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.

  • Primer
  • Published:

Chronic kidney disease

Nature Reviews Disease Primers volume 11, Article number: 8 (2025) Cite this article

Subjects

An Author Correction to this article was published on 21 July 2025

This article has been updated

Abstract

Chronic kidney disease (CKD) is defined by persistent abnormalities of kidney function or structure that have consequences for the health. A progressive decline of excretory kidney function has effects on body homeostasis. CKD is tightly associated with accelerated cardiovascular disease and severe infections, and with premature death. Kidney failure without access to kidney replacement therapy is fatal — a reality in many regions of the world. CKD can be the consequence of a single cause, but CKD in adults frequently relates rather to sequential injuries accumulating over the life course or to the presence of concomitant risk factors. The shared pathomechanism of CKD progression is the irreversible loss of kidney cells or nephrons together with haemodynamic and metabolic overload of the remaining nephrons, leading to further loss of kidney cells or nephrons. The management of patients with CKD focuses on early detection and on controlling all modifiable risk factors. This approach includes reducing the overload of the remaining nephrons with inhibitors of the renin–angiotensin system and the sodium-glucose transporter 2, as well as disease-specific drug interventions, if available. Hypertension, anaemia, metabolic acidosis and secondary hyperparathyroidism contribute to cardiovascular morbidity and reduced quality of life, and require diagnosis and treatment.

Access through your institution
Buy or subscribe

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

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

Fig. 1: Kidney adaptation to injury.
Fig. 2: CKD pathophysiology — an imbalance between kidney capacity and workload.
Fig. 3: Causes, shared pathomechanism and consequences of CKD.
Fig. 4: The KDIGO staging matrix of CKD.
Fig. 5: Primary, secondary and tertiary prevention strategies of CKD.
Fig. 6: Data-driven, multidisciplinary, patient-centred care for CKD.
Fig. 7: Major trials with cardio-renal outcomes in patients with CKD and type 2 diabetes mellitus.

Similar content being viewed by others

Change history

References

  1. Curhan, G. C. Prediabetes, prehypertension … is it time for pre-CKD? Clin. J. Am. Soc. Nephrol. 5, 557–559 (2010).

    Article  PubMed  Google Scholar 

  2. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group KDIGO 2024 Clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 105, S117–S314. Latest definition and classification of CKD, which sets the global standard on how to deal with CKD and all its consequences.

  3. Luyckx, V. A. et al. Nephron overload as a therapeutic target to maximize kidney lifespan. Nat. Rev. Nephrol. 18, 171–183 (2022).

    Article  PubMed  Google Scholar 

  4. Jager, K. J. et al. A single number for advocacy and communication-worldwide more than 850 million individuals have kidney diseases. Kidney Int. 96, 1048–1050 (2019).

    Article  PubMed  Google Scholar 

  5. Kovesdy, C. P. Epidemiology of chronic kidney disease: an update 2022. Kidney Int. Suppl. 12, 7–11 (2022).

    Article  Google Scholar 

  6. Feng, X. et al. Secular trends of epidemiologic patterns of chronic kidney disease over three decades: an updated analysis of the Global Burden of Disease Study 2019. BMJ Open 13, e064540 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Steiger, S. et al. Sex dimorphism in kidney health and disease: mechanistic insights and clinical implication. Kidney Int. 107, 51–67 (2025).

    Article  PubMed  CAS  Google Scholar 

  8. Dimitriadis, E. et al. Pre-eclampsia. Nat. Rev. Dis. Primers 9, 8 (2023).

    Article  PubMed  Google Scholar 

  9. Zhang, J. J. et al. A systematic review and meta-analysis of outcomes of pregnancy in CKD and CKD outcomes in pregnancy. Clin. J. Am. Soc. Nephrol. 10, 1964–1978 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Neugarten, J. & Golestaneh, L. Sex differences in acute kidney injury. Semin. Nephrol. 42, 208–218 (2022).

    Article  PubMed  Google Scholar 

  11. Ene-Iordache, B. et al. Chronic kidney disease and cardiovascular risk in six regions of the world (ISN-KDDC): a cross-sectional study. Lancet Glob. Health 4, e307–e319, (2016).

    Article  PubMed  Google Scholar 

  12. Harambat, J., van Stralen, K. J., Kim, J. J. & Tizard, E. J. Epidemiology of chronic kidney disease in children. Pediatr. Nephrol. 27, 363–373 (2012).

    Article  PubMed  Google Scholar 

  13. Batte, A., Shahrin, L., Claure-Del Granado, R., Luyckx, V. A. & Conroy, A. L. Infections and acute kidney injury: a global perspective. Semin. Nephrol. 43, 151466 (2023).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Kamath, N., Iyengar, A., George, N. & Luyckx, V. A. Risk factors and rate of progression of CKD in children. Kidney Int. Rep. 4, 1472–1477 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Stern-Zimmer, M., Calderon-Margalit, R., Skorecki, K. & Vivante, A. Childhood risk factors for adulthood chronic kidney disease. Pediatr. Nephrol. 36, 1387–1396 (2021).

    Article  PubMed  Google Scholar 

  16. Hill, N. R. et al. Global prevalence of chronic kidney disease — a systematic review and meta-analysis. PLoS ONE 11, e0158765 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Kim, G. H. Primary role of the kidney in pathogenesis of hypertension. Life 14, 119 (2024).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. GBD Chronic Kidney Disease Collaboration Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 395, 709–733 (2020).

    Article  Google Scholar 

  19. Luyckx, V. A. & Brenner, B. M. Birth weight, malnutrition and kidney-associated outcomes—a global concern. Nat. Rev. Nephrol. 11, 135–149 (2015).

    Article  PubMed  Google Scholar 

  20. Luyckx, V. A. et al. Reducing major risk factors for chronic kidney disease. Kidney Int. Suppl. 7, 71–87 (2017).

    Article  Google Scholar 

  21. Luks, A. M., Johnson, R. J. & Swenson, E. R. Chronic kidney disease at high altitude. J. Am. Soc. Nephrol. 19, 2262–2271 (2008).

    Article  PubMed  CAS  Google Scholar 

  22. Zeng, X. et al. Associations between socioeconomic status and chronic kidney disease: a meta-analysis. J. Epidemiol. Community Health 72, 270–279 (2018).

    Article  PubMed  Google Scholar 

  23. Inker, L. A. et al. New creatinine- and cystatin C–based equations to estimate GFR without race. N. Engl. J. Med. 385, 1737–1749 (2021).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Fabian, J. et al. Measurement of kidney function in Malawi, South Africa, and Uganda: a multicentre cohort study. Lancet Glob. Health 10, e1159–e1169 (2022).

    Article  PubMed  CAS  Google Scholar 

  25. Gansevoort, R. T. et al. What should European nephrology do with the new CKD-EPI equation? Nephrol. Dial. Transplant. 38, 1–6 (2023).

    Article  PubMed  Google Scholar 

  26. Knoers, N. et al. Genetic testing in the diagnosis of chronic kidney disease: recommendations for clinical practice. Nephrol. Dial. Transplant. 37, 239–254 (2022).

    Article  PubMed  Google Scholar 

  27. Becherucci, F. et al. A clinical workflow for cost-saving high-rate diagnosis of genetic kidney diseases. J. Am. Soc. Nephrol. 34, 706–720 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Boeckhaus, J. et al. Lifelong effect of therapy in young patients with the COL4A5 Alport missense variant p.(Gly624Asp): a prospective cohort study. Nephrol. Dial. Transplant. 37, 2496–2504 (2022).

    Article  PubMed  CAS  Google Scholar 

  29. Egbuna, O. et al. Inaxaplin for proteinuric kidney disease in persons with two APOL1 variants. N. Engl. J. Med. 388, 969–979 (2023).

    Article  PubMed  CAS  Google Scholar 

  30. Genovese, G. et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 329, 841–845 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Khan, A. et al. Genome-wide polygenic score to predict chronic kidney disease across ancestries. Nat. Med. 28, 1412–1420 (2022).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Priyadarshani, W. V. D., de Namor, A. F. D. & Silva, S. R. P. Rising of a global silent killer: critical analysis of chronic kidney disease of uncertain aetiology (CKDu) worldwide and mitigation steps. Environ. Geochem. Health 45, 2647–2662 (2023).

    Article  PubMed  CAS  Google Scholar 

  33. Villalvazo, P., Carriazo, S., Martin-Cleary, C. & Ortiz, A. Aguascalientes: one of the hottest chronic kidney disease (CKD) hotspots in Mexico and a CKD of unknown aetiology mystery to be solved. Clin. Kidney J. 14, 2285–2294 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Chicas, R. et al. Chronic kidney disease among workers: a review of the Literature. Workplace Health Saf. 67, 481–490 (2019).

    Article  PubMed  Google Scholar 

  35. Luyckx, V. A. et al. Mind the gap in kidney care: translating what we know into what we do. Kidney Int. 105, 406–417 (2024).

    Article  PubMed  Google Scholar 

  36. Foreman, K. J. et al. Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016–40 for 195 countries and territories. Lancet 392, 2052–2090 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  37. GBD 2013 Mortality and Causes of Death Collaborators Global, regional, and national age–sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 385, 117–171 (2015).

    Article  Google Scholar 

  38. Bello, A. K. et al. ISN–global kidney health atlas: a report by the International Society of Nephrology: an assessment of global kidney health care status focussing on capacity, availability, accessibility, affordability and outcomes of kidney disease. International Society of Nephrology https://www.theisn.org/wp-content/uploads/media/ISN%20Atlas_2023%20Digital_REV_2023_10_03.pdf (2023). Latest overview on kidney health care in all regions of the world displaying wide variation of access to nephrology specialists, quality of diagnostic workup and preferences for KRT.

  39. Luyckx, V. A. et al. Equity and quality of global CKD care: what are we waiting for? Am. J. Nephrol. 55, 298–315 (2024).

    Article  PubMed  Google Scholar 

  40. Bello, A. K. et al. An update on the global disparities in kidney disease burden and care across world countries and regions. Lancet Glob. Health 12, e382–e395 (2024).

    Article  PubMed  CAS  Google Scholar 

  41. Huijben, J. A. et al. Increasing numbers and improved overall survival of patients on kidney replacement therapy over the last decade in Europe: an ERA Registry study. Nephrol. Dial. Transplant. 38, 1027–1040 (2023).

    Article  PubMed  Google Scholar 

  42. Lentine, K. L. et al. OPTN/SRTR 2022 annual data report: kidney. Scientific Registry of Transplant Recipients https://srtr.transplant.hrsa.gov/ADR/Chapter?name=Kidney&year=2022 (2022).

  43. Miyazaki, M. et al. Comparison of survival rates between incident hemodialysis patients and peritoneal dialysis patients: a 5-year prospective cohort study with propensity score matching. Clin. Exp. Nephrol. 27, 419–426 (2023).

    Article  PubMed  Google Scholar 

  44. Anders, H. J., Huber, T. B., Isermann, B. & Schiffer, M. CKD in diabetes: diabetic kidney disease versus nondiabetic kidney disease. Nat. Rev. Nephrol. 14, 361–377 (2018).

    Article  PubMed  CAS  Google Scholar 

  45. Bertram, J. F., Douglas-Denton, R. N., Diouf, B., Hughson, M. D. & Hoy, W. E. Human nephron number: implications for health and disease. Pediatr. Nephrol. 26, 1529–1533 (2011).

    Article  PubMed  Google Scholar 

  46. Hingorani, S. et al. Prevalence and risk factors for kidney disease and elevated BP in 2-year-old children born extremely premature. Clin. J. Am. Soc. Nephrol. 17, 1129–1138 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Grams, M. E. et al. Kidney-failure risk projection for the living kidney-donor candidate. N. Engl. J. Med. 374, 411–421 (2016).

    Article  PubMed  CAS  Google Scholar 

  48. Mueller, T. F. & Luyckx, V. A. The natural history of residual renal function in transplant donors. J. Am. Soc. Nephrol. 23, 1462–1466 (2012).

    Article  PubMed  Google Scholar 

  49. Laouari, D. et al. TGF-α mediates genetic susceptibility to chronic kidney disease. J. Am. Soc. Nephrol. 22, 327–335 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Helal, I., Fick-Brosnahan, G. M., Reed-Gitomer, B. & Schrier, R. W. Glomerular hyperfiltration: definitions, mechanisms and clinical implications. Nat. Rev. Nephrol. 8, 293–300 (2012).

    Article  PubMed  CAS  Google Scholar 

  51. Cortinovis, M., Perico, N., Ruggenenti, P., Remuzzi, A. & Remuzzi, G. Glomerular hyperfiltration. Nat. Rev. Nephrol. 18, 435–451 (2022). Important concept of increased kidney workload and its role in the progression of CKD.

    Article  PubMed  Google Scholar 

  52. D’Agati, V. D. et al. Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis. Nat. Rev. Nephrol. 12, 453–471 (2016).

    Article  PubMed  Google Scholar 

  53. Tonneijck, L. et al. Glomerular hyperfiltration in diabetes: mechanisms, clinical significance, and treatment. J. Am. Soc. Nephrol. 28, 1023–1039 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Kopp, J. B. et al. Podocytopathies. Nat. Rev. Dis. Primers 6, 68 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Denic, A. et al. The substantial loss of nephrons in healthy human kidneys with aging. J. Am. Soc. Nephrol. 28, 313–320 (2017). This paper explains how even healthy ageing involves loss of nephrons; thinking in terms of nephrons rather than eGFR or proteinuria provides a better framework to understand the pathophysiology of CKD and why it is more common in the second phase of life.

    Article  PubMed  Google Scholar 

  56. Hodgin, J. B. et al. Glomerular aging and focal global glomerulosclerosis: a podometric perspective. J. Am. Soc. Nephrol. 26, 3162–3178 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Kriz, W. & Lemley, K. V. The role of the podocyte in glomerulosclerosis. Curr. Opin. Nephrol. Hypertens. 8, 489–497 (1999).

    Article  PubMed  CAS  Google Scholar 

  58. Kriz, W. & Lemley, K. V. A potential role for mechanical forces in the detachment of podocytes and the progression of CKD. J. Am. Soc. Nephrol. 26, 258–269 (2015).

    Article  PubMed  Google Scholar 

  59. Bedin, M. et al. Human C-terminal CUBN variants associate with chronic proteinuria and normal renal function. J. Clin. Invest. 130, 335–344 (2020).

    Article  PubMed  CAS  Google Scholar 

  60. Herold, J. M. et al. Population-based reference values for kidney function and kidney function decline in 25- to 95-year-old Germans without and with diabetes. Kidney Int. 106, 699–711 (2024).

    Article  PubMed  Google Scholar 

  61. Xie, X. et al. Renin-angiotensin system inhibitors and kidney and cardiovascular outcomes in patients with CKD: a Bayesian network meta-analysis of randomized clinical trials. Am. J. Kidney Dis. 67, 728–741 (2016).

    Article  PubMed  CAS  Google Scholar 

  62. Barrera-Chimal, J., Jaisser, F. & Anders, H. J. The mineralocorticoid receptor in chronic kidney disease. Br. J. Pharmacol. 179, 3152–3164 (2022).

    Article  PubMed  CAS  Google Scholar 

  63. Verma, S. et al. Aldosterone and aldosterone synthase inhibitors in cardiorenal disease. Am. J. Physiol. Heart Circ. Physiol. 326, H670–H688 (2024).

    Article  PubMed  CAS  Google Scholar 

  64. Schiffrin, E. L. & Pollock, D. M. Endothelin system in hypertension and chronic kidney disease. Hypertension 81, 691–701 (2024).

    Article  PubMed  CAS  Google Scholar 

  65. Nagasawa, H. et al. Sparsentan is superior to losartan in the gddY mouse model of IgA nephropathy. Nephrol. Dial. Transplant. 39, 1494–1503 (2024).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Heerspink, H. J. L. et al. Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial. Lancet 401, 1584–1594 (2023).

    Article  PubMed  CAS  Google Scholar 

  67. Vallon, V. How can inhibition of glucose and sodium transport in the early proximal tubule protect the cardiorenal system? Nephrol. Dial. Transplant. 39, 1565–1573 (2024). The latest concepts about how SGLT2 inhibitors confer their beneficial effects on the kidney and the cardiovascular system.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Nuffield Department of Population Health Renal Studies Group & SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists’ Consortium. Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Lancet 400, 1788–1801 (2022).

    Article  Google Scholar 

  69. Billing, A. M. et al. Metabolic communication by SGLT2 inhibition. Circulation 149, 860–884 (2024).

    Article  PubMed  CAS  Google Scholar 

  70. Ge, M. et al. Empagliflozin reduces podocyte lipotoxicity in experimental Alport syndrome. eLife 12, e83353 (2023).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Ma, Q., Steiger, S. & Anders, H. J. Sodium glucose transporter-2 inhibition has no renoprotective effects on non-diabetic chronic kidney disease. Physiol. Rep. 5, e13228 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Zhu, Z. et al. Finerenone added to RAS/SGLT2 blockade for CKD in Alport syndrome. results of a randomized controlled trial with Col4a3−/− mice. J. Am. Soc. Nephrol. 34, 1513–1520 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  73. Klinkhammer, B. M. et al. Current kidney function parameters overestimate kidney tissue repair in reversible experimental kidney disease. Kidney Int. 102, 307–320 (2022).

    Article  PubMed  CAS  Google Scholar 

  74. Friedrich, J., Bellmann, M., Klank, D., Porubsky, S. & Bergner, R. Clinical and histological comparison of IgA nephritis and renal IgA vasculitis. Nephrol. Dial. Transplant. 40, 182–192 (2024).

    Article  PubMed  Google Scholar 

  75. Lazzeri, E. et al. Endocycle-related tubular cell hypertrophy and progenitor proliferation recover renal function after acute kidney injury. Nat. Commun. 9, 1344 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  76. De Chiara, L., Lazzeri, E. & Romagnani, P. Polyploid tubular cells: a shortcut to stress adaptation. Kidney Int. 105, 709–716 (2024).

    Article  PubMed  Google Scholar 

  77. Li, L., Fu, H. & Liu, Y. The fibrogenic niche in kidney fibrosis: components and mechanisms. Nat. Rev. Nephrol. 18, 545–557 (2022).

    Article  PubMed  CAS  Google Scholar 

  78. Steiger, S. et al. Anti-transforming growth factor β IgG elicits a dual effect on calcium oxalate crystallization and progressive nephrocalcinosis-related chronic kidney disease. Front. Immunol. 9, 619 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  79. Buchtler, S. et al. Cellular origin and functional relevance of collagen I production in the kidney. J. Am. Soc. Nephrol. 29, 1859–1873 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Ninichuk, V. et al. Multipotent mesenchymal stem cells reduce interstitial fibrosis but do not delay progression of chronic kidney disease in collagen4A3-deficient mice. Kidney Int. 70, 121–129 (2006).

    Article  PubMed  CAS  Google Scholar 

  81. Douglas, C. E. et al. Effect of age on hypertension recognition in children with chronic kidney disease: a report from the chronic kidney disease in children study. Hypertension 80, 1048–1056 (2023).

    Article  PubMed  CAS  Google Scholar 

  82. Novak, J. E. & Ellison, D. H. Diuretics in states of volume overload: core curriculum 2022. Am. J. Kidney Dis. 80, 264–276 (2022).

    Article  PubMed  Google Scholar 

  83. Vaz de Castro, P. A. S. et al. Nephrogenic diabetes insipidus: a comprehensive overview. J. Pediatr. Endocrinol. Metab. 35, 421–434 (2022).

    Article  PubMed  CAS  Google Scholar 

  84. Sarafidis, P. et al. A European Renal Association (ERA) synopsis for nephrology practice of the 2023 European Society of Hypertension (ESH) Guidelines for the Management of Arterial Hypertension. Nephrol. Dial. Transplant. 39, 929–943 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  85. Palmer, B. F. & Clegg, D. J. Hyperkalemia treatment standard. Nephrol. Dial. Transplant. 39, 1097–1104 (2024).

    Article  PubMed  CAS  Google Scholar 

  86. Raphael, K. L. Metabolic acidosis and subclinical metabolic acidosis in CKD. J. Am. Soc. Nephrol. 29, 376–382 (2018).

    Article  PubMed  CAS  Google Scholar 

  87. Fan, Z. et al. Correlation between soluble klotho and chronic kidney disease–mineral and bone disorder in chronic kidney disease: a meta-analysis. Sci. Rep. 14, 4477 (2024).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Barrera-Baena, P. et al. Serum phosphate is associated with increased risk of bone fragility fractures in hemodialysis patients. Nephrol. Dial. Transplant. 39, 618–626 (2023).

    Article  PubMed Central  Google Scholar 

  89. Bacchetta, J. et al. Diagnosis and management of mineral and bone disorders in infants with CKD: clinical practice points from the ESPN CKD-MBD and Dialysis working groups and the Pediatric Renal Nutrition Taskforce. Pediatr. Nephrol. 38, 3163–3181 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  90. Steiger, S., Ma, Q. & Anders, H. J. The case for evidence-based medicine for the association between hyperuricaemia and CKD. Nat. Rev. Nephrol. 16, 422 (2020).

    Article  PubMed  Google Scholar 

  91. Badve, S. V. et al. Effects of allopurinol on the progression of chronic kidney disease. N. Engl. J. Med. 382, 2504–2513 (2020).

    Article  PubMed  CAS  Google Scholar 

  92. Ma, Q. et al. Soluble uric acid inhibits β2 integrin–mediated neutrophil recruitment in innate immunity. Blood 139, 3402–3417 (2022).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Ma, Q. et al. Soluble uric acid is an intrinsic negative regulator of monocyte activation in monosodium urate crystal-induced tissue inflammation. J. Immunol. 205, 789–800 (2020).

    Article  PubMed  CAS  Google Scholar 

  94. Steiger, S., Rossaint, J., Zarbock, A. & Anders, H. J. Secondary immunodeficiency related to kidney disease (SIDKD)-definition, unmet need, and mechanisms. J. Am. Soc. Nephrol. 33, 259–278 (2022). This paper introduces a definition and mechanisms for secondary immunodeficiency due to CKD, which may help to understand why infections are the second cause of death in patients with CKD.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Rossaint, J. et al. FGF23 signaling impairs neutrophil recruitment and host defense during CKD. J. Clin. Invest. 126, 962–974 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  96. Meijers, B., Evenepoel, P. & Anders, H. J. Intestinal microbiome and fitness in kidney disease. Nat. Rev. Nephrol. 15, 531–545 (2019).

    Article  PubMed  Google Scholar 

  97. Holle, J. et al. Inflammation in children with CKD linked to gut dysbiosis and metabolite imbalance. J. Am. Soc. Nephrol. 33, 2259–2275 (2022).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Jin, Q. et al. Circulating metabolomic markers linking diabetic kidney disease and incident cardiovascular disease in type 2 diabetes: analyses from the Hong Kong Diabetes Biobank. Diabetologia 67, 837–849 (2024).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Lee, A. M. et al. Circulating metabolomic associations with neurocognitive outcomes in pediatric CKD. Clin. J. Am. Soc. Nephrol. 19, 13–25 (2024).

    Article  PubMed  CAS  Google Scholar 

  100. Le Gall, L. et al. Haemoglobin trajectories in chronic kidney disease and risk of major adverse cardiovascular events. Nephrol. Dial. Transplant. 39, 669–682 (2023).

    Article  Google Scholar 

  101. Barbieri, M. et al. Efficacy of erythropoietin as a neuroprotective agent in CKD-associated cognitive dysfunction: a literature systematic review. Pharmacol. Res. 203, 107146 (2024).

    Article  PubMed  CAS  Google Scholar 

  102. Babitt, J. L. & Lin, H. Y. Mechanisms of anemia in CKD. J. Am. Soc. Nephrol. 23, 1631–1634 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Go, A. S., Chertow, G. M., Fan, D., McCulloch, C. E. & Hsu, C. Y. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N. Engl. J. Med. 351, 1296–1305 (2004).

    Article  PubMed  CAS  Google Scholar 

  104. Speer, T., Dimmeler, S., Schunk, S. J., Fliser, D. & Ridker, P. M. Targeting innate immunity-driven inflammation in CKD and cardiovascular disease. Nat. Rev. Nephrol. 18, 762–778 (2022).

    Article  PubMed  Google Scholar 

  105. Grabner, A. et al. Activation of cardiac fibroblast growth factor receptor 4 causes left ventricular hypertrophy. Cell Metab. 22, 1020–1032 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Anker, S. D. et al. Empagliflozin in heart failure with a preserved ejection fraction. N. Engl. J. Med. 385, 1451–1461 (2021).

    Article  PubMed  CAS  Google Scholar 

  107. McMurray, J. J. V. et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N. Engl. J. Med. 381, 1995–2008 (2019).

    Article  PubMed  CAS  Google Scholar 

  108. Agarwal, R. et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. Eur. Heart J. 43, 474–484 (2022).

    Article  PubMed  CAS  Google Scholar 

  109. Buchanan, C. et al. Intradialytic cardiac magnetic resonance imaging to assess cardiovascular responses in a short-term trial of hemodiafiltration and hemodialysis. J. Am. Soc. Nephrol. 28, 1269–1277 (2017).

    Article  PubMed  Google Scholar 

  110. Fernandez-Fernandez, B. et al. Albumin downregulates Klotho in tubular cells. Nephrol. Dial. Transplant. 33, 1712–1722 (2018).

    Article  PubMed  CAS  Google Scholar 

  111. Chou, J., Kiebalo, T., Jagiello, P. & Pawlaczyk, K. Multifaceted sexual dysfunction in dialyzing men and women: pathophysiology, diagnostics, and therapeutics. Life 11, 311 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  112. van der Heijden, B. J., van Dijk, P. C., Verrier-Jones, K., Jager, K. J. & Briggs, J. D. Renal replacement therapy in children: data from 12 registries in Europe. Pediatr. Nephrol. 19, 213–221 (2004).

    Article  PubMed  Google Scholar 

  113. Tonshoff, B., Kiepe, D. & Ciarmatori, S. Growth hormone/insulin-like growth factor system in children with chronic renal failure. Pediatr. Nephrol. 20, 279–289 (2005).

    Article  PubMed  Google Scholar 

  114. Rhee, C. M. & Kovesdy, C. P. Epidemiology: spotlight on CKD deaths—increasing mortality worldwide. Nat. Rev. Nephrol. 11, 199–200 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  115. Faye, M. et al. Five-year symptom trajectories in nondialysis-dependent CKD patients. Clin. J. Am. Soc. Nephrol. 17, 1588–1597 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  116. Fitzpatrick, J. et al. Frailty, body composition and the risk of mortality in incident hemodialysis patients: the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease study. Nephrol. Dial. Transplant. 34, 346–354 (2019).

    Article  PubMed  CAS  Google Scholar 

  117. Viggiano, D. et al. Mechanisms of cognitive dysfunction in CKD. Nat. Rev. Nephrol. 16, 452–469 (2020).

    Article  PubMed  Google Scholar 

  118. Lu, J. L. et al. Association of age and BMI with kidney function and mortality: a cohort study. Lancet Diabetes Endocrinol. 3, 704–714 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  119. Kim, H. W. et al. Insomnia in patients on incident maintenance dialysis and the risk of major acute cardio-cerebrovascular events and all-cause mortality. Nephrol. Dial. Transplant. 39, 830–837 (2023).

    Article  Google Scholar 

  120. Zhou, X. H. et al. Global prevalence of restless legs syndrome among hemodialysis patients: a systematic review and meta-analysis. Brain Behav. 14, e3378 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  121. Grams, M. E. et al. Estimated glomerular filtration rate, albuminuria, and adverse outcomes: an individual-participant data meta-analysis. JAMA 330, 1266–1277 (2023).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  122. Delanaye, P. et al. CKD: a call for an age-adapted definition. J. Am. Soc. Nephrol. 30, 1785–1805 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Ku, E., Lee, B. J., Wei, J. & Weir, M. R. Hypertension in CKD: core curriculum 2019. Am. J. Kidney Dis. 74, 120–131 (2019).

    Article  PubMed  Google Scholar 

  124. Chu, K. H. et al. Long-term outcomes of living kidney donors: a single centre experience of 29 years. Nephrology 17, 85–88 (2012).

    Article  PubMed  Google Scholar 

  125. Groen In ‘t Woud, S. et al. Clinical management of children with a congenital solitary functioning kidney: overview and recommendations. Eur. Urol. Open Sci. 25, 11–20 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  126. Sanderson, K. R. et al. Albuminuria, hypertension, and reduced kidney volumes in adolescents born extremely premature. Front. Pediatr. 8, 230 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  127. Georgianos, P. I. & Agarwal, R. Hypertension in chronic kidney disease—treatment standard 2023. Nephrol. Dial. Transplant. 38, 2694–2703 (2023).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  128. Keefe, P. & Bokhari, S. R. A. Fanconi syndrome in StatPearls (StatPearls, 2024).

  129. Leung, N., Bridoux, F. & Nasr, S. H. Monoclonal gammopathy of renal significance. N. Engl. J. Med. 384, 1931–1941 (2021).

    Article  PubMed  CAS  Google Scholar 

  130. Kalantar-Zadeh, K. et al. Patient-centred approaches for the management of unpleasant symptoms in kidney disease. Nat. Rev. Nephrol. 18, 185–198 (2022). Good review summarizing the current standards of quality of life-focused treatment approaches in patients with advanced CKD.

    Article  PubMed  Google Scholar 

  131. Akalay, S. et al. Impact of preterm birth on kidney health and development. Front. Med. 11, 1363097 (2024).

    Article  Google Scholar 

  132. Friedman, D. J. & Pollak, M. R. APOL1 nephropathy: from genetics to clinical applications. Clin. J. Am. Soc. Nephrol. 16, 294–303 (2021).

    Article  PubMed  CAS  Google Scholar 

  133. Ataga, K. I., Saraf, S. L. & Derebail, V. K. The nephropathy of sickle cell trait and sickle cell disease. Nat. Rev. Nephrol. 18, 361–377 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  134. Correa-Rotter, R. & García-Trabanino, R. Mesoamerican nephropathy. Semin. Nephrol. 39, 263–271 (2019).

    Article  PubMed  Google Scholar 

  135. Wang, H. et al. Clinicopathological characteristics of high-altitude polycythemia-related kidney disease in Tibetan inhabitants. Kidney Int. 102, 196–206 (2022).

    Article  PubMed  CAS  Google Scholar 

  136. Koirala, A. et al. Etiology and management of edema: a review. Adv. Kidney Dis. Health 30, 110–123 (2023).

    Article  PubMed  Google Scholar 

  137. Kashtan, C. E. Alport syndrome: achieving early diagnosis and treatment. Am. J. Kidney Dis. 77, 272–279 (2021).

    Article  PubMed  CAS  Google Scholar 

  138. Zand, L., Fervenza, F. C. & Coppo, R. Microscopic hematuria as a risk factor for IgAN progression: considering this biomarker in selecting and monitoring patients. Clin. Kidney J. 16, ii19–ii27 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  139. Anders, H. J., Kitching, A. R., Leung, N. & Romagnani, P. Glomerulonephritis: immunopathogenesis and immunotherapy. Nat. Rev. Immunol. 23, 453–471 (2023).

    Article  PubMed  CAS  Google Scholar 

  140. Obrycki, Ł. et al. Kidney length normative values in children aged 0–19 years — a multicenter study. Pediatr. Nephrol. 37, 1075–1085 (2022).

    Article  PubMed  Google Scholar 

  141. Dahl, N. K. et al. The clinical utility of genetic testing in the diagnosis and management of adults with chronic kidney disease. J. Am. Soc. Nephrol. 34, 2039–2050 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  142. Tuttle, K. R. CKD screening for better kidney health: why? Who? How? When? Nephrol. Dial. Transplant. 39, 1537–1539 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  143. Luyckx, V. A. et al. A developmental approach to the prevention of hypertension and kidney disease: a report from the Low Birth Weight and Nephron Number Working Group. Lancet 309, 424–428 (2017).

    Article  Google Scholar 

  144. Benghanem Gharbi, M. et al. Chronic kidney disease, hypertension, diabetes, and obesity in the adult population of Morocco: how to avoid “over”- and “under”-diagnosis of CKD. Kidney Int. 89, 1363–1371 (2016).

    Article  PubMed  Google Scholar 

  145. Clark, W. F. et al. Dipstick proteinuria as a screening strategy to identify rapid renal decline. J. Am. Soc. Nephrol. 22, 1729–1736 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  146. Fink, H. A. et al. Screening for, monitoring, and treatment of chronic kidney disease stages 1 to 3: a systematic review for the U.S. Preventive Services Task Force and for an American College of Physicians Clinical Practice Guideline. Ann. Intern. Med. 156, 570–581 (2012).

    Article  PubMed  Google Scholar 

  147. Imai, E. et al. Kidney disease screening program in Japan: history, outcome, and perspectives. Clin. J. Am. Soc. Nephrol. 2, 1360–1366 (2007).

    Article  PubMed  Google Scholar 

  148. Moyer, V. A. & US Preventive Services Task Force Screening for chronic kidney disease: U.S. Preventive Services Task Force recommendation statement. Ann. Intern. Med. 157, 567–570 (2012).

    Article  PubMed  Google Scholar 

  149. Ozyilmaz, A. et al. Screening for albuminuria with subsequent screening for hypertension and hypercholesterolaemia identifies subjects in whom treatment is warranted to prevent cardiovascular events. Nephrol. Dial. Transplant. 28, 2805–2815 (2013).

    Article  PubMed  Google Scholar 

  150. Pouwels, X. G. L. V. et al. Cost-effectiveness of home-based screening of the general population for albuminuria to prevent progression of cardiovascular and kidney disease. eClinicalMedicine 68, 102414 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  151. Okpechi, I. G. et al. Early identification of CKD—a scoping review of the global populations. Kidney Int. Rep. 7, 1341–1353 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  152. Cordero, L. & Ortiz, A. Decreased life expectancy: a health outcome not corrected by kidney replacement therapy that emphasizes the need for primary prevention of CKD. Clin. Kidney J. 17, sfae053 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  153. Jiang, W. et al. Establishment and validation of a risk prediction model for early diabetic kidney disease based on a systematic review and meta-analysis of 20 cohorts. Diabetes Care 43, 925–933 (2020).

    Article  PubMed  CAS  Google Scholar 

  154. Hoerger, T. J. et al. A health policy model of CKD: 2. The cost-effectiveness of microalbuminuria screening. Am. J. Kidney Dis. 55, 463–473 (2010).

    Article  PubMed  Google Scholar 

  155. Levin, A. et al. Global kidney health 2017 and beyond: a roadmap for closing gaps in care, research, and policy. Lancet 390, 1888–1917 (2017). This article provides a roadmap on how to close gaps in global kidney health.

    Article  PubMed  Google Scholar 

  156. Maddux, F. W. The authority of courage and compassion: healthcare policy leadership in addressing the kidney disease public health epidemic. Semin. Dial. 33, 35–42 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  157. Donohue, J. F. et al. Bridging the “Know-Do” gaps in five non-communicable diseases using a common framework driven by implementation science. J. Healthc. Leadersh. 15, 103–119 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  158. Ndumele, C. E. et al. Cardiovascular-kidney-metabolic health: a presidential advisory from the American Heart Association. Circulation 148, 1606–1635 (2023). Inspired by the latest therapeutic advances, cardiovascular disease, CKD and metabolic disease are interconnected and, therefore, form a clinical syndrome that responds in all aspects to interventions against shared pathomechanisms.

    Article  PubMed  Google Scholar 

  159. Lim, L. L. et al. Gender-associated cardiometabolic risk profiles and health behaviors in patients with type 2 diabetes: a cross-sectional analysis of the Joint Asia Diabetes Evaluation (JADE) program. Lancet Reg. Health West. Pac. 32, 100663 (2023).

    PubMed  Google Scholar 

  160. Neale, E. P. et al. Lifestyle interventions, kidney disease progression, and quality of life: a systematic review and meta-analysis. Kidney Med. 5, 100643 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  161. Kellum, J. A. et al. Acute kidney injury. Nat. Rev. Dis. Primers 7, 52 (2021).

    Article  PubMed  Google Scholar 

  162. Morris, Z. S., Wooding, S. & Grant, J. The answer is 17 years, what is the question: understanding time lags in translational research. J. R. Soc. Med. 104, 510–520 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  163. Lim, L. L. et al. Aspects of multicomponent integrated care promote sustained improvement in surrogate clinical outcomes: a systematic review and meta-analysis. Diabetes Care 41, 1312–1320 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  164. Chan, J. C. et al. Effects of structured versus usual care on renal endpoint in type 2 diabetes: the SURE study: a randomized multicenter translational study. Diabetes Care 32, 977–982 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  165. Chan, J. C. N. et al. Effect of a web-based management guide on risk factors in patients with type 2 diabetes and diabetic kidney disease: a JADE randomized clinical trial. JAMA Netw. Open 5, e223862 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  166. Ueki, K. et al. Effect of an intensified multifactorial intervention on cardiovascular outcomes and mortality in type 2 diabetes (J-DOIT3): an open-label, randomised controlled trial. Lancet Diabetes Endocrinol. 5, 951–964 (2017).

    Article  PubMed  Google Scholar 

  167. Stanifer, J. W., Von Isenburg, M., Chertow, G. M. & Anand, S. Chronic kidney disease care models in low- and middle-income countries: a systematic review. BMJ Glob. Health 3, e000728 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  168. Hawthorne, G., Lightfoot, C. J., Smith, A. C., Khunti, K. & Wilkinson, T. J. Multimorbidity prevalence and patterns in chronic kidney disease: findings from an observational multicentre UK cohort study. Int. Urol. Nephrol. 55, 2047–2057 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  169. Ettehad, D. et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet 387, 957–967 (2016).

    Article  PubMed  Google Scholar 

  170. Emdin, C. A. et al. Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis. JAMA 313, 603–615 (2015).

    Article  PubMed  Google Scholar 

  171. SHARP Collaborative Group Study of Heart and Renal Protection (SHARP): randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease. Am. Heart J. 160, 785–794.e10 (2010).

    Article  PubMed  CAS  Google Scholar 

  172. Agarwal, R. Statin induced proteinuria: renal injury or renoprotection. J. Am. Soc. Nephrol. 15, 2502–2503 (2004).

    Article  PubMed  Google Scholar 

  173. de Zeeuw, D. et al. Renal effects of atorvastatin and rosuvastatin in patients with diabetes who have progressive renal disease (PLANET I): a randomised clinical trial. Lancet Diabetes Endocrinol. 3, 181–190 (2015).

    Article  PubMed  Google Scholar 

  174. Shin, J. I. et al. Association of rosuvastatin use with risk of hematuria and proteinuria. J. Am. Soc. Nephrol. 33, 1767–1777 (2022).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  175. Wijesurendra, R. S. et al. Mechanisms of rosuvastatin-related acute kidney injury following cardiac surgery: the STICS trial. Eur. Heart J. 45, 629–631 (2024).

    Article  PubMed  CAS  Google Scholar 

  176. Birmingham, B. K. et al. Impact of ABCG2 and SLCO1B1 polymorphisms on pharmacokinetics of rosuvastatin, atorvastatin and simvastatin acid in Caucasian and Asian subjects: a class effect. Eur. J. Clin. Pharmacol. 71, 341–355 (2015).

    Article  PubMed  CAS  Google Scholar 

  177. Lewis, E. J., Hunsicker, L. G., Bain, R. P. & Rohde, R. D. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N. Engl. J. Med. 329, 1456–1462 (1993).

    Article  PubMed  CAS  Google Scholar 

  178. Brenner, B. M. et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N. Engl. J. Med. 345, 861–869 (2001).

    Article  PubMed  CAS  Google Scholar 

  179. Parving, H. H. et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N. Engl. J. Med. 345, 870–878 (2001).

    Article  PubMed  CAS  Google Scholar 

  180. Mishima, E., Haruna, Y. & Arima, H. Renin-angiotensin system inhibitors in hypertensive adults with non-diabetic CKD with or without proteinuria: a systematic review and meta-analysis of randomized trials. Hypertens. Res. 42, 469–482 (2019).

    Article  PubMed  CAS  Google Scholar 

  181. Fried, L. F. et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N. Engl. J. Med. 369, 1892–1903 (2013).

    Article  PubMed  CAS  Google Scholar 

  182. Georgianos, P. I. & Agarwal, R. Mineralocorticoid receptor antagonism in chronic kidney disease. Kidney Int. Rep. 6, 2281–2291 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  183. Agarwal, R. et al. Effect of finerenone on ambulatory blood pressure in chronic kidney disease in type 2 diabetes. J. Hypertens. 41, 295–302 (2023).

    Article  PubMed  CAS  Google Scholar 

  184. Rossing, P. et al. Finerenone in predominantly advanced CKD and type 2 diabetes with or without sodium-glucose cotransporter-2 inhibitor therapy. Kidney Int. Rep. 7, 36–45 (2022).

    Article  PubMed  Google Scholar 

  185. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT05047263 (2024).

  186. Fried, L. et al. High unmet treatment needs in patients with chronic kidney disease and type 2 diabetes: real-world evidence from a US claims database. Nephrol. Dial. Transplant. 38, 630–643 (2023).

    Article  PubMed  CAS  Google Scholar 

  187. Agarwal, R., Bills, J. E., Hecht, T. J. & Light, R. P. Role of home blood pressure monitoring in overcoming therapeutic inertia and improving hypertension control: a systematic review and meta-analysis. Hypertension 57, 29–38 (2011).

    Article  PubMed  CAS  Google Scholar 

  188. Ling, J., Ng, J. K. C., Chan, J. C. N. & Chow, E. Use of continuous glucose monitoring in the assessment and management of patients with diabetes and chronic kidney disease. Front. Endocrinol. 13, 869899 (2022).

    Article  Google Scholar 

  189. Gregg, E. W. et al. Association of the magnitude of weight loss and changes in physical fitness with long-term cardiovascular disease outcomes in overweight or obese people with type 2 diabetes: a post-hoc analysis of the Look AHEAD randomised clinical trial. lancet Diabetes Endocrinol. 4, 913–921 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  190. Lachin, J. M., Genuth, S., Cleary, P., Davis, M. D. & Nathan, D. M. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. N. Engl. J. Med. 342, 381–389 (2000).

    Article  PubMed  Google Scholar 

  191. Holman, R. R., Paul, S. K., Bethel, M. A., Matthews, D. R. & Neil, H. A. 10-year follow-up of intensive glucose control in type 2 diabetes. N. Engl. J. Med. 359, 1577–1589 (2008).

    Article  PubMed  CAS  Google Scholar 

  192. Laiteerapong, N. et al. The legacy effect in type 2 diabetes: impact of early glycemic control on future complications (The Diabetes & Aging Study). Diabetes Care 42, 416–426 (2019).

    Article  PubMed  CAS  Google Scholar 

  193. Zoungas, S. et al. Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: a meta-analysis of individual participant data from randomised controlled trials. Lancet Diabetes Endocrinol. 5, 431–437 (2017).

    Article  PubMed  Google Scholar 

  194. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2022 Clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int. 102, S1–S127 (2022). The latest international treatment standards for patients with CKD and diabetes mellitus as a risk factor for fast progression of kidney function loss.

    Article  Google Scholar 

  195. Imai, E. et al. Effects of blood pressure on renal and cardiovascular outcomes in Asian patients with type 2 diabetes and overt nephropathy: a post hoc analysis (ORIENT-blood pressure). Nephrol. Dial. Transplant. 31, 447–454 (2016).

    Article  PubMed  CAS  Google Scholar 

  196. Hammoud, R. & Drucker, D. J. Beyond the pancreas: contrasting cardiometabolic actions of GIP and GLP1. Nat. Rev. Endocrinol. 19, 201–216 (2023).

    Article  PubMed  CAS  Google Scholar 

  197. Marso, S. P. et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 375, 1834–1844 (2016).

    Article  PubMed  CAS  Google Scholar 

  198. Gerstein, H. C. et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet 394, 121–130 (2019).

    Article  PubMed  CAS  Google Scholar 

  199. Rossing, P. et al. The rationale, design and baseline data of FLOW, a kidney outcomes trial with once-weekly semaglutide in people with type 2 diabetes and chronic kidney disease. Nephrol. Dial. Transplant. 38, 2041–2051 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  200. Perkovic, V. et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N. Engl. J. Med. 391, 109–121 (2024).

    Article  PubMed  CAS  Google Scholar 

  201. Chow, E., Yang, A., Chung, C. H. L. & Chan, J. C. N. A clinical perspective of the multifaceted mechanism of metformin in diabetes, infections, cognitive dysfunction, and cancer. Pharmaceuticals 15, 442 (2022).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  202. Yang, A. et al. Clinical outcomes following discontinuation of metformin in patients with type 2 diabetes and advanced chronic kidney disease in Hong Kong: a territory-wide, retrospective cohort and target trial emulation study. eClinicalMedicine 71, 102568 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  203. Yang, A. et al. Clinical outcomes following discontinuation of renin-angiotensin-system inhibitors in patients with type 2 diabetes and advanced chronic kidney disease: a prospective cohort study. eClinicalMedicine 55, 101751 (2023).

    Article  PubMed  Google Scholar 

  204. Bhandari, S. et al. Renin–angiotensin system inhibition in advanced chronic kidney disease. N. Engl. J. Med. 387, 2021–2032 (2022). A clinical trial to investigate whether renin–angiotensin system inhibitors should or should not be stopped as patients approach ultimate kidney failure.

    Article  PubMed  CAS  Google Scholar 

  205. Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO clinical practice guideline for anemia in chronic kidney disease. Kidney Int. Suppl. 2, 279–335 (2012).

    Google Scholar 

  206. Del Vecchio, L. et al. Iron biology. Nephrol. Dial. Transplant. 39, 1404–1415 (2024).

    Article  PubMed  Google Scholar 

  207. Elliott, J., Mishler, D. & Agarwal, R. Hyporesponsiveness to erythropoietin: causes and management. Adv. Chronic Kidney Dis. 16, 94–100 (2009).

    Article  PubMed  Google Scholar 

  208. Agarwal, R., Kusek, J. W. & Pappas, M. K. A randomized trial of intravenous and oral iron in chronic kidney disease. Kidney Int. 88, 905–914 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  209. Macdougall, I. C. Anaemia in CKD—treatment standard. Nephrol. Dial. Transplant. 39, 770–777 (2024).

    Article  PubMed  CAS  Google Scholar 

  210. Wang, C. et al. Comparative risk of anaphylactic reactions associated with intravenous iron products. JAMA 314, 2062–2068 (2015).

    Article  PubMed  CAS  Google Scholar 

  211. Singh, A. K. et al. Daprodustat for the treatment of anemia in patients undergoing dialysis. N. Engl. J. Med. 385, 2325–2335 (2021).

    Article  PubMed  CAS  Google Scholar 

  212. Stoumpos, S. et al. Hypoxia-inducible factor prolyl hydroxylase inhibitors for anaemia in chronic kidney disease: a clinical practice document by the European Renal Best Practice board of the European Renal Association. Nephrol. Dial. Transplant. 39, 1710–1730 (2024).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  213. Evenepoel, P. et al. Recommended calcium intake in adults and children with chronic kidney disease—a European consensus statement. Nephrol. Dial. Transplant. 39, 341–366 (2024).

    Article  PubMed  CAS  Google Scholar 

  214. Rodríguez-Ortiz, M. E. & Rodríguez, M. Recent advances in understanding and managing secondary hyperparathyroidism in chronic kidney disease. F1000Research https://doi.org/10.12688/f1000research.22636.1 (2020).

  215. Markham, A. Tenapanor: first approval. Drugs 79, 1897–1903 (2019).

    Article  PubMed  CAS  Google Scholar 

  216. FDA. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2024/213931Orig1s000TOC.cfm (2024).

  217. Ardelyx. https://ir.ardelyx.com/news-releases/news-release-details/ardelyx-announces-acceptance-new-drug-application-tenapanor (2023).

  218. PMDA. https://www.pmda.go.jp/files/000271700.pdf (2023).

  219. King, A. J. et al. Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. Sci. Transl. Med. 10, eaam6474 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  220. Chertow, G. M. et al. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N. Engl. J. Med. 367, 2482–2494 (2012).

    Article  PubMed  CAS  Google Scholar 

  221. Amaya-Garrido, A. et al. Calprotectin is a contributor to and potential therapeutic target for vascular calcification in chronic kidney disease. Sci. Transl. Med. 15, eabn5939 (2023).

    Article  PubMed  CAS  Google Scholar 

  222. Engler, F., Kerschbaum, J., Keller, F. & Mayer, G. Prevalence, patient burden and physicians’ perception of pruritus in haemodialysis patients. Nephrol. Dial. Transplant. 39, 277–285 (2024).

    Article  PubMed  Google Scholar 

  223. Agarwal, R. et al. Alleviating symptoms in patients undergoing long-term hemodialysis: a focus on chronic kidney disease-associated pruritus. Clin. Kidney J. 16, 30–40 (2023).

    Article  PubMed  CAS  Google Scholar 

  224. Fishbane, S., Jamal, A., Munera, C., Wen, W. & Menzaghi, F. A phase 3 trial of difelikefalin in hemodialysis patients with pruritus. N. Engl. J. Med. 382, 222–232 (2020). A phase 3 trial that led to the approval for a drug to alleviate uraemic pruritus, a very annoying symptom with negative impact on quality of life for patients with kidney failure.

    Article  PubMed  CAS  Google Scholar 

  225. Porter, A. C. et al. Predictors and outcomes of health-related quality of life in adults with CKD. Clin. J. Am. Soc. Nephrol. 11, 1154–1162 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  226. Jesky, M. D. et al. Health-related quality of life impacts mortality but not progression to end-stage renal disease in pre-dialysis chronic kidney disease: a prospective observational study. PLoS ONE 11, e0165675 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  227. Morton, R. L., Tong, A., Howard, K., Snelling, P. & Webster, A. C. The views of patients and carers in treatment decision making for chronic kidney disease: systematic review and thematic synthesis of qualitative studies. BMJ 340, c112 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  228. Hussien, H., Apetrii, M. & Covic, A. Health-related quality of life in patients with chronic kidney disease. Expert Rev. Pharmacoecon. Outcomes Res. 21, 43–54 (2021).

    Article  PubMed  Google Scholar 

  229. Brown, E. A. et al. Burden of kidney disease, health-related quality of life, and employment among patients receiving peritoneal dialysis and in-center hemodialysis: findings from the DOPPS program. Am. J. Kidney Dis. 78, 489–500.e1 (2021).

    Article  PubMed  Google Scholar 

  230. Fletcher, B. R. et al. Symptom burden and health-related quality of life in chronic kidney disease: a global systematic review and meta-analysis. PLoS Med. 19, e1003954 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  231. Murtagh, F. E. et al. Symptoms in advanced renal disease: a cross-sectional survey of symptom prevalence in stage 5 chronic kidney disease managed without dialysis. J. Palliat. Med. 10, 1266–1276 (2007).

    Article  PubMed  Google Scholar 

  232. Eckardt, K. U. et al. Trends and perspectives for improving quality of chronic kidney disease care: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 104, 888–903 (2023).

    Article  PubMed  Google Scholar 

  233. Al Sayah, F., Lahtinen, M., Bonsel, G. J., Ohinmaa, A. & Johnson, J. A. A multi-level approach for the use of routinely collected patient-reported outcome measures (PROMs) data in healthcare systems. J. Patient Rep. Outcomes 5, 98 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  234. Da Silva-Gane, M. et al. Quality of life and survival in patients with advanced kidney failure managed conservatively or by dialysis. Clin. J. Am. Soc. Nephrol. 7, 2002–2009 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  235. Vilar, E. et al. A multicenter feasibility randomized controlled trial to assess the impact of incremental versus conventional initiation of hemodialysis on residual kidney function. Kidney Int. 101, 615–625 (2022).

    Article  PubMed  Google Scholar 

  236. McIntyre, C., McQuillan, R., Bell, C. & Battistella, M. Targeted deprescribing in an outpatient hemodialysis unit: a quality improvement study to decrease polypharmacy. Am. J. Kidney Dis. 70, 611–618 (2017).

    Article  PubMed  Google Scholar 

  237. Moryousef, J. et al. Deprescribing opportunities for hospitalized patients with end-stage kidney disease on hemodialysis: a secondary analysis of the MedSafer cluster randomized controlled trial. Can. J. Kidney Health Dis. 9, 20543581221098778 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  238. Valenzuela, P. L., Castillo-García, A., Saco-Ledo, G., Santos-Lozano, A. & Lucia, A. Physical exercise: a polypill against chronic kidney disease. Nephrol. Dial. Transplant. 39, 1384–1391 (2024).

    Article  PubMed  CAS  Google Scholar 

  239. Time to sound the alarm about the hidden epidemic of kidney disease. Nature 628, 7–8 (2024).

  240. Francis, A. et al. Chronic kidney disease and the global public health agenda: an international consensus. Nat. Rev. Nephrol. 20, 473–485 (2024).

    Article  PubMed  Google Scholar 

  241. Denic, A. et al. Single-nephron glomerular filtration rate in healthy adults. N. Engl. J. Med. 376, 2349–2357 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  242. Rothberg, A. E. & Herman, W. H. How to assess kidney outcomes in obese people with substantial weight loss: the case of GLP1- and dual-receptor agonists. Nephrol. Dial. Transplant. 39, 1060–1062 (2024).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  243. Kotwal, S., Perkovic, E. & Perkovic, V. Combination therapy with kidney protective therapies: optimizing the benefits. Curr. Opin. Nephrol. Hypertens. 33, 136–143 (2024).

    Article  PubMed  CAS  Google Scholar 

  244. Gross, O., Haffner, D., Schaefer, F. & Weber, L. T. SGLT2 inhibitors: approved for adults and cats but not for children with CKD. Nephrol. Dial. Transplant. 39, 907–909 (2024).

    Article  PubMed  Google Scholar 

  245. Afsar, B. et al. Sodium–glucose cotransporter inhibition in polycystic kidney disease: fact or fiction. Clin. Kidney J. 15, 1275–1283 (2022).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  246. Heerspink, H. J. L. et al. Development and validation of a new hierarchical composite end point for clinical trials of kidney disease progression. J. Am. Soc. Nephrol. 34, 2025–2038 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  247. Levey, A. S. et al. Change in albuminuria and GFR as end points for clinical trials in early stages of CKD: a scientific workshop sponsored by the National Kidney Foundation in collaboration with the US Food and Drug Administration and European Medicines Agency. Am. J. Kidney Dis. 75, 84–104 (2020).

    Article  PubMed  CAS  Google Scholar 

  248. Thompson, A. et al. Proteinuria reduction as a surrogate end point in trials of IgA nephropathy. Clin. J. Am. Soc. Nephrol. 14, 469–481 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  249. Zoccali, C. et al. Funding kidney research as a public health priority: challenges and opportunities. Nephrol. Dial. Transplant. 37, 21–28 (2021).

    Article  PubMed  Google Scholar 

  250. Kidney disease: a global health priority. Nat. Rev. Nephrol. 20, 421–423 (2024).

  251. Carriazo, S., Vanessa Perez-Gomez, M. & Ortiz, A. Hypertensive nephropathy: a major roadblock hindering the advance of precision nephrology. Clin. Kidney J. 13, 504–509 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  252. Freedman, B. I. & Cohen, A. H. Hypertension-attributed nephropathy: what’s in a name? Nat. Rev. Nephrol. 12, 27–36 (2016).

    Article  PubMed  CAS  Google Scholar 

  253. Snoek, R. et al. Genetics-first approach improves diagnostics of ESKD patients <50 years old. Nephrol. Dial. Transplant. 37, 349–357 (2022).

    Article  PubMed  Google Scholar 

  254. Heerspink, H. J. L. et al. Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial. Lancet 393, 1937–1947 (2019).

    Article  PubMed  CAS  Google Scholar 

  255. Freeman, M. W. et al. Phase 2 trial of baxdrostat for treatment-resistant hypertension. N. Engl. J. Med. 388, 395–405 (2023).

    Article  PubMed  CAS  Google Scholar 

  256. Narva, A. Population health for CKD and diabetes: lessons from the Indian Health Service. Am. J. Kidney Dis. 71, 407–411 (2018).

    Article  PubMed  Google Scholar 

  257. Beaulieu, M. & Levin, A. Analysis of multidisciplinary care models and interface with primary care in management of chronic kidney disease. Semin. Nephrol. 29, 467–474 (2009).

    Article  PubMed  Google Scholar 

  258. What are the sustainable development goals? United Nations Development Programme https://www.undp.org/sustainable-development-goals (2024).

  259. Karam, S., Wong, M. M. Y. & Jha, V. Sustainable development goals: challenges and the role of the international society of nephrology in improving global kidney health. Kidney360 4, 1494–1502 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  260. Ke, C., Liang, J., Liu, M., Liu, S. & Wang, C. Burden of chronic kidney disease and its risk-attributable burden in 137 low-and middle-income countries, 1990–2019: results from the global burden of disease study 2019. BMC Nephrol. 23, 17 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  261. Nguyen, L. T., Pollock, C. A. & Saad, S. Nutrition and developmental origins of kidney disease. Nutrients 15, 4207 (2023).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  262. Dupuis, L., Varshney, A., Patel, J. & Joshi, S. Climate crisis and nephrology: a review of climate change’s impact on nephrology and how to combat it. Curr. Opin. Nephrol. Hypertens. 33, 110–114 (2024).

    Article  PubMed  Google Scholar 

  263. Sasai, F. et al. Climate change and nephrology. Nephrol. Dial. Transplant. 38, 41–48 (2023).

    Article  PubMed  Google Scholar 

  264. Kaze, A. D., Ilori, T., Jaar, B. G. & Echouffo-Tcheugui, J. B. Burden of chronic kidney disease on the African continent: a systematic review and meta-analysis. BMC Nephrol. 19, 125 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  265. Georgianos, P. I. & Agarwal, R. Ambulatory blood pressure reduction with SGLT-2 inhibitors: dose-response meta-analysis and comparative evaluation with low-dose hydrochlorothiazide. Diabetes Care 42, 693–700 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  266. Carrero, J. J. et al. Plant-based diets to manage the risks and complications of chronic kidney disease. Nat. Rev. Nephrol. 16, 525–542 (2020).

    Article  PubMed  Google Scholar 

  267. Palmer, B. F., Kelepouris, E. & Clegg, D. J. Renal tubular acidosis and management strategies: a narrative review. Adv. Ther. 38, 949–968 (2021).

    Article  PubMed  CAS  Google Scholar 

  268. Matsushita, K. et al. Epidemiology and risk of cardiovascular disease in populations with chronic kidney disease. Nat. Rev. Nephrol. 18, 696–707 (2022).

    Article  PubMed  Google Scholar 

  269. Kalim, S. et al. Protein carbamylation and the risk of ESKD in patients with CKD. J. Am. Soc. Nephrol. 34, 876–885 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  270. Xu, J. et al. Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure. J. Clin. Invest. 115, 1275–1280 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  271. Whitlock, R. et al. The association between dual RAAS inhibition and risk of acute kidney injury and hyperkalemia in patients with diabetic kidney disease: a systematic review and meta-analysis. Nephrol. Dial. Transplant. 38, 2503–2516 (2023).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  272. Anders, H. J., Peired, A. J. & Romagnani, P. SGLT2 inhibition requires reconsideration of fundamental paradigms in chronic kidney disease, ‘diabetic nephropathy’, IgA nephropathy and podocytopathies with FSGS lesions. Nephrol. Dial. Transplant. 37, 1609–1615 (2022).

    Article  PubMed  CAS  Google Scholar 

  273. Ortiz, A., Wanner, C. & Gansevoort, R. Chronic kidney disease as cardiovascular risk factor in routine clinical practice: a position statement by the Council of the European Renal Association. Nephrol. Dial. Transplant. 38, 527–531 (2023).

    Article  PubMed  Google Scholar 

  274. de Zeeuw, D. et al. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. N. Engl. J. Med. 369, 2492–2503 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  275. Lewis, E. J. et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N. Engl. J. Med. 345, 851–860 (2001).

    Article  PubMed  CAS  Google Scholar 

  276. Mann, J. F. et al. Avosentan for overt diabetic nephropathy. J. Am. Soc. Nephrol. 21, 527–535 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  277. Parving, H. H. et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N. Engl. J. Med. 367, 2204–2213 (2012).

    Article  PubMed  CAS  Google Scholar 

  278. Perkovic, V. et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N. Engl. J. Med. 380, 2295–2306 (2019).

    Article  PubMed  CAS  Google Scholar 

  279. Pfeffer, M. A. et al. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N. Engl. J. Med. 361, 2019–2032 (2009).

    Article  PubMed  Google Scholar 

  280. Pitt, B. et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N. Engl. J. Med. 385, 2252–2263 (2021).

    Article  PubMed  CAS  Google Scholar 

  281. Sharma, K. et al. Pirfenidone for diabetic nephropathy. J. Am. Soc. Nephrol. 22, 1144–1151 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  282. Tuttle, K. R., McGill, J. B., Haney, D. J., Lin, T. E. & Anderson, P. W. Kidney outcomes in long-term studies of ruboxistaurin for diabetic eye disease. Clin. J. Am. Soc. Nephrol. 2, 631–636 (2007).

    Article  PubMed  CAS  Google Scholar 

  283. Wanner, C. et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N. Engl. J. Med. 353, 238–248 (2005).

    Article  PubMed  CAS  Google Scholar 

  284. Bakris, G. L. et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N. Engl. J. Med. 383, 2219–2229 (2020).

    Article  PubMed  CAS  Google Scholar 

  285. Herrington, W. G. et al. Empagliflozin in patients with chronic kidney disease. N. Engl. J. Med. 388, 117–127 (2023).

    Article  PubMed  CAS  Google Scholar 

  286. Packham, D. K. et al. Sulodexide fails to demonstrate renoprotection in overt type 2 diabetic nephropathy. J. Am. Soc. Nephrol. 23, 123–130 (2012).

    Article  PubMed  CAS  Google Scholar 

  287. Singh, A. K. & Singh, R. Renin-angiotensin system blockers-SGLT2 inhibitors-mineralocorticoid receptor antagonists in diabetic kidney disease: a tale of the past two decades. World J. Diabetes 13, 471–481 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  288. Lichtnekert, J. & Anders, H. J. Lupus nephritis-related chronic kidney disease. Nat. Rev. Rheumatol. 20, 699–711 (2024).

    Article  PubMed  CAS  Google Scholar 

  289. Yau, K., Kuah, R., Cherney, D. Z. I. & Lam, T. K. T. Obesity and the kidney: mechanistic links and therapeutic advances. Nat. Rev. Endocrinol. 20, 321–335 (2024).

    Article  PubMed  Google Scholar 

  290. Anders, H. J., Davis, J. M. & Thurau, K. Nephron protection in diabetic kidney disease. N. Engl. J. Med. 375, 2096–2098 (2016).

    Article  PubMed  Google Scholar 

  291. Vallon, V. The mechanisms and therapeutic potential of SGLT2 inhibitors in diabetes mellitus. Annu. Rev. Med. 66, 255–270 (2015).

    Article  PubMed  CAS  Google Scholar 

  292. Beers, K. & Patel, N. Kidney physiology in pregnancy. Adv. Chronic Kidney Dis. 27, 449–454 (2020).

    Article  PubMed  Google Scholar 

  293. Perazella, M. A. Pharmacology behind common drug nephrotoxicities. Clin. J. Am. Soc. Nephrol. 13, 1897–1908 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  294. Hall, R. K. et al. Drug stewardship in chronic kidney disease to achieve effective and safe medication use. Nat. Rev. Nephrol. 20, 386–401 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  295. Brenner, B. M., Garcia, D. L. & Anderson, S. Glomeruli and blood pressure. Less of one, more the other? Am. J. Hypertens. 1, 335–347 (1988).

    Article  PubMed  CAS  Google Scholar 

  296. Cirillo, L. et al. Chronic kidney disease in children: an update. Clin. Kidney J. 16, 1600–1611 (2023).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  297. The Low Birth Weight and Nephron Number Working Group The impact of kidney development on the life course: a consensus document for action. Nephron 136, 3–49 (2017).

    Article  Google Scholar 

  298. Trautmann, A. et al. Spectrum of steroid-resistant and congenital nephrotic syndrome in children: the PodoNet registry cohort. Clin. J. Am. Soc. Nephrol. 10, 592–600 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  299. Vivante, A. & Hildebrandt, F. Exploring the genetic basis of early-onset chronic kidney disease. Nat. Rev. Nephrol. 12, 133–146 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  300. Oliveira, B., Kleta, R., Bockenhauer, D. & Walsh, S. B. Genetic, pathophysiological, and clinical aspects of nephrocalcinosis. Am. J. Physiol. Renal Physiol. 311, F1243–F1252 (2016).

    Article  PubMed  CAS  Google Scholar 

  301. Eckardt, K. U. et al. Autosomal dominant tubulointerstitial kidney disease: diagnosis, classification, and management—a KDIGO consensus report. Kidney Int. 88, 676–683 (2015).

    Article  PubMed  CAS  Google Scholar 

  302. Cain, J. E., Di Giovanni, V., Smeeton, J. & Rosenblum, N. D. Genetics of renal hypoplasia: insights into the mechanisms controlling nephron endowment. Pediatr. Res. 68, 91–98 (2010).

    Article  PubMed  Google Scholar 

  303. Uy, N. & Reidy, K. Developmental genetics and congenital anomalies of the kidney and urinary tract. J. Pediatr. Genet. 5, 51–60 (2016).

    Article  PubMed  CAS  Google Scholar 

  304. Yuan, X. et al. Genetic variants of the COL4A3, COL4A4, and COL4A5 genes contribute to thinned glomerular basement membrane lesions in sporadic IgA nephropathy patients. J. Am. Soc. Nephrol. 34, 132–144 (2023).

    Article  PubMed  Google Scholar 

  305. Dummer, P. D. et al. APOL1 kidney disease risk variants: an evolving landscape. Semin. Nephrol. 35, 222–236 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  306. Kruzel-Davila, E. et al. APOL1-mediated cell injury involves disruption of conserved trafficking processes. J. Am. Soc. Nephrol. 28, 1117–1130 (2017).

    Article  PubMed  CAS  Google Scholar 

  307. Köttgen, A. et al. Multiple loci associated with indices of renal function and chronic kidney disease. Nat. Genet. 41, 712–717 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  308. De Chiara, L. et al. Tubular cell polyploidy protects from lethal acute kidney injury but promotes consequent chronic kidney disease. Nat. Commun. 13, 5805 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

P.R. is funded by the European Research Council under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 101019891). H.-J.A. has received support by the Deutsche Forschungsgemeinschaft (AN372/29-1). R.K. is supported by the Rainer Arnhold Grant by Mulago Foundation. The authors thank B. Wang for their contribution in Box 4.

Author information

Authors and Affiliations

  1. Nephrology and Dialysis Unit, Meyer Children’s Hospital IRCCS, Florence, Italy

    Paola Romagnani

  2. Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, University of Florence, Florence, Italy

    Paola Romagnani

  3. Richard L. Roudebush VA Medical Center and Indiana University, Indianapolis, IN, USA

    Rajiv Agarwal

  4. Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences and Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong

    Juliana C. N. Chan

  5. Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

    Adeera Levin

  6. BC Renal, Provincial Health Services Authority, Vancouver, British Columbia, Canada

    Adeera Levin

  7. African Community Center for Social Sustainability, Nakaseke District, Uganda

    Robert Kalyesubula

  8. Department of Physiology, College of Health Sciences, Makerere University, Kampala, Uganda

    Robert Kalyesubula

  9. Division of Nephrology and Hypertension, University of Minnesota, Minneapolis, MN, USA

    Sabine Karam

  10. Department of Internal Medicine, Division of Nephrology and Hypertension, American University of Beirut, Beirut, Lebanon

    Sabine Karam

  11. Division of Nephrology and Endocrinology, The University of Tokyo, Bunkyo City, Tokyo, Japan

    Masaomi Nangaku

  12. Department of Nephrology and Mineral Metabolism, INCMN Salvador Zubirán, Mexico City, Mexico

    Bernardo Rodríguez-Iturbe

  13. Division of Nephrology, Department of Medicine IV, Hospital of the Ludwig-Maximilians University, Munich, Germany

    Hans-Joachim Anders

Authors
  1. Paola Romagnani
    View author publications

    Search author on:PubMed Google Scholar

  2. Rajiv Agarwal
    View author publications

    Search author on:PubMed Google Scholar

  3. Juliana C. N. Chan
    View author publications

    Search author on:PubMed Google Scholar

  4. Adeera Levin
    View author publications

    Search author on:PubMed Google Scholar

  5. Robert Kalyesubula
    View author publications

    Search author on:PubMed Google Scholar

  6. Sabine Karam
    View author publications

    Search author on:PubMed Google Scholar

  7. Masaomi Nangaku
    View author publications

    Search author on:PubMed Google Scholar

  8. Bernardo Rodríguez-Iturbe
    View author publications

    Search author on:PubMed Google Scholar

  9. Hans-Joachim Anders
    View author publications

    Search author on:PubMed Google Scholar

Contributions

All authors contributed equally to all sections of the Primer, with H.-J.A. coordinating the project.

Corresponding author

Correspondence to Hans-Joachim Anders.

Ethics declarations

Competing interests

Related to the content of this paper, H.-J.A. received funding from Boehringer Ingelheim and consultancy fees from Novartis, AstraZeneca, Bayer, Boehringer Ingelheim, Vifor, Otsuka, Roche and Eli Lilly. H.-J.A. received payments from the European Renal Association for his role as Editor-in-Chief of Nephrology Dialysis Transplantation. H.-J.A. is a member of the Western-European Regional board of the International Society of Nephrology (ISN). Related to the content of this paper, M.N. received research funding from Kyowa-Kirin, Daiichi-Sankyo, Astellas, Ono, Mitsubishi-Tanabe, Japan Tobacco, Chugai, Bayer, Torii and Takeda. M.N. received honoraria and advisory fees from Kyowa-Kirin, Astellas, AstraZeneca, GlaxoSmithKline, Daiichi-Sankyo, Mitsubishi-Tanabe, Chugai, Torii, Japan Tobacco, Novo Nordisk and Boehringer Ingelheim. M.N. is President of the ISN, President of the Japanese Society of Nephrology, Immediate President of the Asian Pacific Society of Nephrology, President of the Japanese Society of Internal Medicine and Vice President of the Japanese Medical Science Federation. A.L. has no conflicts of interest regarding her contribution to this article, although she was the co-chair of the KDIGO Update on Chronic Kidney Disease Evaluation and Management 2024. B.R.-I. and P.R. declare no competing interests. R.A. reports personal fees from Akebia Therapeutics, Inc., Bayer Healthcare Pharmaceuticals Inc., Boehringer Ingelheim, Chinook, Vertex, Alynlam, Intercept, Eloxx and Novartis. R.A. is an associate editor at Nephrology Dialysis Transplantation and American Journal of Nephrology, and acting Editor in Chief of American Journal of Nephrology. He is a section editor of nephrology at UpToDate. J.C.N.C. reports receiving grants (through institutions) and/or honoraria for consultancy or giving lectures from Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Celltrion, Eli Lilly, Hua Medicine, Powder Pharmaceuticals, Roche, Merck, MSD, Pfizer, Sanofi, Servier, Viatris and Zuellig Therapeutics. She is a co-inventor of patents assigned to the Chinese University of Hong Kong with claims of using genetic and multiomic markers to identify patients at high risk for diabetes and its complications for personalized treatment. She is the co-founder of GemVCare, a technology company, with partial support from the Hong Kong Government, which uses biogenetic markers and information technology to implement precision diabetes care and prevention through partnerships. J.C.N.C. is the Chief Executive Officer (pro bono) of the Asia Diabetes Foundation that developed the web-based JADE platform for implementation of data-driven diabetes care. She is a member of the Global Council of the European Association for Study of Diabetes and a member of the International Diabetes Federation Global Guidelines for type 2 diabetes and member of working groups of KDIGO. R.K. is a member of the African board of the ISN. S.K. is a member of the North American board of the ISN, an adviser to the Middle-East board of the ISN, a member of the education workgroup and the social media team of the ISN, a member of the core program committee of the ISN, and the chair of the young nephrologists committee of the ISN. S.K. is also a member of the clinical nephrology commission of the Société Francophone de Néphrologie Dialyse et Transplantation (SFNDT) and of the webinars committee of the SFNDT. She is also the co-chair of the education committee of the American Society of Onco-nephrology.

Peer review

Peer review information

Nature Reviews Disease Primers thanks S. H. Han, K. Kalantar-Zadeh, I. Ulasi and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

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

Informed consent

The authors affirm that patient participants provided informed consent for publication of their experiences.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Romagnani, P., Agarwal, R., Chan, J.C.N. et al. Chronic kidney disease. Nat Rev Dis Primers 11, 8 (2025). https://doi.org/10.1038/s41572-024-00589-9

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41572-024-00589-9

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