Understanding Chronic Kidney Disease in Patients with Diabetes

Approximately 1 out of 3 patients with type 1 and 2 diabetes mellitus (DM) has CKD.¹ As clinicians, it is crucial to understand the pathophysiology, diagnosis, and management of CKD when treating patients with DM.

Presentation of CKD include abnormalities in kidney structure/function that are typically are present for 3 months or longer.² Characteristics involve elevated serum creatinine (Scr) at steady state, Blood Urea Nitrogen (BUN) Scr ratio around 10:1 compared to that of 20:1 in acute kidney injury (AKI), and urinary albumin to creatinine ratio (UACR) ratio of over 30 (albuminuria). Structural abnormality can be detected via imaging and functional abnormality can be typically detected via changes in estimated glomerular filtration rate (eGFR). Staging of CKD can be done by utilizing GFR (MDRD is used since it is indexed to BSA, but Cockgroft is not).¹ Monitoring of UACR and eGFR is recommended for timely diagnosis of CKD.

Exposure to any risk factor (nephrotoxin, DM, smoking, obesity, hypertension, etc) results in nephron mass loss. The remaining nephrons compensate via hypertrophy which leads to development of glomerular HTN on a long run. Consistent glomerular hypertension leads to impairment of glomerular permeability barrier resulting in increased excretion of albumin. Albuminuria poses direct cellular damage along with cytokines (monocyte chemoattractant protein-1 (MCP-1)) and angiotensin II.^2,3

Classification of CKD using MDRD^4,5

eGFR

Stage

Severity

90≤

1

Albumuria

60-89

2

Mild

30-59

3

Moderate

15-29

4

Severe

<15

5

End Stage Renal Disease (ESRD)

According to the JNC 8 guideline, target goal of blood pressure (BP) would be <140/90mmHg in patients with DM and CKD who under the age of 60 years.⁶ For individuals who are older than age 60 years, target BP would be <150/90mmHg regardless of comorbidity. JNC8 suggests renin-angiotensin-aldosterone system (RAAS) blocker to be prescribed to all population who are age18 years and older with CKD due to its class effect of providing renal protection. In addition, ADA guideline recommends patients with albuminuria to take RAAS blocker.⁴ It is important to not prescribe angiotensin-converting-enzyme inhibitor (ACEI) and angiotensin II receptor blockers (ARB) together due to potential risk of hyperkalemia.

Clinicians may need to be cautious about prescribing medications undergo renal excretion such as metformin, sulfonylurea, and Sodium-Glucose Cotransporter 2 (SGLT2). Even though there is concern with SGLT2 inhibitors promoting acute kidney injury (AKI) and CKD via volume depletion⁴, results from the recently published CREDENCE study suggest that canagliflozin, a SGLT2 inhibitor may provide renal benefit to individuals with diabetes when prescribed as an add-on therapy to RAAS blocker therapy.⁷ Emgaliflozin, liraglutide, and semaglutide are medications that reduce the risk of worsening nephropathy in patients with diabetes.⁴

As a part of diabetes therapy, it is important to monitor, assess, and manage comorbidities such as CKD. Although it is important to optimize medication therapy regimen as a clinician, it is also crucial to implement non-pharmacologic interventions. For example, limiting the dietary protein intake (0.8g/kg/day) and sodium intake (<2,300mg/day) are convenient and effective methods. As a result, CKD management in patients with DM will be effectively achieved through collaborative efforts of clinicians and patients.

References

• Chronic Kidney Disease (CKD) Surveillance System. Centers for Disease Control and Prevention. https://nccd.cdc.gov/CKD/FactorsOfInterest.aspx?type=Diabetes. Accessed June 7, 2019.
• Wazny LD, Hudson JQ. Chapter 29. Chronic Kidney Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e New York, NY: McGraw-Hill; 2014. http://accesspharmacy.mhmedical.com.ezproxymcp.flo.org/content.aspx?bookid=689§ionid=48811469. Accessed October 16, 2017.
• Abbate M, Zoja C, Remuzzi G. How does proteinuria cause progressive renal damage? J Am Soc Nephrol 2006;17:2974—2984.
• American Diabetes Association. Standards of medical care in diabetes-2019. The Journal of Clinical and Applied Research and Education Volume 42, Supplement 1. ISSN: 0149-5992
• Kidney Disease: Improving Global Outcomes CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Inter 2013;3(1):1—150.
• Cardiovascular Disorders. In: David JA, Esherick JS. eds. CURRENT Practice Guidelines in Primary Care 2019 New York, NY: McGraw-Hill; . http://accesspharmacy.mhmedical.com.ezproxymcp.flo.org/content.aspx?bookid=2587§ionid=212538189. Accessed June 08, 2019.
• Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. New England Journal of Medicine. 2019. doi:10.1056/nejmoa1811744.