YOU ARE NOW CONNECTED TO THE TOXLINE (1981 FORWARD, NON-ROYALTY) FILE. ==KIDNEY, POLYCYSTIC== 1 AUTHOR Martinez JR AUTHOR Grantham JJ TITLE Polycystic kidney disease: etiology, pathogenesis, and treatment. SOURCE Dis Mon; VOL 41, ISS 11, 1995, P693-765 (REF: 292) ABSTRACT Once viewed as hopelessly incurable disorders and the dustbin for careers in academic medicine, the polycystic kidney diseases have emerged as prime targets of pathophysiologic study and palliative and definitive treatment in the era of molecular medicine. Polycystic kidney disease (PKD) may be hereditary or acquired. The major inherited types are autosomal dominant (AD) and autosomal recessive (AR). ADPKD is caused by at least two (and possibly three) genes located on separate chromosomes, while ADPKD-1 is due to a 14 kb transcript in a duplicated region on the short arm of chromosome 16 very near the alpha-globin gene cluster and the gene for one form of tuberous sclerosis. ADPKD-2 has been assigned to the long arm of chromosome 4. ARPKD is due to a mutated gene on both copies of the long arm of chromosome 6. Cysts originate in renal tubules. Proliferation of tubule epithelial cells modulated by endocrine, paracrine, and autocrine factors is a major element in the pathogenesis of renal cystic diseases. In addition, fluid that is abnormally accumulated within the cysts is derived from glomerular filtrate and, to a greater extent, by transepithelial fluid secretion. Abnormal synthesis and degradation of matrix components associated with interstitial inflammation are additional features in the pathogenesis of renal cystic diseases. The ADPKD genotypes are characterized by bilateral kidney cysts, hypertension, hematuria, renal infection, stones, and renal insufficiency. ADPKD is a systemic disorder; cysts appear with decreasing frequency in the kidneys, liver, pancreas, brain, spleen, ovaries, and testis. Cardiac valvular disorders, abdominal and inguinal hernias, and aneurysms of cerebral and coronary arteries and aorta are also associated with ADPKD. Treatment is supportive: dietary regulation of salt and protein intake, control of hypertension and renal stones, and dialysis and transplantation at the end stage. ARPKD is a relatively rare disease that causes clinical symptoms at birth, with significant mortality in the first month of life. The cysts develop primarily in the collecting ducts because of a failure in the maturation process. Early complications include Potter's syndrome; excessive size of the kidneys, causing respiratory dysfunction; hypertension; and renal insufficiency. Hepatic fibrosis is an associated extrarenal problem that results in significant morbidity in young children and adolescents. Treatment includes supportive care, dialysis, and renal transplantation. Acquired cysts (solitary/simple) are commonplace in older persons. Multiple cysts may be seen in association with potassium deficiency, congenital disorders, metabolic diseases, and toxic renal injury.(ABSTRACT TRUNCATED AT 400 WORDS) 5 AUTHOR Grantham JJ TITLE Polycystic kidney disease: a predominance of giant nephrons. SOURCE Am J Physiol; VOL 244, ISS 1, 1983, PF3-10 (REF: 46) ABSTRACT Polycystic kidney disease is a bilateral disorder that affects approximately 200,000-400,000 persons in the United States. The most common form of the disease is inherited as an autosomal dominant trait (ADPKD). It typically causes renal insufficiency by the fifth or sixth decade of life. The disease is characterized by the progressive enlargement of a portion of renal tubule segments (proximal, distal, loop of Henle, collecting duct). The tubules enlarge from a normal diameter of 40 microns to several centimeters in diameter, causing marked gross and microscopic anatomic distortion. The cause of the cystic change in the tubules is unknown, but current possibilities include obstruction of tubule fluid flow by hyperplastic tubule cells, increased compliance of the tubule basement membranes, and/or increased radial growth of cells in specific portions of the renal tubule. Several studies show that the epithelia of the cysts continue to transport Na+, K+, Cl-, H+, and organic cations and anions in a qualitative fashion similar to that of the tubule segment from which they were derived. ADPKD, then, is a disease in which some gigantic renal tubules, over a period of several decades, impair the function of nonaffected nephrons and thereby lead to renal failure. 5 AUTHOR Kubota K TITLE [Structure and function of the experimental polycystic kidney induced by diphenylthiazole with special reference to renal micropuncture study] SOURCE Nippon Jinzo Gakkai Shi 1992 Aug;34(8):859-69 ABSTRACT Autosomal dominant polycystic kidney disease (ADPKD) is one of the major causative diseases leading to renal failure and dialysis treatment. Although the genetic study on the disease has been progressed so far, the initial trigger for cyst formation and several factors enhancing the progression of ADPKD remain to be clarified. Using an animal model of ADPKD, induced by 2-amino-4,5-diphenylthiazole hydrochloride (DPT), we examined the early events in cytogenesis. Especially the role of tubular obstruction in the model in triggering off tubular dilatation was investigated by means of renal micropuncture and tubular microperfusion techniques. Light and electron microscopic studies demonstrated epithelial hyperplasia along collecting ducts after 2 weeks of DPT feeding. In addition, some collecting ducts revealed partial obstruction with hyperplastic cells. Cystic change became prominent over 8 weeks of the treatment. Then micropuncture and microperfusion experiments were performed to measure intratubular pressure in the rats fed DPT for 2-5 weeks (PKD rats) and pair-fed control Sprague-Dawley rats (control rats). Free flow pressure in proximal segments of PKD rats (21.5 +/- 1.0mmHg) was not significantly elevated, as compared with that in control rats (21.3 +/- 1.0mmHg). During the stepwise increments in proximal tubular flow rate, proximal tubular pressure in PKD rats significantly increased especially at higher flow rate, 41.0 +/- 3.6 mmHg in PKD rats and 19.4 +/- 3.1mmHg in control rats (P < 0.01) at 40nl/min. On the other hand, the transit time of loop of Henle was longer in PKD rats (38.9 +/- 2.4 sec) than in control rats (24.9 +/- 0.6 sec, P < 0.01). These results suggest that cyst formation in PKD rats could be preceded by the elevation of tubular resistance, which might be explained by the partial obstruction of collecting ducts. Moreover, these tubular obstruction in the distal segments might be the trigger for the cyst formation in this model.