Diabetes-Induced Congenital Anomalies of the Kidney and Urinary Tract (CAKUT): Nurture and Nature at Work?

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT): An Emerging Relationship With Pregestational Diabetes Mellitus Among First Nations and Non-First Nations People in Saskatchewan—Results From the DIP: ORRIIGENSS Project

Hepatocyte nuclear factor 1β (HNF1β)-associated disease is a recently recognized clinical entity with a variable multisystem phenotype. Early reports described an association between HNF1B mutations and maturity-onset diabetes of the young. These patients often presented with renal cysts and renal function decline that preceded the diabetes, hence it was initially referred to as renal cysts and diabetes syndrome. However, it is now evident that many more symptoms occur, and diabetes and renal cysts are not always present. The multisystem phenotype is probably attributable to functional promiscuity of the HNF1β transcription factor, involved in the development of the kidney, urogenital tract, pancreas, liver, brain, and parathyroid gland. Nephrologists might diagnose HNF1β-associated kidney disease in patients referred with a suspected diagnosis of autosomal dominant polycystic kidney disease, medullary cystic kidney disease, diabetic nephropathy, or CKD of unknown cause. Associated renal or extrarenal symptoms should alert the nephrologist to HNF1β-associated kidney disease. A considerable proportion of these patients display hypomagnesemia, which sometimes mimics Gitelman syndrome. Other signs include early onset diabetes, gout and hyperparathyroidism, elevated liver enzymes, and congenital anomalies of the urogenital tract. Because many cases of this disease are probably undiagnosed, this review emphasizes the clinical manifestations of HNF1β-associated disease for the nephrologist.

Background . Children with CAKUT-syndrome (congenital malformations of the urinary tract) quickly develop an inflammatory process, which, in combination with dysplasia and/or urodynamic disorders, creates a high risk of developing early chronic renal failure. Purpose of the study : to identify the main factors of the formation, features of the clinical course of nephropathies, morphometric parameters and features of the organ blood flow of the kidneys in young children against the background of CAKUT syndrome. Methods . Study design: It carried out a cohort prospective study. The main group included 26 children with pyelonephritis against the background of CAKUT syndrome at the age from zero to 36 months of life, the comparison group consisted of 29 children with non-obstructive pyelonephritis of the same age. It carried out a comparative analysis of antenatal and postnatal anamnesis, clinical, laboratory and instrumental data in the considered groups of children with nephro-urological pathology. Additionally, it researches the morphometric parameters of the kidneys and the Doppler indices of the renal vessels. The research conducted during 2016–2018. Results . In children with a chronic course of nephropathy in combination with CAKUT-syndrome, possible predictors of an early onset of the disease are: anemia, damage to the urinary tract with pathological urinary syndrome during pregnancy and a combination with defects of this system in the woman herself, and the development of placental insufficiency. In the group with CAKUT syndrome, a decrease in renal filtration function (in 88.5% of children) and persistent trace proteinuria (in 65.4% of children) are recorded by the end of the first year of life. According to ultrasound, in addition to signs of obstructive nephropathy, it recorded decreases in the thickness of the parenchyma and a violation of organ hemodynamics with an increase in the resistance index. In the observed group of children, CAKUT syndrome combined in 100% of cases with connective tissue dysplasia syndrome also. Conclusion . Thus, CAKUT syndrome leads to early realization of nephropathies in children with a rapid decline in renal function.

ObjectiveSince Asians are particularly vulnerable to the risk of gestational diabetes mellitus (GDM), the lifecourse health implications of which are far beyond pregnancy, we aimed to summarize the literature to understand the research gaps on current GDM research among Asians.MethodsWe systematically searched the articles in PubMed, Web of Science, Embase, and Scopus by 30 June 2021 with keywords applied on three topics, namely “GDM prevalence in Asians”, “GDM and maternal health outcomes in Asians”, and “GDM and offspring health outcomes in Asians”.ResultsWe observed that Asian women (natives and immigrants) are at the highest risk of developing GDM and subsequent progression to type 2 diabetes among all populations. Children born to GDM-complicated pregnancies had a higher risk of macrosomia and congenital anomalies (i.e. heart, kidney and urinary tract) at birth and greater adiposity later in life.ConclusionThis review summarized various determinants underlying the conversion between GDM and long-term health outcomes in Asian women, and it might shed light on efforts to prevent GDM and improve the lifecourse health in Asians from a public health perspective.Systematic Review RegistrationProspero, CRD42021286075.

A Systematic Review and Meta-Analysis of Diabetes During Pregnancy and Congenital Genitourinary Abnormalities

Congenital anomalies of kidney and urinary tract (CAKUT) constitute an average of 25 % of the total number of all genetic anomalies diagnosed in utero and include both individual anomalies of kidney or urinary tract and a combination of such. One of the important problems of pediatric nephrology is the early diagnosis of congenital anomalies of kidney and urinary tract, since untimely detected pathologies lead to a decrease in renal function. The cause of such violations can be genetic factors, environmental factors affecting the woman's body before or during pregnancy. Genetic factor contributes significantly to the formation of CAKUT based on the proven role of mutations in more than 200 genes associated with the development of these anomalies. Since the classical methods of molecular diagnostics do not allow in 90 % of cases to determine occurring mutations, there is a need to apply new genetic testing technologies to identify mutations of genes associated with this group of diseases. Next generation sequencing allows to detect rare genetic variants and concurrently test a large number of genes within a short period of time for the presence of clinically important mutations in them. In addition, the use of next-generation sequencing expands the search for new candidate genes of CAKUT. There are ethnic differences regarding genes involved in the development of congenital anomalies of kidney and urinary tract. The most promising present-day strategy is based on the study of the specific region of patient’s whole exome and the subsequent development of a diagnostic panel.