Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

ONCONEPHROLOGY

The adjuvant treatment of kidney cancer: a multidisciplinary outlook

Nature Reviews Nephrology volume 15, pages 423–433 (2019)Cite this article

Subjects

Abstract

Approximately 70% of cases of kidney cancer are localized or locally advanced at diagnosis. Among patients who undergo surgery for these cancers, 30–35% will eventually develop potentially fatal metachronous distant metastases. Effective adjuvant treatments are urgently needed to reduce the risk of recurrence of kidney cancer and of dying of metastatic disease. To date, almost all of the tested adjuvant agents have failed to demonstrate any benefit. Only two trials of an autologous renal tumour cell vaccine and of the vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor sunitinib have shown positive results, but these have been criticized for methodological reasons and conflicting data, respectively. The results of two additional trials of targeted agents as adjuvant therapies have not yet been published. Novel immune checkpoint inhibitors are promising approaches to adjuvant therapy in kidney cancer, and a number of trials are now underway. An important component of the management of patients with kidney cancer, particularly those who undergo radical resection for localized renal cell carcinoma, is the preservation of kidney function to reduce morbidity and mortality. The optimal management of these patients therefore requires a multidisciplinary approach involving nephrologists, oncologists, urologists and pathologists.

Key points

  • Effective adjuvant treatments for kidney cancer are needed to reduce the risk of recurrence and of dying of metastatic disease.

  • To date, almost all of the tested adjuvant agents have failed to demonstrate any benefit in clinical trials; the two positive trials were criticized for methodological reasons and conflicting results.

  • Only one drug — sunitinib — has been approved for the adjuvant treatment of kidney cancer in the USA; however, this drug has not been approved as an adjuvant therapy in Europe.

  • Positive results with immune checkpoint inhibitors in metastatic renal cell carcinoma (RCC) suggest that these agents might also be effective adjuvant therapies; trials of these agents are underway.

  • Preservation of kidney function in patients with RCC is important to reduce morbidity; therefore, multidisciplinary management should be mandatory for almost all patients with radically resected kidney cancer.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Mechanisms of action of targeted therapies in renal cell carcinoma.
Fig. 2: Mechanisms of action of immune checkpoint inhibitors in renal cell carcinoma.
Fig. 3: The role of nephrologists in the management of resected renal cell carcinoma.

Similar content being viewed by others

References

  1. Ferlay, J. et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 136, E359–E386 (2015).

    Article  CAS  Google Scholar 

  2. American Cancer Society. Key statistics about kidney cancer. cancer.org https://www.cancer.org/cancer/kidney-cancer/about/key-statistics.html (updated 4 Jan 2018).

  3. Lam, J. S., Leppert, J. T., Figlin, R. A. & Belldegrun, A. S. Surveillance following radical or partial nephrectomy for renal cell carcinoma. Curr. Urol. Rep. 6, 7–18 (2005).

    Article  Google Scholar 

  4. Gupta, K., Miller, J. D., Li, J. Z., Russel, M. W. & Charbonneau, C. Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review. Cancer Treat. Rev. 34, 193–205 (2008).

    Article  Google Scholar 

  5. American Cancer Society. Survival rates for kidney cancer. cancer.org https://www.cancer.org/cancer/kidney-cancer/detection-diagnosis-staging/survival-rates.html (updated 31 Jan 2019).

  6. Massari, F. et al. Adjuvant therapy in renal cell carcinoma. Cancer Treat. Rev. 60, 152–157 (2017).

    Article  CAS  Google Scholar 

  7. Porta, C., Chiellino, S., Ferrari, A., Mariucci, S. & Liguigli, W. Pharmacotherapy for treating metastatic clear cell renal cell carcinoma. Expert Opin. Pharmacother. 18, 205–216 (2017).

    Article  CAS  Google Scholar 

  8. Zisman, A. et al. Improved prognostication of renal cell carcinoma using an integrated staging system. J. Clin. Oncol. 19, 1649–1657 (2001).

    Article  CAS  Google Scholar 

  9. Leibovich, B. C. et al. Prediction of progression after radical nephrectomy for patients with clear cell renal cell carcinoma: a stratification tool for prospective clinical trials. Cancer 97, 1663–1671 (2003).

    Article  Google Scholar 

  10. Tan, M. H. et al. Comparison of the UCLA Integrated Staging System and the Leibovich score in survival prediction for patients with nonmetastatic clear cell renal cell carcinoma. Urology 75, 1365–1370 (2010).

    Article  Google Scholar 

  11. Frank, I. et al. An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: the SSIGN score. J. Urol. 168, 2395–2400 (2002).

    Article  Google Scholar 

  12. Karakiewicz, P. I. et al. Multi-institutional validation of a new renal cancer-specific survival nomogram. J. Clin. Oncol. 25, 1316–1322 (2007).

    Article  Google Scholar 

  13. Kattan, M. W., Reuter, V., Motzer, R. J., Katz, J. & Russo, P. A postoperative prognostic nomogram for renal cell carcinoma. J Urol. 166, 63–67 (2001).

    Article  CAS  Google Scholar 

  14. Pal, S. K. & Haas, N. B. Adjuvant therapy for renal cell carcinoma: past, present, and future. Oncologist 19, 851–859 (2014).

    Article  CAS  Google Scholar 

  15. Brooks, S. A. et al. ClearCode34: a prognostic risk predictor for localized clear cell renal cell carcinoma. Eur. Urol. 66, 77–84 (2014).

    Article  CAS  Google Scholar 

  16. Brannon, A. R. et al. Molecular stratification of clear cell renal cell carcinoma by consensus clustering reveals distinct subtypes and survival patterns. Genes Cancer 1, 152–163 (2010).

    Article  CAS  Google Scholar 

  17. Rini, B. et al. A 16-gene assay to predict recurrence after surgery in localised renal cell carcinoma: development and validation studies. Lancet Oncol. 16, 676–685 (2015).

    Article  CAS  Google Scholar 

  18. Kapur, P. et al. Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell carcinoma: a retrospective analysis with independent validation. Lancet Oncol. 14, 159–167 (2013).

    Article  CAS  Google Scholar 

  19. Kjaer, M. et al. A randomized trial of postoperative radiotherapy versus observation in stage II and III renal adenocarcinoma. A study by the Copenhagen Renal Cancer Study Group. Scand. J. Urol. Nephrol. 21, 285–289 (1987).

    Article  CAS  Google Scholar 

  20. Pizzocaro, G. et al. Interferon adjuvant to radical nephrectomy in Robson stages II and III renal cell carcinoma: a multicentric randomized study. J. Clin. Oncol. 19, 425–431 (2001).

    Article  CAS  Google Scholar 

  21. Messing, E. M. et al. Phase III study of interferon alfa-NL as adjuvant treatment for resectable renal cell carcinoma: an Eastern Cooperative Oncology Group/Intergroup trial. J. Clin. Oncol. 21, 1214–1222 (2003).

    Article  CAS  Google Scholar 

  22. Clark, J. I. et al. Adjuvant high-dose bolus interleukin-2 for patients with high-risk renal cell carcinoma: a Cytokine Working Group randomized trial. J. Clin. Oncol. 21, 3133–3140 (2003).

    Article  CAS  Google Scholar 

  23. Atzpodien, J. et al. Adjuvant treatment with interleukin-2- and interferon-alpha2a-based chemoimmunotherapy in renal cell carcinoma post tumour nephrectomy: results of a prospectively randomised trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN). Br. J. Cancer 92, 843–846 (2005).

    Article  CAS  Google Scholar 

  24. Passalacqua, R. et al. Adjuvant low-dose Interleukin-2 (IL-2) plus Interferon-α (IFN-α) in operable renal cell carcinoma (RCC): a phase III, randomized, multicentre trial of the Italian Oncology Group for Clinical Research (GOIRC). J. Immunother. 37, 440–447 (2014).

    Article  CAS  Google Scholar 

  25. Aitchison, M. et al. Adjuvant 5-flurouracil, alpha-interferon and interleukin-2 versus observation in patients at high risk of recurrence after nephrectomy for renal cell carcinoma: results of a phase III randomised European Organisation for Research and Treatment of Cancer (Genito-Urinary Cancers Group)/National Cancer Research Institute trial. Eur. J. Cancer 50, 70–77 (2014).

    Article  CAS  Google Scholar 

  26. Adler, A. et al. Active specific immunotherapy of renal cell carcinoma patients: a prospective randomized study of hormono-immuno-versus hormonotherapy. Preliminary report of immunological and clinical aspects. J. Biol. Response Mod. 6, 610–624 (1987).

    CAS  PubMed  Google Scholar 

  27. Galligioni, E. et al. Adjuvant immunotherapy treatment of renal carcinoma patients with autologous tumor cells and bacillus Calmette-Guèrin: five-year results of a prospective randomized study. Cancer 77, 2560–2566 (1996).

    Article  CAS  Google Scholar 

  28. Jocham, D. et al. Adjuvant autologous renal tumour cell vaccine and risk of tumour progression in patients with renal-cell carcinoma after radical nephrectomy: phase III, randomised controlled trial. Lancet 363, 594–599 (2004). This trial is the only formally positive study of adjuvant therapy in RCC; however, it has been heavily criticized.

    Article  CAS  Google Scholar 

  29. Wood, C. et al. An adjuvant autologous therapeutic vaccine (HSPPC-96; vitespen) versus observation alone for patients at high risk of recurrence after nephrectomy for renal cell carcinoma: a multicentre, open-label, randomised phase III trial. Lancet 372, 145–154 (2008).

    Article  CAS  Google Scholar 

  30. Pizzocaro, G. et al. Adjuvant medroxyprogesterone acetate to radical nephrectomy in renal cancer: 5-year results of a prospective randomized study. J. Urol. 138, 1379–1381 (1987).

    Article  CAS  Google Scholar 

  31. Naito, S. et al. Postoperative UFT adjuvant and the risk factors for recurrence in renal cell carcinoma: a long-term follow-up study. Kyushu University Urological Oncology Group. Int. J. Urol. 4, 8–12 (1997).

    Article  CAS  Google Scholar 

  32. Margulis, V. et al. Randomized trial of adjuvant thalidomide versus observation in patients with completely resected high-risk renal cell carcinoma. Urology 73, 337–341 (2009).

    Article  Google Scholar 

  33. Chamie, K. et al. Adjuvant weekly girentuximab following nephrectomy for high-risk renal cell carcinoma: the ARISER randomized clinical trial. JAMA Oncol. 3, 913–920 (2017).

    Article  Google Scholar 

  34. Supuran, C. T. Carbonic anhydrase inhibition and the management of hypoxic tumors. Metabolites 7, 48 (2017).

    Article  Google Scholar 

  35. Kramar, A. et al. Guidelines for the definition of time-to-event end points in renal cell cancer clinical trials: results of the DATECAN project. Ann. Oncol. 26, 2392–2398 (2015).

    CAS  PubMed  Google Scholar 

  36. Massari, F. et al. Adjuvant treatment for resected renal cell carcinoma: are all strategies equally negative? Potential implications for trial design with targeted agents. Clin. Genitourin. Cancer 11, 471–476 (2013).

    Article  Google Scholar 

  37. Gnarra, J. R. et al. Mutations of the VHL tumour suppressor gene in renal carcinoma. Nat. Genet. 7, 85–90 (1994).

    Article  CAS  Google Scholar 

  38. Shuin, T. et al. Frequent somatic mutations and loss of heterozygosity of the von Hippel-Lindau tumor suppressor gene in primary human renal cell carcinomas. Cancer Res. 54, 2852–2855 (1994).

    CAS  PubMed  Google Scholar 

  39. Herman, J. G. et al. Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc. Natl Acad. Sci. USA 91, 9700–9704 (1994).

    Article  CAS  Google Scholar 

  40. Gruber, M. & Simon, M. C. Hypoxia-inducible factors, hypoxia, and tumor angiogenesis. Curr. Opin. Hematol. 13, 169–174 (2006).

    Article  CAS  Google Scholar 

  41. Shen, C. & Kaelin, W. G. The VHL/HIF axis in clear cell renal carcinoma. Semin. Cancer Biol. 23, 18–25 (2013).

    Article  CAS  Google Scholar 

  42. Haas, N. B. et al. Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet 387, 2008–2016 (2016). This trial of a targeted agent as adjuvant therapy reports negative results.

    Article  CAS  Google Scholar 

  43. Ravaud, A. et al. Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy. N. Engl. J. Med. 375, 2246–2254 (2016). This adjuvant study of sunitinib in RCC is positive in terms of DFS (its primary end point) but not in terms of OS.

    Article  CAS  Google Scholar 

  44. Motzer, R. J. et al. Randomized phase III trial of adjuvant pazopanib versus placebo after nephrectomy in patients with localized or locally advanced renal cell carcinoma. J. Clin. Oncol. 35, 3916–3923 (2017). This trial of a targeted agent as adjuvant therapy also reports negative results.

    Article  CAS  Google Scholar 

  45. Gross-Goupil, M. et al. Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma: results from the phase III randomized ATLAS trial. Ann. Oncol. 29, 2371–2378 (2018).

    Article  CAS  Google Scholar 

  46. US National Library of Medicine. ClinicalTrials.gov https://www.clinicaltrials.gov/ct2/show/NCT00492258 (2013). This is the latest negative trial investigating a VEGFR TKI.

  47. U.S. Food and Drug Administration. FDA approves sunitinib malate for adjuvant treatment of renal cell carcinoma. FDA.gov https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm585686.htm (updated 16 Aug 2018).

  48. Haas, N. B. et al. Adjuvant treatment for high-risk clear cell renal cancer: updated results of a high-risk subset of the ASSURE randomized trial. JAMA Oncol. 3, 1249–1252 (2017).

    Article  Google Scholar 

  49. Sternberg, C. et al. Pazopanib exposure relationship with clinical efficacy and safety in the adjuvant treatment of advanced renal cell carcinoma. Clin. Cancer Res. 24, 3005–3013 (2018).

    Article  CAS  Google Scholar 

  50. Bex, A. et al. Updated European Association of Urology guidelines regarding adjuvant therapy for renal cell carcinoma. Eur. Urol. 71, 719–722 (2017).

    Article  Google Scholar 

  51. European Medicines Agency. Withdrawal assessment report: Sutent. ema.europa.eu https://www.ema.europa.eu/documents/withdrawal-report/withdrawal-assessment-report-sutent_en.pdf (2018).

  52. US National Library of Medicine. ClinicalTrials.gov https://www.clinicaltrials.gov/ct2/show/NCT01120249 (2018).

  53. Vasudev, N. S. & Reynolds, A. R. Anti-angiogenic therapy for cancer: current progress, unresolved questions and future directions. Angiogenesis 17, 471–494 (2014).

    Article  CAS  Google Scholar 

  54. Kim, B. J. et al. The role of targeted agents in the adjuvant treatment of colon cancer: a meta-analysis of randomized phase III studies and review. Oncotarget 8, 31112–31118 (2017).

    PubMed  PubMed Central  Google Scholar 

  55. Motzer, R. J. et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N. Engl. J. Med. 373, 1803–1813 (2015).

    Article  CAS  Google Scholar 

  56. Motzer, R. J. et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N. Engl. J. Med. 378, 1277–1290 (2018). This trial establishes a new standard of care for the first-line treatment of metastatic RCC.

    Article  CAS  Google Scholar 

  57. Motzer, R. J. et al. IMmotion151: a randomized phase III study of atezolizumab plus bevacizumab versus sunitinib in untreated metastatic Renal Cell Carcinoma (mRCC) [abstract]. J. Clin. Oncol. 36 (Suppl. 6), 578 (2018).

    Article  Google Scholar 

  58. Motzer, R. J. et al. JAVELIN Renal 101: a randomized, phase 3 study of avelumab+axitinib versus sunitinib as first-line treatment of advanced renal cell carcinoma (aRCC) [abstract]. Ann. Oncol. 29 (Suppl. 8), LBAA6_PR (2018).

    Google Scholar 

  59. US National Library of Medicine. ClinicalTrials.gov https://www.clinicaltrials.gov/ct2/show/NCT03055013 (2019).

  60. US National Library of Medicine. ClinicalTrials.gov https://www.clinicaltrials.gov/ct2/show/NCT03024996 (2019).

  61. US National Library of Medicine. ClinicalTrials.gov https://www.clinicaltrials.gov/ct2/show/NCT03142334 (2019).

  62. US National Library of Medicine. ClinicalTrials.gov https://www.clinicaltrials.gov/ct2/show/NCT03288532 (2018).

  63. US National Library of Medicine. ClinicalTrials.gov https://www.clinicaltrials.gov/ct2/show/NCT03138512 (2019).

  64. Liu, J. et al. Improved efficacy of neoadjuvant compared to adjuvant immunotherapy to eradicate metastatic disease. Cancer Discov. 6, 1382–1399 (2016).

    Article  CAS  Google Scholar 

  65. Hung, P. H. et al. Increased risk of end-stage renal disease in patients with renal cell carcinoma: a 12-year nationwide follow-up study. Medicine (Baltimore) 93, e52 (2014).

    Article  Google Scholar 

  66. Barlow, L. J., Korets, R., Laudano, M., Benson, M. & McKiernan, J. Predicting renal functional outcomes after surgery for renal cortical tumours: a multifactorial analysis. BJU Int. 106, 489–492 (2010).

    Article  Google Scholar 

  67. Jeon, H. G., Jeong, I. G., Lee, J. W., Lee, S. E. & Lee, E. Prognostic factors for chronic kidney disease after curative surgery in patients with small renal tumors. Urology 74, 1064–1068 (2009).

    Article  Google Scholar 

  68. Li, L. et al. Risk of chronic kidney disease after cancer nephrectomy. Nat. Rev. Nephrol. 10, 135–145 (2014).

    Article  Google Scholar 

  69. Cho, A. et al. Post-operative acute kidney injury in patients with renal cell carcinoma is a potent risk factor for new-onset chronic kidney disease after radical nephrectomy. Nephrol. Dial. Transplant. 26, 3496–3501 (2011).

    Article  Google Scholar 

  70. Lam, A. Q. & Humphreys, B. D. Onco-nephrology: AKI in the cancer patient. Clin. J. Am. Soc. Nephrol. 7, 1692–1700 (2012).

    Article  CAS  Google Scholar 

  71. Gallieni, M. et al. Acute kidney injury in cancer patients. Contrib. Nephrol. 13, 137–148 (2018).

    Article  Google Scholar 

  72. Cosmai, L. et al. Opening an onconephrology clinic: recommendations and basic requirements. Nephrol. Dial. Transplant. 33, 1503–1510 (2018). This paper discusses the requirements needed to run an onco-nephrology clinic as well as its field of interest.

    Article  Google Scholar 

  73. Taylor, A. T. Radionuclides in nephrourology, part 2: pitfalls and diagnostic applications. Nucl. J. Med. 55, 786–798 (2014).

    Article  CAS  Google Scholar 

  74. Srigley, J. R. et al. Protocol for the examination of specimens from patients with invasive carcinoma of renal tubular origin. Arch. Pathol. Lab. Med. 134, e25–e30 (2010).

    PubMed  Google Scholar 

  75. Algaba, F. et al. Handling and reporting of nephrectomy specimens for adult renal tumors: a survey by the European Network of Uropathology. J. Clin. Pathol. 65, 106–113 (2012).

    Article  Google Scholar 

  76. Gupta, S. et al. Safety and efficacy of molecularly targeted agents in patients with metastatic kidney cancer with renal dysfunction. Anticancer Drugs. 22, 794–800 (2011).

    Article  CAS  Google Scholar 

  77. Nouhaud, F. X. et al. Baseline chronic kidney disease is associated with toxicity and survival in patients treated with targeted therapies for metastatic renal cell carcinoma. Anticancer Drugs. 26, 866–871 (2015).

    Article  CAS  Google Scholar 

  78. Zabor, E. C. et al. Factors associated with recovery of renal function following radical nephrectomy for kidney neoplasm. Clin. J. Am. Soc. Nephrol. 11, 101–107 (2016).

    Article  CAS  Google Scholar 

  79. Huang, W. C. et al. Chronic kidney disease after nephrectomy in patients with renal cortical tumours: a retrospective cohort study. Lancet Oncol. 7, 735–740 (2006).

    Article  Google Scholar 

  80. Calvo, E. et al. Improvement in survival end points of patients with metastatic renal cell carcinoma through sequential targeted therapy. Cancer Treat. Rev. 50, 109–117 (2016).

    Article  Google Scholar 

  81. Escudier, B. et al. Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 27 (Suppl. 5), v58–v68 (2016).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Reviewer information

Nature Reviews Nephrology thanks H. Hammers, M. H. Rosner and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, University of Pavia, Pavia, Italy

    Camillo Porta

  2. Division of Translational Oncology, I.R.C.C.S. Istituti Clinici Scientifici Maugeri, Pavia, Italy

    Camillo Porta

  3. Division of Nephrology, A.S.S.T. Santi Paolo e Carlo, San Carlo Borromeo Hospital, Milan, Italy

    Laura Cosmai & Maurizio Gallieni

  4. Department of Urology, Mayo Clinic, Rochester, MN, USA

    Bradley C. Leibovich

  5. Barts Cancer Institute Experimental Medicine Centre, Queen Mary University of London St Bartholomew’s Hospital, London, UK

    Thomas Powles

  6. Department of Clinical and Biomedical Sciences “Luigi Sacco”, University of Milan, Milan, Italy

    Maurizio Gallieni

  7. Department of Urology, Netherlands Cancer Institute, Amsterdam, Netherlands

    Axel Bex

Authors
  1. Camillo Porta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laura Cosmai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bradley C. Leibovich
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thomas Powles
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maurizio Gallieni
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Axel Bex
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors researched the data, contributed to discussions of the content, wrote the article and reviewed or edited the manuscript before submission.

Corresponding author

Correspondence to Camillo Porta.

Ethics declarations

Competing interests

C.P. and A.B. contributed to the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) discussion regarding approval of sunitinib as an adjuvant treatment for resected renal cell carcinoma. The other authors declare no competing interests.

Additional information

Publisher’s note

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

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Porta, C., Cosmai, L., Leibovich, B.C. et al. The adjuvant treatment of kidney cancer: a multidisciplinary outlook. Nat Rev Nephrol 15, 423–433 (2019). https://doi.org/10.1038/s41581-019-0131-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41581-019-0131-x

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing