Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Han:SPRD (PKD) rat is a new animal model of autosomal dominant polycystic kidney disease (ADPKD) which resembles many clinical and pathoanatomical features of human ADPKD. The aim of the present study was to analyse age-dependent changes in renal haemodynamics and renal renin secretion which could be of pathophysiological importance in the course of the disease. We investigated glomerular filtration rate (GFR), renal blood flow (RBF), renal vascular resistance (RVR), plasma renin activity (PRA), the autoregulatory behaviour of RBF and the pressure-dependent plasma renin activity in conscious PKD rats compared with age-matched controls. Experiments were performed in conscious chronically instrumented PKD rats (age: 3 and 9 months) and their age-matched genetic controls. GFR in 3-(0.52 +/- 0.07 ml/min/100 g; n = 9) and 9-month-old (0.42 +/- 0.03 ml/min/100 g; n = 21) PKD rats were significantly lower (P < 0.05) than 3- (0.92 +/- 0.07 ml/min/100 g; n = 17) and 9-month-old (0.67 +/- 0.05 ml/min/100 g; n = 17) controls. Nine-month-old PKD revealed a significant (P < 0.005) resetting of the breakpoint of RBF autoregulation towards lower pressures (85.5 +/- 4.4 mmHg; n = 10) than either age-matched controls (102.8 +/- 2.5 mmHg; n = 11) or young PKD (107.5 +/- 4.4 mmHg; n = 6). The basal plasma renin activity was significantly (P < 0.05) lower in 3-month-old PKD than in old PKD and age-matched controls. A significant shift of threshold pressure for pressure-dependent renin release to lower pressures was observed in PKD rats. The observed improvement of autoregulatory reserve, at least in the low pressure range, could be of pathophysiological importance in delaying the progression of chronic renal failure in ADPKD. The suppression of the renin angiotensin system in young PKD could explain the fact that we did not observe hypertension in PKD rats, which is a major difference between this animal model and human ADPKD.
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PMID:Autoregulation of renal blood flow and pressure-dependent renin release in autosomal dominant polycystic kidney disease of rats. 904 29

Diagnosis and treatment of autosomal dominant polycystic kidney disease (ADPKD) is rapidly changing. Cellular pathways that involve the polycystins are being mapped and involve the primary cilium, intracellular calcium and cAMP regulation, and the mammalian target of rapamycin (mTOR) pathway. With the use of new imaging approaches, earlier diagnosis of hepatic cystic disease is possible, and measurement of kidney and cystic growth as well as kidney blood flow is possible over relatively short periods. PKD gene type, gender, proteinuria, and the presence of hypertension relate to the rate of kidney growth in ADPKD. On the basis of risk factors for progression to ESRD and the pathogenic roles that intracellular cAMP and mTOR play in cystogenesis, novel therapies are now being tested, including maximal inhibition of the renin-angiotensin system, inhibition of renal intracellular cAMP using vasopressin V2 receptor antagonists, and somatostatin analogues, as well as inhibitors of mTOR. This review addresses the current understanding of the pathogenesis and the natural history of ADPKD; accuracy and reliability of diagnostic approaches in utero, childhood, and adulthood; the value of reliable magnetic resonance imaging to measure disease progression early in the course of ADPKD; and novel therapeutic approaches that are being evaluated in ADPKD.
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PMID:Autosomal dominant polycystic kidney disease: time for a change? 1742 47

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disease characterized by a prolonged subclinical course of gradual renal cyst expansion, resulting in massively enlarged kidneys and renal failure by the fifth to sixth decade. Renal cyst expansion results in intrarenal ischemia and activation of the renin-angiotensin-aldosterone system (RAAS) and relates to the development and maintenance of hypertension in ADPKD. Hypertension relates to disease progression in ADPKD with regard to renal volume, proteinuria, cardiovascular complications, and progression to end-stage renal disease. Novel magnetic resonance imaging methods developed in the Consortium for Radiologic Imaging for the Study of Polycystic Kidney Disease (CRISP) provide accurate estimates of change in renal volume over a short period of time in ADPKD patients with intact renal function. In CRISP an increase in renal volume of 63.4 ml/yr was found. PKD1 status, male gender, hypertension, reduced renal blood flow, and proteinuria are associated with increased renal volume and change in renal volume over time. HALT-Polycystic Kidney Disease (HALT-PKD) is designed to test whether blockade of RAAS and/or rigorous blood pressure control play a role in slowing renal progression during early (using magnetic resonance imaging methods developed in CRISP) and during late (using measures, including composite of time to doubling of serum creatinine, onset of end-stage renal disease, or death) phases in ADPKD. Findings from CRISP and the rationale for interventions in ADPKD are described, and the design of the HALT-PKD clinical trial is outlined.
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PMID:Approaches to testing new treatments in autosomal dominant polycystic kidney disease: insights from the CRISP and HALT-PKD studies. 1857 74

The relationship between renal volume and hypertension in autosomal dominant polycystic kidney disease (ADPKD) occurs in childhood. Hypertension is associated not only with increased kidney volume but also with significantly increased left ventricular mass index. Moreover, this increase in left ventricular mass index occurs in children who have ADPKD with borderline hypertension (75th to 95th percentile) and is prevented with angiotensin-converting enzyme inhibitor (ACEI) monotherapy. Progression from borderline to overt hypertension (> or =95th percentile) occurs during a 5-yr follow-up in approximately 50% of children with ADPKD and borderline hypertension. Renal cyst enlargement in ADPKD in adults is associated with stimulation of both the circulating and intrarenal renin-angiotensin-aldosterone system. In addition to hypertension, the resultant angiotensin in ADPKD is a pivotal factor in cyst proliferation and expansion, increased sympathetic and endothelin activity, oxidant injury, and fibrosis. There is a close correlation between the level of hypertension, left ventricular hypertrophy, deterioration of GFR, and the progressive enlargement of the cystic kidneys in adult ADPKD. Randomized clinical investigation indicates that ACEI and a BP goal of 120/80 mmHg are associated in a 7-yr study to reverse left ventricular hypertrophy. The effect of renin-angiotensin-aldosterone system inhibition with dual blockade, ACEI and angiotensin receptor antagonists, on renal volume and kidney function is under study in the Halt Progression of Polycystic Kidney Disease (HALT PKD) trial.
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PMID:Renal volume, renin-angiotensin-aldosterone system, hypertension, and left ventricular hypertrophy in patients with autosomal dominant polycystic kidney disease. 1969 26

Autosomal dominant polycystic kiney disease is a hereditary systemic disorder, characterized by the developement of cysts, mainly in the kidney and liver, also with gastrointestinal and cardiovascular abnormalities. It affects 4 to 6 million people wordwide and accounts for end-stage renal disease in 7-10% of dialysis patients. The genetic penetrance is 100%, all affected individuals develop renal cysts until 70 years of age, and because of a great renal function reserve only about 50% of patients develop some degree of renal failure until the age of 60. Autosomal dominant polycystic kiney disease is a heterogeneous disorder, from a clinical as well as from a genetic point of view. There are at least three genes responsible for the disease: PKD-1 gene localized on chromosome 16p in the 16p13.3 segment which encodes Polycystin 1 protein similar to membrane receptor, PKD-2 gene localized on chromosome 4q in 4q13-23 segment which encodes Polycystin 2 protein wery similar to voltage L type Ca++ channel as well as Na+ channel and PKD-3 gene of unknown localization. Specific proteins participate in regulation od cell proliferation, apoptosis, secretion, polarity, cell-matrix interactions as cell-cell interactions and lead to the developement of cystic kidney disease. Renal manifestations of disease include structural (cyst development), functional (concentration alility falls), endocrine (renin erythropoietin) abnormalities and extra- renal manifestations. A routine diagnostic methods are good case-history about cystic kidney disease in family, ultrasonographic examination of kidneys and computerized tomography. In therapy of autosomal dominant polycystic kiney disease, low protein diets may help, treatment of arterial hypertension with ACE inhibitors and angiotensin II receptor blockers, the vasopressin V2 antagonists (VSR), rapamycin and long-acting somatostatin analogue may have some benefit.
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PMID:[Autosomal dominant polycystic kidney disease]. 2080 5

Autosomal dominant polycystic kidney disease is the most frequent life-threatening hereditary disease. Prognostic factors for progressive renal impairment have been identified such as gender, race, age, proteinuria, hematuria, hypertension. Hypertension is the only risk factor for renal dysfunction in autosomal dominant polycystic kidney disease, which is presently treatable. Better understanding of the pathophysiology of hypertension will help in defining appropriate interventions. The renin-angiotensin-aldosterone-system is the pivotal factor in the pathogenesis of hypertension in autosomal dominant polycystic kidney disease. Basic research and clinical studies in autosomal dominant polycystic kidney disease implicated activation of the renin-angiotensin-aldosterone-system. Therapy of hypertension in autosomal dominant polycystic kidney disease with angiotensin-converting enzyme inhibitors or angiotensin receptor blocker has the potential to prevent cardiovascular complications and slow the progression of renal disease. The results of two large multicenter double-blind placebo controlled randomized clinical trials (the HALT-PKD trials) possibly will elucidate the beneficial effects of the renin-angiotensin-aldosterone-system inhibition in autosomal dominant polycystic kidney disease.
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PMID:Renin-Angiotensin-aldosterone system in autosomal dominant polycystic kidney disease. 2397 39

Left ventricular hypertrophy (LVH) has been recognized as an early and important complication in patients with autosomal dominant polycystic kidney disease (ADPKD). LVH is associated with arrhythmias, congestive heart failure, and increased cardiac mortality. The increase in left ventricular mass is attributed to the compensatory myocardial remodeling associated with systemic hypertension, which is also highly prevalent in those with ADPKD. Several observational studies over the past decades using echocardiography have estimated the prevalence of LVH in adults to range from 20-40%. More recently, the HALT-PKD study detected an LVH prevalence of less than 4% using magnetic resonance imaging. Some of the differences may relate to the imaging modality, variations in parameters used to define LVH, or demographic differences in the study populations. Nonetheless, there likely exists a shift in the pathophysiology of LVH in patients with ADPKD. Factors that explain this evolving trend include earlier detection and treatment of hypertension, more rigorous blood pressure control, and an increased use of renin-angiotensin-aldosterone system (RAAS) antagonists. The use of RAAS inhibitors has been shown to induce regression of LVH, and this may continue to play an important role in the cardiovascular risk management in patients with ADPKD. The results of ongoing studies will help elucidate these relationships.
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PMID:Left ventricular hypertrophy in ADPKD: changing demographics. 2397 41

Hypertension is common and occurs in the majority of autosomal dominant polycystic kidney disease (ADPKD) patients prior to loss of kidney function. Hypertension relates to progressive kidney enlargement, and is a significant independent risk factor for progression to end-stage renal disease. The pathogenesis of hypertension in ADPKD is complex and depends on many factors that influence each other. High expression of PKD1 and PKD2 genes is present in the cilia of tubular epithelial cells, in endothelial cells and in vascular smooth muscle cells. Decreased or absent polycystin-1 or -2 expression is associated with abnormal vascular structure and function. PKD1/PKD2 deficiency results in reduced nitric oxide levels, altered endothelial response to shear stress with attenuation in vascular relaxation. Activation of the renin-angiotensin-aldosterone system occurs in ADPKD due to decreased nitric oxide production as well as bilateral cyst expansion and intra-renal ischemia. With increasing cyst size, further activation of the renin-angiotensin-aldosterone system occurs, blood pressure increases and a vicious cycle ensues with enhanced cyst growth and hypertension ultimately leading to end-stage renal disease. Inhibition of the angiotensin-aldosterone system is possible with angiotensin-converting enzyme inhibitors and seems to be the first-line treatment for hypertension in these subjects. As suggested by the HALT-PKD study, an aggressive blood pressure control is safe and recommended and is associated with preservation of kidney function and a reduction in total kidney volume over time. A collaborative multidisciplinary approach between nephrologists and cardiologists is necessary for the monitoring of kidney and heart complications.
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PMID:[Cardiovascular risk in polycystic kidney disease]. 2641 87