking hypertension, proteinuria and reduced kidney function after workup will not possess APOL1 high-risk genotypes, genetic testing is unlikely to markedly increase donor declines and may reassure donors with regard to their long-term kidney outcomes, potentially increasing the number of African American donors.

Early or Late Transplantation in Congenital Nephrotic Syndrome: Which is Effective for Optimal Growth?

Congenital nephrotic syndrome (CNS) is a genetic disease that is present in the antenatal period or during the first 3 months of life. In this study, we aimed to compare growth parameters of patients with CNS who received kidney transplants and either (1) had a normal glomerular filtration rate (GFR) at the time of transplant or (2) chronic kidney disease (CKD) at the time of transplant. Patients with a diagnosis of CNS who had a minimum follow-up period of 6 months were evaluated retrospectively. Children at stages 4 or 5 CKD or patients receiving dialysis during the pretransplant period were defined as group 1; patients with normal GFR at the time of transplantation were classified as group 2. Short stature and low weight were defined as less than -2 standard deviation scores (SDS) for height and weight according to their age. A total of 17 patients were included in the study. Thirteen of 17 patients had NPHS1 gene mutations. Group 1 and group 2 consisted of 8 and 9 patients, respectively. Mean height SDS and mean weight SDS in group 2 were higher than group 1 in the pretransplant period (-4.34 ± 1.74 vs -2.84 ± 1.56; P = .011 and -3.54 ± 0.93 vs -1.83 ± 1.13; P = .008). In the post-transplant period, the significant difference in height SDS continued in favor of group 2 (-3.16 ± 1.11 vs -1.16 ± 0.87; P = .002). The short stature rate was 83% in group 1 and 72% in group 2 in the pretransplant period (P = .62), and 83% in group 1 and 27% in group 2 in the post-transplant period (P = .02). Early renal transplantation seems to be effective for optimal height gain in children with CNS.

Urine biochemistry to predict long-term outcomes in fetuses with posterior urethral valves.

OBJECTIVE: Because the literature on the predictive value of fetal urinalysis is controversial in fetuses with lower urinary tract obstruction, we determined the best model of fetal urine biochemical markers correlated with long-term postnatal renal function based on glomerular filtration rate (GFR). METHOD: This retrospective study concerned 89 fetuses with lower urinary tract obstruction and their renal function after 10 years of age. We correlated fetal urine biochemical markers (total protein, ß2-microglobulin, sodium, chloride, glucose, calcium, and phosphorus) with GFR at 10 to 30 years of age in 89 patients with posterior urethral valves. We defined five stages of chronic kidney disease (CKD). RESULTS: Of the 89 patients, 18 (20%) are 20 years old or over. Postnatal renal function was good in 67.4% (GFR > 60 mL/min/1.73 m2 ) and poor in 17% (GFR < 30 mL/min/1.73 m2 ). All fetal urine markers differed between CKD stage 1 + 2 and CKD stage 4 + 5 (P < 0.001). ß2-microblobulin showed an 87% sensitivity for a 72% specificity. A combination of ß2-microglobulin and chloride gave the best results (93% sensitivity and 71% specificity) versus amniotic fluid volume (80% sensitivity and 73% specificity). CONCLUSION: Fetal urine biochemistry predicts long-term (10-30 years) postnatal renal function.

[Chronic kidney disease in children up to 2 years of age - a single center data analysis]. / Przewlekla choroba nerek u dzieci do 2. roku zycia ­ analiza danych z jednego osrodka.

Although anomalies in the urinary tract are the leading cause of chronic kidney disease (CKD) in the pediatric population, there are few studies focusing on etiological discrepancies between younger and older children. AIM: The aim of the study was to perform a comparative analysis of etiology of CKD in children hospitalized in the Department of Pediatric Nephrology at the Wroclaw Medical University, with reference to the patients' age and gender. MATERIALS AND METHODS: The retrospective analysis considered medical records of 174 patients aged 0-18 years, diagnosed with CKD, hospitalized in our Department in the years 2011-2017. The analyzed population was divided regarding the patients' age. Group A contained children up to 2 years of age (45 patients), group B - children aged 2-18 years (129 patients). RESULTS: In younger children, boys prevailed, in older children gender distribution was equal. The most common causative factors of CKD in group A were: urinary tract anomalies (66,7%), perinatal acute kidney injury (17,8%) and hereditary renal disorders (8,9%). In children over 2 years of age, urinary tract anomalies were also the leading cause of CKD (48,8%), followed by glomerulopathies (16,3%) and hereditary renal disorders (15,5%). CONCLUSIONS: Anomalies within the urinary tract are the predominant cause of CKD in children, irrespective of age. Male predominance concerned only children up to 2 years of age. The second causative factor for CKD in the youngest children is acute kidney injury, mainly in the perinatal period. Glomerulopathies and hereditary renal disorders are significant etiological factors for CKD in older children.

Role of biomechanical forces in hyperfiltration-mediated glomerular injury in congenital anomalies of the kidney and urinary tract.

Congenital anomalies of the kidney and urinary tract (CAKUT) including solitary kidney constitute the main cause of progressive chronic kidney disease (CKD) in children. Children born with CAKUT develop signs of CKD only during adolescence and do not respond to renin-angiotensin-aldosterone system blockers. Early cellular changes underlying CKD progression to end-stage renal disease by early adulthood are not well understood. The mechanism of maladaptive hyperfiltration that occurs from loss of functional nephrons, including solitary kidney, is not clear. We re-examine the phenomenon of hyperfiltration in the context of biomechanical forces with special reference to glomerular podocytes. Capillary stretch exerts tensile stress on podocytes through the glomerular basement membrane. The flow of ultrafiltrate over the cell surface directly causes fluid flow shear stress (FFSS) on podocytes. FFSS on the podocyte surface increases 1.5- to 2-fold in animal models of solitary kidney and its effect on podocytes is a subject of ongoing research. Podocytes (i) are mechanosensitive to tensile and shear forces, (ii) use prostaglandin E2, angiotensin-II or nitric oxide for mechanoperception and (iii) use specific signaling pathways for mechanotransduction. We discuss (i) the nature of and differences in cellular responses to biomechanical forces, (ii) methods to study biomechanical forces and (iii) effects of biomechanical forces on podocytes and glomeruli. Future studies on FFSS will likely identify novel targets for strategies for early intervention to complement and strengthen the current regimen for treating children with CAKUT.

Progression of renal fibrosis in congenital CKD model rats with reduced number of nephrons.

A congenital reduction in the number of nephrons is a critical risk factor for both onset of chronic kidney disease (CKD) and its progression to end-stage kidney disease (ESKD). Hypoplastic kidney (HPK) rats have only about 20% of the normal number of nephrons and show progressive CKD. This study used an immunohistological method to assess glomerular and interstitial pathogenesis in male HPK rats aged 35-210days. CD68 positive-macrophages were found to infiltrate into glomeruli in HPK rats aged 35 and 70days and to infiltrate into interstitial tissue in rats aged 140 and 210days. HPK rats aged 35 and 70days showed glomerular hypertrophy, loss of normal linear immunostaining of podocine, and increased expression of PDGFr-ß, TGF-ß, collagens, and fibronectin, with all of these alterations gradually deteriorating with age. α-SMA-positive myofibroblasts were rarely detected in glomerular tufts, whereas α-SMA-positive glomerular parietal epithelium (GPE) cells were frequently observed along Bowman's capsular walls. The numbers of PDGFr-ß-positive fibroblasts in interstitial tissue were increased in rats aged 35days and older, whereas interstitial fibrosis, characterized by the increased expression of tubular PDGF-BB, the appearance of myofibroblasts doubly positive for PDGFr-ß and α-SMA, and increased expression of collagens and fibronectin, were observed in rats aged 70 and older. These results clearly indicate that congenital CKD with only 20% of nephrons cause renal fibrosis in rats.

Maternal obesity is associated with congenital anomalies of the kidney and urinary tract in offspring.

BACKGROUND: Congenital abnormalities of the kidney and urinary tract (CAKUT) are diagnosed in up to 1 % of pregnancies and account for 20-30 % of the abnormalities identified in the prenatal period. In previous studies, maternal obesity has been associated with congenital malformations in offspring. Our aim was to evaluate the association between maternal obesity [body mass index (BMI) ≥ 30 kg/m2] and CAKUT in offspring. METHODS: We conducted a population-based, case-control study using linked birth-hospital discharge records from Washington State, 2003-2012. We identified 3093 CAKUT cases using International Classification of Diseases, Ninth Revision (ICD-9) codes. Controls were defined as births without any ICD-9 codes denoting congenital malformations, matched to cases by year of birth in an approximate 4:1 ratio. RESULTS: Compared to controls, mothers giving birth to infants with CAKUT were more likely to be obese [odds ratio (OR) 1.24, 95 % confidence interval (CI) 1.11-1.38]. We found a significant positive trend between odds of CAKUT in offspring and increasing severity of obesity (score test for trend of odds p < 0.001). This association remained significant in offspring with isolated CAKUT (OR 1.19, 95 % CI 1.06-1.35) and upper urinary tract anomalies (OR 1.26, 95 % CI 1.13-1.41). Maternal overweight (BMI 25-29.9 kg/m2) was not associated with CAKUT in offspring. CONCLUSIONS: Our results demonstrate a positive association between maternal obesity and CAKUT in offspring, as well as between obesity severity and the odds of CAKUT in offspring. These findings provide additional evidence for the public health importance of obesity, particularly as a potentially modifiable risk factor.

Averting the legacy of kidney disease - focus on childhood.

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, in that the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease as a consequence of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, although only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that the World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

Averting the legacy of kidney disease - focus on childhood

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, in that the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease as a consequence of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, although only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that the World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

Early kidney transplantation improves neurocognitive outcome in patients with severe congenital chronic kidney disease.

Renal replacement therapy has become available for the majority of patients suffering from severe congenital chronic kidney disease (CKD). Data on the long-term neurocognitive outcome and the impact of early kidney transplantation (KTx) in this setting is unclear. Neurocognitive outcomes in 15 patients (11 male) with isolated congenital CKD (stage 3-5) requiring KTx at a mean age of 2.8 ± 1.3 were assessed at a mean age of 8.3 ± 1.4 years. Patients underwent neurological examination and testing for neuromotor and neurocognitive function using three independent tests. Pre-emptive KTx was performed in six patients, and nine patients were dialyzed prior to KTx for a mean period of 11.1 ± 8.6 months. Neuromotor function was abnormal in 8/15 patients. HAWIK-III showed a global intelligence quotient (IQ) of 93.5 ± 11.4 (P = 0.05) due to a significantly reduced performance IQ of 89.1 ± 11.3 (P < 0.01). In three patients, the global IQ was clinically significantly reduced by >1 SD to <85. In patients with neuromotor dysfunction, performance IQ was lower than in patients with normal neuromotor function (83.8 ± 10.2 vs. 96.2 ± 9.0, P = 0.04). Time on dialysis was inversely correlated to verbal IQ (r = 0.78, P = 0.02). Pre-emptive KTx and duration of dialysis treatment <3 months was associated with superior neurocognitive outcome. Early (pre-emptive) KTx results in superior long-term neurocognitive outcome in children with severe congenital CKD.

Predictors of renal replacement therapy and mortality in children with chronic kidney disease.

OBJECTIVES: To study the epidemiology of chronic kidney disease (CKD) in children, and to look for risk factors to predict renal replacement therapy (RRT) and mortality. METHODS: This is a retrospective cohort study conducted at King Abdulaziz University Hospital, Jeddah, Saudi Arabia between 2006 and 2014, where the files of 1,000 children with CKD were reviewed. We determined the effect of consanguinity and hypertension, and being a Saudi indigene on mortality and RRT. We compared children with congenital versus non-congenital causes of CKD. RESULTS: The mean±standard deviation age at presentation was 4.9±4.3 years. The median duration of follow up was 1.5 (interquartile range [IQR]: 0.4-4.0) years. Only 9.7% of children received RRT, and 8.3% died. The underlying etiology for CKD was congenital in 537 children. The congenital CKD group presented at a younger age group (3.5±4.0 versus 6.6±3.9 years, p<0.0001), had more advanced stages of CKD (p<0.0001), higher rates of consanguinity (75.4% versus 47.1%, p<0.0001), and RRT (p<0.004) than children with non-congenital CKD. Risk factors for RRT among children with CKD include being a Saudi indigene (relative risk [RR]=1.49, 95% confidence interval (CI): 1.01-2.21), and hypertensive (RR=5.29, 95% CI: 3.54-7.91). The risk factor for mortality was hypertension (RR=2.46, 95% CI: 1.66-3.65). CONCLUSION: Congenital causes of CKD represent the main etiology of CKD in children living in the western province of Saudi Arabia. Significant risk factors for RRT include congenital CKD, Saudi nationality, and hypertension. Hypertension is also a predictor of mortality in children with CKD.

Familial Takayasu arteritis in a mother and daughter. A report of two cases.

Takayasu arteritis (TA) is a chronic granulomatous panarteritis, predominantly affecting the aorta and its main branches. Infections, genetic factors as suggested by familial clustering, and autoimmunity may play a role in its pathogenesis. In this report, we describe familial TA in a mother and daughter with diverse clinical manifestations. In addition to being a familial form of vasculitis, both of our cases demonstrated amyloidosis, chronic renal disease thought to be due to ischemic nephropathy, and hypertensive nephrosclerosis.

Displasia renal em cão da raça Rotweiller / Renal dysplasia in a dog breed Rotweiller

Descreveram-se os achados clínicos e patológicos de um caso de displasia renal em um cão da raça Rotweiller com oito meses de idade. O animal apresentou vômitos, emagrecimento, polidpsia e poliúria. Houve elevação sanguínea de creatinina, cálcio e da fosfatase alcalina. À necropsia, notaram-se os rins diminuídos de tamanho, com estruturas císticas proeminentes sobre a superfície natural do órgão e, ao corte, firmes e com estruturas císticas distribuídas pelo parênquima. Na avaliação histológica, havia glomérulos imaturos, fibroplasia intersticial e dilatação cística tubular.

In this study we describe the clinical and pathological findings of a case of renal dysplasia in a dog from the Rottweiler breed at 8 months of age. The animal presented vomiting, weight loss, polydipsia and polyuria. There was an increase of blood creatinine, calcium, and alkaline phosphatase. At necropsy it was noted that the kidneys were reduced in size, with prominent cystic structures on the natural surface of the body and the cutting and firm with cystic structures distributed throughout the parenchyma. The histological evaluation was immature glomeruli, interstitial fibroplasia and tubular cystic dilation.

Long-term clinical consequences of urinary tract infections during childhood: a review.

UNLABELLED: Kidney scarring related to urinary tract infection in childhood has been considered the cause of serious long-term clinical consequences. This assumption is now debated, as the advent of routine antenatal ultrasound in the 1980s has shown that a consistent part of the changes previously attributed to postinfectious scarring is mainly due to congenital malformations. With the aim of determining what is presently known on the long-term clinical consequences of urinary tract infections (UTIs) in childhood, we performed a review of the literature on the relation between UTIs and blood pressure, renal function, growth and pregnancy-related complications. By searching Medline/PubMed and Embase from 1980 to 2011, we identified 20 cohorts of children from 23 papers. CONCLUSIONS: Renal function: there are no clear data to establish long-term consequences following UTIs during childhood. Most data seem to show that the outcome of renal function can already be delineated at first presentation or in the initial years of follow-up; only 0.4% of children with normal renal function at start presented a decrease during follow-up. Hypertension: there is a low risk, associated with renal damage. Growth and pregnancy-related complications: the few available data seem to exclude a major influence of UTIs.