This study examined the burden of CKD in adult T2DM patients in a suburban community in Thailand. We found that CKD is a common diabetes-related complication among T2DM patients. Within a primary care setting, the estimated prevalence of CKD stages 3–5 (eGFR <60 mL/min/1.73 m2) in T2DM patients was 24.4% (95% CI, 21.9–27.0), with substantial variation by age and glycaemic control status. From a clinical perspective, risk factors for the development of CKD in our study can help inform the clinical decision-making process and the formation of the appropriate care strategy for T2DM patients. As such, our study can lay the foundation for routine surveillance for T2DM patients who are at high risk of CKD in the primary care setting.
The treatment of diabetes generally differs by CKD status because individuals without CKD are treated with oral antidiabetic drugs, while those with CKD receive insulin therapy. According to strategies targeting kidney-specific disease, T2DM patients in our study were more commonly prescribed renin-angiotensin system (RAS) inhibitors (59.0%), whereas the utilisation of these agents varied across diabetes care practices worldwide as 29.6–56.0%22,23,24,25. Despite an improvement in diabetes care over time, suboptimal glycaemic control remains observed in our study, with only 36.1% meeting the glycaemic goal of haemoglobin A1c < 7%, particularly those with CKD. We also found that T2DM patients with CKD were more likely to have diabetes-related complications including ischaemic heart disease, cerebrovascular disease, diabetic retinopathy, and albuminuria than those without CKD. Taken together, these figures are in line with previous nationwide reports in Thailand26.
Recently, large randomised controlled trials suggest that the use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors or glucagon-like peptide 1 (GLP-1) receptor agonists shown to reduce the risk of CKD progression and improve kidney outcomes27,28,29,30. However, during the study period, the novelty of the new drug class of SGLT-2 inhibitors and GLP-1 receptor agonists were not available in the National Medicines Formulary in Thailand under the health benefits package. As such, further studies are needed on treatments modifying the risk of development of CKD among T2DM in the real-world primary care settings.
To our knowledge, our finding suggests a lower prevalence and is comparable to a national study of CKD in adult T2DM patients in Thailand found at 24.4% vs. 35.4%, respectively17. A similar trend in the prevalence of CKD was observed in elderly patients (>65 years) with T2DM—at 40.5% and 56.1% in our study and national level in Thailand, respectively31. Unlike urbanised areas, CKD rates among the T2DM patients in our study were comparable to those reported in previous studies of less urbanised communities or regional areas in Thailand19,20. According to the Global Burden Disease-CKD study, CKD due to diabetes accounted for 30.7% of CKD populations, in which T2DM was the only cause of CKD to illustration a substantial increase in the age-standardised rate (changed by 9.5% from 1990 to 2017)32. Globally, the overall prevalence of CKD among T2DM patients varied at 6.0–39.3% (our result found at 24.4%)17,25,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47. These discrepancies acros s different settings may be attributed to the variations in diagnostic methods used and ethnicities such as the black race, which is associated with a greater rate of GFR decline48. Overall, our result parallels the global rates of diabetes populations, which are expected to occur lower than in the rural areas or less urbanised community1, suggesting that our findings have general relevance.
In this study, several diabetes-specific and general risk factors in the literature for CKD among T2DM patients were investigated (Supplementary Table S1). However, we did not find an association between hypertension or blood pressure and the risk of CKD among T2DM patients, which was reported in previous studies18,21,39,40,41,42. The lack of this relationship could be attributable to in part to increasing usage of RAS inhibitors for protection against kidney disease and improved blood pressure control in our diabetes practice. Moreover, since most of our study patients were already receiving antihypertensive agents, the lack of association between blood pressure and the risk of CKD is not surprising. Consequently, six independent significant risk factors of CKD were identified including older age (>55 years), retinopathy, albuminuria, haemoglobin A1c ≥ 7%, anaemia (haemoglobin <12 g/dL in females or <13 g/dL in males), and uric acid>7.5 mg/dL.
With respect to non-modifiable risk factors, managing elderly patients with T2DM is challenging, as this population has a high rate of comorbid conditions as also associated with a greater risk of developing CKD. Our findings showed that T2DM patients aged 56–65, 66–75, and>75 years had more than 2.8-fold, 5.4-fold, and 27.4-fold higher adjusted ORs for CKD, respectively. This result reaffirms that of previous studies that older age was associated with a higher risk of CKD among T2DM patients33,37,39,40,41,42,44. Cardiovascular disease, obesity, and multimorbidity via endothelial cell dysfunction and sympathetic nervous system activation resulting in increased atherosclerosis, hypertension, and progressive nephrosclerosis are believed to explain the mechanisms underlying older age and the risk of CKD49,50.
With respect to modifiable risk factors, glycaemic control was the most determinant of the development of diabetes-related complications and the risk of CKD in T2DM. Based on our findings, the presence of albuminuria, diabetic retinopathy, and poor glycaemic control (haemoglobin A1c ≥ 7%) are independent risk factors for the development of CKD among T2DM patients. Indeed, albuminuria and diabetic retinopathy are components of diabetes-related microvascular complications, especially in those with poor glycaemic control. These factors have been previously recognised as risk factors for the development of CKD in T2DM patients18,37,39,41,42. In concordance with previous reports42,51, our study demonstrates that anaemia, defined as haemoglobin <12 g/dL in females or <13 g/dL in males, commonly occurs in T2DM patients (38.5%), particularly in the elderly and those with more comorbid conditions. As expected, a significant association was observed that T2DM patients with a naemia had more than a 3.0-fold higher risk of CKD. Our finding corresponds well with previous studies that hyperuricemia is a strong independent risk factor of the development of CKD52,53,54,55. Evidence illustrates that the GFR deterioration is associated with progressive impairment in uric acid excretion, resulting in insulin resistance and hypertension. Experimental studies also revealed that increased serum uric acid concentrations are associated with kidney damage via stimulating RAS activity and promoting endothelial damage along with oxidative stress56,57,58.
This study was based on patient-level information by the retrieval and linking of routinely collecting data, which provide detailed primary care practice on diabetes and kidney care. Our study delivers previously unrecognised data on the prevalence and risk factors of CKD among T2DM in a suburban community through a comprehensive process and rigorous statistical approaches. Moreover, the consistency of findings was observed based on our set of sensitivity analyses.
However, our findings should be interpreted in the context of certain limitations. First, the causal inference and the chronicity of the observations must be considered because our findings were based on the observational cross-sectional nature of the analyses. Moreover, longitudinal data were not obtained in this study; thus, temporal trends in prevalence and dynamic risk prediction for CKD among T2DM patients cannot be established over time. Second, this study was conducted within a single centre and was limited by the unique organisation of the Sansai Hospital, the suburban community care protocol implemented throughout the primary care unit and village health volunteers of this community. Accordingly, the generalisability of our finding to other T2DM populations and healthcare settings other than in primary care practice in Thailand is uncertain and warrants further study. Third, although we performed a series of sensitivity analyses using different equations for estimating GF R, misclassification (potential errors relating to CKD staging) is possible because eGFR alone is insufficient to evaluate kidney function, particularly in cases of advanced CKD. Moreover, urinary protein tests were not routinely available in our primary care practice. Therefore, detection bias should be noticed as it was not considered in our definition of CKD. Finally, contextual factors related to diabetes control including, patient comorbidities, health behaviours (e.g. dietary intake and physical activity), mental health problems (e.g. depression, social support, and coping skills), and social determinants of health (education and literacy, income and social status, physical environments, employment status, and health inequity) were obtained. Moreover, novel biomarkers and relevant inflammatory markers were not available in our primary diabetic care practices. In this circumstance, the residual risk factors may also influence the prevalence and risk factors of CKD among T2DM pa tients. However, the risk factors for development CKD in our study illustrated an excellent performance of the model prediction in terms of discriminative ability, which explained 87.3% of the probability of CKD among T2DM patients.
Due to rapid urbanisation and the dramatic increase in the elderly population, our findings support the well-recognised fact that routine surveillance is mandatory to prevent the development of ESRD to decrease the healthcare burden and costs-related to RRT treatment. This study may also contribute to improved diabetes care management by the early identification and targeting of T2DM patients who are at high risk of developing CKD. Further studies are needed to assess the utility of integrating the clinical predictive factors of CKD among T2DM patients as a part of routine diabetes care and call for strategic goals and actions upon their recognition to reduce the CKD incidence or slow CKD progression. Ultimately, long-term holistic healthcare services in a primary care practice should be targeted based on multimorbidity concepts, particularly in the elderly, to reduce the prevalence of CKD and mitigate the large public health effect of CKD in T2DM patients.
In summary, here we found a relatively high prevalence of CKD among T2DM patients in a suburban community in Thailand, particularly in elderly patients and those with diabetes complications related to poor glycaemic control. Our study also underscores an important opportunity to identify T2DM patients who are at high risk of CKD through readily available and routinely obtained factors in the primary care setting. Early identification may help optimise care and prevention programs for these populations.
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