Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polycystin-2 represents one of so far two proteins found to be mutated in patients with autosomal-dominant polycystic kidney disease. Evidence obtained from experiments carried out in cell lines and with native kidney tissue strongly suggests that polycystin-2 is located in the endoplasmic reticulum. In the kidney, polycystin-2 is highly expressed in cells of the distal and connecting tubules, where it is located in the basal compartment. It is not known whether the expression of polycystin-2 in the kidney changes or whether it can be manipulated under certain instances. Therefore, the distribution of polycystin-2 under conditions leading to acute and chronic renal failure was analyzed. During ischemic acute renal failure, which affects primarily the S3 segment of the proximal tubule, a pronounced upregulation of polycystin-2 and a predominantly combined homogeneous and punctate cytoplasmic distribution in damaged cells was observed. After thallium-induced acute injury to thick ascending limb cells, polycystin-2 staining assumed a chicken wire-like pattern in damaged cells. In the (cy/+) rat, a model for autosomal-dominant polycystic kidney disease in which cysts originate predominantly from the proximal tubule, polycystin-2 immunoreactivity was lost in some distal tubules. In kidneys from (pcy/pcy) mice, a model for autosomal-recessive polycystic kidney disease in which cyst formation primarily affects distal tubules and collecting ducts, a minor portion of cyst-lining cells cease to express polycystin-2, whereas in the remaining cells, polycystin-2 is retained in their basal compartment. Data show that the expression and cellular distribution of polycystin-2 in different kinds of renal injuries depends on the type of damage and on the nephron-specific response to the injury. After ischemia, polycystin-2 may be upregulated by the injured cells to protect themselves. It is unlikely that polycystin-2 plays a role in cyst formation in the (cy/+) rat and in the (pcy/pcy) mouse.
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PMID:Altered expression pattern of polycystin-2 in acute and chronic renal tubular diseases. 1208 81

Kidney injury molecule-1 (Kim-1) is a type 1 membrane protein maximally upregulated in proliferating and dedifferentiated tubular cells after renal ischemia. Because epithelial dedifferentiation, proliferation, and local ischemia may play a role in the pathophysiology of autosomal dominant polycystic kidney disease, we investigated Kim-1 expression in a mouse model of this disease. In the Pkd2(WS25/-) mouse model for autosomal dominant polycystic kidney disease, cystic kidneys show markedly upregulated Kim-1 levels compared with noncystic control kidneys. Kim-1 is present in a subset of cysts of different sizes and segmental origins and in clusters of proximal tubules near cysts. Kim-1-expressing tubular cells show decreased complexity and quantity of basolateral staining for Na-K-ATPase. Other changes in polarity characteristic of ischemic injury are not present in Kim-1-expressing pericystic tubules. Polycystin-2 expression is preserved in Kim-1-expressing tubules. The interstitium surrounding Kim-1-expressing tubules shows high proliferative activity and staining for smooth muscle alpha-actin, characteristic of myofibroblasts. Although the functional role of the protein in cysts remains unknown, Kim-1 expression in tubules is strongly associated with partial dedifferentiation of epithelial cells and may play a role in the development of interstitial fibrosis.
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PMID:Kidney injury molecule-1 expression in murine polycystic kidney disease. 1238 82

Acute visual loss secondary to ischemic optic neuropathy in children is extremely rare. The causes are usually hypotension or anemia. We describe the clinical course of a 9-year-old boy with a functional renal transplant who presented to the emergency room hemodynamically stable after waking up with complete bilateral loss of vision (no light perception). Examination showed that he had suffered massive nocturnal blood loss from esophageal varices secondary to portal hypertension. The patient's end-stage renal disease was secondary to autosomal recessive polycystic kidney disease (ARPKD), an entity comprised of renal cysts and hepatic fibrosis. Ophthalmologic findings in ARPKD are rarely cited in the literature. A literature search revealed 3 other cases of sudden visual loss reported in nonophthalmologic journals in patients with ARPKD. Funduscopic examination showed bilateral optic nerve head pallor and swelling with associated flame hemorrhages. The fact that this patient already had mildly pale nerves on presentation, along with hemodynamically compensated blood pressure and pulse, suggested chronic as well as acute ischemia. Based on our findings and other reported cases in the literature, ophthalmologic examinations may be indicated in all patients with ARPKD.
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PMID:Acute visual loss in a child with autosomal recessive polycystic kidney disease: case report and review of the literature. 1282 65

Na-K-ATPase, also known as the sodium pump, is a crucial enzyme that regulates intracellular sodium homeostasis in mammalian cells. In epithelial cells Na-K-ATPase function is also involved in the formation of tight junctions through RhoA GTPase and stress fibers. In this review, a new two-step model for the assembly of tight junctions is proposed: step 1, an E-cadherin-dependent formation of partial tight junction strands and of the circumferential actin ring; and step 2, active actin polymerization-dependent tethering of tight junction strands to form functional tight junctions, an event requiring normal function of Na-K-ATPase in epithelial cells. A new role for stress fibers in the assembly of tight junctions is proposed. Also, implications of Na-K-ATPase function on tight junction assembly in diseases such as cancer, ischemia, hypomagnesemia, and polycystic kidney disease are discussed.
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PMID:Role of Na-K-ATPase in the assembly of tight junctions. 1289 Jun 62

Several studies in patients with chronic kidney diseases have shown that men have a more rapid disease progression than women. Also, with ageing, men exhibit greater decrements in renal function and increased glomerular sclerosis than women. Data from meta-analysis studies indicate that women with several non-diabetic renal diseases such as membranous nephropathy, IgA nephropathy and polycystic kidney disease present a slower progression, but in diabetic renal disease this is not yet established. Thus, men appear to be at greater risk for renal injury than are women, but the underlying mechanisms are unknown. Sex hormones may mediate the effects of gender on chronic renal disease, through the interaction with the renin-angiotensin system, the modulation of nitric oxide synthesis and the downregulation of collagen degradation. New observations indicate that androgens may contribute to continuous loss of kidney cells though the stimulation of apoptotic pathways. Apoptosis is an unique type of programmed cell death which is activated in several chronic kidney diseases. Studies in vitro indicate that androgens prime a Fas/FasL dependent apoptotic pathway in kidney tubule cells. This apoptotic cell death pathway is receptor-linked and interacts with the mitochondrial pathway, which may be activated by other mechanisms, such as toxins and ischemia. Therefore, the mechanisms to cell death which are primed by androgens may interact with others occurring in several conditions leading to the loss of renal cells. These findings are consistent with a role for androgens to promote chronic renal injury in men.
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PMID:Gender and the progression of chronic renal diseases: does apoptosis make the difference? 1519 27

A yearly history of serum creatinine levels was made in a selected cohort of cadaver donor transplant patients who survived 10 years. 1. A stepwise increase in serum creatinine levels was noted with increasing age of the donor. 2. A similar increase was found with increasing recipient weight. 3. In all analyses of kidney size in relation to recipient weight, such as sex of the donor and races, a corresponding relationship to the serum creatinine was noted. That is, whenever the kidney was smaller, or the recipient was larger, an increased level of serum creatinine was found. 4. Rejection at discharge and cold ischemia time had a small long-term effect on serum creatinine levels. Kidneys from donors who had a stroke had higher serum creatinine levels than those who died of anoxia or head trauma. 5. In general, patients with polycystic kidney disease had the lowest serum creatinine levels, whereas those with SLE and GN had higher serum creatinine levels. 6. Patients with 0-A,B,DR mismatched kidneys had the lowest serum creatinine levels every year from the first year on through the tenth year. 7. The rates at which serum creatinine increases with time was established for patients with various original diseases, as well as in the total population. The increase in serum creatinine levels in those who failed after 5 years was similar to those who failed in 10 years.
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PMID:Serum creatinine levels in 10-year survivors of cadaveric kidney transplants. 1538 28

Despite recent improvement, significant racial disparities in outcome still persist after renal transplantation among African American patients in the United States. This study evaluated the association of race and ethnicity with allograft outcomes in a French population of 952 Caucasian (Cauc) patients and 140 African European (AE) patients who underwent renal transplantation in our center between 1987 and 2003. Demographic characteristics were similar for the two cohorts other than cause of end-stage renal failure (more hypertension among AE and more polycystic kidney disease among Cauc) and cold ischemia time (significantly longer for AE). Immunosuppressive treatment was comparable between groups. There were no significant differences between AE and Cauc in the incidence of acute rejection (31% vs. 30%). At 5 years post-transplant, patient survival (93% vs. 92%), graft survival (83% in both groups) and graft function (creatinine clearance 48 mL/min vs. 45 mL/min) were also similar among the AE and Cauc patients. We demonstrate that ethnic origin does not affect outcome after renal transplantation in France. Therefore, differences observed in the United States cannot be only related to immunologic or pharmacologic factors. The results of renal transplantation in patients of African origin could be improved with universal immunosuppressive drug coverage.
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PMID:Kidney transplant in black recipients: are African Europeans different from African Americans? 1621 17

Primary cilia have been shown to play an important role in embryonic development as well as in postnatal life. Dysfunctional cilia are associated with situs inversus, retinal abnormalities, impaired mucociliary clearance, infertility, hydrocephalus, and congenital renal cysts. In autosomal dominant polycystic kidney disease, mutations of the ciliary proteins polycystin1 or the transient receptor potential (TRP) channel family protein polycystin2 (TRPP2) cause progressive cyst formation and destruction of the kidney. Primary cilia act as flow sensors and respond to flow-mediated bending with a prolonged intracellular calcium increase, which appears to require an intact polycystin protein complex. We have established a novel flow chamber system, which allows us to study renal epithelial cells by live cell imaging. We show that MDCK cells respond to flow by a delayed increase in intracellular calcium and that this response requires these cells to be ciliated. We show that a novel interactor of TRPP2, kidney injury molecule-1 (Kim1), which is expressed at low levels in the normal kidney and upregulated after ischemia, in renal cell cancer and in PKD is targeted to primary cilia when stably expressed in MDCK cells. We demonstrate that expression of tyrosine mutant Kim1, lacking a conserved tyrosine in the intracellular tail, abolishes the calcium increase in response to flow in a dominant negative manner. These results establish Kim1 as a novel regulatory molecule of flow-induced calcium signaling.
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PMID:Ciliary calcium signaling is modulated by kidney injury molecule-1 (Kim1). 1720 56

It is known that many tubular proteins are involved in the pathogenesis of autosomal-dominant polycystic kidney disease (ADPKD), which causes 8-10% of the cases of end-stage renal disease (ESRD) worldwide. Neutrophil gelatinase-associated lipocalin (NGAL) is a protein expressed on tubular cells of which the production is markedly increased in response to harmful stimuli such as ischemia or toxicity. In the present study, serum and urinary NGAL levels were evaluated in 26 ADPKD subjects. Both levels were significantly higher in patients than in controls (sNGAL 174 +/- 52 vs. 50 +/- 27 ng/ml, p < 0.05; uNGAL 119 +/- 42 vs. 7 +/- 6 ng/ml, p < 0.005) and a close correlation was also found between these parameters and the residual renal function (sNGAL/GFR: r = -0.8, p = 0.006; sNGAL/Creatinine: r = 0.9, p = 0.007; uNGAL/GFR: r = -0.49, p < 0.05; uNGAL/Creatinine: r = 0.84, p < 0.001). Patients were further divided into two groups according to the cystic development assessed with echotomography; subjects with higher cystic growth (HCG) presented higher sNGAL and uNGAL levels with respect to others (sNGAL: 242 +/- 89 vs. 88 +/- 34 ng/ml, p < 0.05; uNGAL: 158 +/- 45 vs. 73 +/- 27 ng/ml, p < 0.05). The strict correlation between NGAL levels and residual renal function is perfectly in accord with recent studies on patients with other ESRD-associated diseases. We can hypothesize that tubular cells produce big quantities of NGAL as a consequence of increased apoptosis following chronic damage or as a compensatory response, similar to that observed in acute stress conditions (ischemia, toxicity ...). Finally, our last finding that patients with HCG showed higher levels of NGAL suggests that this protein could be also involved in the cyst growth process, as previously reported about epithelial and tumoral expansion.
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PMID:Neutrophil gelatinase-associated lipocalin in patients with autosomal-dominant polycystic kidney disease. 1757 Sep 4

We describe laparoscopic partial nephrectomy in a patient with autosomal dominant polycystic kidney disease. Reconstruction was accomplished despite the abnormal quality of the renal tissue. In this patient, with borderline renal function, the warm-ischemia time (50 minutes) was longer than the normally accepted time and was poorly tolerated. In order to avoid the damaging effects of warm ischemia, alternatives to hilar clamping should be employed, and open partial nephrectomy should be considered.
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PMID:Case report: technical and functional implications of hand-assisted laparoscopic partial nephrectomy in a patient with autosomal dominant polycystic kidney disease. 1763 59


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