Congenital anomalies of the kidney and urinary tract (CAKUT): from the prenatal diagnosis to patient's care and prognosis
Creators: name: Parvex, Paloma Maria
Publisher: name: Université de Genève
Year: 2013
Subjects: info:eu-repo/classification/ddc/618
Cystatin C
CAKUT
Neonatal renal function
Renal endowment

description: Congenital kidney malformations of the kidney and urinary tract (CAKUT) include a large spectrum of diseases occurring subsequently to a misdevelopement in kidney development during gestation. The majority of theses diseases are prenatally diagnosed, for this reason accurate diagnosis is needed for counseling to parents and to decide of the better management at birth. Since 2008, we create a database to establish a cohort of neonates diagnosed with CAKUT to include prospectively pre and postnatal data to improve knowledge in these diseases. CAKUT are the most frequent cause of end stage renal disease during childhood. The wide variability of these pathologies is due to the complexity of kidney development. CAKUT may be secondary to an anomaly of tissue interaction at an early stage or to a modification of a molecular pathway at different steps of nephrogenesis. Hence, nephrogenesis may lead in the majority of the cases to low renal endowment similarly to what is observed in premature and neonates borne small for age. With the first nephrons, primitive renal function appears and small amount of urine began to be produced at 10 weeks of gestation and increased progressively to reach a mature glomerular filtration rate at the age on one year. Since renal function at birth is immature, its evaluation is chief to discriminate among neonates, those who may present a possible low renal endowment and subsequently an increased risk of renal progression. However in this population, the evaluation of renal function is challenging, because of the difficulty to validate potential renal markers with a gold standard. In these work, we proposed to present a new approach for CAKUT disease with the measure of renal function since birth using Cystatin C (CysC), a renal marker, recognized to be sensible for neonates. Reference interval of Cystatin C for this age is proposed in the literature and we validate in our center a reference interval for CysC in normal term babies. When comparing CysC values of this control group, to neonates from our cohort with kidney malformation, we showed that neonates with bilateral kidney malformation had a statistically CysC increased value compared to the control group. We proposed a cut-off value for Cystatin C, above which it may indicate an increased risk to present impaired renal endowment. The majority of renal and urinary tract malformation will be revealed prenatally and the most frequent presentation is the detection on the ultrasounds of an antenatal pelvic dilatation. Many authors have proposed guidelines for the management at birth of antenatal pelvic dilatation with variable cut-off's of posterior anterior diameter. These guidelines are important to identify neonates at risk of severe obstruction or who need an imaging evaluation to rule out vesico-ureteral reflux and avoid subsequent infections and renal scars. For the future, the target will be to succeed to delay renal function. With early and multidisciplinary management of these neonates since the last decade, we already noticed a delay in renal function progression, however there is a strong need to identify predictor factors to improve long term prognosis. Indeed renal endowment increased the risk to present renal progression but also hypertension and in adulthood cardio-vascular diseases. For this purpose, we followed, our cohort of neonates with CAKUT, two years after birth to analyzed predictors of renal function progression using CysC and creatinine as markers for renal function. We found that the bilateralism of the renal malformation and or the relative renal function asymmetry detected by the initial scintigraphy were factors of renal progression. Another approach, proposed to decrease renal function progression is to target the treatment of proteinuria with ACE inhibitors. Finally, to accurately assess neonatal renal function, the validation of Cystatin C with a gold standard will be essential. Likewise, neonates with CAKUT, premature and small for age neonates, because of possible impaired renal endowment will benefit of a useful clinical tool for the measure of renal function, often undeerdiagnosed in thie population.