Skip to main content

Advertisement

SpringerLink
Log in

The CKiD study: overview and summary of findings related to kidney disease progression

  • Educational Review
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

The Chronic Kidney Disease in Children (CKiD) cohort study is a North American (USA and Canada) multicenter, prospective study of children with chronic kidney disease (CKD). The original aims of the study were (1) to identify novel risk factors for CKD progression; (2) to measure the impact of kidney function decline on growth, cognition, and behavior; and (3) to characterize the evolution of cardiovascular disease risk factors. CKiD has developed into a national and international resource for the investigation of a variety of factors related to CKD in children. This review highlights notable findings in the area of CKD progression and outlines ongoing opportunities to enhance understanding of CKD progression in children. CKiD’s contributions to the clinical care of children with CKD include updated and more accurate glomerular filtration rate estimating equations for children and young adults, and resources designed to help estimate the CKD progression timeline. In addition, results from CKiD have strengthened the evidence that treatment of hypertension and proteinuria should continue as a primary strategy for slowing the rate of disease progression in children.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Furth SL, Cole SR, Moxey-Mims M, Kaskel F, Mak R, Schwartz G, Wong C, Muñoz A, Warady BA (2006) Design and methods of the Chronic Kidney Disease in Children (CKiD) prospective cohort study. Clin J Am Soc Nephrol 1:1006–1015

    PubMed  PubMed Central  Google Scholar 

  2. Schwartz GJ, Haycock GB, Edelmann CM, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263

    CAS  PubMed  Google Scholar 

  3. Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637

    PubMed  PubMed Central  Google Scholar 

  4. Ng DK, Schwartz GJ, Jacobson LP, Palella FJ, Margolick JB, Warady BA, Furth SL, Muñoz A (2011) Universal GFR determination based on two time points during plasma iohexol disappearance. Kidney Int 80:423–430

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Ng DK, Levey AS, Shlipak MG, Muñoz A, Inker LA, Shafi T (2019) Validation of a simple equation for glomerular filtration rate measurement based on plasma iohexol disappearance. Clin Kidney J. https://doi.org/10.1093/ckj/sfz083

  6. Schwartz GJ, Schneider MF, Maier PS, Moxey-Mims M, Dharnidharka VR, Warady BA, Furth SL, Muñoz A (2012) Improved equations estimating GFR in children with chronic kidney disease using an immunonephelometric determination of cystatin C. Kidney Int 82:445–453

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Ng DK, Schwartz GJ, Schneider MF, Furth SL, Warady BA (2018) Combination of pediatric and adult formulas yield valid glomerular filtration rate estimates in young adults with a history of pediatric chronic kidney disease. Kidney Int 94:170–177

    PubMed  PubMed Central  Google Scholar 

  8. Selistre L, De Souza V, Cochat P, Antonello IC, Hadj-Aissa A, Ranchin B, Dolomanova O, Varennes A, Beyerle F, Bacchetta J, Dubourg L (2012) GFR estimation in adolescents and young adults. J Am Soc Nephrol 23:989–996

    CAS  PubMed  Google Scholar 

  9. Ng DK, Schwartz GJ, Warady BA, Furth SL, Muñoz A (2017) Relationships of measured iohexol GFR and estimated GFR with CKD-related biomarkers in children and adolescents. Am J Kidney Dis 70:397–405

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Levin A, Stevens PE, Bilous RW, Coresh J, De Francisco ALM, De Jong PE, Griffith KE, Hemmelgarn BR, Iseki K, Lamb EJ, Levey AS, Riella MC, Shlipak MG, Wang H, White CT, Winearls CG (2013) Kidney disease: improving global outcomes (KDIGO) CKD work group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 3. https://doi.org/10.1038/kisup.2012.73

  11. Furth SL, Pierce C, Hui WF, White CA, Wong CS, Schaefer F, Wühl E, Abraham AG, Warady BA, Chronic Kidney Disease in Children (CKiD); Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) Study Investigators (2018) Estimating time to ESRD in children with CKD. Am J Kidney Dis 71:783–792

    PubMed  PubMed Central  Google Scholar 

  12. ESCAPE Trial Group, Wühl E, Trivelli A, Picca S, Litwin M, Peco-Antic A, Zurowska A, Testa S, Jankauskiene A, Emre S, Caldas-Afonso A, Anarat A, Niaudet P, Mir S, Bakkaloglu A, Enke B, Montini G, Wingen AM, Sallay P, Jeck N, Berg U, Caliskan S, Wygoda S, Hohbach-Hohenfellner K, Dusek J, Urasinski T, Arbeiter K, Neuhaus T, Gellermann J, Drozdz D, Fischbach M, Möller K, Wigger M, Peruzzi L, Mehls O, Schaefer F (2009) Strict blood-pressure control and progression of renal failure in children. N Engl J Med 361:1639–1650

    Google Scholar 

  13. Warady BA, Abraham AG, Schwartz GJ, Wong CS, Muñoz A, Betoko A, Mitsnefes M, Kaskel F, Greenbaum LA, Mak RH, Flynn J, Moxey-Mims MM, Furth S (2015) Predictors of rapid progression of glomerular and nonglomerular kidney disease in children and adolescents: the Chronic Kidney Disease in Children (CKiD) cohort. Am J Kidney Dis

  14. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (2004) The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114(2 Suppl 4th Report):555–576

    Google Scholar 

  15. Dell KM, Matheson M, Hartung EA, Warady BA, Furth SL, Chronic Kidney Disease in Children (CKiD) Study (2016) Kidney disease progression in autosomal recessive polycystic kidney disease. J Pediatr 171:196–201.e1

    PubMed  PubMed Central  Google Scholar 

  16. Fathallah-Shaykh SA, Flynn JT, Pierce CB, Abraham AG, Blydt-Hansen TD, Massengill SF, Moxey-Mims MM, Warady BA, Furth SL, Wong CS (2015) Progression of pediatric CKD of nonglomerular origin in the CKiD cohort. Clin J Am Soc Nephrol 10:571–577

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Flynn JT, Mitsnefes M, Pierce C, Cole SR, Parekh RS, Furth SL, Warady BA, Chronic Kidney Disease in Children Study Group (2008) Blood pressure in children with chronic kidney disease: a report from the Chronic Kidney Disease in Children study. Hypertension 52:631–637

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Barletta GM, Pierce C, Mitsnefes M, Samuels J, Warady BA, Furth S, Flynn J (2018) Is blood pressure improving in children with chronic kidney disease?: a period analysis. Hypertension 71:444–450

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Fuhrman DY, Schneider MF, Dell KM, Blydt-Hansen TD, Mak R, Saland JM, Furth SL, Warady BA, Moxey-Mims MM, Schwartz GJ (2017) Albuminuria, proteinuria, and renal disease progression in children with CKD. Clin J Am Soc Nephrol 12:912–920

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD (1993) The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 329:1456–1462

    CAS  PubMed  Google Scholar 

  21. Ruggenenti P, Perna A, Gherardi G, Benini R, Remuzzi G (2000) Chronic proteinuric nephropathies: outcomes and response to treatment in a prospective cohort of 352 patients with different patterns of renal injury. Am J Kidney Dis 35:1155–1165

    CAS  PubMed  Google Scholar 

  22. Ruggenenti P, Perna A, Gherardi G, Garini G, Zoccali C, Salvadori M, Scolari F, Schena FP, Remuzzi G (1999) Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria. Lancet 354:359–364

    CAS  PubMed  Google Scholar 

  23. Wright JT Jr, Bakris G, Greene T, Agodoa LY, Appel LJ, Charleston J, Cheek D, Douglas-Baltimore JG, Gassman J, Glassock R, Hebert L, Jamerson K, Lewis J, Phillips RA, Toto RD, Middleton JP, Rostand SG, African American Study of Kidney Disease and Hypertension Study Group (2002) Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. J Am Med Assoc 288:2421–2431

    CAS  Google Scholar 

  24. Abraham AG, Betoko A, Fadrowski JJ, Pierce C, Furth SL, Warady BA, Muñoz A (2017) Renin–angiotensin II–aldosterone system blockers and time to renal replacement therapy in children with CKD. Pediatr Nephrol 32:643–649

    PubMed  Google Scholar 

  25. Portale AA, Wolf MS, Messinger S, Perwad F, Jüppner H, Warady BA, Furth SL, Salusky IB (2016) Fibroblast growth factor 23 and risk of CKD progression in children. Clin J Am Soc Nephrol 11:1989–1998

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Mitsnefes MM, Betoko A, Schneider MF, Salusky IB, Wolf MS, Jüppner H, Warady BA, Furth SL, Portale AA (2018) FGF23 and left ventricular hypertrophy in children with CKD. Clin J Am Soc Nephrol 13:45–52

    CAS  PubMed  Google Scholar 

  27. Rodenbach KE, Schneider MF, Furth SL, Moxey-Mims MM, Mitsnefes MM, Weaver DJ, Warady BA, Schwartz GJ (2015) Hyperuricemia and progression of CKD in children and adolescents: the Chronic Kidney Disease in Children (CKiD) cohort study. Am J Kidney Dis 66:984–992

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Ng DK, Moxey-Mims M, Warady BA, Furth SL, Muñoz A (2016) Racial differences in renal replacement therapy initiation among children with a nonglomerular cause of chronic kidney disease. Ann Epidemiol 26:780–787.e1

    PubMed  PubMed Central  Google Scholar 

  29. Genovese G, Tonna SJ, Knob AU, Appel GB, Katz A, Bernhardy AJ, Needham AW, Lazarus R, Pollak MR (2010) A risk allele for focal segmental glomerulosclerosis in African Americans is located within a region containing APOL1 and MYH9. Kidney Int 78:698–704

    PubMed  PubMed Central  Google Scholar 

  30. Parsa A, Kao WH, Xie D, Astor BC, Li M, Hsu CY, Feldman HI, Parekh RS, Kusek JW, Greene TH, Fink JC, Anderson AH, Choi MJ, Wright JT Jr, Lash JP, Freedman BI, Ojo A, Winkler CA, Raj DS, Kopp JB, He J, Jensvold NG, Tao K, Lipkowitz MS, Appel LJ, AASK Study Investigators; CRIC Study Investigators (2013) APOL1 risk variants, race, and progression of chronic kidney disease. N Engl J Med 369:2183–2196

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Friedman DJ, Kozlitina J, Genovese G, Jog P, Pollak MR (2011) Population-based risk assessment of APOL1 on renal disease. J Am Soc Nephrol

  32. Ng DK, Robertson CC, Woroniecki RP, Limou S, Gillies CE, Reidy KJ, Winkler CA, Hingorani S, Gibson KL, Hjorten R, Sethna CB, Kopp JB, Moxey-Mims M, Furth SL, Warady BA, Kretzler M, Sedor JR, Kaskel FJ, Sampson MG (2017) APOL1-associated glomerular disease among African-American children: a collaboration of the chronic kidney disease in children (CKiD) and nephrotic syndrome study network (NEPTUNE) cohorts. Nephrol Dial Transplant 32:983–990

    PubMed  Google Scholar 

  33. Wuttke M, Wong CS, Wühl E, Epting D, Luo L, Hoppmann A, Doyon A, Li Y, CKDGen Consortium, Sözeri B, Thurn D, Helmstädter M, Huber TB, Blydt-Hansen TD, Kramer-Zucker A, Mehls O, Melk A, Querfeld U, Furth SL, Warady BA, Schaefer F, Köttgen A (2016) Genetic loci associated with renal function measures and chronic kidney disease in children: the Pediatric Investigation for Genetic Factors Linked with Renal Progression Consortium. Nephrol Dial Transplant 31:262–269

    CAS  PubMed  Google Scholar 

  34. Flynn JT, Ng DK, Chan GJ, Samuels J, Furth S, Warady B, Greenbaum LA, Chronic Kidney Disease in Children Study (2014) The effect of abnormal birth history on ambulatory blood pressure and disease progression in children with chronic kidney disease. J Pediatr 165:154–162.e1

    PubMed  PubMed Central  Google Scholar 

  35. Atkinson MA, Pierce CB, Zack RM, Barletta GM, Yadin O, Mentser M, Warady BA, Furth SL (2010) Hemoglobin differences by race in children with CKD. Am J Kidney Dis 55:1009–1017

    CAS  PubMed  PubMed Central  Google Scholar 

  36. DeWalt DA, Hink A (2009) Health literacy and child health outcomes: a systematic review of the literature. Pediatrics 124(Suppl 3):S265–S274

    PubMed  Google Scholar 

  37. Ricardo AC, Pereira LN, Betoko A, Goh V, Amarah A, Warady BA, Moxey-Mims M, Furth S, Lash JP, Chronic Kidney Disease in Children (CKiD) Cohort Investigators (2018) Parental health literacy and progression of chronic kidney disease in children. Pediatr Nephrol

  38. Baker DW, Williams MV, Parker RM, Gazmararian JA, Nurss J (1999) Development of a brief test to measure functional health literacy. Patient Educ Couns 38:33–42

    CAS  PubMed  Google Scholar 

  39. Hidalgo G, Ng DK, Moxey-Mims M, Minnick ML, Blydt-Hansen T, Warady BA, Furth SL (2013) Association of income level with kidney disease severity and progression among children and adolescents with CKD: a report from the chronic kidney disease in children (CKiD) study. Am J Kidney Dis 62:1087–1094

    PubMed  Google Scholar 

  40. Kumar J, McDermott K, Abraham AG, Friedman LA, Johnson VL, Kaskel FJ, Furth SL, Warady BA, Portale AA, Melamed ML (2016) Prevalence and correlates of 25-hydroxyvitamin D deficiency in the Chronic Kidney Disease in Children (CKiD) cohort. Pediatr Nephrol 31:121–129

    PubMed  Google Scholar 

  41. Altemose KE, Kumar J, Portale AA, Warady BA, Furth SL, Fadrowski JJ, Atkinson MA (2018) Vitamin D insufficiency, hemoglobin, and anemia in children with chronic kidney disease. Pediatr Nephrol 33:2131–2136

    PubMed  PubMed Central  Google Scholar 

  42. Patel HP, Saland JM, Ng DK, Jiang S, Warady BA, Furth SL, Flynn JT (2017) Waist circumference and body mass index in children with chronic kidney disease and metabolic, cardiovascular, and renal outcomes. J Pediatr 191:133–139

    PubMed  PubMed Central  Google Scholar 

  43. Blydt-Hansen TD, Pierce CB, Cai Y, Samsonov D, Massengill S, Moxey-Mims M, Warady BA, Furth SL (2014) Medication treatment complexity and adherence in children with CKD. Clin J Am Soc Nephrol 9:247–254

    PubMed  Google Scholar 

  44. Fadrowski JJ, Abraham AG, Navas-Acien A, Guallar E, Weaver VM, Furth SL (2013) Blood lead level and measured glomerular filtration rate in children with chronic kidney disease. Environ Health Perspect 121:965–970

    PubMed  PubMed Central  Google Scholar 

  45. Chen W, Ducharme-Smith K, Davis L, Hui WF, Warady BA, Furth SL, Abraham AG, Betoko A (2017) Dietary sources of energy and nutrient intake among children and adolescents with chronic kidney disease. Pediatr Nephrol 32:1233–1241

    PubMed  PubMed Central  Google Scholar 

  46. Saran R, Li Y, Robinson B, Ayanian J, Balkrishnan R, Bragg-Gresham J, Chen JT, Cope E, Gipson D, He K, Herman W, Heung M, Hirth RA, Jacobsen SS, Kalantar-Zadeh K, Kovesdy CP, Leichtman AB, Lu Y, Molnar MZ, Morgenstern H, Nallamothu B, O'Hare AM, Pisoni R, Plattner B, Port FK, Rao P, Rhee CM, Schaubel DE, Selewski DT, Shahinian V, Sim JJ, Song P, Streja E, Kurella Tamura M, Tentori F, Eggers PW, Agodoa LY, Abbott KC (2015) US renal data system 2014 annual data report: epidemiology of kidney disease in the United States. Am J Kidney Dis 66(1 Suppl 1):Svii, S1-305

    PubMed  Google Scholar 

  47. Gore JL, Danovitch GM, Litwin MS, Pham PTT, Singer JS (2009) Disparities in the utilization of live donor renal transplantation. Am J Transplant

  48. Anyaegbu EI, Shaw AS, Hruska KA, Jain S (2015) Clinical phenotype of APOL1 nephropathy in young relatives of patients with end-stage renal disease. Pediatr Nephrol 30:983–989

    PubMed  Google Scholar 

  49. Li Y, Greenbaum LA, Warady BA, Furth SL, Ng DK (2019) Short stature in advanced pediatric CKD is associated with faster time to reduced kidney function after transplant. Pediatr Nephrol 34:897–905

    PubMed  PubMed Central  Google Scholar 

Download references

Funding

The CKiD study is funded by 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 (UO1-DK-66143, UO1-DK-66174, U01-DK-082194, and UO1-DK66116).

Author information

Authors and Affiliations

  1. Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA

    Meredith A. Atkinson

  2. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA

    Derek K. Ng

  3. Children’s Mercy Hospital, Kansas City, MO, 64108, USA

    Bradley A. Warady

  4. Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Susan L. Furth

  5. Seattle Children’s Hospital, Seattle, WA, 98105, USA

    Joseph T. Flynn

Authors
  1. Meredith A. Atkinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Derek K. Ng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bradley A. Warady
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Susan L. Furth
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Joseph T. Flynn
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M.A. and J.F. conceptualized the article, performed the literature search, reviewed the data analyses, and drafted and critically revised the work. D.N., B.W., and S.F. conceptualized the article, contributed to the literature search, and critically revised the work.

Corresponding author

Correspondence to Meredith A. Atkinson.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Answers: 1. d; 2. b; 3. c; 4. b, 5. a

Publisher’s note

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

Electronic supplementary material

Supplemental Table 1

: Distribution of persons, person-years, chronic kidney disease (CKD) diagnosis (dx), and events by categories of baseline glomerular filtration rate (GFR) and urine protein-creatinine ratio (UPCR), N = 1169. Each cell in the table describes the number of participants, overall and distributed by cohort affiliation; prevalence of glomerular CKD; number of events; number of person-years (p-y); and empirical incidence rate (IR; per 100 person-years) of the composite outcome event (50% GFR decline, renal replacement therapy, or GFR <15 mL/min/1.73 m2) with 95% confidence interval. Cell coloring defines the final 6 GFR/proteinuria risk stages ordered from best to worst prognosis as follows: A (dark green), B (light green), C (gold), D (tan), E (salmon), and F (red). IRs expressed as events per 100 person-years. Cells with fewer than 15 participants do not have an IR calculated. Abbreviations: CKiD, Chronic Kidney Disease in Children; ESCAPE, European Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients. Reproduced from [11], used with permission (PDF 220 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Atkinson, M.A., Ng, D.K., Warady, B.A. et al. The CKiD study: overview and summary of findings related to kidney disease progression. Pediatr Nephrol 36, 527–538 (2021). https://doi.org/10.1007/s00467-019-04458-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-019-04458-6

Keywords

Search

Navigation