Dents disease (or Dent disease) is a rare X-linked recessive inherited condition that affects the proximal renal tubules of the kidney. It is one cause of Fanconi syndrome, and is characterized by tubular proteinuria, excess calcium in the urine, formation of calcium kidney stones, nephrocalcinosis, and chronic kidney failure. "Dents disease" is often used to describe an entire group of familial disorders, including X-linked recessive nephrolithiasis with kidney failure, X-linked recessive hypophosphatemic rickets, and both Japanese and idiopathic low-molecular-weight proteinuria. About 60% of patients have mutations in the CLCN5 gene (Dent 1), which encodes a kidney-specific chloride/proton antiporter, and 15% of patients have mutations in the OCRL1 gene (Dent 2). Signs and symptoms
Dents disease often produces the following signs and symptoms:
Extreme thirst combined with dehydration, which leads to frequent urination
Nephrolithiasis (kidney stones)
Hypercalciuria (high urine calcium - >300 mg/d or >4 mg/kg per d with normal levels blood/serum calcium)
Aminoaciduria (amino acids in urine)
Phosphaturia (phosphate in urine)
Glycosuria (glucose in urine)
Kaliuresis (potassium in urine)
Hyperuricosuria (excessive amounts of uric acid in the urine)
Impaired urinary acidification
RicketsIn a study of 25 patients with Dents disease, 9 of 15 men, and one of 10 women had end-stage kidney disease by the age of 47. Genetics
Dent disease 1
Dents disease is a X-linked recessive disorder.
Prostacyclin (also called prostaglandin I2 or PGI2) is a prostaglandin member of the eicosanoid family of lipid molecules. It inhibits platelet activation and is also an effective vasodilator. When used as a drug, it is also known as epoprostenol. The terms are sometimes used interchangeably. Function
Prostacyclin (PGI2) chiefly prevents formation of the platelet plug involved in primary hemostasis (a part of blood clot formation). It does this by inhibiting platelet activation. It is also an effective vasodilator. Prostacyclins interactions contrast with those of thromboxane (TXA2), another eicosanoid. Both molecules are derived from arachidonic acid, and work together with opposite platelet aggregatory effects. These strongly suggest a mechanism of cardiovascular homeostasis between these two hormones in relation to vascular damage. Medical uses
It is used to treat pulmonary arterial hypertension (PAH), pulmonary fibrosis, as well as atherosclerosis. Specifically, epoprostenol is given to patients with class III  or class IV PAH. Degradation
Prostacyclin, which has a half-life of 42 seconds, is broken down into 6-keto-PGF1, which is a much weaker vasodilator. A way to stabilize prostacyclin in its active form, especially during drug delivery, is to prepare prostacyclin in alkaline buffer. Even at physiological pH, prostacyclin can rapidly form the inactive hydration product 6-keto-prostaglandin F1α. Mechanism
As mentioned above, prostacyclin (PGI2) is released by healthy endothelial cells and performs its function through a paracrine signaling cascade that involves G protein-coupled receptors on nearby platelets and endothelial cells. The platelet Gs protein-coupled receptor (prostacyclin receptor) is activated when it binds to PGI2.