pituitrin and Kidney-Diseases--Cystic

ADH is a hormone secreted by neurohypophysis that plays different roles based on the target organ. At the renal level, this peptide is capable of causing electrolyte-free water absorption, thus playing a key role in the hydro-electrolytic balance. There are pathologies and disorders that jeopardize this balance and, in this field, ADH receptor inhibitors such as Vaptans could play a key role. By inhibiting the activation pathway of vasopressin, they are potentially useful in euvolemic and hypervolemic hypotonic hyponatremia. However, clinical trials in heart failure have not given favourable results on clinical outcomes. Even in SIADH, despite their wide use, there is no agreement by experts on their use. Since vaptans inhibit the cAMP pathway in tubular cells, their use has been proposed to inhibit cystogenesis. A clinical trial has shown favourable effects on ADPKD progression. Because vaptans have been shown to be effective in models of renal cysts disorders other than ADPKD, their use has been proposed in diseases such as nephronophthisis and recessive autosomal polycystic disease. Other possible uses of vaptans could be in kidney transplantation and cardiorenal syndrome. Due to the activity of ADH in coagulation and haemostasis, ADH's activation pathway by Desmopressin Acetate could be a useful strategy to reduce the risk of bleeding in biopsies in patients with haemorrhagic risk.

Topics: Antidiuretic Hormone Receptor Antagonists; Cadaver; Cyclic AMP; Forecasting; Humans; Hyponatremia; Kidney Diseases; Kidney Diseases, Cystic; Kidney Transplantation; Kidney Tubules, Collecting; Molecular Targeted Therapy; Neurophysins; Polycystic Kidney, Autosomal Dominant; Protein Precursors; Receptors, Vasopressin; Second Messenger Systems; Tissue Donors; Vasopressins; Water-Electrolyte Imbalance

The cystic kidney disease nephronophthisis (NPHP) is the commonest genetic cause of end-stage renal failure in young people and children. Histologically the disease is characterized by interstitial fibrosis, tubular atrophy with corticomedullary cyst development and disruption of the tubular basement membrane. Affected children present with polydipsia and polyuria, secondary to a urinary concentration defect, before these structural changes develop. Recently, molecular genetic advances have identified several genes mutated in NPHP, providing novel insights into its pathophysiology for the first time in decades. Here we review the normal physiological mechanisms of urinary concentration and explain, in the context of recent discoveries, the possible mechanisms underlying urinary concentration defects in patients with NPHP. The pattern of a ciliary and adherens junction subcellular localization of nephrocystin proteins is discussed. Recent animal models of cystic kidney disease and treatment with vasopressin V2 receptor antagonists are reviewed and a hypothesis regarding urinary concentration defects in NPHP is proposed. Understanding the cellular mechanisms underlying NPHP and other cystic kidney diseases will provide the rationale for therapeutic interventions in this disease. Early urinary concentration defects provide both a clue to clinical diagnosis of NPHP and potential therapeutic targets for pharmacological treatment of this condition.

Topics: Aquaporins; Humans; Kidney Diseases, Cystic; Urinary Tract Physiological Phenomena; Urine; Vasopressins

Topics: Adult; Aged; Blood Circulation Time; Blood Flow Velocity; Bradykinin; Female; Humans; Kidney; Kidney Diseases; Kidney Diseases, Cystic; Kidney Neoplasms; Male; Middle Aged; Radiography; Regional Blood Flow; Renal Artery; Technology, Radiologic; Vasopressins

Topics: Adolescent; Child; Child, Preschool; Cystinosis; Diabetes Insipidus; Diuresis; Glomerulonephritis; Humans; Hydronephrosis; Infant; Infant, Newborn; Kidney Diseases; Kidney Diseases, Cystic; Polyuria; Pyelonephritis; Uremia; Vasopressins