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Polycystic Kidney Disease Treatment

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9 papers 0 to 25 followers
By Faye Kehler Family Physician and GP Anesthetist since 1987 interested in all aspects of Medicine
Olivier Devuyst, Vicente E Torres
PURPOSE OF REVIEW: Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent inherited nephropathy. This review will focus on the vasopressin and 3'-5'-cyclic adenosine monophosphate (cAMP) signaling pathways in ADPKD and will discuss how these insights offer new possibilities for the follow-up and treatment of the disease. RECENT FINDINGS: Defective osmoregulation is an early manifestation of ADPKD and originates from both peripheral (renal effect of vasopressin) and central (release of vasopressin) components...
July 2013: Current Opinion in Nephrology and Hypertension
Andreas L Serra, Diane Poster, Andreas D Kistler, Fabienne Krauer, Shagun Raina, James Young, Katharina M Rentsch, Katharina S Spanaus, Oliver Senn, Paulus Kristanto, Hans Scheffel, Dominik Weishaupt, Rudolf P Wüthrich
BACKGROUND: In autosomal dominant polycystic kidney disease (ADPKD), aberrant activation of the mammalian target of rapamycin (mTOR) pathway is associated with progressive kidney enlargement. The drug sirolimus suppresses mTOR signaling. METHODS: In this 18-month, open-label, randomized, controlled trial, we sought to determine whether sirolimus halts the growth in kidney volume among patients with ADPKD. We randomly assigned 100 patients between the ages of 18 and 40 years to receive either sirolimus (target dose, 2 mg daily) or standard care...
August 26, 2010: New England Journal of Medicine
Esther Meijer, Joost P H Drenth, Hedwig d'Agnolo, Niek F Casteleijn, Johan W de Fijter, Tom J Gevers, Peter Kappert, Dorien J M Peters, Mahdi Salih, Darius Soonawala, Edwin M Spithoven, Vicente E Torres, Folkert W Visser, Jack F M Wetzels, Robert Zietse, Ron T Gansevoort
BACKGROUND: There are limited therapeutic options to slow the progression of autosomal dominant polycystic kidney disease (ADPKD). Recent clinical studies indicate that somatostatin analogues are promising for treating polycystic liver disease and potentially also for the kidney phenotype. We report on the design of the DIPAK 1 (Developing Interventions to Halt Progression of ADPKD 1) Study, which will examine the efficacy of the somatostatin analogue lanreotide on preservation of kidney function in ADPKD...
March 2014: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
Susanne N E Boehn, Sonja Spahn, Sabine Neudecker, Andrea Keppler, Marie-Thérèse Bihoreau, Bettina Kränzlin, Priyanka Pandey, Sigrid C Hoffmann, Li Li, Vicente E Torres, Hermann-Josef Gröne, Norbert Gretz
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common human inherited diseases. Modifier genes seem to modulate the disease progression and might therefore be promising drug targets. Although a number of modifier loci have been already identified, no modifier gene has been proven to be a real modifier yet. METHODS: Gene expression profiling of two substrains of the Han:SPRD rat, namely PKD/Mhm and PKD/US, both harboring the same mutation, was conducted in 36-day-old animals...
August 2013: Nephrology, Dialysis, Transplantation
Xueqi Wang, Suhua Zhang, Yang Liu, Daniela Spichtig, Sarika Kapoor, Hermann Koepsell, Nilufar Mohebbi, Stephan Segerer, Andreas L Serra, Daniel Rodriguez, Olivier Devuyst, Changlin Mei, Rudolf P Wüthrich
Renal tubular epithelial cell proliferation and transepithelial cyst fluid secretion are key features in the progression of polycystic kidney disease (PKD). As the role of the apical renal sodium-glucose cotransporters in these processes is not known, we tested whether phlorizin inhibits cyst growth and delays renal disease progression in a rat model of PKD. Glycosuria was induced by subcutaneous injection of phlorizin in male heterozygous (Cy/+) and wild-type Han:SPRD rats. Phlorizin induced immediate and sustained glycosuria and osmotic diuresis in these rats...
November 2013: Kidney International
Miki Aihara, Hiroyuki Fujiki, Hiroshi Mizuguchi, Katsuji Hattori, Koji Ohmoto, Makoto Ishikawa, Keisuke Nagano, Yoshitaka Yamamura
Tolvaptan, a selective vasopressin V2 receptor antagonist, slows the increase in total kidney volume and the decline in kidney function in patients with the results of the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Outcome (TEMPO) 3:4 trial. However, it was unclear which dose of tolvaptan was optimal or whether tolvaptan was able to delay progression to end-stage renal disease (ESRD). Here we examined the relationship with aquaresis and the inhibitory effect on cyst development in short-term treatment and mortality as an index of ESRD in long-term treatment with tolvaptan using DBA/2FG-pcy mice, an animal model of nephronophthisis...
May 2014: Journal of Pharmacology and Experimental Therapeutics
Z Su, X Wang, X Gao, Y Liu, C Pan, H Hu, R P Beyer, M Shi, J Zhou, J Zhang, A L Serra, R P Wüthrich, C Mei
OBJECTIVES: The complement system is involved in many immune complex-mediated kidney diseases, yet its role in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) has not been examined in detail. METHODS AND RESULTS: Screening of the glycoproteome of urine samples from ADPKD patients revealed that levels of complement factor B (CFB), serpin peptidase inhibitor, complement component 1 inhibitor (SERPING1) and complement component 9 (C9) increased, whereas complement component 1, r subcomponent-like (C1RL), CD55 and CD59 levels decreased with disease progression...
November 2014: Journal of Internal Medicine
Zlata Novalic, Annemieke M van der Wal, Wouter N Leonhard, Gudrun Koehl, Martijn H Breuning, Edward K Geissler, Emile de Heer, Dorien J M Peters
Inhibition of the mammalian target of rapamycin (mTOR) shows beneficial effects in animal models of polycystic kidney disease (PKD); however, two clinical trials in patients with autosomal dominant PKD failed to demonstrate a short-term benefit in either the early or progressive stages of disease. The stage of disease during treatment and the dose of mTOR inhibitors may account for these differing results. Here, we studied the effects of a conventional low dose and a higher dose of sirolimus (blood levels of 3 ng/ml and 30-60 ng/ml, respectively) on mTOR activity and renal cystic disease in two Pkd1-mutant mouse models at different stages of the disease...
May 2012: Journal of the American Society of Nephrology: JASN
Kevin F Erickson, Glenn M Chertow, Jeremy D Goldhaber-Fiebert
UNLABELLED: Chinese translation BACKGROUND: In the TEMPO (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes) trial, tolvaptan significantly reduced expansion of kidney volume and loss of kidney function. OBJECTIVE: To determine how the benefits of tolvaptan seen in TEMPO may relate to longer-term health outcomes, such as progression to end-stage renal disease (ESRD) and death, and cost-effectiveness...
September 17, 2013: Annals of Internal Medicine
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