Association of Kidney-Related Safety Events with Incident Chronic Kidney Disease in Veterans

Research Article

Austin J Nephrol Hypertens. 2021; 8(2): 1095.

Association of Kidney-Related Safety Events with Incident Chronic Kidney Disease in Veterans

Helman SR1, Stewart PM2, Siddiqui T3,4, Fink JC1,4 and Weiner S1*

1Department of Medicine, University of Maryland School of Medicine, USA

2Pharmaceutical Research Computing, University of Maryland School of Pharmacy, USA

3Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, USA

4Division of Nephrology, University of Maryland School of Medicine, USA

*Corresponding author: Weiner S, Department of Medicine, University of Maryland School of Medicine, 419 West Redwood Street, Suite 620, Baltimore, MD 21201, USA

Received: June 18, 2021; Accepted: July 15, 2021; Published: July 22, 2021


Objective: The impact of Nonsteroidal Anti-Inflammatory Drugs (NSAID) and iodine-based contrast exposures on developing Chronic Kidney Disease (CKD) is controversial. We examined the association of these exposures with the development of CKD in a Veteran population.

Methods: A retrospective case-control study of 154,448 veterans from the Veterans Affairs (VA) Corporate Data Warehouse (CDW) database between 2005 and 2014 was conducted to assess the association between incident stage 3 CKD with Acute Kidney Injury (AKI), NSAID use, iodine-based contrast exposures, and comorbid conditions. Stepwise logistic regression was used to determine multivariable adjusted Odds Ratios (OR).

Results: The mean age was 59 (SD±13), and the median eGFR was 84 (IQR: 73, 96). AKI was associated with increased odds of CKD (inpatient: OR=3.76, 95% CI: 3.44, 4.11; outpatient: OR=4.73, 95% CI: 4.09, 5.46) and demonstrated escalated odds with >1 episode (inpatient: OR=5.72, 95% CI: 4.71, 6.95; outpatient: OR=8.36, 95% CI: 6.32, 11.06). Months of NSAID prescriptions was associated with CKD, with ORs at >0-6 months, >6-12 months, and >12 months of 1.27 (95% CI: 1.23, 1.32), 1.54 (95% CI: 1.46, 1.63), and 1.69 (95% CI: 1.62, 1.77) respectively. Iodine-based contrast exposure was associated with increased odds of CKD, with ORs for 1-2 Computed Tomography (CT) scans, ≥3CT scans, and left heart catheterization of 1.29 (95% CI: 1.24, 1.35), 1.29 (95% CI: 1.20, 1.28), and 1.38 (95% CI: 1.17, 1.63) respectively.

Conclusion: AKI events, NSAID use, and iodine-based contrast exposures are associated with increased odds for developing stage 3 CKD in veterans.

Keywords: Chronic kidney disease; Acute kidney injury; Iodine-based contrast; Nonsteroidal anti-inflammatory drugs


AKI: Acute Kidney Injury; CAD: Coronary Artery Disease; CDW: Corporate Data Warehouse; CHF: Congestive Heart Failure; CKD: Chronic Kidney Disease; CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration; CT: Computed Tomography; DM: Diabetes Mellitus; eGFR: Estimated Glomerular Filtration Rates; ESKD: End-Stage Kidney Disease; HTN: Hypertension; LHC: Left Heart Catheterizations; NSAID: Nonsteroidal Anti-Inflammatory Drugs; VA: Veterans Affairs


Chronic Kidney Disease (CKD) affects up to 15% of the United States population and is responsible for significant morbidity, mortality, and health care costs [1-3]. Patients with other chronic medical conditions, such as hypertension, diabetes, and cardiovascular disease are at increased risk for developing CKD and progressive disease compared to the general population [4-15]. The compounded impact of these chronic medical conditions creates a need to optimize how we manage patients at risk for CKD to minimize morbidity and mortality.

Kidney-associated safety events due to medical care are common and put patients with comorbidities at risk for incident CKD or disease progression [16-18]. Several studies have demonstrated the effects of individual categories of kidney-associated safety events on CKD. Acute kidney injury (AKI) is intimately tied to CKD [19] and shown to be independently associated with both incident CKD and progression to End-Stage Kidney Disease (ESKD) [20-22]. In addition to AKI, use of nephrotoxic agents, including Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and iodine-based contrast, may impact kidney function and contribute to incident CKD risk. NSAIDs inhibit prostanoid synthesis, which is believed to interfere in both renal and cardiovascular function [23]. Another possible mechanism of NSAIDs’ effect on renal function is via AKI, but AKI events secondary to NSAIDs are relatively rare in patients with higher Estimated Glomerular Filtration Rates (eGFRs) [24,25]. Iodine-based contrast can directly affect the kidney through toxic effects on tubular cells and indirectly by affecting kidney hemodynamics [26]. The role contrast agents play in directly causing AKI and CKD is still disputed, and may be affected by the indication for and location of dye administration [26], with arterial infusion possibly carrying a higher risk of kidney damage than venous infusion [27]. Like NSAIDs, AKI secondary to contrast use is now considered relatively rare in patients with higher eGFRs [26,28]. In those with existing CKD, contrast exposure has been associated with nephropathy and progression to ESKD in small studies [29,30]. Less is known about the association of contrast exposures with incident CKD.

How these common kidney-associated safety events affect the development of CKD is unknown. We conducted a case-control study and developed a model to assess associations of AKI events, NSAID use, and iodine-based contrast exposure with incident stage 3 CKD.

Materials and Methods

Study population

Data from the nationwide Corporate Data Warehouse (CDW) database was used to conduct a retrospective case-control study (Figure 1). 374,395 patients in the CDW database had a baseline eGFR measurement of >60mL/min/1.73m² between June 1, 2005 to December 31, 2008. Patients’ labs were followed through December 31, 2014. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to calculate eGFR. White race was used for 18% of patients with missing race data since 80% of veterans on average are white. 243,215 patients with at least 2 eGFR measurements >60mL/min/1.73m² and no eGFR measurements <60mL/min/1.73m² were available as controls to identify a strict cohort of stable kidney function above stage 3 CKD. 45,347 possible cases were identified and had a minimum of 180 days before their first eGFR <60mL/min/1.73m² and two eGFR measures in the stage 3 CKD range that were 90 days apart. The study was approved by the University of Maryland, Baltimore Institutional Review Board and the Baltimore VA Research and Development Committee.