Chronic Kidney Disease: Treatment of Comorbidities II (Hypertension, Anemia, and Electrolyte Management)

  • Deepa H. ChandEmail author
  • Rudolph P. Valentini
Pediatric Nephrology (BP Dixon and E Nehus, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Pediatric Nephrology


Purpose of review

While the causes of chronic kidney disease (CKD) are different in children than their adult counterparts, many comorbidities are commonly encountered by both populations. Particularly concerning is that these entities contribute to the decrease in lifespan in children with CKD. Amongst these conditions are hypertension, anemia, and electrolyte abnormalities. While these can cause metabolic derangements individually, they each contribute to the development and progression of cardiovascular disease, which in turn, exponentially increases mortality (Vidi Curr Opin Pediatr 30 (2): 247-251, 2018). It has been estimated that the mortality rate of children with CKD is 30 times higher than their healthy peers (Ferris et al. Blood Purif 41 (1-3): 205-10, 2016). As these conditions are each treatable, optimization of medical management can lessen the risk of death in this high-risk population.

Recent findings

Hypertension remains underdiagnosed in children with CKD despite a high prevalence. The American Academy of Pediatrics released the Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents in 2007, in which experts outline the need for aggressive diagnosis and treatment of hypertension. While the mainstay of anemia management remains correction of iron deficiency and erythropoiesis stimulating agents, long-acting erythropoietic agents offer an alternative option to traditional management. Electrolyte abnormalities including metabolic acidosis and hyperkalemia must be addressed in order to optimize clinical outcomes.


The care of children with CKD remains complex with the need for a wholistic approach. Although the injury initiates within the kidneys, the associated comorbidities have systemic consequences. Some of these include hypertension, anemia, and electrolyte abnormalities. The early identification of these conditions as well as aggressive treatment can improve the health of these children.


Chronic kidney disease Hypertension Anemia Electrolyte abnormalities 


Compliance with Ethical Standards

Conflict of Interest

Deepa H. Chand is an employee and shareholder of AbbVie.

Rudolph P. Valentini declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


  1. 1.
    •• United States Renal Data System. USRDS annual data report: epidemiology of kidney disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2018. Along with producing the Annual Data Report on ESRD & Chronic Kidney Disease (CKD) in the United States, the USRDS also fulfills data requests, provides standard analysis files and specialized datasets to researchers, produces the Researcher’s Guide, and presents the results of its research at national conferences and in peer-reviewed journals. Six central goals define the mission of the USRDS: to characterize the ESRD population; to describe the prevalence and incidence of ESRD along with trends in mortality and disease rates; to investigate relationships among patient demographics, treatment modalities, and morbidity; to report the costs of ESRD treatments and total burden of ESRD program in the United States; to identify new areas for special renal studies and support investigator-initiated research; and to provide data sets and samples of national data to support research by the Special Studies Centers.Google Scholar
  2. 2.
    Gallibois CM, Jawa NA, Noone DG. Hypertension in pediatric patients with chronic kidney disease: management challenges. Int J Nephrol Renovasc Dis. 2017;10:205–13. eCollection 2017.CrossRefGoogle Scholar
  3. 3.
    Faul C, Amaral AP, Oskouei B, Hu MC, Sloan A, isakova T, et al. FGF23 induces left ventricular hypertrophy. J Clin Invest. 2011;121:4393–408.CrossRefGoogle Scholar
  4. 4.
    Halbach S, Flynn J. Treatment of hypertension in children with chronic kidney disease. Curr Hypertens Rep. 2015;17(1):503. CrossRefGoogle Scholar
  5. 5.•
    Vidi SR. Role of hypertension in progression of chronic kidney disease in children. Curr Opin Pediatr. 2018;30(2):247–51. Hypertension is an independent risk factor for progression of chronic kidney disease (CKD) in children. Children with early CKD develop hypertension secondary to renal disease. This review aims to highlight recent advances that help us better understand the current role of hypertension in progression of CKD in children.
  6. 6.
    Bello H, Norton GR, Ballim I, Libhaber CD, Sareli P, Woodiwiss AJ. Contributions of aortic pulse wave velocity and backward wave pressure to variations in left ventricular mass are independent of each other. J Am Soc Hypertens. 2017;11(5):265–274.e2. Epub 2017 Mar 14.CrossRefGoogle Scholar
  7. 7.
    Weaver DJ, Mitsnefes M. Cardiovascular disease in children and adolescents with chronic kidney disease. Semin Nephrol. 2018;38(6):559–69. Scholar
  8. 8.
    •• Flynn JT, Kaelber DC, Baker-Smith CM, Blowey D, Carroll AE, Daniels SR, de Ferranti SD, Dionne JM, Falkner B, Flinn SK, Gidding SS, Goodwin C, Leu MG, Powers ME, Rea C, Samuels J, Simasek M, Thaker VV, Urbina EM. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics. 2017;140(3). pii: e20171904. Epub 2017 Aug 21.These pediatric hypertension guidelines are an update to the 2004 “Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents.” These guidelines include 30 Key Action Statements and 27 additional recommendations derived from a comprehensive review of almost 15 000 published articles between January 2004 and July 2016. Each Key Action Statement includes level of evidence, benefit-harm relationship, and strength of recommendation. This clinical practice guideline, endorsed by the American Heart Association, is intended to foster a patient- and family-centered approach to care, reduce unnecessary and costly medical interventions, improve patient diagnoses and outcomes, support implementation, and provide direction for future research.
  9. 9.
    Paoli S, Mitsnefes MM. Coronary artery calcification and cardiovascular disease in children with chronic kidney disease. Curr Opin Pediatr. 2014;26(2):193–7. Scholar
  10. 10.
    Cheung AK, Rahman M, Reboussin DM, Craven TE, Greene T, Kimmel PL, et al. SPRINT Research Group. Effects of intensive BP control in CKD. J Am Soc Nephrol. 2017;28(9):2812–23. Epub 2017 Jun 22.CrossRefGoogle Scholar
  11. 11.
    ESCAPE Trial Group, Wühl E, Trivelli A, Picca S, Litwin M, Peco-Antic A, et al. Strict blood-pressure control and progression of renal failure in children. N Engl J Med. 2009;361(17):1639–50. CrossRefGoogle Scholar
  12. 12.
    World Health Organization. Iron deficiency anemia: assessment, prevention, and control-a guide for program managers. Geneva, Switzerland: World Health Organization; 2001. WHO/NHD/01.3Google Scholar
  13. 13.
    Fishbane S, Spinowitz B. Update on anemia in ESRD and earlier stages of CKD: Core Curriculum 2018. Am J Kidney Dis. 2018;71(3):423–35. Published online January 11, 2018. Scholar
  14. 14.
    Warady BA, Barcia J, Benador N, Jankauskiene A, Olson K, Podracka L, et al. De novo weekly and biweekly darbepoetin alfa dosing in pediatric patients with chronic kidney disease. Pediatr Nephrol. 2018;33:125–37. Scholar
  15. 15.
    •• KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease. Chapter 2: Use of iron to treat anemia in CKD. Kidney Int Suppl. 2012;2(4):292–8.The development of clinical practice guidelines for the treatment of anemia in chronic kidney disease has been instrumental in identifying and reducing variations in the use of erythropoiesis-stimulating agents and iron replacement. Challenges to the effectiveness and safety of recommendations made in these guidelines were magnified when recent clinical trials showed no benefit or harm with respect to cardiovascular outcomes in subjects randomized to higher target hemoglobin levels. To address these concerns, Kidney Disease: Improving Global Outcomes (KDIGO) convened an international conference to examine the problems and shortcomings of existing anemia guidelines, which are a prime example of duplication of efforts to derive recommendations from a limited evidence base. The meeting was attended by representatives of the major guideline developing organizations, who agreed to avoid future duplicative efforts and to save resources in generating a common evidence report, whose recommendations could then be prioritized and implemented locally. This is a report to the international nephrology community of the recommendations for and timeline of the next anemia guidelines. It has been reviewed by the conference participants and approved as a position statement by the KDIGO Board of Directors.CrossRefGoogle Scholar
  16. 16.
    • Kraut JA, Madias NE. Metabolic acidosis of CKD: an update. Am J Kidney Dis. 2016;67(2):307–17. Epub 2015 Oct 23. The kidney has the principal role in the maintenance of acid-base balance. Therefore, a decrease in renal ammonium excretion and a positive acid balance often leading to a reduction in serum bicarbonate concentration are observed in the course of chronic kidney disease (CKD). The decrease in serum bicarbonate concentration is usually absent until glomerular filtration rate decreases to <20 to 25mL/min/1.73 m(2), although it can develop with lesser degrees of decreased kidney function. Non-anion gap acidosis, high-anion gap acidosis, or both can be found at all stages of CKD. The acidosis can be associated with muscle wasting, bone disease, hypoalbuminemia, inflammation, progression of CKD, and increased mortality. Administration of base may decrease muscle wasting, improve bone disease, and slow the progression of CKD. Base is suggested when serum bicarbonate concentration is <22 mEq/L, but the target serum bicarbonate concentration is unclear. Evidence that increments in serum bicarbonate concentration > 24 mEq/L might be associated with worsening of cardiovascular disease adds complexity to treatment decisions. Further study of the mechanisms through which metabolic acidosis contributes to the progression of CKD, as well as the pathways involved in mediating the benefits and complications of base therapy, is warranted.CrossRefGoogle Scholar
  17. 17.
    Molitoris B, Froment DH, Mackenzie TA, et al. Citrate: a major factor in the toxicity of orally administered aluminum compounds. Kidney Int. 1989;36:949–53.CrossRefGoogle Scholar
  18. 18.
    Chan WY, Clark AB, Wilson AM, Loke YK, on behalf of the TIPAC investigators. The effect of co-trimoxazole on serum potassium concentration: safety evaluation of a randomized controlled trial. Br J Clin Pharmacol. 2017;83(8):1808–14. Epub 2017 Mar 20.CrossRefGoogle Scholar
  19. 19.
    Perazella MA. Trimethoprim-induced hyperkalaemia: clinical data, mechanism, prevention and management. Drug Saf. 2000;22(3):227–36.CrossRefGoogle Scholar
  20. 20.
    Thompson K, Flynn J, Okamura D, Zhou L. Pretreatment of formula or expressed breast milk with sodium polystyrene sulfonate (Kayexalate(®)) as a treatment for hyperkalemia in infants with acute or chronic renal insufficiency. J Ren Nutr. 2013 Sep;23(5):333–9.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Patient Safety and Pharmacovigilance, Research and DevelopmentAbbVie Inc.North ChicagoUSA
  2. 2.Division of Pediatric Nephrology, Department of PediatricsWashington University School of MedicineSt. LouisUSA
  3. 3.Group Chief Medical Officer: Michigan and Illinois Markets, Pediatric Nephrology, Children’s Hospital of MichiganWayne State University School of MedicineDetroitUSA

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