Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a previously nephrectomized patient with a well functioning renal allograft, acute renal failure with massive polyuria and hypertension developed. Relief of a periureteric obstruction resulted in rapid correction of all three. Pathogenesis of hypotonic polyuria is thought to be a defect in the collecting duct permeability to water, stimulating nephrogenic diabetes insipidus. Normal urinary dilution and acidification suggest intact function of the ascending loop of Henle and distal convoluted tubules. The quick reversal of polyuria and renal failure after obtaining relief of the obstruction suggest that both the decrease in the glomerular filtration rate and tubular dysfunctions are due to functional changes in the nephron rather than to organic damage, a possibility also borne out by the findings in a renal biopsy specimen showing normal glomeruli and intact tubular epithelial cells. Ureteric obstruction should be considered in any patient with renal failure and polyuria; it may be a correctable cause of hypertension.
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PMID:Obstructive polyuric renal failure following renal transplantation. 79 85

The C57BL/6J-cpk mouse has a form of autosomal-recessive polycystic kidney disease characterized by the rapid growth of large collecting duct cysts and the development of severe renal failure usually by three to four weeks of age. Previous studies had shown higher steady-state levels of proto-oncogene mRNA in these cystic kidneys. It is now shown using nuclear run-on transcription that the c-fos and c-myc proto-oncogenes are transcribed at higher rates in cystic kidneys, and thus that increased transcription, in part, may account for the increased mRNA levels. c-myc mRNA was detected by in situ hybridization in nephron anlagen and elongating tubules of normal and cystic kidneys during late fetal and early neonatal kidney development. Localization of c-myc expression in the normal kidney decreased with age over the three-week postnatal period. By contrast, c-myc mRNA was found in cysts as early as three days of age, with increased levels at two and three weeks. c-myc expression was also elevated in apparently normal, non-dividing proximal tubules in three-week-old cystic animals. On the basis of these findings, we suggest that c-myc expression is linked to the proliferation of cells engaged in the primary cystogenic process, and that expression of this gene in proximal tubule cells of severely azotemic animals reflects the compensatory response of residual tubular epithelial cells to progressive renal dysfunction.
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PMID:Localization of overexpressed c-myc mRNA in polycystic kidneys of the cpk mouse. 155 5

The roles of growth factors in the pathogenesis of various forms of acute and chronic renal disease are largely putative. Nevertheless, there is a growing body of information that links specific growth factors to particular forms of renal injury. In all instances, it is supposed that such associations are not necessarily unique and that multiple cytokines probably interact to determine the pattern of injury or the regenerative response to such injury. Regeneration of tubular epithelium after acute tubular necrosis involves upregulation of the epidermal growth factor (EGF) receptor. Early studies of exogenously administered EGF indicate that the severity and duration of renal failure may be attenuated by this growth factor. Thus far, the observed responses have been limited and the role of EGF as a therapeutic agent requires more study. The mechanism of generation of tubulointerstitial injury in most forms of renal disease is difficult to understand. Early in vitro studies of growth factor production by tubular cells (in the absence of any infiltrating cells) indicate that platelet-derived growth factor produced by the medullary collecting duct is mitogenic for renal medullary fibroblasts, suggesting a paracrine growth system in this region of the kidney. Insulin-like growth factor I has also been shown to be produced by collecting duct cells. Its production is increased by EGF, and its association with certain forms of renal hypertrophy, i.e., diabetes and hypersomatotrophic states, implies its participation in the hypertrophic growth response. Platelet-derived growth factor is a potent mitogen for glomerular mesangial cells, and its production is regulated by a variety of cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evolving role of growth factors in the renal response to acute and chronic disease. 159 57

There are two known forms of hereditary polycystic kidney disease (PKD) in humans. Although both forms initiate early in life, autosomal recessive PKD is rapidly progressive to kidney failure shortly after birth whereas autosomal dominant PKD is slowly progressive, taking many years to end stage. Research in this field has been limited by the availability of suitable animal models of PKD. Recently the C57BL/6J-cpk mouse has been used to study the pathogenesis of rapidly progressive hereditary PKD. The study presented here describes a slowly progressive PKD in the DBA/2-pcy mouse. The disease trait is transmitted in an autosomal recessive pattern and was localized to chromosome 9 through linkage to the dilute coat color and transferrin genes. Whereas some cystic changes were seen in fetal and newborn affected mice, renal enlargement did not develop until after 8 weeks of age and azotemia did not develop until after 18 weeks of age. Renal cysts were identified in all segments of the nephron and collecting duct and progressively enlarged with age. Individual cysts were found to be lined by a single layer of epithelial cells in most areas, with focal polyps and mounds of cells principally in collecting duct cysts. Early stages of cyst formation were associated with some abnormalities of tubular and glomerular basement membranes and accelerated eruption of incisors. Late stages of the disease were characterized by azotemia and chronic renal interstitial inflammatory infiltrates in all affected animals and cerebral vascular aneurysms in a few. We conclude that the DBA/2-pcy mouse has a form of renal cystic disease that appears similar in many respects to that seen in the dominant form of human PKD.
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PMID:A hereditary model of slowly progressive polycystic kidney disease in the mouse. 188 68

The C57BL/6J-cpk mouse has an inheritable form of polycystic kidney disease similar to the autosomal recessive disorder seen in humans. Between approximately 1 and 3 weeks of age, affected cpk mice develop numerous large cysts in the collecting tubule segment of kidney nephrons. The present study examined the ontogeny of renal and submandibular gland prepro-epidermal growth factor (preproEGF) gene expression in the cpk mouse using Northern blot hybridization and immunohistochemistry. There was a virtual absence of renal preproEGF gene expression in cystic kidneys over the 3-week postnatal period, during which time renal preproEGF mRNA and proEGF/EGF protein normally reach significant levels. PreproEGF mRNA was expressed in salivary glands of cystic mice; however, this mRNA could not be further elevated with testosterone suggesting that there are abnormalities in the regulation of the preproEGF gene in the submandibular gland, as well as in the kidney. Since renal preproEGF expression during the early postnatal period occurs when collecting duct cysts form, it is possible that a deficiency in renal proEGF or EGF contributes to the rapid development of collecting duct cysts and the concomitant renal failure in the C57BL/6J-cpk cystic mouse.
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PMID:Defective epidermal growth factor gene expression in mice with polycystic kidney disease. 196 5

Cis-dichlorodiammine platinum (II), or cisplatin, has emerged as a principal chemotherapeutic agent in the treatment of otherwise resistant solid tumors and is currently among the most widely used agents in the chemotherapy of cancer. The chief limit to its greater efficacy is its nephrotoxicity, which has made it necessary both to lower its dosage and actively hydrate patients to reduce it. The vulnerability of the kidney to cisplatin is almost certainly related to its primary role in the excretion of cisplatin. Cisplatin enters renal cells by a process that depends on normal oxygen utilization and is specifically inhibited by organic bases. Greater localization of platinum to the S3 segment of the proximal tubules suggests that the vulnerability of this segment may depend on its specific uptake of the drug. The majority of intracellular platinum is bound to macromolecules, including protein and DNA, yet a significant portion of cell platinum is biotransformed to a nonmutagenic and possibly nontoxic compound. Polyuria and hypomagnesemia, which are commonly associated with cisplatin nephrotoxicity, may be due to defects in deep nephron or collecting duct fluid and solute transport. Low single nephron glomerular filtration rates (SNGFR) during early cisplatinum-induced acute renal failure is accompanied by reduced renal blood flow and transglomerular hydrostatic pressure without elevated intratubular hydrostatic pressure, suggesting preglomerular vasoconstriction as an important determinant of renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cisplatin nephrotoxicity. 353 59

Previous morphologic studies on kidneys from adult patients with autosomal dominant polycystic kidney disease (ADPKD) indicates that the cysts developed from nephrons and collecting ducts in association with hyperplasia of epithelial cells lining the cyst walls. In the present study, we systematically evaluated by scanning electron microscopy 387 cysts in polycystic kidneys obtained from 10 adult patients. Some cysts were lined by cells typical of collecting duct (7.2%), proximal tubule (1.8%) or glomerular visceral (2.1%) epithelium. The remaining cysts were lined by a single layer of phenotypically undefined (84.0%) or markedly hyperplastic (4.9%) epithelium. The median plane surface area of individual cells within cysts was 182 X 10(-8) cm2. Among all cysts the surface area of single epithelial cells ranged between 22 and 2530 X 10(-8) cm2, but within single cysts the range of individual cell surface areas was more narrow. Mean cell surface area did not increase in direct proportion to cyst diameter; thus, epithelial hyperplasia is a central element in the progressive enlargement of cysts. In some cysts hyperplasia was accentuated by projections into cyst lumens of polyps, small adenomas and cord-like arrangements of cells. Epithelial polyps were found in the cysts of one non-azotemic patient, excluding renal failure as a cause of this accentuated type of epithelial proliferation. Morphologic evidence that cysts compressed adjacent renal parenchyma was observed in all kidneys. In 11 cysts bisected and then both halves thoroughly examined by scanning electron microscopy, one or two tubule openings were seen in one of the hemisections in three cysts (27.3%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyst formation and growth in autosomal dominant polycystic kidney disease. 359 54

Comprehensive one-day renal function tests in 20 patients with a history of analgesic abuse showed varying degrees of chronic renal failure in all. There was no evidence of a selective defect in proximal tubular function, while a defective concentrating mechanism, usually considered necessary for the diagnosis of analgesic-induced renal damage, could be demonstrated in only 16 patients. A urinary acidification defect associated with a concentrating defect was found in nine cases and was thought to reflect specific collecting duct dysfunction. Urinary ammonium excretion was reduced in 13 subjects, owing to a reduced number of functioning nephrons or inadequate acidification, or both. Low citrate excretion was frequently encountered, and this, as well as defective urinary acidification, may play some part in predisposing patients with analgesic nephropathy to intrarenal calcification and progressive renal failure.
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PMID:Renal function in analgesic nephropathy. 578 Apr 28

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.
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PMID:Polycystic kidney disease: a predominance of giant nephrons. 633 12

Nine patients with the unusual combination of renal failure, nephrotic-range proteinuria, and biopsy-proved interstitial nephritis are described. Six of these patients had received nonsteroidal anti-inflammatory agents (three fenoprofen, one ibuprofen, one zomepirac, and one tolmetin). The remaining three patients had no history of exposure to drugs known to cause interstitial nephritis. Immunologic characterization of the infiltrating cells with monoclonal antibodies showed that the majority of cells in most cases were cytotoxic T cells, although some B cells were present in all cases. Giant collecting duct cells were seen in half the patients with drug exposure but in none of the others. Otherwise, there were no conspicuous morphologic differences between patients with and without drug exposure. Many of the patients had associated glomerular abnormalities. Only the zomepirac and tolmetin recipients showed pure interstitial disease. The three fenoprofen recipients and the zomepirac and tolmetin recipients regained normal renal function after the drug was discontinued. The combination of renal failure, nephrotic range proteinuria, and interstitial nephritis is one form of nephrotoxicity observed in patients treated with nonsteroidal anti-inflammatory agents. However, this lesion, which may be mediated by cytotoxic T cells, may also be seen rarely in patients with no apparent drug exposure.
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PMID:Interstitial nephritis, proteinuria, and renal failure caused by nonsteroidal anti-inflammatory drugs. Immunologic characterization of the inflammatory infiltrate. 637 63


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