Alport syndrome (AS) is one of the most frequent hereditary nephritis leading to end-stage renal disease (ESRD). Although X-linked (XLAS) inheritance is the most common form, cases with autosomal recessive inheritance with mutations in COL4A3 or COL4A4 are being increasingly recognized. A systematic review was conducted on autosomal recessive Alport syndrome (ARAS). Electronic databases were searched using related terms (until Oct 10th, 2018). From 1601 articles searched, there were 26 eligible studies with 148 patients. Female and male patients were equally affected. About 62% of patients had ESRD, 64% had sensorineural hearing loss (SNHL) and 17% had ocular manifestation. The median at onset was 2.5 years for hematuria (HU), 21 years for ESRD, and 13 years for SNHL. Patients without missense mutations had more severe outcomes at earlier ages, while those who had one or two missense mutations had delayed onset and lower prevalence of extrarenal manifestations. Of 49 patients with kidney biopsy available for electron microscopy (EM) pathology, 42 (86%) had typical glomerular basement membrane (GBM) changes, while 5 (10%) patients showed GBM thinning only. SNHL developed earlier than previously reported. There was a genotype phenotype correlation according to the number of missense mutations. Patients with missense mutations had delayed onset of hematuria, ESRD, and SNHL and lower prevalence of extrarenal manifestations.

Steroid-resistant nephrotic syndrome (SRNS) is one of the major causes of end-stage renal disease (ESRD) in childhood and is mostly associated with focal segmental glomerulosclerosis (FSGS). More than 50 monogenic causes of SRNS or FSGS have been identified. Recently, the mutation detection rate in pediatric patients with SRNS has been reported to be approximately 30%. In this study, genotype-phenotype correlations in a cohort of 291 Korean pediatric patients with SRNS/FSGS were analyzed. The overall mutation detection rate was 43.6% (127 of 291 patients). WT1 was the most common causative gene (23.6%), followed by COQ6 (8.7%), NPHS1 (8.7%), NUP107 (7.1%), and COQ8B (6.3%). Mutations in COQ6, NUP107, and COQ8B were more frequently detected, and mutations in NPHS2 were less commonly detected in this cohort than in study cohorts from Western countries. The mutation detection rate was higher in patients with congenital onset, those who presented with proteinuria or chronic kidney disease/ESRD, and those who did not receive steroid treatment. Genetic diagnosis in patients with SRNS provides not only definitive diagnosis but also valuable information for decisions on treatment policy and prediction of prognosis. Therefore, further genotype-phenotype correlation studies are required.

Hypertension is becoming one of the most common health conditions in children and adolescents due to increasing childhood obesity. We aimed to provide the auscultatory blood pressure (BP) normative reference values for Korean non-overweight children and adolescents. BP measurements in children and adolescents aged 10 to 18 years were performed in the Korean National Health and Nutrition Examination Survey (KNHANES) from 1998 to 2016. BP was measured using a mercury sphygmomanometer. Sex-, age- and height-specific systolic BP (SBP) and diastolic BP (DBP) percentiles were calculated in the non-overweight children (n=10,442). We used the General Additive Model for Location Scale and Shape method to calculate BP percentiles. The 50th, 90th, 95th, and 99th percentiles of SBP and DBP tables and graphs of non-overweight children and adolescents aged 10 to 18 years were presented by age and height percentiles. We found that the SBP and DBP at the 95th percentile were well correlated with height. The BP tables presented by height contained BP values from 124 cm to 190 cm for boys and from 120 cm to 178 cm for girls. Boys had higher SBP and DBP. We provided the sex-, age- and height-specific auscultatory BP values using the KNHANES big data. These may be useful in diagnosis and treatment of hypertension in Korean children and adolescents.

HNF1B mutations, one of the most common causes of congenital anomalies of the kidney and urinary tract, manifest as various renal and extrarenal phenotypes. We analyzed the genotype-phenotype correlations in 14 pediatric patients with HNF1B mutations. Genetic studies revealed total gene deletion in six patients (43%). All patients had bilateral renal abnormalities, primarily multiple renal cysts. Twelve patients exhibited progressive renal functional deterioration, and six of them progressed to kidney failure. The annual reduction in estimated glomerular filtration rate was−2.1 mL/min/1.73 m². Diabetes developed in five patients (36%), including one patient with new-onset diabetes after transplantation. Neurological deficits were noted in three patients (21%), one with total gene deletion and two with missense mutations. Pancreatic abnormalities were more frequent in patients with missense mutations than in patients with other types of mutations. Genotype showed no significant correlation with renal outcomes or other extrarenal manifestations. The HNF1B scores at the times of onset and genetic diagnosis were <8 in two patients and one patient, respectively. Diagnosis of HNF1B mutations is clinically difficult because of extreme phenotypic variability and incomplete penetrance. Furthermore, some phenotypes develop with age. Therefore, patient age should be taken into consideration to increase the diagnostic rate, because some phenotypes develop with age.

Yang EM, et al. J Korean Med Sci. 2017 Nov;32(11):1828-1834. https://doi.org/10.3346/jkms.2017.32.11.1828

The global prevalence of chronic kidney disease (CKD) is increasing. In children, CKD exhibits unique etiologies and can have serious impacts on children’s growth and development. Therefore, an aggressive approach to preventing the progression of CKD and its complications is imperative. To improve the understanding and management of Asian pediatric patients with CKD, we designed and launched KNOW-Ped CKD (KoreaN cohort study for Outcome in patients With Pediatric Chronic Kidney Disease), a nationwide, prospective, and observational cohort study of pediatric CKD with funding from the Korean government. From seven major centers, 450 patients <20 years of age with CKD stages I to V are recruited for the comprehensive assessment of clinical findings, structured follow-up, and bio-specimen collection. The primary endpoints include CKD progression, defined as a decline of estimated glomerular filtration rate by 50 %, and a requirement for renal replacement therapy or death. The secondary outcomes include the development of left ventricular hypertrophy or hypertension, impairment of growth, neuropsychological status, behavioral status, kidney growth, and quality of life. With this study, we expect to obtain more information on pediatric CKD, which can be translated to better management for the patients. NCT02165878 (ClinicalTrials.gov), submitted on June 11, 2014.