Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 one of the most common causes of chronic renal failure. Currently, there are no established specific treatments to prevent or slow down the progression of the disease. The last decade, however, has witnessed a significant effort to improve the prognosis of patients with ADPKD. Patients with chronic renal failure are now offered different therapies such as a low-protein diet, angiotensin II converting enzyme inhibitors or receptor blockers, and statins. In addition, a number of important breakthroughs have greatly advanced our understanding of the pathogenesis of ADPKD. These have led to several novel therapeutic approaches directed either at inhibiting the proliferation of cyst epithelium (antisense C-myc oligonucleotides, EGFR tyrosine kinase inhibitors, caspase inhibitors, paclitaxel, rapamycin, CDK inhibitors) or at decreasing cyst fluid secretion (Na transport inhibition, vasopressin V2 receptor antagonists, somatostatin). Some of these novel approaches have not yet been tested in the clinical setting, others are the object of ongoing studies. It seems likely that in the next few years treatment of patients with ADPKD will radically change from one of passive follow-up to one of active treatment, probably with protocols combining different drugs targeting the different pathogenetic mechanisms of the disease.
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PMID:[New therapies for ADPKD]. 1827 56

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common causes of end stage renal failure (ESRF). Nevertheless, until now the standard therapy of ADPKD consists merely of nephroprotection and treatment of complications. In the sixth decade of life in about 50% of patients renal replacement therapy is initiated. Surgery procedures such as nephrectomy and renal contraction therapy are performed in some patients. In 21st century numerous studies concerning patophysiology of the disease (role of polycystins, intracellular calcium, cAMP) were published and gave an impulse for searching new drugs that could slower progression of ADPKD. Somatostatin receptor agonists, vasopressin V2 receptor antagonists, rapamycin, and tyrosine kinase inhibitors are among medications that are thought to be effective. Although it is unclear if any of these drugs will be really effective there are strong theoretical backgrounds and promising results of experimental studies on animals. Nephrologists and their patients are waiting for the results of clinical trials that are performed now.
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PMID:[Modern treatment of autosomal dominant polycystic kidney disease]. 1914 40

Autosomal dominant polycystic kidney disease (ADPKD), the most frequent cause of genetic renal disease affecting approximately 4 to 7 million individuals worldwide and accounting for 7%-15% of patients on renal replacement therapy, is a systemic disorder mainly involving the kidney but cysts can also occur in other organs such as the liver, pancreas, arachnoid membrane and seminal vesicles. Though computed tomography and magnetic resonance imaging (MRI) were similar in evaluating 81% of cystic lesions of the kidney, MRI may depict septa, wall thickening or enhancement leading to upgrade in cyst classification that can affect management. A screening strategy for intracranial aneurysms would provide 1.0 additional year of life without neurological disability to a 20-year-old patient with ADPKD and reduce the financial impact on society of the disease. Current treatment strategies include reducing: cyclic adenosine monophosphate levels, cell proliferation and fluid secretion. Several randomised clinical trials (RCT) including mammalian target of rapamycin inhibitors, somatostatin analogues and a vasopressin V2 receptor antagonist have been performed to study the effect of diverse drugs on growth of renal and hepatic cysts, and on deterioration of renal function. Prophylactic native nephrectomy is indicated in patients with a history of cyst infection or recurrent haemorrhage or to those in whom space must be made to implant the graft. The absence of large RCT on various aspects of the disease and its treatment leaves considerable uncertainty and ambiguity in many aspects of ADPKD patient care as it relates to end stage renal disease (ESRD). The outlook of patients with ADPKD is improving and is in fact much better than that for patients in ESRD due to other causes. This review highlights the need for well-structured RCTs as a first step towards trying newer interventions so as to develop updated clinical management guidelines.
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PMID:Current management of autosomal dominant polycystic kidney disease. 2638 Jan 98

Autosomal dominant polycystic kidney disease (ADPKD), the most common monogenic cause of ESKD, is characterized by relentless development of kidney cysts, hypertension, and destruction of the kidney parenchyma. Over the past few years, major advancements in diagnosing, prognosticating, and understanding the pathogenesis and natural course of the disease have been made. Currently, no kidney disease is more suitable for nephron-protective strategies. Early nephrology referral and implementation of these strategies may have a substantial effect. Total kidney volume is a good prognostication marker and allows stratification of patients into slow or rapid progressing disease, with implications for their management. Measurement of total kidney volume, disease stratification, and prognostication are possible using readily available tools. Although some patients require only monitoring and basic optimized kidney protective measures, such as rigorous BP control and various lifestyle and dietary changes, others will benefit from disease-modifying treatments. Vasopressin V2 receptor antagonists, a likely disease-modifying treatment, has been approved in several countries and recently by the US Food and Drug Administration; other therapies, such as somatostatin analogs and other novel agents, are currently in clinical trials. The purpose of this article is to present our views on the optimal management to delay kidney disease progression in ADPKD.
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PMID:Recent Advances in the Management of Autosomal Dominant Polycystic Kidney Disease. 3004 49

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a systemic disorder associated with polycystic liver disease (PLD) and other extrarenal manifestations, the most common monogenic cause of end-stage kidney disease, and a major burden for public health. Many studies have shown that alterations in G-protein and cAMP signaling play a central role in its pathogenesis. As for many other diseases (35% of all approved drugs target G-protein coupled receptors (GPCRs) or proteins functioning upstream or downstream from GPCRs), treatments targeting GPCR have shown effectiveness in slowing the rate of progression of ADPKD. Tolvaptan, a vasopressin V2 receptor antagonist is the first drug approved by regulatory agencies to treat rapidly progressive ADPKD. Long-acting somatostatin analogs have also been effective in slowing the rates of growth of polycystic kidneys and liver. Although no treatment has so far been able to prevent the development or stop the progression of the disease, these encouraging advances point to G-protein and cAMP signaling as a promising avenue of investigation that may lead to more effective and safe treatments. This will require a better understanding of the relevant GPCRs, G-proteins, cAMP effectors, and of the enzymes and A-kinase anchoring proteins controlling the compartmentalization of cAMP signaling. The purpose of this review is to provide an overview of general GPCR signaling; the function of polycystin-1 (PC1) as a putative atypical adhesion GPCR (aGPCR); the roles of PC1, polycystin-2 (PC2) and the PC1-PC2 complex in the regulation of calcium and cAMP signaling; the cross-talk of calcium and cAMP signaling in PKD; and GPCRs, adenylyl cyclases, cyclic nucleotide phosphodiesterases, and protein kinase A as therapeutic targets in ADPKD.
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PMID:Modulation of polycystic kidney disease by G-protein coupled receptors and cyclic AMP signaling. 3233 59