Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pain is the most common symptom reported by ADPKD patients, afflicting approximately 60% of cases and may result from renal hemorrhage, calculi, urinary tract infections, cyst rupture, or due to stretching of the capsule or traction of the renal pedicle. We have recently investigated pain patterns in AD-PKD patients using a translated version of a pain questionnaire specific for AD-PKD population. The questionnaire revealed that 67% patients with ADPKD exhibited some type of pain. The findings of that study emphasized that pain appeared early in the course of ADPKD, when patients still exhibited preserved renal function. In the present study, a multivariate logistic regression analysis disclosed that renal volume (9-fold increased risk) and nephrolithiasis (4-fold increased risk) were the most important determinant factors for pain in ADPKD patients with preserved renal function, after adjustments for the presence of hypertension and duration of the disease.
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PMID:Pain determinants of pain in autosomal dominant polycystic kidney disease. 2410 Jul 45

Autosomal dominant polycystic kidney disease is the most frequent hereditary kidney disease. However it lacks a specific treatment. Its prevalence is 1/800 and causes the need for renal replacement therapy in 8-10% of patients on dialysis or kidney transplant. It is caused by mutations in the PKD1 and PKD2 genes, which cause a series of alterations in the polycystic cells, which have become therapeutic targets. There are many molecules that are being tested to counteract the alterations of these therapeutic targets. There are studies in all phases of research, from phase i to phase iv. Some of the molecules being tested are tolvaptan, mTOR inhibitors and, among many other, somatostatin analogues. These drugs are extensively reviewed in this article. Based on the accumulated experience the primary objective of the trials is the slowing of the increase in renal volume. Yet other renal end points such as renal function and hypertension are necessary. It is expected that in the coming years we can have specific, well tolerated, effective and affordable drugs for the treatment of autosomal dominant polycystic kidney disease.
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PMID:[Treatment of autosomal dominant polycystic kidney disease]. 2424 5

Autosomal dominant polycystic kidney disease (ADPKD) is the most commonly inherited kidney disease, characterized by progressive cyst growth and renal enlargement, resulting in renal failure. Hypertension is common and occurs early, prior to loss of kidney function. Whether hypertension in ADPKD is a primary vasculopathy secondary to mutations in the polycystin genes or secondary to activation of the renin-angiotensin-aldosterone system by cyst expansion and intrarenal ischemia is unclear. Dysregulation of the primary cilium causing endothelial and vascular smooth muscle cell dysfunction is a component of ADPKD. In this article, we review the epidemiology, pathophysiology and clinical characteristics of hypertension in ADPKD and give specific recommendations for its treatment.
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PMID:Mechanisms and management of hypertension in autosomal dominant polycystic kidney disease. 2446 89

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by bilateral renal cysts, kidney pain, hypertension, and progressive loss of renal function. It is a leading cause of end-stage renal disease and the most common inherited kidney disease in the United States. Despite its prevalence, disease-modifying treatment options do not currently exist. Tolvaptan is an orally active, selective arginine vasopressin V2 receptor antagonist already in use for hyponatremia. Tolvaptan exhibits dose-proportional pharmacokinetics with a half-life of ~12 hours. Metabolism occurs through the cytochrome P450 3A4 isoenzyme, and tolvaptan is a substrate for P-glycoprotein, resulting in numerous drug interactions. Recent research has highlighted the beneficial effect of tolvaptan on delaying the progression of ADPKD, which is the focus of this review. Pharmacologic, preclinical, and phase II and III clinical trial studies have demonstrated that tolvaptan is an effective treatment option that targets underlying pathogenic mechanisms of ADPKD. Tolvaptan delays the increase in total kidney volume (surrogate marker for disease progression), slows the decline in renal function, and reduces kidney pain. However, tolvaptan has significant adverse effects including aquaretic effects (polyuria, nocturia, polydipsia) and elevation of aminotransferase enzyme concentrations with the potential for acute liver failure. Appropriate patient selection is critical to optimize long-term benefits while minimizing adverse effects and hepatotoxic risk factors. Overall, tolvaptan is the first pharmacotherapeutic intervention to demonstrate significant benefit in the treatment of ADPKD, but practitioners and regulatory agencies must carefully weigh the risks versus benefits. Additional research should focus on incidence and risk factors of liver injury, cost-effectiveness, clinical management of drug-drug interactions, and long-term disease outcomes.
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PMID:Review of tolvaptan for autosomal dominant polycystic kidney disease. 2470 79

Autosomal dominant polycystic kidney disease (ADPKD) is a systemic disorder mainly involving the kidney. It affects one in 400-1000 live births. Early hypertension and progressive renal failure due to massive enlargement of cysts and fibrosis are hallmarks of the disease. ADPKD accounts for ~5-10% of cases requiring renal replacement therapy. But not only the kidneys are affected in ADPKD: cysts also occur in other organs such as the liver, pancreas, arachnoid membrane and seminal vesicles. Non-cystic manifestations of the diseases are intracranial aneurysms, hernias and valvular abnormalities. Complications in ADPKD usually result from kidney involvement and include cyst bleeding and cyst infection. However, serious extrarenal features such as subarachnoid haemorrhage can also occur. There is no specific treatment for ADPKD currently, but many molecules targeting up- or downregulated molecules in the renal epithelial cells are being tested. A clinical trial using tolvaptan (a vasopressin receptor antagonist) has demonstrated efficacy, while mTOR inhibitors have shown no positive effect in ADPKD. ACEIs and ARBs are the drugs of choice for treating hypertension in ADPKD. Until a specific therapy becomes available, early treatment of hypertension and lifestyle changes are encouraged.
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PMID:Autosomal dominant policystic kidney disease, more than a renal disease. 2473 82

Autosomal dominant polycystic kidney disease is a genetic disorder associated with substantial variability in its natural course within and between affected families. Understanding predictors for rapid progression of this disease has become increasingly important with the emergence of potential new treatments. This systematic review of the literature since 1988 evaluates factors that may predict and/or effect autosomal dominant polycystic kidney disease progression. Predicting factors associated with early adverse structural and/or functional outcomes are considered. These factors include PKD1 mutation (particularly truncating mutation), men, early onset of hypertension, early and frequent gross hematuria, and among women, three or more pregnancies. Increases in total kidney volume and decreases in GFR and renal blood flow greater than expected for a given age also signify rapid disease progression. Concerning laboratory markers include overt proteinuria, macroalbuminuria, and perhaps, elevated serum copeptin levels in affected adults. These factors and others may help to identify patients with autosomal dominant polycystic kidney disease who are most likely to benefit from early intervention with novel treatments.
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PMID:Predictors of autosomal dominant polycystic kidney disease progression. 2492 19

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited disease of the kidneys and is marked by progressive cyst growth and decline in kidney function, resulting in end-stage renal disease (ESRD). Hypertension is thought to be a significant modifying factor in the progression of renal failure in ADPKD. A number of genetic variations involved in renin-angiotensin-aldosterone system (RAAS) pathway genes have clinical or physiological impacts on pathogenesis of hypertension-induced ESRD in ADPKD. Information on RAAS pathway gene polymorphisms and their association with ESRD and ADPKD, published till March 2013, was collected using MEDLINE search. The present review deals with RAAS gene polymorphisms focused on hypertension-induced ESRD in ADPKD in different populations. The results were inconclusive and limited by heterogeneity in the study designs and the population stratification. In lieu of applying next generation sequencing technologies to study complex diseases, it is also possible to apply the same to unravel the complexity of ESRD in ADPKD.
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PMID:Role of renin-angiotensin-aldosterone system gene polymorphisms and hypertension-induced end-stage renal disease in autosomal dominant polycystic kidney disease. 2500 Nov 32

Sympathetic overactivity plays a crucial role in the genesis and aggravation of arterial hypertension in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD). Renal denervation has been shown to be effective and safe in reducing blood pressure (BP) in patients with treatment-resistant hypertension, even with chronic kidney disease (CKD). However, there are no cases in hypertensive patients with ADPKD. We report the exceptional case of a woman with stage 4 CKD secondary to ADPKD and uncontrolled treatment-resistant hypertension. Because of the ineffectiveness of all pharmacological and surgical therapeutic strategies, including the uninephrectomy, renal denervation by radiofrequency ablation of the renal artery was performed. The patient decreased the requirement of antihypertensive medication and the BP showed a remarkable reduction, that resulted stable 12 months after the procedure.
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PMID:[Renal denervation in ADPKD: an exceptional case]. 2503 10

Genetic disorders of the kidney include cystic diseases, metabolic diseases and immune glomerulonephritis. Cystic diseases include autosomal dominant and recessive polycystic kidney disease (ADPKD, ARPKD, respectively). Neonates with enlarged, cystic kidneys should be evaluated for PKD. Patients with ADPKD have cysts and renal enlargement. Most patients present with hypertension, hematuria or flank pain; the most common extrarenal manifestation is polycystic liver disease. Oligohydramnios, bilaterally enlarged kidneys and decreased urine are featured in utero in ARPKD. Medullary sponge kidney is uncommon and features nephrocalcinosis, recurrent calcium stones and a history of polyuria/nocturia and/or urinary tract infections. Alport syndrome (AS) is an inherited disease of the glomerular basement membrane that is usually inherited as an X-linked dominant trait. Most patients with AS present in the first two decades of life with persistent microscopic or gross hematuria. Later, proteinuria is seen and its presence portends disease progression. Other findings may include sensorineural hearing loss and ocular abnormalities. There are various inherited tubulopathies, including Bartter syndrome, a group of renal tubular disorders that consist of two phenotypes with four genotypes. Patients usually present early in life with salt wasting, hypokalemia and metabolic alkalosis. Other features, depending on genotype, may include polyhydramnios and premature birth. Gitelman syndrome is also a salt-losing tubulopathy characterized by hypokalemic alkalosis. The majority of patients with Gitelman syndrome present during adolescence or early adulthood.
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PMID:Inherited renal diseases. 2508 62

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent cause of genetic renal disease and accounts for 6-10% of patients on renal replacement therapy (RRT). Very few prospective, randomized trials or clinical studies address the diagnosis and management of this relatively frequent disorder. No clinical guidelines are available to date. This is a consensus statement presenting the recommendations of the Spanish Working Group on Inherited Kidney Diseases, which were agreed to following a literature search and discussions. Levels of evidence found were C and D according to the Centre for Evidence-Based Medicine (University of Oxford). The recommendations relate to, among other topics, the use of imaging and genetic diagnosis, management of hypertension, pain, cyst infections and bleeding, extra-renal involvement including polycystic liver disease and cranial aneurysms, management of chronic kidney disease (CKD) and RRT and management of children with ADPKD. Recommendations on specific ADPKD therapies are not provided since no drug has regulatory approval for this indication.
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PMID:Spanish guidelines for the management of autosomal dominant polycystic kidney disease. 2516 91


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