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Kidney disease in children: latest advances and remaining challenges


To mark World Kidney Day 2016, Nature Reviews Nephrology invited six leading researchers to highlight the key advances and challenges within their specialist field of paediatric nephrology. Here, advances and remaining challenges in the fields of prenatal patterning, acute kidney injury, renal transplantation, genetics, cardiovascular health, and growth and nutrition, are all discussed within the context of paediatric and neonatal patients with kidney disease. Our global panel of researchers describe areas in which further studies and clinical advances are needed, and suggest ways in which research in these areas should progress to optimize renal care and long-term outcomes for affected patients.

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Figure 1: Morphologic stages of metanephric kidney development.
Figure 2: Milestones in paediatric acute kidney injury (AKI) research.
Figure 3: Renal allograft failure rate according to age in patients first transplanted <40 years of age.
Figure 4: Bone disease and arterial calcification due to dysregulated mineral homeostasis in children with advanced chronic kidney disease (CKD).
Figure 5: Height and weight Z scores at the time of kidney transplantation for recipients included in the NAPRTCS registry between 1987 and 2013.


  1. 1

    Little, M. H. Kidney Development, Disease, Repair and Regeneration (Elsevier Academic Press, 2016).

    Google Scholar 

  2. 2

    Park, J. -S. & McMahon, A. P. in Kidney Development, Disease, Repair and Regeneration (ed Little, M. H.) 67–74 (Elsevier Academic Press, 2016).

    Book  Google Scholar 

  3. 3

    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  Google Scholar 

  4. 4

    Zhang, Z. et al. A common RET variant is associated with reduced newborn kidney size and function. J. Am. Soc. Nephrol. 19, 2027–2034 (2008).

    CAS  Article  Google Scholar 

  5. 5

    Hughson, M., Farris, A. B. 3rd, Douglas-Denton, R., Hoy, W. E. & Bertram J. F. Glomerular number and size in autopsy kidneys: the relationship to birth weight. Kidney Int. 63, 2113–2122 (2003).

    Article  Google Scholar 

  6. 6

    Costantini, F. in Kidney Development, Disease, Repair and Regeneration (ed Little, M. H.) 41–56 (Elsevier Academic Press, 2016).

    Book  Google Scholar 

  7. 7

    Oxburgh, L. in Kidney Development, Disease, Repair and Regeneration (ed Little, M. H.) 75–86 (Elsevier Academic Press, 2016).

    Book  Google Scholar 

  8. 8

    Park, J. -S. & Kopan, R. in Kidney Development, Disease, Repair and Regeneration (ed Little, M. H.) 87–93 (Elsevier Academic Press, 2016).

    Book  Google Scholar 

  9. 9

    McMahon, A. P. et al. GUDMAP: the genitourinary developmental molecular anatomy project. J. Am. Soc. Nephrol. 19, 667–671 (2008).

    Article  Google Scholar 

  10. 10

    Harding, S. D. et al. The GUDMAP database — an online resource for genitourinary research. Development 138, 2845–2853 (2011).

    CAS  Article  Google Scholar 

  11. 11

    Luyckx, V. A. et al. Effect of fetal and child health on kidney development and long-term risk of hypertension and kidney disease. Lancet 382, 273–283 (2013).

    Article  Google Scholar 

  12. 12

    Moritz, K. M. in Kidney Development, Disease, Repair and Regeneration (ed Little, M. H.) 177–190 (Elsevier Academic Press, 2016).

    Book  Google Scholar 

  13. 13

    Nicolaou, N., Renkema, K. Y., Bongers, E. M., Giles, R. H. & Knoers, N. V. Genetic, environmental, and epigenetic factors involved in CAKUT. Nat. Rev. Nephrol. 11, 720–731 (2015).

    CAS  Article  Google Scholar 

  14. 14

    Beeman, S. C. et al. MRI-based glomerular morphology and pathology in whole human kidneys. Am. J. Physiol. Renal 306, F1381–F1390 (2014).

    CAS  Article  Google Scholar 

  15. 15

    Sutherland, M. R. et al. Accelerated maturation and abnormal morphology in the preterm neonatal kidney. J. Am. Soc. Nephrol. 22, 1365–1374 (2011).

    Article  Google Scholar 

  16. 16

    Sutherland, S. M. et al. AKI in hospitalized children: epidemiology and clinical associations in a national cohort. Clin. J. Am. Soc. Nephrol. 8, 1661–1669 (2013).

    Article  Google Scholar 

  17. 17

    Sanchez-Pinto, L. N., Goldstein, S. L., Schneider, J. B. & Khemani, R. G. Association between progression and improvement of acute kidney injury and mortality in critically ill children. Pediatr. Crit. Care Med. 16, 703–710 (2015).

    Article  Google Scholar 

  18. 18

    Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO clinical practice guideline for acute kidney injury. Kidney Int. Suppl. 2, 1–138 (2012).

  19. 19

    Kellum, J. A., Bellomo, R. & Ronco, C. Kidney attack. JAMA 307, 2265–2266 (2012).

    CAS  Article  Google Scholar 

  20. 20

    Goldstein, S. L. & Chawla, L. S. Renal angina. Clin. J. Am. Soc. Nephrol. 5, 943–949 (2010).

    Article  Google Scholar 

  21. 21

    Basu, R. K. et al. Derivation and validation of the renal angina index to improve the prediction of acute kidney injury in critically ill children. Kidney Int. 85, 659–667 (2014).

    Article  Google Scholar 

  22. 22

    Basu, R. K. et al. Incorporation of biomarkers with the renal angina index for prediction of severe AKI in critically ill children. Clin. J. Am. Soc. Nephrol. 9, 654–662 (2014).

    Article  Google Scholar 

  23. 23

    Basu, R. K. et al. Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology in critically ill children (AWARE): study protocol for a prospective observational study. BMC Nephrol. 16, 24 (2015).

    Article  Google Scholar 

  24. 24

    Hui-Stickle, S., Brewer, E. D. & Goldstein, S. L. Pediatric ARF epidemiology at a tertiary care center from 1999 to 2001. Am. J. Kidney Dis. 45, 96–101 (2005).

    Article  Google Scholar 

  25. 25

    Zappitelli, M., Moffett, B. S., Hyder, A. & Goldstein, S. L. Acute kidney injury in non-critically ill children treated with aminoglycoside antibiotics in a tertiary healthcare centre: a retrospective cohort study. Nephrol. Dial. Transplant. 26, 144–150 (2011).

    Article  Google Scholar 

  26. 26

    Goldstein, S. L. et al. Electronic health record identification of nephrotoxin exposure and associated acute kidney injury. Pediatrics 132, e756–e767 (2013).

    Article  Google Scholar 

  27. 27

    Askenazi, D. J., Ambalavanan, N. & Goldstein, S. L. Acute kidney injury in critically ill newborns: what do we know? What do we need to learn? Pediatr. Nephrol. 24, 265–274 (2009).

    Article  Google Scholar 

  28. 28

    White, S. L. et al. Is low birth weight an antecedent of CKD in later life? A systematic review of observational studies. Am. J. Kidney Dis. 54, 248–261 (2009).

    Article  Google Scholar 

  29. 29

    Ronco, C. et al. Continuous renal replacement therapy in neonates and small infants: development and first-in-human use of a miniaturised machine (CARPEDIEM). Lancet 383, 1807–1813 (2014).

    Article  Google Scholar 

  30. 30

    Coulthard, M. G. et al. Haemodialysing babies weighing &lt;8 kg with the Newcastle infant dialysis and ultrafiltration system (Nidus): comparison with peritoneal and conventional haemodialysis. Pediatr. Nephrol. 29, 1873–1881 (2014).

    Article  Google Scholar 

  31. 31

    Frei, U. & Schober-Halstenberg, H. -J. Nierenersatztherapie in Deutschland. Bericht über Dialysebehandlung und Nierentransplantation in Deutschland. Bundesverband Niere E.V. [online], (2008).

  32. 32

    Foster, B. J. Heightened graft failure risk during emerging adulthood and transition to adult care. Pediatr. Nephrol. 30, 567–576 (2015).

    Article  Google Scholar 

  33. 33

    Foster, B. J. et al. Association between age and graft failure rates in young kidney transplant recipients. Transplantation 92, 1237–1243 (2011).

    Article  Google Scholar 

  34. 34

    Watson, A. R. Non-compliance and transfer from paediatric to adult transplant unit. Pediatr. Nephrol. 14, 469–472 (2000).

    CAS  Article  Google Scholar 

  35. 35

    Prestidge, C., Romann, A., Djurdjev, O. & Matsuda-Abedini, M. Utility and cost of a renal transplant transition clinic. Pediatr. Nephrol. 27, 295–302 (2012).

    Article  Google Scholar 

  36. 36

    Harden, P. N. et al. Bridging the gap: an integrated paediatric to adult clinical service for young adults with kidney failure. BMJ 344, e3718 (2012).

    CAS  Article  Google Scholar 

  37. 37

    Kreuzer, M. et al. The TRANSNephro-study examining a new transition model for post-kidney transplant adolescents and an analysis of the present health care: study protocol for a randomized controlled trial. Trials 15, 505 (2014).

    Article  Google Scholar 

  38. 38

    Brunkhorst, L. C. et al. Efficacy and safety of an everolimus- versus a mycophenolate mofetil-based regimen in pediatric renal transplant recipients. PLoS ONE 10, e0135439 (2015).

    Article  Google Scholar 

  39. 39

    Ahlenstiel-Grunow, T. et al. A multicenter, randomized, open-labeled study to steer immunosuppressive and antiviral therapy by measurement of virus (CMV, ADV, HSV)-specific T cells in addition to determination of trough levels of immunosuppressants in pediatric kidney allograft recipients (IVIST01-trial): study protocol for a randomized controlled trial. Trials 15, 324 (2014).

    Article  Google Scholar 

  40. 40

    Miettinen, J. et al. Donor-specific HLA antibodies and graft function in children after renal transplantation. Pediatr. Nephrol. 27, 1011–1019 (2012).

    Article  Google Scholar 

  41. 41

    Einecke, G. et al. Antibody-mediated microcirculation injury is the major cause of late kidney transplant failure. Am. J. Transplant. 9, 2520–2531 (2009).

    CAS  Article  Google Scholar 

  42. 42

    Billing, H. et al. Successful treatment of chronic antibody-mediated rejection with IVIG and rituximab in pediatric renal transplant recipients. Transplantation 86, 1214–1221 (2008).

    CAS  Article  Google Scholar 

  43. 43

    Hartmann, H. et al. Early kidney transplantation improves neurocognitive outcome in patients with severe congenital chronic kidney disease. Transpl. Int. 28, 429–436 (2015).

    Article  Google Scholar 

  44. 44

    Offner, G. et al. Kidney transplanted children come of age. Kidney Int. 55, 1509–1517 (1999).

    CAS  Article  Google Scholar 

  45. 45

    Devuyst, O., Knoers, N. V., Remuzzi, G. & Schaefer, F. Rare inherited kidney diseases: challenges, opportunities, and perspectives. Lancet 383, 1844–1859 (2014).

    Article  Google Scholar 

  46. 46

    Sadowski, C. E. et al. A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome. J. Am. Soc. Nephrol. 26, 1279–1289 (2015).

    CAS  Article  Google Scholar 

  47. 47

    Lipska, B. S. et al. Genotype–phenotype associations in WT1 glomerulopathy. Kidney Int. 85, 1169–1178 (2014).

    CAS  Article  Google Scholar 

  48. 48

    Cramer, M. T. et al. Expanding the phenotype of proteinuria in Dent disease. A case series. Pediatr. Nephrol. 29, 2051–2054 (2014).

    Article  Google Scholar 

  49. 49

    Weber, S. et al. Prevalence of mutations in renal developmental genes in children with renal hypodysplasia: results of the ESCAPE study. J. Am. Soc. Nephrol. 17, 2864–2870 (2006).

    CAS  Article  Google Scholar 

  50. 50

    Bockenhauer, D. & Jaureguiberry, G. HNF1B-associated clinical phenotypes: the kidney and beyond. Pediatr Nephrol. (2015).

  51. 51

    Wong, E. K., Goodship, T. H. & Kavanagh, D. Complement therapy in atypical haemolytic uraemic syndrome (aHUS). Mol. Immunol. 56, 199–212 (2013).

    CAS  Article  Google Scholar 

  52. 52

    Heeringa, S. F. et al. COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness. J. Clin. Invest. 121, 2013–2024 (2011).

    CAS  Article  Google Scholar 

  53. 53

    Korkmaz, E. et al. ADCK4-associated glomerulopathy causes adolescence-onset FSGS. J. Am. Soc. Nephrol. 27, 63–68 (2015).

    Article  Google Scholar 

  54. 54

    Nicolaou, N., Renkema, K. Y., Bongers, E. M., Giles, R. H. & Knoers, N. V. Genetic, environmental, and epigenetic factors involved in CAKUT. Nat. Rev. Nephrol. 11, 11720–11731 (2015).

    Article  Google Scholar 

  55. 55

    Dart, A. B., Ruth, C. A., Sellers, E. A., Au, W. & Dean, H. J. Maternal diabetes mellitus and congenital anomalies of the kidney and urinary tract (CAKUT) in the child. Am. J. Kidney Dis. 65, 684–691 (2015).

    Article  Google Scholar 

  56. 56

    USRDS. USRDS 2011 annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States. [online], (2011).

  57. 57

    Borzych, D. et al. The bone and mineral disorder of children undergoing chronic peritoneal dialysis. Kidney Int. 78, 1295–1304 (2010).

    Article  Google Scholar 

  58. 58

    Shroff, R., Long, D. A. & Shanahan, C. Mechanistic insights into vascular calcification in CKD. J. Am. Soc. Nephrol. 24, 179–189 (2013).

    CAS  Article  Google Scholar 

  59. 59

    Shroff, R. et al. Dialysis accelerates medial vascular calcification in part by triggering smooth muscle cell apoptosis. Circulation 118, 1748–1757 (2008).

    CAS  Article  Google Scholar 

  60. 60

    Ragnauth, C. D. et al. Prelamin A acts to accelerate smooth muscle cell senescence and is a novel biomarker of human vascular aging. Circulation 121, 2200–2210 (2010).

    CAS  Article  Google Scholar 

  61. 61

    Goodman, W. G. et al. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N. Engl. J. Med. 342, 1478–1483 (2000).

    CAS  Article  Google Scholar 

  62. 62

    J. Oh et al. Advanced coronary and carotid arteriopathy in young adults with childhood-onset chronic renal failure. Circulation 106, 100–105 (2002).

    Article  Google Scholar 

  63. 63

    Brady, T. M. et al. Carotid intima-media thickness in children with CKD: results from the CKiD study. Clin. J. Am. Soc. Nephrol. 7, 1930–1937 (2012).

    Article  Google Scholar 

  64. 64

    Kupferman, J. C. et al. BP control and left ventricular hypertrophy regression in children with CKD. J. Am. Soc. Nephrol. 25, 167–174 (2014).

    Article  Google Scholar 

  65. 65

    Khouzam, N. M., Wesseling-Perry, K. & Salusky, I. B. The role of bone in CKD-mediated mineral and vascular disease. Pediatr. Nephrol. 30, 1379–1388 (2015).

    Article  Google Scholar 

  66. 66

    Denburg, M. R. et al. Fracture burden and risk factors in childhood CKD: results from the CKiD Cohort Study. J. Am. Soc. Nephrol. (2015).

  67. 67

    Salusky, B. et al. Sevelamer controls parathyroid hormone-induced bone disease as efficiently as calcium carbonate without increasing serum calcium levels during therapy with active vitamin D sterols. J. Am. Soc. Nephrol. 16, 2501–2508 (2005).

    CAS  Article  Google Scholar 

  68. 68

    KDIGO. Clinical practice guideline for the diagnosis KDIGO evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int. 76 (Suppl. 113), S1 (2009).

  69. 69

    Hahn, D. & Hodson, E. M., & Craig, J. C. Interventions for metabolic bone disease in children with chronic kidney disease. Cochrane Database Syst. Rev. 11, CD008327 (2015).

    Google Scholar 

  70. 70

    Querfeld, U. et al. The Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study: objectives, design, and methodology. Clin. J. Am. Soc. Nephrol. 5, 1642–1648 (2010).

    Article  Google Scholar 

  71. 71

    Guthrie, L. G. Chronic interstitial nephritis in childhood. Lancet 149, 585 (1897).

    Article  Google Scholar 

  72. 72

    Furth, S. L., Stablein, D., Fine R. N., Powe, N. R. & Fivush, B. A. Adverse clinical outcomes associated with short stature at dialysis initiation: a report of the North American Pediatric Renal Transplant Cooperative study. Pediatrics 109, 909–913 (2002).

    Article  Google Scholar 

  73. 73

    Rosenkranz, J. et al. Psychosocial rehabilitation and satisfaction with life in adults with childhood-onset of end-stage renal disease. Pediatr. Nephrol. 20, 1288–1294 (2005).

    Article  Google Scholar 

  74. 74

    Martz, K. & Stablein, D. M. North American Pediatric Renal Trials and Cooperative Studies (NAPRTCS) 2008 annual report. Emmes [online], (2008).

    Google Scholar 

  75. 75

    Rodig, N. M. et al. Growth in children with chronic kidney disease: a report from the Chronic Kidney Disease in Children Study. Pediatr. Nephrol. 29, 1987–1995 (2014).

    Article  Google Scholar 

  76. 76

    North American Pediatric Renal Trials and Cooperative Studies (NAPRTCS) 2011 annual dialysis report. Emmes [online], (2011).

  77. 77

    North American Pediatric Renal Trials and Cooperative Studies (NAPRTCS) 2014 annual transplant report. Emmes [online], (2014).

  78. 78

    Karlberg, J. et al. Early age-dependent growth impairment in chronic renal failure. Pediatr. Nephrol. 10, 283–287 (1996).

    CAS  Article  Google Scholar 

  79. 79

    NKF-KDOQI clinical practice guideline for nutrition in children with CKD. Am. J. Kidney Dis. 53 (Suppl. 2), S1–S124 (2009).

  80. 80

    Wong, C. S. et al. Anthropometric measures and risk of death in children with end-stage renal disease. Am. J. Kidney Dis. 36, 811–819 (2000).

    CAS  Article  Google Scholar 

  81. 81

    Mak, R. H., Cheung, W. W. & Roberts, C. T. Jr. The growth hormone-insulin-like growth factor-I axis in chronic kidney disease. Growth Horm. IGF Res. 18, 17–25 (2008).

    CAS  Article  Google Scholar 

  82. 82

    Mehls, O. et al. Long-term growth hormone treatment in short children with CKD does not accelerate decline of renal function: results from the KIGS registry & ESCAPE trial. Pediatr. Nephrol. 30, 2145–2151 (2015).

    Article  Google Scholar 

  83. 83

    Fischbach, M. et al. Daily online haemodiafiltration promotes catch-up growth in children on chronic dialysis. Nephrol Dial. Transplant. 25, 867–873 (2010).

    CAS  Article  Google Scholar 

  84. 84

    Watson, A. R. et al. Transition from pediatric to adult renal services: a consensus statement by the International Society of Nephrology (ISN) and the International Pediatric Nephrology Association (IPNA). Pediatr. Nephrol. 26, 1753–1757 (2011).

    Article  Google Scholar 

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The authors would like to thank their colleagues in the field and the efforts of the World Kidney Day initiative, for which the focus for 2016 is “Kidney Disease & Children. Act Early to Prevent It”. J.F.B. is supported by grants from the National Health and Medical Research Council (NHMRC) of Australia, the Diabetes Australia Research Trust (DART), and Monash University. S.L.G. has received funding from the agency for Healthcare Research (grant numbers AHRQ CERT 1U19HS021114 and AHRQ 1R18HS023763-01), the Casey Lee Ball Foundation, and the National Institute for Diabetes, Digestive and Kidney Diseases (grant number NIH P50 DK096418). L.P. has received support for this work from the KfH Foundation for Preventive Medicine. F.S. has received support for this work from the EU 7th Framework Programme (grant number 2012–305608), the KfH Foundation for Preventive Medicine, and the Research Programme of the European Renal Association–European Dialysis and Transplant Association. R.C.S. was supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. B.A.W. receives support from the National Institute of Diabetes and Digestive and Kidney Diseases, with additional funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Heart, Lung and Blood Institute (grants UO1-DK-66143, UO1-DK-66174, UO1-DK-82194, and UO1-DK-66116).

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All authors contributed equally to the preparation of this manuscript.

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Correspondence to John F. Bertram or Stuart L. Goldstein or Lars Pape or Franz Schaefer or Rukshana C. Shroff or Bradley A. Warady.

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Competing interests

S.L.G. has received research grants and consultancy fees, and is a member of the expert panel and speaker's bureau for Baxter and Gambro Renal Products, is a consultant for Akebia, Bellco, and AM Pharma, and is a member of the steering committee for trials for both Otsuka and La Pharmaceuticals. L.P. has received travel support and speaker honoraria from Alexion, Novartis, and Raptor as well as research grants from Novartis. F.S. has received consultancy fees and speaker honoraria from Alexion. R.C.S. has received speaker honoraria from Fresenius Medical Care and Amgen. B.A.W. has received speaker honoraria from Alexion and consultancy fees from Amgen. J.F.B. declares no competing interests.

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Bertram, J., Goldstein, S., Pape, L. et al. Kidney disease in children: latest advances and remaining challenges. Nat Rev Nephrol 12, 182–191 (2016).

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