Introduction to Nephrogenic Syndrome

What is/are Nephrogenic Syndrome?

Nephrogenic Syndrome - Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is an X-linked disease caused by activating mutations in the arginine vasopressin (AVP) receptor-2 (AVPR2) gene. ^[1] This chapter discusses the relevance of the altered vasopressin-aquaporin-2 pathway in some diseases associated with water balance disorders, including congenital nephrogenic diabetes insipidus, syndrome of inappropriate secretion of antidiuretic hormone, nephrogenic syndrome of inappropriate antidiuresis, and autosomal dominant polycystic kidney disease. ^[2] In this study, we investigated the possibility of drug-induced nephrogenic syndrome of inappropriate antidiuresis (NSIAD) using haloperidol, sertraline, and carbamazepine. ^[3] In this review, we will discuss two conditions that can determine euvolemic hyponatremia: the cerebral/renal salt wasting (CRSW) syndrome and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), including the two subtypes: reset osmostat (RO) and nephrogenic syndrome of inappropriate antidiuresis (NSIAD) and their differential diagnoses. ^[4] BACKGROUND Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a rare inherited disorder characterised by hyponatraemia. ^[5] Objective: To analyze the clinical and genetic features, as well as the treatment outcomes of two boys with nephrogenic syndrome of inappropriate antidiuresis (NSIAD) caused by gain-of-function mutations in the V2 vasopressin receptor gene (AVPR2). ^[6] Analysis of two ternary complex structures revealed distinct agonist and G protein binding modes, and provided insights into the mechanisms by which specific V2R mutations might affect V2R activity and Gs coupling, resulting in distinct Xlinked genetic diseases: congenital nephrogenic diabetes insipidus and nephrogenic syndrome of inappropriate antidiuresis. ^[7] This review highlights some of the new insights and recent advances in therapeutic intervention targeting the dysfunctions in the vasopressin–AQP2 pathway causing diseases characterized by water balance disorders such as congenital nephrogenic diabetes insipidus, syndrome of inappropriate antidiuretic hormone secretion, nephrogenic syndrome of inappropriate antidiuresis, and autosomal dominant polycystic kidney disease. ^[8] Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is the mirror image of nephrogenic diabetes insipidus (NDI): in NDI, the kidneys cannot concentrate the urine, whereas in NSIAD, urinary dilution is impaired, independent of the presence or absence of vasopressin. ^[9] METHODS We performed whole-exome sequencing in two families with dominantly inherited nephrogenic syndrome of inappropriate antidiuresis (NSIAD) as a salient phenotype after excluding a gain-of-function variant of AVPR2 and functional studies for identified variants. ^[10] Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a syndrome of inappropriate antidiuretic hormone secretion (SIADH) with low plasmatic vasopressin. ^[11] Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a recently identified chromosome X-linked disease associated with gain-of-function mutations of the V2 vasopressin receptor (V2R), a G-protein-coupled receptor. ^[12] If neural or hormonal regulation fails to operate the normal function of AVP-V2R-AQP2 system, it can result in various diseases such as diabetes insipidus (DI) or nephrogenic syndrome of inappropriate diuresis (NSIAD). ^[13] Although contrast-enhanced MRI (CE-MRI) is considered as the imaging modality of choice for multiple sclerosis (MS), due to disease chronicity, applying multiple doses of gadolinium-based contrast agents (GBCAs) increases the risk of nephrogenic syndrome in patients with acute (ARF) and chronic renal syndromes (CRF). ^[14]