Kidney and Blood Pressure Research
Review
Free Access
Autosomal Dominant Polycystic Kidney Disease: New Treatment Options and How to Test Their EfficacyWüthrich R.P. · Serra A.L. · Kistler A.D.Division of Nephrology, University Hospital, Zürich, Switzerland
Prof. Rudolf P. Wüthrich Division of Nephrology, University Hospital Rämistrasse 100 CH–8091 Zürich (Switzerland) Tel. +41 44 255 33 84, Fax +41 44 255 45 93, E-Mail rudolf.wuethrich@usz.ch |
|
Kidney Blood Press Res 2009;32:380–387
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) represents a slowly progressing cystic kidney disorder which evolves into end-stage renal disease in the majority of patients. Currently, there are no established treatments to retard the progression of the disease, but several promising therapeutic options are being tested in ongoing clinical trials. An inherent dilemma for the investigation of therapies in ADPKD is the dissociation of the early onset and constant rate of cyst growth from the delayed but accelerated loss of renal function. In order to prevent the latter, one needs to act on the former, i.e. current belief by experts in the field is that (1) retardation of cyst growth will ultimately improve the loss of glomerular filtration rate, and (2) cyst volume is an ideal surrogate parameter for outcome in early ADPKD. The present review will discuss the utility and the techniques for kidney and cyst volume measurements to assess disease progression in ADPKD, and summarizes ongoing clinical trials testing novel therapeutic options.
© 2009 S. Karger AG, Basel
Related Articles:
References
- Torres VE, Harris PC, Pirson Y: Autosomal dominant polycystic kidney disease. Lancet 2007;369:1287–1301.
- Grantham JJ: Clinical practice: autosomal dominant polycystic kidney disease. N Engl J Med. 2008;359:1477–1485.
- Cheong B, Muthupillai R, Rubin MF, Flamm SD: Normal values for renal length and volume as measured by magnetic resonance imaging. Clin J Am Soc Nephrol 2007;2:38–45.
- Churchill DN, Bear JC, Morgan J, Payne RH, McManamon PJ, Gault MH: Prognosis of adult onset polycystic kidney disease re-evaluated. Kidney Int 1984;26:190–193.
- Hateboer N, v Dijk MA, Bogdanova N, Coto E, Saggar-Malik AK, San Millan JL, Torra R, Breuning M, Ravine D: Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1-PKD2 Study Group. Lancet 1999;353:103–107.
- Dalgaard OZ: Bilateral polycystic disease of the kidneys; a follow-up of two hundred and eighty-four patients and their families. Acta Med Scand Suppl 1957;328:1–255.
- Fick-Brosnahan GM, Belz MM, McFann KK, Johnson AM, Schrier RW: Relationship between renal volume growth and renal function in autosomal dominant polycystic kidney disease: a longitudinal study. Am J Kidney Dis 2002;39:1127–1134.
- Fick-Brosnahan GM, Tran ZV, Johnson AM, Strain JD, Gabow PA: Progression of autosomal-dominant polycystic kidney disease in children. Kidney Int 2001;59:1654–1662.
- Grantham JJ, Torres VE, Chapman AB, Guay-Woodford LM, Bae KT, King BF Jr, Wetzel LH, Baumgarten DA, Kenney PJ, Harris PC, Klahr S, Bennett WM, Hirschman GN, Meyers CM, Zhang X, Zhu F, Miller JP; CRISP Investigators: Volume progression in polycystic kidney disease. N Engl J Med 2006;354:2122–2130.
- Kistler AD, Poster D, Krauer F, Weishaupt D, Raina S, Senn O, Binet I, Spanaus K, Wüthrich RP, Serra AL: Increases in kidney volume in autosomal dominant polycystic kidney disease can be detected within 6 months. Kidney Int 2009;75:235–241.
- Grantham JJ, Chapman AB, Torres VE: Volume progression in autosomal dominant polycystic kidney disease: the major factor determining clinical outcomes. Clin J Am Soc Nephrol 2006;1:148–157.
- King BF, Reed JE, Bergstralh EJ, Sheedy PF 2nd, Torres VE: Quantification and longitudinal trends of kidney, renal cyst, and renal parenchyma volumes in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2000;11:1505–1511.
- Sise C, Kusaka M, Wetzel LH, Winklhofer F, Cowley BD, Cook LT, Gordon M, Grantham JJ: Volumetric determination of progression in autosomal dominant polycystic kidney disease by computed tomography. Kidney Int 2000;58:2492–2501.
- Antiga L, Piccinelli M, Fasolini G, Ene-Iordache B, Ondei P, Bruno S, Remuzzi G, Remuzzi A: Computed tomography evaluation of autosomal dominant polycystic kidney disease progression: a progress report. Clin J Am Soc Nephrol 2006;1:754–760.
- Bae KT, Tao C, Zhu F, Bost JE, Chapman AB, Grantham JJ, Torres VE, Guay-Woodford LM, Meyers CM, Bennett WM; Consortium for Radiologic Imaging Studies Polycystic Kidney Disease: MRI-based kidney volume measurements in ADPKD: reliability and effect of gadolinium enhancement. Clin J Am Soc Nephrol 2009;4:719–725.
- Torres VE, Harris PC: Mechanisms of disease: autosomal dominant and recessive polycystic kidney diseases. Nat Clin Pract Nephrol 2006;2:40–55.
- Torres VE, Harris PC: Polycystic kidney disease: genes, proteins, animal models, disease mechanisms and therapeutic opportunities. J Intern Med 2007;261:17–31.
- Torres VE, Harris PC: Autosomal dominant polycystic kidney disease: the last 3 years. Kidney Int 2009;76:149–168.
- Tao Y, Kim J, Schrier RW, Edelstein CL: Rapamycin markedly slows disease progression in a rat model of polycystic kidney disease. J Am Soc Nephrol 2005;16:46–51.
- Wahl PR, Serra AL, Le Hir M, Molle KD, Hall MN, Wüthrich RP: Inhibition of mTOR with sirolimus slows disease progression in Han:SPRD rats with autosomal dominant polycystic kidney disease (ADPKD). Nephrol Dial Transplant 2006;21:598–604.
- Shillingford JM, Murcia NS, Larson CH, Low SH, Hedgepeth R, Brown N, Flask CA, Novick AC, Goldfarb DA, Kramer-Zucker A, Walz G, Piontek KB, Germino GG, Weimbs T: The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease. Proc Natl Acad Sci USA 2006;103:5466–5471.
-
Wu M, Wahl PR, Le Hir M, Wackerle-Men Y, Wüthrich RP, Serra AL: Everolimus retards cyst growth and preserves kidney function in a rodent model for polycystic kidney disease. Kidney Blood Press Res 2007;30:253–259.
- Mostov KE: mTOR is out of control in polycystic kidney disease. Proc Natl Acad Sci USA 2006;103:5247–5248.
- Serra AL, Kistler AD, Poster D, Struker M, Wüthrich RP, Weishaupt D, Tschirch F: Clinical proof-of-concept trial to assess the therapeutic effect of sirolimus in patients with autosomal dominant polycystic kidney disease: SUISSE ADPKD study. BMC Nephrol 2007;8:13.
- Torres VE, Wang X, Qian Q, Somlo S, Harris PC, Gattone VH 2nd: Effective treatment of an orthologous model of autosomal dominant polycystic kidney disease. Nat Med 2004;10:363–364.
- Torres VE: Vasopressin antagonists in polycystic kidney disease. Semin Nephrol 2008;28:306–317.
- Reubi JC, Horisberger U, Studer UE, Waser B, Laissue JA: Human kidney as target for somatostatin: high affinity receptors in tubules and vasa recta. J Clin Endocrinol Metab 1993;77:1323–1328.
- Ruggenenti P, Remuzzi A, Ondei P, Fasolini G, Antiga L, Ene-Iordache B, Remuzzi G, Epstein FH: Safety and efficacy of long-acting somatostatin treatment in autosomal-dominant polycystic kidney disease. Kidney Int 2005;68:206–216.
-
van Keimpema L, Nevens F, Vanslembrouck R, van Oijen MG, Hoffmann AL, Dekker HM, de Man RA, Drenth JP: Lanreotide reduces the volume of polycystic liver: a randomized, double-blind, placebo-controlled trial. Gastroenterology 2009 [Epub ahead of print].
- Schrier RW: Optimal care of autosomal dominant polycystic kidney disease patients. Nephrology (Carlton) 2006;11:124–130.
- Ecder T, Edelstein CL, Fick-Brosnahan GM, Johnson AM, Chapman AB, Gabow PA, Schrier RW: Diuretics versus angiotensin-converting enzyme inhibitors in autosomal dominant polycystic kidney disease. Am J Nephrol 2001;21:98–103.
- Ecder T, Chapman AB, Brosnahan GM, Edelstein CL, Johnson AM, Schrier RW: Effect of antihypertensive therapy on renal function and urinary albumin excretion in hypertensive patients with autosomal dominant polycystic kidney disease. Am J Kidney Dis 2000;35:427–432.
- van Dijk MA, Breuning MH, Duiser R, van Es LA, Westendorp RG: No effect of enalapril on progression in autosomal dominant polycystic kidney disease. Nephrol Dial Transplant 2003;18:2314–2320.
- Cadnapaphornchai MA, McFann K, Strain JD, Masoumi A, Schrier RW: Prospective change in renal volume and function in children with ADPKD. Clin J Am Soc Nephrol 2009;4:820–829.
- Chapman AB: Approaches to testing new treatments in autosomal dominant polycystic kidney disease: insights from the CRISP and HALT-PKD studies. Clin J Am Soc Nephrol 2008;3:1197–1204.
Article / Publication Details
First-Page Preview
Published online: November 03, 2009
Issue release date: November 2009
Number of Print Pages: 8
Number of Figures: 1
Number of Tables: 2
ISSN: 1420-4096 (Print)
eISSN: 1423-0143 (Online)
For additional information: https://www.karger.com/KBR
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
Get Permission
PubMed ID
