For an endocrinologist, nephrogenic diabetes insipidus (NDI) is an end-organ disease, that is the antidiuretic hormone, arginine-vasopressin (AVP) is normally produced but not recognized by the kidney with an inability to concentrate urine despite elevated plasma concentrations of AVP. Polyuria with hyposthenuria and polydipsia are the cardinal clinical manifestations of the disease. For a geneticist, hereditary NDI is a rare disease with a prevalence of five per million males secondary to loss of function of the vasopressin V2 receptor, an X-linked gene, or loss of function of the water channel AQP2. These are small genes, easily sequenced, with a number of both recurrent and private mutations described as disease causing. Other inherited disorders with mild, moderate or severe inability to concentrate urine include Bartter’s syndrome and cystinosis. MAGED2 mutations are responsible for a transient form of Bartter’s syndrome with severe polyhydramnios. The purpose of this review is to describe classical phenotype findings that will help physicians to identify early, before dehydration episodes with hypernatremia, patients with familial NDI. A number of patients are still diagnosed late with repeated dehydration episodes and large dilations of the urinary tract leading to a flow obstructive nephropathy with progressive deterioration of glomerular function. Families with ancestral X-linked AVPR2 mutations could be reconstructed and all female heterozygote patients identified with subsequent perinatal genetic testing to recognize affected males within 2 weeks of birth. Prevention of dehydration episodes is of critical importance in early life and beyond and decreasing solute intake will diminish total urine output.
T Mary Fujiwara, Kenneth Morgan, and Daniel G Bichet
In congenital nephrogenic diabetes insipidus, the renal collecting ducts are resistant to the antidiuretic action of arginine-vasopressin, or to its antidiuretic analog dDAVP (1, 2). This is a rare, but now well described entity secondary to either mutations in the AVPR2 gene that codes for the vasopressin antidiuretic (V2) receptor or to mutations in the AQP2 gene that codes for the vasopressin-dependent water channel (3, 4). Of 75 families with congenital nephrogenic diabetes insipidus referred to our laboratory in Montreal, 71 families have AVPR2 mutations and four have AQP2 mutations. The AVPR2 gene is located in chromosome region Xq28 and as a consequence males who have an AVPR2 mutation have a phenotype characterized by early dehydration episodes, hypernatremia and hyperthermia as early as the first week of life. The dehydration episodes can be so severe that they lower arterial blood perfusion pressure to a degree that is not sufficient
Goce Spasovski, Raymond Vanholder, Bruno Allolio, Djillali Annane, Steve Ball, Daniel Bichet, Guy Decaux, Wiebke Fenske, Ewout J Hoorn, Carole Ichai, Michael Joannidis, Alain Soupart, Robert Zietse, Maria Haller, Sabine van der Veer, Wim Van Biesen, and Evi Nagler
Hyponatraemia, defined as a serum sodium concentration <135 mmol/l, is the most common disorder of body fluid and electrolyte balance encountered in clinical practice. It can lead to a wide spectrum of clinical symptoms, from subtle to severe or even life threatening, and is associated with increased mortality, morbidity and length of hospital stay in patients presenting with a range of conditions. Despite this, the management of patients remains problematic. The prevalence of hyponatraemia in widely different conditions and the fact that hyponatraemia is managed by clinicians with a broad variety of backgrounds have fostered diverse institution- and speciality-based approaches to diagnosis and treatment. To obtain a common and holistic view, the European Society of Intensive Care Medicine (ESICM), the European Society of Endocrinology (ESE) and the European Renal Association – European Dialysis and Transplant Association (ERA–EDTA), represented by European Renal Best Practice (ERBP), have developed the Clinical Practice Guideline on the diagnostic approach and treatment of hyponatraemia as a joint venture of three societies representing specialists with a natural interest in hyponatraemia. In addition to a rigorous approach to methodology and evaluation, we were keen to ensure that the document focused on patient-important outcomes and included utility for clinicians involved in everyday practice.