The rising global prevalence of endstage kidney disease (ESKD), despite optimal management of traditional risk factors, poses a significant public health challenge, researchers report in BMC Nephrology.

“Early onset of diabetes and hypertension, male sex, nonwhite ethnicity, deprivation, poor glycemic control, and prolonged hyperglycemia are significant risk factors for ESKD,” Debasish Kar, MD, MSc, and colleagues wrote.

“These findings highlight the complexity of ESKD and the need for multifactorial targeted interventions in high-risk populations.”

Findings From the UK Biobank

The investigators conducted a cross-sectional analysis using data from 502,408 participants aged 40 to 69. Participants completed a medical history questionnaire about smoking status, alcohol use, diet, and exercise. Their height, weight, and blood pressure were recorded, and their blood and urine samples were analyzed.

Overall, 1,191 (0.2%) had ESKD. Th e mean age among participants with ESKD was 59 years versus 57 years among those without ESKD; 63.2% of participants with ESKD and 45.6% without ESKD were male.

Non-White participants comprised 12.97% of the ESKD group despite representing only 5.76% of the study population. In the non-ESKD group, the distribution across deprivation quintiles was relatively even, but in the ESKD group, 70% of participants belonged to the moderate to most deprived quintiles. Glycemic status also differed markedly: 26.1% of people with ESKD had prediabetes- or diabetes- level HbA1c versus 8.3% in the non-ESKD group.

Smoking history was more common among people with ESKD, with 51.7% of ESKD patients identifying as current or former smokers versus 45.1% of those without.

Higher Risk With Early-Onset Disease

The researchers used multivariable logistic regression to assess ESKD risk factors.

Early diabetes and hypertension onset conferred substantial added risk. Participants diagnosed with diabetes before age 40 had greater odds of developing ESKD than those diagnosed between 40 and 60 years (adjusted odds ratio [aOR] 2.26; 95% CI, 1.57-3.24), and early-onset hypertension also raised the risk (aOR 1.73; 95% CI, 1.21-2.44).

Diabetes diagnosis after age 60 was associated with significantly lower ESKD odds compared to diagnosis between ages 40 and 60 (aOR 0.36; 95% CI, 0.20-0.63). Each added year of diabetes duration increased the odds of ESKD by 2%.

Hypertension duration was not significantly associated with ESKD.

Albuminuria & Cardiovascular Comorbidities

Albuminuria levels were strongly predictive. Participants with macroalbuminuria had nearly tenfold higher odds of ESKD than those with microalbuminuria (aOR 9.47; 95% CI, 7.95-11.27). By contrast, normoalbuminuria was associated with 73% lower odds of ESKD than those with microalbuminuria (aOR 0.27; 95% CI, 0.22-0.32).

Cardiovascular conditions were strongly associated with higher ESKD odds, including stroke (aOR 5.97; 95% CI, 3.99-8.72), hypertension (aOR 5.35; 95% CI, 4.38-6.56), myocardial infarction (aOR 4.94; 95% CI, 3.56-6.78), and angina (aOR 4.89; 95% CI, 3.47-6.81).

Men had a 22% higher risk compared with women (aOR 1.22; 95% CI, 1.04-1.43).

Ethnicity & Deprivation

Non-White ethnicity was associated with a 70% higher risk for ESKD compared to White ethnicity after adjusting for sex, age, deprivation, and duration of diabetes and hypertension.

Participants in the most socioeconomically deprived quintile had 83% higher odds of ESKD than those in the least deprived quintile (aOR 1.83; 95% CI, 1.48-2.26).

Glycemic Control & Weight

HbA1c directly correlated with risk for ESKD, with each unit increasing the odds by 2%. Serum cholesterol negatively correlated with ESKD (aOR 0.63; 95% CI, 0.59-0.67), possibly due to secondary preventive therapy among patients with ESKD. Smoking was not significantly associated with ESKD.

Compared with individuals with normal weight, those in the underweight quartile were at 2.21 times higher risk for ESKD, and those in the overweight and obese quartile were at 20% and 45% lower risk for ESKD, respectively.

A Growing Public Health Challenge

Younger age at diagnosis and longer disease duration among patients with young-onset type 2 diabetes and ESKD contribute significantly to poor outcomes, especially among ethnic minorities and people in low- and middle-income countries, Dr. Kar and colleagues wrote.

“Urgent action is needed to develop an effective and affordable public health policy by which the emerging challenges of the rising trend of ESKD can be tackled on a global scale,” they advised. “Screening high-risk groups of people for microalbuminuria and individually tailored, targeted management may reduce the rising surge of ESKD cases worldwide.”