Tubulopathy: the clinical and genetic approach in diagnosis

Remarkable advances in genetic diagnosis expanded our knowledge about inherited tubulopathies and other genetic kidney diseases. This review suggests a simple categorization of inherited tubular disease, clarifies the concept of autosomal dominant tubulointerstitial kidney disease (ADTKD), and introduces novel therapies developed for tubulopathies. Facing patients with suspicious tubular disorders, clinicians should first evaluate the status of volume and acid-base. This step helps the clinicians to localize the affected segment and to confirm genetic diagnosis. ADTKD is a recently characterized disease entity involving tubules. The known causative genes are UMOD, MUC1, REN, and HNF1β. Still, only half of ADTKD patients show mutations for these four identified genes. Whole exome sequencing is a suitable diagnostic tool for tubulopathies, especially for ADTKD. Genetic approaches to treat tubulopathies have progressed recently. Despite the practical obstacles, novel therapies targeting inherited tubulopathies are currently in development.

Diverse renal manifestations of Alagille syndrome in Korean children

Purpose@#To determine the prevalence, clinical manifestations, and outcomes of renal involvements in pediatric Alagille syndrome (ALGS). @*Methods@#A total of 21 patients diagnosed with ALGS at age under 18 years who visited Samsung Medical Center from March 1999 to March 2022 were enrolled. ALGS was diagnosed either by clinical manifestations, targeted JAG1 sequencing, and/or liver biopsy. Medical records including sex, age, renal manifestations, urinalysis, serum creatinine, JAG1 sequencing, and ultrasonography were retrospectively reviewed. @*Results@#The male to female ratio was 9:12. The mean age of patients at confirmative diagnosis of ALGS was 18.4 months. Sanger sequencing was performed for 17 patients. Sixteen of 21 patients (76.1%) showed JAG1 mutations. Renal involvement was found in 10 patients (47.6%). The most common type of anomaly was renal dysplasia (40%). One patient having renal dysplasia was pathologically confirmed with glomerular lipid deposition. Two patients (20%) manifested nephrocalcinosisephrolithiasis. Among eight renal-involved patients who survived, four (50%) progressed to chronic kidney disease stage 3. Two of these chronic kidney disease patients were diagnosed with hepatorenal syndrome. The other four patients had renal functions preserved, including two without any interventions and two who underwent urological interventions. @*Conclusions@#The current study revealed a high prevalence of renal involvement in Korean pediatric ALGS with diverse phenotypes.