Skip to main content
Give
Division of Nephrology
DepartmentsDepartment of MedicineDivisionsDivision of NephrologyPolycystic Kidney Disease

Polycystic Kidney Disease

What is Polycystic Kidney Disease?

Polycystic kidney diseases (PKD) are a group of disorders characterized by dilated segments of renal tubules that pinch off to form fluid-filled structures or cysts. As cysts gradually enlarge, they compress normal kidney tissue and prevent it from functioning normally.

This can result in high blood pressure and kidney failure, which may require dialysis or transplantation. As kidney cysts enlarge, they also can cause a number of other problems including pain, infection and hemorrhage. Kidney stones are also more common in individuals with cystic kidney disease.

One form of PKD, called autosomal dominant polycystic kidney disease (ADPKD), is the most common single-gene disorder that causes kidney failure. It is estimated that approximately 600,000 individuals in the United States alone have ADPKD. ADPKD is the fourth-most common cause of kidney failure in the U.S. and occurs in people of all races and ethnicities.

Genetics of Kidney Diseases

A number of acquired and genetic diseases can result in polycystic kidneys. The various forms differ with respect to the way in which they are inherited (autosomal dominant, autosomal recessive or X-linked); the range of renal and extra-renal manifestations that accompany the cystic disease; the age at which renal failure most commonly presents (childhood vs. adult); and the mutant gene responsible for causing the disorder.

Some of the disorders associated with kidney cysts and/or liver cysts:

Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Individuals with one mutant copy of the gene (PKD1 or PKD2) develop the disease. A parent with the disease has a 50 percent chance of passing the mutant gene to his/her children. ADPKD is associated with slowly progressive cystic kidney disease that results in kidney failure in about 50 percent of affected individuals. The age at onset of kidney failure is variable and 50 percent of individuals with ADPKD develop kidney failure by age 60. Hypertension, cerebral aneurysms, cardiac valvular abnormalities, liver cysts, kidney stones, and aortic aneurysms are important complications.

Autosomal Dominant Polycystic Liver Disease (PLD)
This is an autosomal dominant disorder that is biologically related to ADPKD. Several genes are known to cause PLD (for example, Sec 63, PRKCSH, ALG8, ALG9 and Ganab), but there are others that have not yet been identified. Individuals with PLD develop liver cysts and may have a small number of kidney cysts, but typically don’t develop kidney failure.

Autosomal Recessive Polycystic Kidney Disease (ARPKD; also called PKHD1)
This is a relatively rare disorder occurring in 1 in 20,000 individuals. The disease results when both copies of the fibrocystin gene on chromosome 6 are mutated. Parents are carriers and unaffected. Affected offspring inherit a mutant copy from each parent. A couple in which both partners are carriers for the disease have a 25 percent chance of having a child with the disease. The disease usually presents during infancy or in childhood, with up to 50 percent of affected children dying in the first year of life. Older children and adults may have severe liver disease requiring transplantation.

Nephronophthisis
This is a collection of recessive diseases in which parents are unaffected carriers and offspring develop kidney disease between infancy and adolescence. Some forms of the disease are associated with eye abnormalities.

Bardet-Biedl Syndrome
This is a group of recessive disorders that present with eye disease (retinopathy), obesity, hypogonadism, a variety of kidney abnormalities, extra digits on the hand or feet, and mental retardation.

Medullary Cystic Disease
This is an autosomal dominant disease caused by mutations in the gene for uromodulin on chromosome 16. Mutations in the mucin gene on chromosome 1 were also shown to be associated with medullary cystic disease. Although individuals do have some kidney cysts, interstitial scarring of the kidneys is prominent and kidneys tend to be small. Recently, another gene, DNAJB11, was also shown to cause kidney cysts with interstitial scarring. Renal failure typically develops in adulthood; other complications include high uric acid levels and gout.

Tuberous Sclerosis
Tuberous sclerosis (TSC) is an autosomal dominant disease that is caused by mutations in genes called TSC1 or TSC2. Tuberous sclerosis is associated with benign tumors in multiple organs. Kidney cancer is a rare complication of TSC. Individuals with TSC may have a few renal cysts but a subset can present with polycystic kidney disease resembling ADPKD. This may be caused by mutations that affect both genes.

Von Hippel Lindau Syndrome
This is an autosomal dominant disorder that presents with tumors in the nervous system, adrenal gland tissue, kidney cancer and kidney cysts.

Is There a Treatment for PKD?

In April 2018, the FDA approved a new drug called Tolvaptan, or Jynarque, for the treatment of ADPKD. Tolvaptan is a V2R antagonist that blocks vasopressin signaling, a key driver of cyst growth in ADPKD due to the resulting intracellular increase in cyclic adenosine monophosphate.

There are other experimental drugs being tested in mouse models of PKD and some in clinical trials. In addition, healthcare providers continue to manage complications of the various forms of the disease, such as treating hypertension or infections.

PKD Care

Drs. Terry Watnick, Stephen Seliger, Valeriu Cebotaru and Songul Onder staff the University of Maryland Inherited Renal Disease Clinic. The clinic forms the translational arm of the PKD group at the University of Maryland and receives national and international referrals of patients who require diagnosis and/or management of complicated cystic kidney disease. Dr. Stephen Seliger directs the Clinical Research Program, which is involved in numerous clinical trials.

The team at the University of Maryland provides multidisciplinary expertise in many subspecialty fields involved in treating ADPKD complications, including Gastroenterology and Hepatology, Neurosurgery, and Interventional Radiology

Kidney Transplants

The University of Maryland Comprehensive Transplant Program performs around 250 kidney transplants per year and is the largest program in Maryland.

PKD Research

PKD poses special challenges for investigators seeking therapies.

Polycystic kidney disease is frequently a progressive disease that evolves over decades. The risk of a therapy must be less than the potential benefit. The University of Maryland team and collaborators are tackling the problem on two parallel tracks. In the first, the investigators seek to define the pathophysiology of the disease as a means of identifying steps for possible intervention. The second approach is aimed at determining the normal functions of the PKD proteins, seeking to identify ways that their activity may be replaced in disease tissue.

Although we have made significant progress since the first human PKD gene was discovered, significant questions remain. We still do not know why some patients develop severe disease or aneurysms while family members with the same mutation do not. Are there other underlying genetic factors that determine the severity of disease or its rate of progression? Why do some mutations result in severe disease more frequently? How does loss of PKD proteins cause the vascular manifestations that are observed? How do dietary or lifestyle factors affect progression of disease? Do any of the experimental therapies used in other forms of mouse PKD work in the form that most commonly affects humans? Future NIH clinical studies propose to use changes in the amount of kidney tissue as a means of assessing response to therapy. Is this really a suitable surrogate marker for functional response?

  • Maryland Polycystic Kidney Disease Research and Translation Core Center (MPKD-RTCC): The University of Maryland is home to one of three NIH-sponsored PKD Research and Translation Core Centers. The Center is comprised of four biomedical Cores that are charged with developing and distributing state-of-the-art research reagents to a national and international group of PKD researchers. The goal of the Center is to foster a greater understanding of the fundamental aspects of PKD biology.
  • Identify PKD signaling pathways: Most PKD genes encode proteins that sit on the surface of cells and transmit information across the cell boundary into the cell interior. The cell uses this information to respond to its environment. In PKD, the cell is either unable to acquire this information because the sensor is defective or is unable to respond properly to the signal. University of Maryland researchers are seeking to define the types of information that PKD proteins sense and the pathways inside the cell that PKD proteins regulate.
  • Characterize the cellular biology of PKD proteins: Many PKD proteins are found in primary cilia, a small hair-like structure on the surface of the cell that is required for proper cell function. Polycystic kidney disease results when cilia aren’t properly formed or when signaling proteins don’t make it to the primary cilia. University of Maryland Investigators are using a variety of tools to study how PKD proteins reach the cilia in kidney cells. One of our investigators has found that a biochemical reaction that cuts the PKD1 protein is required for PKD1 and PKD2 to reach the cilia.
  • Determine how PKD proteins help to preserve normal blood vessel structure and function: The cardiovascular complications of PKD are an important cause of premature death and morbidity, especially brain aneurysms that can occur in a sub-group of patients with ADPKD. Studies of patients with ADPKD and of mouse models of human ADPKD show that PKD proteins are essential for normal blood vessels. University of Maryland nephrology investigators are seeking to understand the genetic factors that predispose certain patients to develop aneurysms and to define the signaling pathway that may be altered in ADPKD blood vessels. The proposed studies aim to understand this process in the hope that future screening strategies and treatments may be directed at preventing these complications.
  • Engineer and manipulate mouse models of human PKD: The University of Maryland team has used transgenic technologies to produce mice with cystic kidney disease very similar to the disorder that affects humans (both ADPKD and ARPKD). These powerful models can be used to test various therapies for PKD in a cost-effective manner before they are tested in humans.
  • Determine the function of the ARPKD protein (called fibrocystin or polyductin): The University of Maryland team has recently developed animal and cell culture systems that can be used to model the human disease and the ARPKD protein’s function. Preliminary studies at University of Maryland suggest that fibrocystin and the polycystins may work together as a complex to ensure proper formation of the kidney tubule.
  • Use simple systems to study PKD proteins: We have developed a fruit fly with mutations in the PKD2 gene. University of Maryland investigators are using this simple system to examine how PKD proteins reach the tip of the cilium.
  • Longitudinal cohort study: Progression of autosomal dominant polycystic kidney disease to kidney failure is highly variable. A number of factors including age, genotype and incidence of cardiovascular disease determine how quickly the disorder progresses. Dr. Stephen Seliger, who directs the Clinical and Translation Core for the MPKD-RTCC, is collecting baseline data on a large cohort of individuals with ADPKD. The goal of the cohort study is to better understand the factors that influence PKD progression. In addition, this study will establish a high-quality biorepository with specimens collected under standardized conditions. This biorepository has been a valuable resource for PKD investigators. Learn more >

 

PKD Publications

Authored by University of Maryland Department of Nephrology Faculty Members

  1. Ishimoto Y, Menezes LF, Zhou F, Yoshida T, Komori T, Qiu J, Young MF, Lu H, Potapova S, Outeda P, Watnick T, Germino GG. A novel ARPKD mouse model with near complete deletion of the Polycystic Kidney and Hepatic Disease 1 (Pkhd1) genomic locus presents with multiple phenotypes but not renal cysts. Kidney Int. 2023 Jul 5:S0085-2538(23)00482-9. doi: 10.1016/j.kint.2023.05.027. Epub ahead of print. PMID: 37419448.
  2. Yanda MK, Zeidan A, Cebotaru L. Ameliorating liver disease in an autosomal recessive polycystic kidney disease mouse model. Am J Physiol Gastrointest Liver Physiol. 2023 May 1;324(5):G404-G414. doi: 10.1152/ajpgi.00255.2022. Epub 2023 Mar 7. PMID: 36880660; PMCID: PMC10085553.
  3. Hallows KR, Abebe KZ, Li H, Saitta B, Althouse AD, Bae KT, Lalama CM, Miskulin DC, Perrone RD, Seliger SL, Watnick TJ. Association of Longitudinal Urinary Metabolic Biomarkers With ADPKD Severity and Response to Metformin in TAME-PKD Clinical Trial Participants. Kidney Int Rep. 2022 Dec 5;8(3):467-477. doi: 10.1016/j.ekir.2022.11.019. PMID: 36938071; PMCID: PMC10014337.
  4. Muto Y, Dixon EE, Yoshimura Y, Wu H, Omachi K, Ledru N, Wilson PC, King AJ, Eric Olson N, Gunawan MG, Kuo JJ, Cox JH, Miner JH, Seliger SL, Woodward OM, Welling PA, Watnick TJ, Humphreys BD. Defining cellular complexity in human autosomal dominant polycystic kidney disease by multimodal single cell analysis. Nat Commun. 2022 Oct 30;13(1):6497. doi: 10.1038/s41467-022-34255-z. PMID: 36310237; PMCID: PMC9618568.
  5. Mader G, Mladsi D, Sanon M, Purser M, Barnett CL, Oberdhan D, Watnick T, Seliger S. A disease progression model estimating the benefit of tolvaptan on time to end-stage renal disease for patients with rapidly progressing autosomal dominant polycystic kidney disease. BMC Nephrol. 2022 Oct 18;23(1):334. doi: 10.1186/s12882-022-02956-8. PMID: 36258169; PMCID: PMC9578187.
  6. Hoover E, Perrone RD, Rusconi C, Benson B, Dahl NK, Gitomer B, Manelli A, Mrug M, Park M, Seliger SL, Phadnis MA, Thewarapperuma N, Watnick TJ. Design and Basic Characteristics of a National Patient-Powered Registry in ADPKD. Kidney360. 2022 May 20;3(8):1350-1358. doi: 10.34067/KID.0002372022. PMID: 36176661; PMCID: PMC9416821.
  7. Senum SR, Li YSM, Benson KA, Joli G, Olinger E, Lavu S, Madsen CD, Gregory AV, Neatu R, Kline TL, Audrézet MP, Outeda P, Nau CB, Meijer E, Ali H, Steinman TI, Mrug M, Phelan PJ, Watnick TJ, Peters DJM, Ong ACM, Conlon PJ, Perrone RD, Cornec-Le Gall E, Hogan MC, Torres VE, Sayer JA; Genomics England Research Consortium, the HALT PKD, CRISP, DIPAK, ADPKD Modifier, and TAME PKD studies; Harris PC. Monoallelic IFT140 pathogenic variants are an important cause of the autosomal dominant polycystic kidney-spectrum phenotype. Am J Hum Genet. 2022 Jan 6;109(1):136-156. doi: 10.1016/j.ajhg.2021.11.016. Epub 2021 Dec 9. PMID: 34890546; PMCID: PMC8764120.
  8. Yanda MK, Cebotaru L. VX-809 mitigates disease in a mouse model of autosomal dominant polycystic kidney disease bearing the R3277C human mutation. FASEB J. 2021 Nov;35(11):e21987. doi: 10.1096/fj.202101315R. PMID: 34662459; PMCID: PMC9062831.
  9. Yao Q, Outeda P, Xu H, Walker R, Basquin D, Qian F, Cebotaru L, Watnick T, Cebotaru V. Polycystin-1 dependent regulation of polycystin-2 via GRP94, a member of HSP90 family that resides in the endoplasmic reticulum. FASEB J. 2021 Oct;35(10):e21865. doi: 10.1096/fj.202100325RR. PMID: 34486178; PMCID: PMC8477617.
  10. Yanda MK, Tomar V, Cebotaru L. Therapeutic Potential for CFTR Correctors in Autosomal Recessive Polycystic Kidney Disease. Cell Mol Gastroenterol Hepatol. 2021;12(5):1517-1529. doi: 10.1016/j.jcmgh.2021.07.012. Epub 2021 Jul 27. PMID: 34329764; PMCID: PMC8529398.
  11. Hallows KR, Althouse AD, Li H, Saitta B, Abebe KZ, Bae KT, Miskulin DC, Perrone RD, Seliger SL, Watnick TJ. Association of Baseline Urinary Metabolic Biomarkers with ADPKD Severity in TAME-PKD Clinical Trial Participants. Kidney360. 2021 May;2(5):795-808. doi: 10.34067/KID.0005962020. PMID: 34316721; PMCID: PMC8312696.
  12. Perrone RD, Abebe KZ, Watnick TJ, Althouse AD, Hallows KR, Lalama CM, Miskulin DC, Seliger SL, Tao C, Harris PC, Bae KT. Primary results of the randomized trial of metformin administration in polycystic kidney disease (TAME PKD). Kidney Int. 2021 Sep;100(3):684-696. doi: 10.1016/j.kint.2021.06.013. Epub 2021 Jun 27. PMID: 34186056; PMCID: PMC8801184.
  13. Cordido A, Nuñez-Gonzalez L, Martinez-Moreno JM, Lamas-Gonzalez O, Rodriguez-Osorio L, Perez-Gomez MV, Martin-Sanchez D, Outeda P, Chiaravalli M, Watnick T, Boletta A, Diaz C, Carracedo A, Sanz AB, Ortiz A, Garcia-Gonzalez MA. TWEAK Signaling Pathway Blockade Slows Cyst Growth and Disease Progression in Autosomal Dominant Polycystic Kidney Disease. J Am Soc Nephrol. 2021 Aug;32(8):1913-1932. doi: 10.1681/ASN.2020071094. Epub 2021 Jun 21. PMID: 34155062; PMCID: PMC8455272.
  14. Seliger SL, Watnick T, Althouse AD, Perrone RD, Abebe KZ, Hallows KR, Miskulin DC, Bae KT. Baseline Characteristics and Patient-Reported Outcomes of ADPKD Patients in the Multicenter TAME-PKD Clinical Trial. Kidney360. 2020 Dec 31;1(12):1363-1372. doi: 10.34067/KID.0004002020. PMID: 33768205; PMCID: PMC7990324.
  15. Li W, Liang J, Outeda P, Turner S, Wakimoto BT, Watnick T. A genetic screen in Drosophila reveals an unexpected role for the KIP1 ubiquitination-promoting complex in male fertility. PLoS Genet. 2020 Dec 30;16(12):e1009217. doi: 10.1371/journal.pgen.1009217. PMID: 33378371; PMCID: PMC7802972.
  16. Cho Y, Tong A, Craig JC, Mustafa RA, Chapman A, Perrone RD, Ahn C, Fowler K, Torres V, Gansevoort RT, Ong ACM, Coolican H, Tze-Wah Kao J, Harris T, Gutman T, Shen JI, Viecelli AK, Johnson DW, Au E, El-Damanawi R, Logeman C, Ju A, Manera KE, Chonchol M, Odland D, Baron D, Pei Y, Sautenet B, Rastogi A, Sharma A, Rangan G; SONG-PKD Workshop Investigators. Establishing a Core Outcome Set for Autosomal Dominant Polycystic Kidney Disease: Report of the Standardized Outcomes in Nephrology-Polycystic Kidney Disease (SONG-PKD) Consensus Workshop. Am J Kidney Dis. 2021 Feb;77(2):255-263. doi: 10.1053/j.ajkd.2020.05.024. Epub 2020 Aug 6. PMID: 32771648.
  17. Dixon EE, Maxim DS, Halperin Kuhns VL, Lane-Harris AC, Outeda P, Ewald AJ, Watnick TJ, Welling PA, Woodward OM. GDNF drives rapid tubule morphogenesis in a novel 3D in vitro model for ADPKD. J Cell Sci. 2020 Jul 16;133(14):jcs249557. doi: 10.1242/jcs.249557. PMID: 32513820; PMCID: PMC7375472.
  18. Chen H, Watnick T, Hong SN, Daly B, Li Y, Seliger SL. Left ventricular hypertrophy in a contemporary cohort of autosomal dominant polycystic kidney disease patients. BMC Nephrol. 2019 Oct 25;20(1):386. doi: 10.1186/s12882-019-1555-z. PMID: 31653199; PMCID: PMC6815023.
  19. Wang K, Zelnick LR, Chen Y, Hoofnagle AN, Watnick T, Seliger S, Kestenbaum B. Alterations of Proximal Tubular Secretion in Autosomal Dominant Polycystic Kidney Disease. Clin J Am Soc Nephrol. 2020 Jan 7;15(1):80-88. doi: 10.2215/CJN.05610519. Epub 2019 Oct 18. PMID: 31628117; PMCID: PMC6946073.
  20. Yanda MK, Cha B, Cebotaru CV, Cebotaru L. Pharmacological reversal of renal cysts from secretion to absorption suggests a potential therapeutic strategy for managing autosomal dominant polycystic kidney disease. J Biol Chem. 2019 Nov 8;294(45):17090-17104. doi: 10.1074/jbc.RA119.010320. Epub 2019 Sep 30. PMID: 31570523; PMCID: PMC6851297.
  21. Lassen MCH, Qasim AN, Biering-Sørensen T, Reeh JLT, Watnick T, Seliger SL, Chen H, Sawan MA, Nguyen D, Li Y, Hong SN, Park M. Cardiac function assessed by myocardial deformation in adult polycystic kidney disease patients. BMC Nephrol. 2019 Aug 16;20(1):324. doi: 10.1186/s12882-019-1500-1. PMID: 31419965; PMCID: PMC6697983.
  22. Woodward OM, Watnick T. Molecular Structure of the PKD Protein Complex Finally Solved. Am J Kidney Dis. 2019 May;73(5):620-623. doi: 10.1053/j.ajkd.2018.12.022. Epub 2019 Jan 28. PMID: 30704879.
  23. Chebib FT, Perrone RD, Chapman AB, Dahl NK, Harris PC, Mrug M, Mustafa RA, Rastogi A, Watnick T, Yu ASL, Torres VE. A Practical Guide for Treatment of Rapidly Progressive ADPKD with Tolvaptan. J Am Soc Nephrol. 2018 Oct;29(10):2458-2470. doi: 10.1681/ASN.2018060590. Epub 2018 Sep 18. PMID: 30228150; PMCID: PMC6171265.
  24. Hofherr A, Seger C, Fitzpatrick F, Busch T, Michel E, Luan J, Osterried L, Linden F, Kramer-Zucker A, Wakimoto B, Schütze C, Wiedemann N, Artati A, Adamski J, Walz G, Kunji ERS, Montell C, Watnick T, Köttgen M. The mitochondrial transporter SLC25A25 links ciliary TRPP2 signaling and cellular metabolism. PLoS Biol. 2018 Aug 6;16(8):e2005651. doi: 10.1371/journal.pbio.2005651. PMID: 30080851; PMCID: PMC6095617.
  25. Cai J, Song X, Wang W, Watnick T, Pei Y, Qian F, Pan D. A RhoA-YAP-c-Myc signaling axis promotes the development of polycystic kidney disease. Genes Dev. 2018 Jun 1;32(11-12):781-793. doi: 10.1101/gad.315127.118. Epub 2018 Jun 11. PMID: 29891559; PMCID: PMC6049514.
  26. Seliger SL, Abebe KZ, Hallows KR, Miskulin DC, Perrone RD, Watnick T, Bae KT. A Randomized Clinical Trial of Metformin to Treat Autosomal Dominant Polycystic Kidney Disease. Am J Nephrol. 2018;47(5):352-360. doi: 10.1159/000488807. Epub 2018 May 18. PMID: 29779024; PMCID: PMC6010317.
  27. Liu Y, Pejchinovski M, Wang X, Fu X, Castelletti D, Watnick TJ, Arcaro A, Siwy J, Mullen W, Mischak H, Serra AL. Dual mTOR/PI3K inhibition limits PI3K-dependent pathways activated upon mTOR inhibition in autosomal dominant polycystic kidney disease. Sci Rep. 2018 Apr 3;8(1):5584. doi: 10.1038/s41598-018-22938-x. PMID: 29615724; PMCID: PMC5882886.
  28. Gulati A, Bae KT, Somlo S, Watnick T. Genomic Analysis to Avoid Misdiagnosis of Adults With Bilateral Renal Cysts. Ann Intern Med. 2018 Jul 17;169(2):130-131. doi: 10.7326/L17-0644. Epub 2018 Mar 27. PMID: 29582070; PMCID: PMC7196958.
  29. Lin CC, Kurashige M, Liu Y, Terabayashi T, Ishimoto Y, Wang T, Choudhary V, Hobbs R, Liu LK, Lee PH, Outeda P, Zhou F, Restifo NP, Watnick T, Kawano H, Horie S, Prinz W, Xu H, Menezes LF, Germino GG. A cleavage product of Polycystin-1 is a mitochondrial matrix protein that affects mitochondria morphology and function when heterologously expressed. Sci Rep. 2018 Feb 9;8(1):2743. doi: 10.1038/s41598-018-20856-6. PMID: 29426897; PMCID: PMC5807443.
  30. Besse W, Dong K, Choi J, Punia S, Fedeles SV, Choi M, Gallagher AR, Huang EB, Gulati A, Knight J, Mane S, Tahvanainen E, Tahvanainen P, Sanna-Cherchi S, Lifton RP, Watnick T, Pei YP, Torres VE, Somlo S. Isolated polycystic liver disease genes define effectors of polycystin-1 function. J Clin Invest. 2017 Sep 1;127(9):3558. doi: 10.1172/JCI96729. Epub 2017 Sep 1. Erratum for: J Clin Invest. 2017 May 1;127(5):1772-1785. PMID: 28862642; PMCID: PMC5669574.
  31. Kaimori JY, Lin CC, Outeda P, Garcia-Gonzalez MA, Menezes LF, Hartung EA, Li A, Wu G, Fujita H, Sato Y, Nakanuma Y, Yamamoto S, Ichimaru N, Takahara S, Isaka Y, Watnick T, Onuchic LF, Guay-Woodford LM, Germino GG. NEDD4-family E3 ligase dysfunction due to PKHD1/Pkhd1 defects suggests a mechanistic model for ARPKD pathobiology. Sci Rep. 2017 Aug 10;7(1):7733. doi: 10.1038/s41598-017-08284-4. PMID: 28798345; PMCID: PMC5552802.
  32. Outeda P, Menezes L, Hartung EA, Bridges S, Zhou F, Zhu X, Xu H, Huang Q, Yao Q, Qian F, Germino GG, Watnick T. A novel model of autosomal recessive polycystic kidney questions the role of the fibrocystin C-terminus in disease mechanism. Kidney Int. 2017 Nov;92(5):1130-1144. doi: 10.1016/j.kint.2017.04.027. Epub 2017 Jul 18. PMID: 28729032; PMCID: PMC6005173.
  33. Besse W, Dong K, Choi J, Punia S, Fedeles SV, Choi M, Gallagher AR, Huang EB, Gulati A, Knight J, Mane S, Tahvanainen E, Tahvanainen P, Sanna-Cherchi S, Lifton RP, Watnick T, Pei YP, Torres VE, Somlo S. Isolated polycystic liver disease genes define effectors of polycystin-1 function. J Clin Invest. 2017 May 1;127(5):1772-1785. doi: 10.1172/JCI90129. Epub 2017 Apr 4. Erratum in: J Clin Invest. 2017 Sep 1;127(9):3558. PMID: 28375157; PMCID: PMC5409105.
  34. Ta MH, Schwensen KG, Liuwantara D, Huso DL, Watnick T, Rangan GK. Constitutive renal Rel/nuclear factor-κB expression in Lewis polycystic kidney disease rats. World J Nephrol. 2016 Jul 6;5(4):339-57. doi: 10.5527/wjn.v5.i4.339. PMID: 27458563; PMCID: PMC4936341.
  35. Porath B, Gainullin VG, Cornec-Le Gall E, Dillinger EK, Heyer CM, Hopp K, Edwards ME, Madsen CD, Mauritz SR, Banks CJ, Baheti S, Reddy B, Herrero JI, Bañales JM, Hogan MC, Tasic V, Watnick TJ, Chapman AB, Vigneau C, Lavainne F, Audrézet MP, Ferec C, Le Meur Y, Torres VE; Genkyst Study Group, HALT Progression of Polycystic Kidney Disease Group; Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease; Harris PC. Mutations in GANAB, Encoding the Glucosidase IIα Subunit, Cause Autosomal-Dominant Polycystic Kidney and Liver Disease. Am J Hum Genet. 2016 Jun 2;98(6):1193-1207. doi: 10.1016/j.ajhg.2016.05.004. PMID: 27259053; PMCID: PMC4908191.
  36. Kim S, Nie H, Nesin V, Tran U, Outeda P, Bai CX, Keeling J, Maskey D, Watnick T, Wessely O, Tsiokas L. The polycystin complex mediates Wnt/Ca(2+) signalling. Nat Cell Biol. 2016 Jul;18(7):752-764. doi: 10.1038/ncb3363. Epub 2016 May 23. PMID: 27214281; PMCID: PMC4925210.
  37. Yanda MK, Liu Q, Cebotaru L. A potential strategy for reducing cysts in autosomal dominant polycystic kidney disease with a CFTR corrector. J Biol Chem. 2018 Jul 20;293(29):11513-11526. doi: 10.1074/jbc.RA118.001846. Epub 2018 Jun 6. PMID: 29875161; PMCID: PMC6065164.
  38. Wu X, Indzhykulian AA, Niksch PD, Webber RM, Garcia-Gonzalez M, Watnick T, Zhou J, Vollrath MA, Corey DP. Hair-Cell Mechanotransduction Persists in TRP Channel Knockout Mice. PLoS One. 2016 May 19;11(5):e0155577. doi: 10.1371/journal.pone.0155577. PMID: 27196058; PMCID: PMC4873267.
  39. Cebotaru L, Liu Q, Yanda MK, Boinot C, Outeda P, Huso DL, Watnick T, Guggino WB, Cebotaru V. Inhibition of histone deacetylase 6 activity reduces cyst growth in polycystic kidney disease. Kidney Int. 2016 Jul;90(1):90-9. doi: 10.1016/j.kint.2016.01.026. Epub 2016 Mar 25. PMID: 27165822; PMCID: PMC4912414.
  40. de Lemos Barbosa CM, Souza-Menezes J, Amaral AG, Onuchic LF, Cebotaru L, Guggino WB, Morales MM. Regulation of CFTR Expression and Arginine Vasopressin Activity Are Dependent on Polycystin-1 in Kidney-Derived Cells. Cell Physiol Biochem. 2016;38(1):28-39. doi: 10.1159/000438606. Epub 2016 Jan 8. PMID: 26741910.
  41. Hofherr A, Wagner CJ, Watnick T, Köttgen M. Targeted rescue of a polycystic kidney disease mutation by lysosomal inhibition. Kidney Int. 2016 Apr;89(4):949-55. doi: 10.1016/j.kint.2015.11.015. Epub 2016 Jan 6. PMID: 26924047; PMCID: PMC4801696.
  42. Perrone RD, Malek AM, Watnick T. Vascular complications in autosomal dominant polycystic kidney disease. Nat Rev Nephrol. 2015 Oct;11(10):589-98. doi: 10.1038/nrneph.2015.128. Epub 2015 Aug 11. PMID: 26260542; PMCID: PMC4904833.
  43. Chapman AB, Devuyst O, Eckardt KU, Gansevoort RT, Harris T, Horie S, Kasiske BL, Odland D, Pei Y, Perrone RD, Pirson Y, Schrier RW, Torra R, Torres VE, Watnick T, Wheeler DC; Conference Participants. Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2015 Jul;88(1):17-27. doi: 10.1038/ki.2015.59. Epub 2015 Mar 18. PMID: 25786098; PMCID: PMC4913350.
  44. Kim H, Xu H, Yao Q, Li W, Huang Q, Outeda P, Cebotaru V, Chiaravalli M, Boletta A, Piontek K, Germino GG, Weinman EJ, Watnick T, Qian F. Ciliary membrane proteins traffic through the Golgi via a Rabep1/GGA1/Arl3-dependent mechanism. Nat Commun. 2014 Nov 18;5:5482. doi: 10.1038/ncomms6482. PMID: 25405894; PMCID: PMC4237283.
  45. Tan M, Wettersten HI, Chu K, Huso DL, Watnick T, Friedlander S, Landesman Y, Weiss RH. Novel inhibitors of nuclear transport cause cell cycle arrest and decrease cyst growth in ADPKD associated with decreased CDK4 levels. Am J Physiol Renal Physiol. 2014 Dec 1;307(11):F1179-86. doi: 10.1152/ajprenal.00406.2014. Epub 2014 Sep 18. PMID: 25234309; PMCID: PMC4254973.
  46. Outeda P, Huso DL, Fisher SA, Halushka MK, Kim H, Qian F, Germino GG, Watnick T. Polycystin signaling is required for directed endothelial cell migration and lymphatic development. Cell Rep. 2014 May 8;7(3):634-44. doi: 10.1016/j.celrep.2014.03.064. Epub 2014 Apr 24. PMID: 24767998; PMCID: PMC4040350.
  47. Fonseca JM, Bastos AP, Amaral AG, Sousa MF, Souza LE, Malheiros DM, Piontek K, Irigoyen MC, Watnick TJ, Onuchic LF. Renal cyst growth is the main determinant for hypertension and concentrating deficit in Pkd1-deficient mice. Kidney Int. 2014 May;85(5):1137-50. doi: 10.1038/ki.2013.501. Epub 2014 Jan 15. PMID: 24429399; PMCID: PMC4510986.
  48. Liu D, Wang CJ, Judge DP, Halushka MK, Ni J, Habashi JP, Moslehi J, Bedja D, Gabrielson KL, Xu H, Qian F, Huso D, Dietz HC, Germino GG, Watnick T. A Pkd1-Fbn1 genetic interaction implicates TGF-β signaling in the pathogenesis of vascular complications in autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2014 Jan;25(1):81-91. doi: 10.1681/ASN.2012050486. Epub 2013 Sep 26. PMID: 24071006; PMCID: PMC3871766.
  49. Watnick TJ, Germino GG. Polycystic kidney disease: Polycystin-1 and polycystin-2--it's complicated. Nat Rev Nephrol. 2013 May;9(5):249-50. doi: 10.1038/nrneph.2013.73. Epub 2013 Apr 9. PMID: 23567275.
  50. Rowe I, Chiaravalli M, Mannella V, Ulisse V, Quilici G, Song X, Xu H, Pema M, Mari S, Qian F, Pei Y, Musco G, and Boletta A. Defective Glucose Metabolism in Polycystic Kidney Disease Identifies A Novel Therapeutic Paradigm. Nat Med.19:488-93, 2013.
  51. Kwon M, Pavlov TS, Nozu K, Rasmussen S, Ilatovskaya DV, Lerch-Gaggl A, North LM, Kim H, Qian F, Sweeney, WE Jr. Avner ED, Blumer JB, Staruschenko A, Park F. G protein signaling modulator 1 deficiency accelerates cystic disease in an orthologous mouse model of ADPKD. Proc Natl Acad Sci U S A, 109: 21462-7, 2012.
  52. Pei Y, Lan Z, Wang K, Garcia-Gonzalez M, He N, Dicks E, Parfrey P, Germino G, Watnick T. A Missense Mutation in PKD1attenuates the severity of Renal Disease. Kidney Int. 81: 412-7, 2012.
  53. Foy RL, Chitalia VC, Panchenko MV, Zeng L, Lopez D, Lee JW, Rana SV, Boletta A, Qian F, Tsiokas L, Piontek KB, Germino GG, Zhou MI, Cohen HT. Polycystin-1 regulates the stability and ubiquitination of transcription factor Jade-1. Hum Mol Genet. 21: 5456-71,2012.