Skip to main content

Factors predicting decline in renal function and kidney volume growth in autosomal dominant polycystic kidney disease: a prospective cohort study (Japanese Polycystic Kidney Disease registry: J-PKD)

Clinical and Experimental Nephrology volume 25, pages 970–980 (2021)Cite this article

Abstract

Background

Factors affecting decline in renal function and cyst growth in patients with autosomal polycystic kidney disease (ADPKD) are not fully described, particularly in Japan.

Methods

This was the first multi-facility, prospective, observational cohort study conducted in ADPKD patients at 14 centers in Japan. Patients in the J-PKD registry were assessed from December 2009 to June 2012 (follow-up until June 2017). Patients’ data including estimated glomerular filtration rate (eGFR) and total kidney volume (TKV) were assessed initially and a maximum of five times annually. Contributing factors to eGFR decline and TKV growth were identified using multiple linear regression analysis.

Results

Of the 340 patients in the J-PKD registry, data analysis was performed for 192 patients in whom serial changes for both eGFR and TKV were obtained. eGFR slope, eGFR change, and TKV change values were as follows: − 2.7 (− 4.2 to − 1.5) (ml/min/1.73 m2/year), − 5.0 (− 9.6 to − 2.3) (%/year), and 4.78 (0.86–8.22) (%/year), respectively. Lower high-density lipoprotein (HDL) cholesterol was an independent predictor of eGFR decline, using both eGFR slope and change (P = 0.04, P = 0.02, respectively), whereas lower hemoglobin and higher uric acid were significantly associated with greater eGFR change only (P = 0.02, P = 0.002, respectively). Younger age and higher fasting blood sugar were independent predictors of greater TKV change (P = 0.01, P = 0.02, respectively).

Conclusions

This real-world study in Japan identified risk factors for renal function decline in ADPKD patients. These included lower HDL cholesterol, lower hemoglobin and higher uric acid for eGFR decline, and youth and higher blood sugar levels for TKV growth.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2

References

  1. Cornec-Le Gall E, Alam A, Perrone RD. Autosomal dominant polycystic kidney disease. Lancet. 2019;393:919–35.

    Article  PubMed  Google Scholar 

  2. Nitta K, Masakane I, Hanafusa N, Taniguchi M, Hasegawa T, Nakai S, et al. Annual dialysis data report 2017, JSDT renal data registry. Ren Replace Ther. 2019;5:53.

    Article  Google Scholar 

  3. Gabow PA, Johnson AM, Kaehny WD, Kimberling WJ, Lezotte DC, Duley IT, et al. Factors affecting the progression of renal disease in autosomal-dominant polycystic kidney disease. Kidney Int. 1992;41:1311–9.

    Article  CAS  PubMed  Google Scholar 

  4. Johnson AM, Gabow PA. Identification of patients with autosomal dominant polycystic kidney disease at highest risk for end-stage renal disease. J Am Soc Nephrol. 1997;8:1560–7.

    Article  CAS  PubMed  Google Scholar 

  5. 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;39:1127–34.

    Article  PubMed  Google Scholar 

  6. Torres VE, King BF, Chapman AB, Brummer ME, Bae KT, Glockner JF, et al. Magnetic resonance measurements of renal blood flow and disease progression in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2007;2:112–20.

    Article  PubMed  Google Scholar 

  7. Torres VE, Grantham JJ, Chapman AB, Mrug M, Bae KT, King BF Jr, et al. Potentially modifiable factors affecting the progression of autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2011;6:640–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tokiwa S, Muto S, China T, Horie S. The relationship between renal volume and renal function in autosomal dominant polycystic kidney disease. Clin Exp Nephrol. 2011;15:539–45.

    Article  CAS  PubMed  Google Scholar 

  9. Higashihara E, Horie S, Muto S, Mochizuki T, Nishio S, Nutahara K. Renal disease progression in autosomal dominant polycystic kidney disease. Clin Exp Nephrol. 2012;16:622–8.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Higashihara E, Nutahara K, Kojima M, Tamakoshi A, Yoshiyuki O, Sakai H, et al. Prevalence and renal prognosis of diagnosed autosomal dominant polycystic kidney disease in Japan. Nephron. 1998;80:421–7.

    Article  CAS  PubMed  Google Scholar 

  11. Nowak KL, You Z, Gitomer B, Brosnahan G, Torres VE, Chapman AB, et al. Overweight and obesity are predictors of progression in early autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2018;29:571–8.

    Article  CAS  PubMed  Google Scholar 

  12. Coresh J, Turin TC, Matsushita K, Sang Y, Ballew SH, Appel LJ, et al. Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality. JAMA. 2014;311:2518–31.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Yu ASL, Shen C, Landsittel DP, Harris PC, Torres VE, Mrug M, et al. Baseline total kidney volume and the rate of kidney growth are associated with chronic kidney disease progression in Autosomal Dominant Polycystic Kidney Disease. Kidney Int. 2018;93:691–9.

    Article  PubMed  Google Scholar 

  14. Perrone RD, Mouksassi MS, Romero K, Czerwiec FS, Chapman AB, Gitomer BY, et al. Total kidney volume is a prognostic biomarker of renal function decline and progression to end-stage renal disease in patients with autosomal dominant polycystic kidney disease. Kidney Int Rep. 2017;2:442–50.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Grantham JJ, Torres VE, Chapman AB, Guay-Woodford LM, Bae KT, King BF Jr, et al. Volume progression in polycystic kidney disease. N Engl J Med. 2006;354:2122–30.

    Article  CAS  PubMed  Google Scholar 

  16. Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Grantham JJ, Higashihara E, et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012;367:2407–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Klahr S, Breyer JA, Beck GJ, Dennis VW, Hartman JA, Roth D, et al. Dietary protein restriction, blood pressure control, and the progression of polycystic kidney disease. Modification of Diet in Renal Disease Study Group. J Am Soc Nephrol. 1995;5:2037–47.

    Article  CAS  PubMed  Google Scholar 

  18. Nutahara K, Higashihara E, Horie S, Kamura K, Tsuchiya K, Mochizuki T, et al. Calcium channel blocker versus angiotensin II receptor blocker in autosomal dominant polycystic kidney disease. Nephron Clin Pract. 2005;99:c18-23.

    Article  CAS  PubMed  Google Scholar 

  19. 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;4:820–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sarnak MJ, Greene T, Wang X, Beck G, Kusek JW, Collins AJ, et al. The effect of a lower target blood pressure on the progression of kidney disease: long-term follow-up of the modification of diet in renal disease study. Ann Intern Med. 2005;142:342–51.

    Article  PubMed  Google Scholar 

  21. de Boer IH, Katz R, Fried LF, Ix JH, Luchsinger J, Sarnak MJ, et al. Obesity and change in estimated GFR among older adults. Am J Kidney Dis. 2009;54:1043–51.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Siu YP, Leung KT, Tong MK, Kwan TH. Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis. 2006;47:51–9.

    Article  CAS  Google Scholar 

  23. Bash LD, Erlinger TP, Coresh J, Marsh-Manzi J, Folsom AR, Astor BC. Inflammation, hemostasis, and the risk of kidney function decline in the Atherosclerosis Risk in Communities (ARIC) Study. Am J Kidney Dis. 2009;53:596–605.

    Article  PubMed  Google Scholar 

  24. Lanktree MB, Thériault S, Walsh M, Paré G. HDL cholesterol, LDL cholesterol, and triglycerides as risk factors for CKD: a Mendelian randomization study. Am J Kidney Dis. 2018;71:166–72.

    Article  CAS  PubMed  Google Scholar 

  25. Kronenberg F. HDL in CKD—the devil is in the detail. J Am Soc Nephrol. 2018;29:1356–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Chronic Kidney Disease Prognosis Consortium, Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet. 2010;375:2073–81.

    Article  Google Scholar 

  27. Hallan SI, Matsushita K, Sang Y, Mahmoodi BK, Black C, Ishani A, et al. Age and association of kidney measures with mortality and end-stage renal disease. JAMA. 2012;308:2349–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Irazabal MV, Rangel LJ, Bergstralh EJ, Osborn SL, Harmon AJ, Sundsbak JL, et al. Imaging classification of autosomal dominant polycystic kidney disease: a simple model for selecting patients for clinical trials. J Am Soc Nephrol. 2015;26:160–72.

    Article  CAS  PubMed  Google Scholar 

  29. Tsubakihara Y, Akizawa T, Iwasaki M, Shimazaki R. High hemoglobin levels maintained by an erythropoiesis-stimulating agent improve renal survival in patients with severe renal impairment. Ther Apher Dial. 2015;19:457–65.

    Article  CAS  PubMed  Google Scholar 

  30. Palmer SC, Navaneethan SD, Craig JC, Johnson DW, Tonelli M, Garg AX, et al. Meta-analysis: erythropoiesis-stimulating agents in patients with chronic kidney disease. Ann Intern Med. 2010;153:23–33.

    Article  PubMed  Google Scholar 

  31. Ushio Y, Kataoka H, Sato MA, Manabe S, Watanabe S, Akihisa T, et al. Association between anemia and renal prognosis in autosomal dominant polycystic kidney disease: a retrospective study. Clin Exp Nephrol. 2020;24:500–8.

    Article  CAS  PubMed  Google Scholar 

  32. Kim H, Koh J, Park SK, Kim YH, Kim Y, Ahn C, et al. Baseline characteristics of the autosomal-dominant polycystic kidney disease sub-cohort of the Korean cohort study for outcomes in patients with chronic kidney disease. Nephrology (Carlton). 2019;24:422–9.

    Article  Google Scholar 

  33. Kimura K, Hosoya T, Uchida S, Inaba M, Makino H, Maruyama S, et al. Febuxostat therapy for patients with stage 3 CKD and asymptomatic hyperuricemia: a randomized trial. Am J Kidney Dis. 2018;72:798–810.

    Article  CAS  PubMed  Google Scholar 

  34. Rowe I, Chiaravalli M, Mannella V, Ulisse V, Quilici G, Pema M, et al. Defective glucose metabolism in polycystic kidney disease identifies a new therapeutic strategy. Nat Med. 2013;19:488–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Chiaravalli M, Rowe I, Mannella V, Quilici G, Canu T, Bianchi V, et al. 2-Deoxy-d-glucose ameliorates PKD progression. J Am Soc Nephrol. 2016;27:1958–69.

    Article  CAS  PubMed  Google Scholar 

  36. Liu C, Zhang Y, Yuan L, Fu L, Mei C. Rosiglitazone inhibits insulin-like growth factor-1-induced polycystic kidney disease cell growth and p70S6 kinase activation. Mol Med Rep. 2013;8:861–4.

    Article  PubMed  Google Scholar 

  37. Takiar V, Nishio S, Seo-Mayer P, King JD Jr, Li H, Zhang L, et al. Activating AMP-activated protein kinase (AMPK) slows renal cystogenesis. Proc Natl Acad Sci USA. 2011;108:2462–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Mao Z, Xie G, Ong AC. Metabolic abnormalities in autosomal dominant polycystic kidney disease. Nephrol Dial Transplant. 2015;30:197–203.

    Article  CAS  PubMed  Google Scholar 

  39. Torres VE, Abebe KZ, Schrier RW, Perrone RD, Chapman AB, Yu AS, et al. Dietary salt restriction is beneficial to the management of autosomal dominant polycystic kidney disease. Kidney Int. 2017;91:493–500.

    Article  CAS  PubMed  Google Scholar 

  40. Harris PC, Bae KT, Rossetti S, Torres VE, Grantham JJ, Chapman AB, et al. Cyst number but not the rate of cystic growth is associated with the mutated gene in autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2006;17:3013–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported in part by a Grant-in-Aid for Intractable Renal Diseases Research, Research on rare and intractable diseases, Health and Labour Sciences Research Grants from the Ministry of Health, Labour and Welfare of Japan. Medical writing support, in accordance with GPP guidelines, was provided by Mediwrite Asia Inc Pte Ltd and included editorial and proofreading services. We thank all the participants in this registry and the clinicians who referred their patients and contributed to the clinical data acquisition.

Author information

Authors and Affiliations

  1. Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

    Kiyotaka Uchiyama

  2. Clinical Research Division for Polycystic Kidney Disease, Department of Nephrology, Tokyo Women’s Medical University, Tokyo, Japan

    Toshio Mochizuki, Hiroshi Kataoka & Michihiro Mitobe

  3. Department of Nephrology, Tokyo Women’s Medical University, Tokyo, Japan

    Toshio Mochizuki, Hiroshi Kataoka & Michihiro Mitobe

  4. Intelligent Systems Laboratory, SECOM CO., LTD., Mitaka, Tokyo, Japan

    Yosuke Shimada

  5. Department of Medical Electronic Intelligence Management, Juntendo University Graduate School, Bunkyo, Tokyo, Japan

    Yosuke Shimada

  6. Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Hokkaido, Japan

    Saori Nishio

  7. Department of Blood Purification, Tokyo Woman’s Medical University, Tokyo, Japan

    Ken Tsuchiya

  8. Department of General Internal Medicine, Jikei University School of Medicine, Tokyo, Japan

    Kazushige Hanaoka

  9. Department of Nephrology, Toranomon Hospital, Tokyo, Japan

    Yoshifumi Ubara, Tatsuya Suwabe & Akinari Sekine

  10. Department of Urology, Kyorin University School of Medicine, Tokyo, Japan

    Kikuo Nutahara

  11. Department of Integrated Therapy for Chronic Kidney Disease, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Kazuhiko Tsuruya

  12. Department of Nephrology, Nara Medical University, Kashihara, Nara, Japan

    Kazuhiko Tsuruya

  13. Department of Nephrology, Osaka City University Graduate School of Medicine, Osaka, Japan

    Eiji Ishimura

  14. Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan

    Shinya Nakatani

  15. Department of Cardiorenal and Cerebrovascular Medicine, Kagawa University, Kagawa, Japan

    Tadashi Sofue

  16. Department of Nephrology, Shizuoka General Hospital, Shizuoka, Japan

    Satoshi Tanaka

  17. Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medicine and Dental Science, Niigata, Japan

    Ichiei Narita

  18. Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Shoichi Maruyama

  19. Department of Advanced Informatics for Genetic Disease, Juntendo University, Tokyo, Japan

    Shigeo Horie & Satoru Muto

  20. Department of Urology, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Shigeo Horie & Satoru Muto

Authors
  1. Kiyotaka Uchiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Toshio Mochizuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yosuke Shimada
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Saori Nishio
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroshi Kataoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michihiro Mitobe
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ken Tsuchiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kazushige Hanaoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yoshifumi Ubara
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tatsuya Suwabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Akinari Sekine
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Kikuo Nutahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Kazuhiko Tsuruya
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Eiji Ishimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Shinya Nakatani
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Tadashi Sofue
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Satoshi Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Ichiei Narita
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Shoichi Maruyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Shigeo Horie
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Satoru Muto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Satoru Muto.

Ethics declarations

Conflict of interest

Toshio Mochizuki received travel fees and honoraria for lectures from Otsuka Pharmaceutical Co. Toshio Mochizuki and Hiroshi Kataoka belong to an endowed department sponsored by Otsuka Pharmaceutical Co, Chugai Pharmaceutical Co, Kyowa Hakko Kirin Co, and JMS Co. Satoru Muto received travel fees and honoraria for lectures from Otsuka Pharmaceutical Co., Ltd. Shigeo Horie and Satoru Muto belong to an endowed department sponsored by Otsuka Pharmaceutical Co., Ltd., JENESIS Co., Ltd., Nippon Shinyaku Co., Ltd., Shokubunka Co., Ltd., and Rohto Pharmaceutical Co., Ltd..

Ethical approval

The study was conducted in accordance with the guidelines written in the Declaration of Helsinki. Ethics committees from each of the 14 institutions approved the study, and the Japanese Society of Nephrology approved the study (No. 6).

Informed consent

Written informed consent was obtained from all individual participants included in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 26 KB)

About this article

Verify currency and authenticity via CrossMark

Cite this article

Uchiyama, K., Mochizuki, T., Shimada, Y. et al. Factors predicting decline in renal function and kidney volume growth in autosomal dominant polycystic kidney disease: a prospective cohort study (Japanese Polycystic Kidney Disease registry: J-PKD). Clin Exp Nephrol 25, 970–980 (2021). https://doi.org/10.1007/s10157-021-02068-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10157-021-02068-x

Keywords

  • Autosomal dominant polycystic kidney disease
  • Renal function
  • Total kidney volume
  • J-PKD
  • High-density lipoprotein cholesterol