CKD Common in Patients with Prediabetes, Especially with Hypertension or ASCVD

New research is shedding light on a potential association between prediabetes and chronic kidney disease (CKD).1

Leveraging data from the the Providence- and University of California Los Angeles Health-based Kidney Disease Research, Education, and Hope (CURE-CKD) Registry, study findings highlight frequent rapid-onset CKD in patients with prediabetes, especially in the presence of hypertension or atherosclerotic cardiovascular disease (ASCVD).1

“People with prediabetes have heightened risks of diabetes and cardiovascular disease,” Radica Alicic, MD, associate director for research at Providence Health Care and a clinical professor at the University of Washington School of Medicine, and colleagues wrote. “Emerging data suggest that prediabetes may also lead to CKD, a major public health problem that may be attenuated by control of hyperglycaemia and other risk factors such as hypertension.”1

A condition in which blood glucose exceeds normal levels but is not high enough for a diagnosis of diabetes, prediabetes was estimated to affect more than 1 in 3 US adults in 2021, equating to roughly 97.6 million people ≥ 18 years of age.2 According to the US Centers for Disease Control and Prevention, having prediabetes increases the risk of developing type 2 diabetes, heart disease, and stroke, but emerging evidence suggests it may also incur a heightened risk of CKD.3

To estimate CKD incidence in patients with prediabetes, investigators examined data from the CURE-CKD Registry, which includes electronic health records from Providence and University of California Los Angeles Health for persons with or at risk of CKD from diabetes, hypertension, and prediabetes. For inclusion in the present analysis, patients were required to be ≥ 18 years of age adults and meet the American Diabetes Association definition-based criteria for prediabetes:

• HbA1c of 5.7%–6.4%
• 2 fasting blood glucose measures of 100–125 mg/dL
• 2 random blood glucose measures of 140–199 mg/dL

Individuals were included in the analysis at the first identification of prediabetes any time between 2013–2020, regardless of the date of entry, if they were tested for CKD and diabetes at baseline and during follow-up, which ended at the onset of CKD or diabetes, or the last encounter before December 2020.1

The primary outcome was CKD onset, identified by 2 estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2; urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g; urine protein-to-creatinine ratio (UPCR) ≥ 0.15 g/g for ≥90 days; or by a new administrative code for CKD.1

Of note, investigators removed individuals who developed diabetes before CKD from the risk set at the time of diabetes identification, which was based on HbA1c ≥ 6.5%; 2 blood glucose measures (≥126 mg/dL fasting/≥200 mg/dL random); administrative codes; or a prescription for blood glucose-lowering medication.1

In total, the study included 281,933 individuals with prediabetes. Among the cohort, the mean age was 57 (Standard deviation [SD], 15) years and 55% of patients were female. Baseline HbA1c was 5.9 (SD, 0.2%), BMI was 30 (SD, 7) kg/m2, and eGFR was 93.3 (SD, 15.7) mL/min/1.73 m2.1

During a median follow-up of 2.5 (interquartile range, 1.3–4.2) years, 3.6% (n = 10,104) of persons with prediabetes developed CKD, mostly ascertained by eGFR <60 mL/min/1.73 m2 (81.4%).1

The overall age-, sex-, and race and ethnicity-standardized CKD incidence was 10.9 (95% CI, 10.5–11.2) cases per 1000 person-years. Investigators pointed out the incidence of CKD was lower for females than males (incidence rate ratio [IRR], 0.92; 95% CI, 0.87–0.98; P = .009), increased exponentially with age, and was greater among Native Hawaiian/Pacific Islander (IRR, 7.94; 95% CI, 1.66–37.95; P = .01) and non-Hispanic Black (IRR, 1.56; 95% CI, 1.36–1.78; P <.001) populations compared with the non-Hispanic White population.1

They also called attention to an increased incidence of CKD in participants with hypertension or ASCVD at baseline (11.9 cases per 1000 person-years; 95% CI, 11.5–12.3). In those without hypertension or ASCVD, CKD incidence was 9.4 cases per 1000 person-years (95% CI, 8.9–9.9).1

“Relatively rapid-onset CKD was common in persons with prediabetes, especially if they also had hypertension or ASCVD,” investigators concluded.1 “The population with prediabetes, and certain subgroups characterized by older age, male sex, Native Hawaiian or Pacific Islander or NH Black race, may benefit from proactive monitoring and interventions to reduce CKD risks such as the control of glycaemia and hypertension.”

References

1. Alicic RZ, Duru OK, Jones CR, et al. Incidence of chronic kidney disease among adults with prediabetes in the CURE-CKD registry, 2013–2020. Diabetes, Obesity and Metabolism. https://doi.org/10.1111/dom.16365

2. National Institute of Diabetes and Digestive and Kidney Diseases. Diabetes Statistics. January 2024. Accessed April 3, 2025. https://www.niddk.nih.gov/health-information/health-statistics/diabetes-statistics

3. US Centers for Disease Control and Prevention. Prediabetes – Your Chance to Prevent Type 2 Diabetes. May 15, 2024. Accessed April 3, 2025. https://www.cdc.gov/diabetes/prevention-type-2/prediabetes-prevent-type-2.html