Nephrogenic

Stmctural defects at the receptor level are determinant for a number of receptor diseases. In nephrogenic diabetes insipidus, where patients void large volumes of dilute urine even in the presence of vasopressin (antidiuretic hormone) (105), the disease is linked to mutations in three discrete regions of the G-protein-linked vasopressin (V2) receptor (106,107). 

Paradoxically, the thia2ides are efficacious, especially if combined with a prostaglandin synthetase inhibitor such as indomethacin or aspirin, in the treatment of nephrogenic diabetes insidipus, in which the patient s renal tubules fail to reabsorb water despite the excessive production of ADH (28). Thia2ides can decrease the urine volume up to 50% in these patients. 

Deen PM, Marr N, Kamsteeg EJ et al (2000) Nephrogenic diabetes insipidus. Curr Opin Nephrol Hypertens 9 591-595... 

Robben JH, Knoers NV, Deen PM (2006) Cell biological aspects of the vasopressin 1ype-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus. Am J Physiol Renal Physiol 291 F257-F270... 

In nephrogenic diabetes insipidus the kidney s ability to respond to AVP is impaired by different causes, such as drugs (e.g. lithium), chronic disorders (e.g. sickle cell disease, kidney failure) or inherited genetic disorders (X-linked or autosomal NDI). This type of diabetes insipidus can not be treated by exogenous administration of AVP or AVP analogues. Instead, diuretics (hydrochlorothiazide combined or not with amiloride) and NSAI (indomethacin) are administrated to ameliorate polyuria. 

X-linked nephrogenic diabetes insipidus Vasopressin V2 receptor (V2R) SR121463, SR49059... 

Congenital Nephrogenic Diabetes Insipidus (X-llnkedf Autosomal)... 

Congenital nephrogenic diabetes insipidus (NDI) is a rare disease, characterized by an inability to concentrate urine despite normal or elevated AVP plasma... 

Oksche A, Rosenthal W (1998) The molecular basis of nephrogenic diabetes insipidus. JMol Med 76 326-337... 

X-linked nephrogenic diabetes insipidus (NDI) is caused by mutations in the gene for the vasopressin V2 receptor leading to an insensitivity of the kidney for the antidiuretic hormone arginine vasopressin (AVP). The main symptom of the disease is diuresis, i.e., the production of a large amount of diluted urine. Due to the massive loss of water, the patients suffer from thirst and are in danger of dehydration. The disease usually becomes evident shortly after birth. 

X-linked Nephrogenic Diabetes Insipidus X-ray Contrast Agents... 

Nephrotoxicity IDV potentially TDF Onset IDV—months after therapy TDF—weeks to months after therapy Symptoms IDV—asymptomatic rarely develop end-stage renal disease TDF—asymptomatic to symptoms of nephrogenic diabetes insipidus, Fanconi syndrome 1. History of renal disease 2. Concomitant use of nephrotoxic drugs Avoid use of other nephrotoxic drugs adequate hydration if on IDV monitor creatinine, urinalysis, serum potassium and phosphorus in patients at risk D/C offending agent, generally reversible supportive care electrolyte replacement as indicated... 

Daram SR, Cortese CM, Bastani B. Nephrogenic fibrosing dermopathy/nephro-genic systemic fibrosis report of a new case with literature review. Am J Kidney Dis 2005 46(4) 754-759. 

Which of the following may cause nephrogenic diabetes insipidus ... 

The answer is c. (Katzung, p 493.) Lithium treatment frequently causes polyuria and polydipsia. The collecting tubule of the kidney loses the capacity to conserve water via anti diuretic hormone. This results in significant free-water clearance, which is referred to as nephrogenic diabetes insipidus. 

A patient with nephrogenic diabetes insipidus is best treated with which of the following ... 

The answer is a. (Katzung, pp 255-256.) Thiazide diuretics can be used in the treatment of nephrogenic diabetes insipidus. Its other uses include the treatment of hypertension, CHF, and nephrolithiasis due to idiopathic hypercalcuria. 

Lithium reduces the kidney s ability to concentrate urine and may cause a nephrogenic diabetes insipidus with low urine specific gravity and low osmolality polyuria (urine volume greater than 3 L/day). This may be treated with loop diuretics, thiazide diuretics, or triamterene. If a thiazide diuretic is used, lithium doses should be decreased by 50% and lithium and potassium levels monitored. 

Patients with nephrogenic DI should decrease their ECF volume with a thiazide diuretic and dietary sodium restriction (2,000 mg/day), which often decreases urine volume by as much as 50%. Other treatment options include drugs with antidiuretic properties (Table 78-2). 

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