Chronic Kidney Disease: Laboratory Support of Diagnosis and Management

Chronic kidney disease (CKD) affects about 37 million people in the United States, with about 90% not knowing they have it.¹ The disease affects kidney structure and function yet may have no signs or symptoms in its early stages. However, patients with CKD can progress to end-stage renal disease (ESRD) and the need for dialysis, and have a higher risk of cardiovascular events and death.^2,3 As such, diagnosis of CKD and monitoring of kidney function in patients with CKD are important for decreasing morbidity and mortality.⁴

This article will discuss CKD, its risk factors and comorbidities, and how the laboratory can assist in diagnosis and management.

Scope of the Problem and Risk Factors for CKD

The National Kidney Foundation estimates that around 80 million persons in the United States are at risk for developing CKD,⁵ and the risk of cardiovascular events and death increases with increasing CKD severity.² Patients at high risk for ESRD are more than 10 times as likely as low-risk patients to have kidney failure within 5 years, but about half of them are not aware they have CKD.³ Knowing an individual has CKD can help guide lifestyle changes that mitigate risk factors common to kidney- and cardiac-related disease.³

Assessing Kidney Function and Damage

CKD is defined as an abnormality of kidney structure or function that is present for more than 3 months and can adversely affect health.⁶ The primary diagnostic criterion is a decreased glomerular filtration rate (GFR).⁶ CKD may also be diagnosed based on the presence of 1 or more other markers of kidney damage, such as histological abnormalities, structural abnormalities, history of kidney transplantation, abnormal urine sediment, tubular disorder-caused electrolyte abnormality, or an increased urinary albumin level (albuminuria).⁶

GFR and Kidney Function

GFR can be measured directly, but direct measurement methods are complicated and not suitable for use in general clinical practice.⁶ Hence, GFR is typically assessed using an estimated (eGFR) value calculated based on either serum creatinine or cystatin C levels:

• Creatinine-based eGFR is recommended for initial assessment of GFR, according to the Kidney Disease Improving Global Outcomes (KDIGO) 2012 international guideline.⁶ The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation⁷ is generally used to calculate the eGFR (See Sidebar).
  • An eGFR based on serum creatinine level, however, is influenced by diet and muscle mass.⁷ Thus, results may not accurately reflect the true GFR in patients with serious comorbid conditions, individuals with extremes of muscle mass (eg, bodybuilders, patients who have had an amputation), patients who are malnourished or obese, persons who are vegetarians or are on a low-meat diet, people taking creatine dietary supplements, and pregnant women.
• Cystatin C-based eGFR uses serum cystatin C levels to calculate an eGFR and is therefore less influenced by diet and muscle mass.¹²
  • An eGFR based on cystatin C has been shown to improve overall risk stratification for adverse outcomes, including cardiovascular disease-related death, ESRD, and all-cause mortality.¹³ On the other hand, a cystatin C-based eGFR may be more affected than creatinine-based eGFR by conditions such as thyroid disorders, corticosteroid use, smoking, diabetes, obesity, and inflammation.^13-15

Given the above considerations, creatinine-based eGFR is recommended for patients who do not have contraindications.⁶ The KDIGO guideline recommends using cystatin C-based eGFR to confirm CKD when creatinine-based eGFR indicates a mild to moderately high risk of CKD progression (45 to 59 mL/min/1.73 m²) in a patient without albuminuria.⁶

Urine Albumin-Creatinine Ratio and Kidney Damage

The presence of albuminuria indicates increased glomerular permeability, which is a characteristic of CKD and an indication of kidney damage.⁶ Albuminuria is assessed with either the urine albumin-creatinine ratio (ACR) or albumin excretion rate over 24 hours.⁶

A urine ACR ≥30 mg/g (albumin excretion rate ≥30 mg/24 hours) is diagnostic of albuminuria (30 to 300 mg/g was formerly referred to as microalbuminuria, and >300 mg/g as macroalbuminuria).⁶

Proteinuria (urinary total protein-creatinine ratio ≥150 mg/g) may indicate increased glomerular permeability and CKD but can also be seen in other conditions (eg, myeloma).⁶

Management of CKD: eGFR and ACR

An eGFR <60 mL/min/1.73 m² for >3 months and/or urine ACR ≥30 mg/g for >3 months indicates the presence of CKD.⁶ An eGFR and ACR provide a “kidney profile” recommended by the National Kidney Foundation for diagnosing and managing chronic kidney disease in at-risk patients.^2,4,6,16 Importantly, the results are independent risk predictors of major adverse cardiovascular events (myocardial infarction or stroke).¹⁷

A summary of the frequency of monitoring CKD based on the risk of disease progression as assessed using eGFR and urine ACR (kidney profile) is available at Laboratory Testing for Chronic Kidney Disease Diagnosis and Management.

In addition, the Kidney Failure Risk equation (KidneyFailureRisk.com) uses ACR and eGFR to estimate the risk of persons developing CKD and progressing to ESRD.

CKD and COVID-19

Data are still accumulating on the relation between COVID-19 and CKD. However, research is showing that prior CKD can be associated with more severe COVID-19 disease and that COVID-19 can result in acute kidney injury.^18,19

Risk Factors for Developing Chronic Kidney Disease

Risk Factors for developing CKD include³

• Diabetes mellitus
• Hypertension
• Heart disease
• Obesity
• Family history of CKD
• History of kidney damage
• Older age

Decreasing the Risk of Chronic Kidney Disease

Actions to mitigate risk of CKD include³

• Eating a balanced diet
• Regular exercise
• Maintaining a healthy body weight

The CKD-EPI Equation, eGFR, and Race

The CKD-EPI equation used to calculate eGFR is based on serum creatinine level and patient age, sex, and race.⁸ With this equation, individuals identified as black will have higher eGFR, suggesting better kidney function, than their white counterparts. Some have argued that this approach may overestimate kidney function among black individuals.⁹ Although use of the CKD-EPI equation remains standard, the issue of using race in the calculation of eGFR is currently the subject of discussion among nephrologists and specialty societies.^10,11

How the Laboratory Can Help

Quest Diagnostics offers many tests and panels, including the Kidney Profile , for diagnosis and management of chronic kidney disease. Test offerings range from health screenings for abnormal eGFR, proteinuria, and albuminuria, to tests for management of CKD, its comorbidities, and its complications.

More information about CKD is available at

• QuestDiagnostics.com/Home/Physicians/Health-Trends/Trends/Kidney-Disease/
• QuestDiagnostics.com/Home/Patients/Tests-A-Z/Diabetes-Testing/Diabetes-Chronic-Kidney-Disease/

References

1. Chronic kidney disease in the United States, 2019. Centers for Disease Control and Prevention. Reviewed March 11, 2019. Accessed January 23, 2021. https://www.cdc.gov/kidneydisease/publications-resources/2019-national-facts.html

2. National Kidney Foundation Laboratory Engagement Advisory Group. Laboratory engagement plan: transforming kidney disease detection. National Kidney Foundation and ASCP. Published February 2018. Accessed January 26, 2021. https://www.ascp.org/content/docs/default-source/get-involved-pdfs/istp-ckd/laboratory-engagement-plan.pdf

3. Chu CD, McCulloch CE, Banerjee T, et al. CKD awareness among US adults by future risk of kidney failure. Am J Kidney Dis. 2020;76(2):174-183. doi:10.1053/j.ajkd.2020.01.007

4. Vassalotti JA, Centor R, Turner BJ, et al. Practical approach to detection and management of chronic kidney disease for the primary care clinician. Am J Med. 2016;129(2):153-162.e7. doi:10.1016/j.amjmed.2015.08.025

5. Kidney disease: the basics. National Kidney Foundation. Accessed January 23, 2021. https://www.kidney.org/news/newsroom/factsheets/KidneyDiseaseBasics

6. 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. 2013;3(1):1-150. doi:10.1038/kisup.2012.76

7. Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604-612. doi:10.7326/0003-4819-150-9-200905050-00006

8. CKD-EPI creatinine equation (2009). National Kidney Foundation. Accessed February 3, 2021. https://www.kidney.org/content/ckd-epi-creatinine-equation-2009

9. Vyas DA, Eisenstein LG, Jones DS. Hidden in plain sight - reconsidering the use of race correction in clinical algorithms. N Engl J Med. 2020;383(9):874-882. doi:10.1056/NEJMms2004740

10. Inserro A. Flawed racial assumptions in eGFR have care implications in CKD. American Journal of Managed Care. Published October 25, 2020. Accessed February 3, 2021.

11. Eneanya ND, Yang W, Reese PP. Reconsidering the consequences of using race to estimate kidney function. JAMA. 2019;322(2):113-114. doi:10.1001/jama.2019.5774

12. Gounden V, Bhatt H, Jialal I. Renal function tests. In: StatPearls [Internet]. StatPearls Publishing; 2020. Updated July 20, 2020. Accessed January 26, 2021.  https://www.ncbi.nlm.nih.gov/books/NBK507821/

13. Shlipak MG, Matsushita K, Ärnlöv J, et al. Cystatin C versus creatinine in determining risk based on kidney function. N Engl J Med. 2013;369(10):932-943. doi:10.1056/NEJMoa1214234

14. Stevens LA, Schmid CH, Greene T, et al. Factors other than glomerular filtration rate affect serum cystatin C levels. Kidney Int. 2009;75(6):652-660. doi:10.1038/ki.2008.638

15. Levey AS, Coresh J, Tighiouart H, et al. Measured and estimated glomerular filtration rate: current status and future directions. Nat Rev Nephrol. 2020;16(1):51-64. doi:10.1038/s41581-019-0191-y

16. Myers GL, Miller WG, Coresh J, et al. Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program. Clin Chem. 2006;52(1):5-18. doi:10.1373/clinchem.2005.0525144

17. Currie CJ, Berni ER, Berni TR, et al. Major adverse cardiovascular events in people with chronic kidney disease in relation to disease severity and diabetes status. PLoS One. 2019;14(8):e0221044. doi:10.1371/journal.pone.0221044

18. Hassanein M, Radhakrishnan Y, Sedor J, et al. COVID-19 and the kidney. Cleve Clin J Med. 2020;87(10):619-631. doi:10.3949/ccjm.87a.20072

19. Henry BM, Lippi G. Chronic kidney disease is associated with severe coronavirus disease 2019 (COVID-19) infection. Int Urol Nephrol. 2020;52(6):1193-1194. doi:10.1007/s11255-020-02451-9

Models used for illustrative purposes only.

Published date: Feb 2021