More than half of our patients with T2D had DKD, and this prevalence falls between the 27.1% to 83.7% range reported worldwide5. This wide range of prevalence could be due to differences in DKD definition, patient profiles, healthcare settings, and health systems5,25. Our result closely approximates the global prevalence (56%) reported in the DEMAND (Developing Education on Microalbuminuria for Awareness of renal and cardiovascular risk in Diabetes) study1,26. Moreover, the composition of DKD by reduced eGFR and positive albuminuria among our patients is also similar to the global average; most DKD diagnoses are due to albuminuria with normal eGFR, followed by reduced eGFR and positive albuminuria, and finally, non-proteinuric kidney disease1,26. Indeed, a review article reported that non-proteinuric rather than proteinuric kidney diseases are the leading cause of ESKD, and non-proteinuric DKD prevails over the proteinuric form among T2D diabetes27.
Our prevalence of DKD is also comparable with 53% reported in a Singaporean study among a multi-ethnic group of primary care patients with T2D25. Again, the composition of DKD is similar to ours: 21% of their patients had reduced eGFR, while 48% had albuminuria25. The breakdown by GFR categories from stage G3a to G5 was also comparable with our study25. Besides that, a similar prevalence of reduced GFR and prevalence by GFR stages were reported in northern Thailand among T2D patients in the primary care setting28.
Overall, DKD is a common complication in patients with T2D in Malaysia. These results have important clinical and public health implications. Clinically, it implies the need to manage patients more aggressively to prevent the progression to ESKD, especially since diabetes was already the main contributor to dialysis in Malaysia10,20. DKD screening activities must also be intensified urgently, particularly because many patients in early DKD are asymptomatic and called the ‘silent majority’6. The clinical practice guidelines recommend screening for DKD during the initial visit and annually thereafter20. The lack of adherence to these recommendations constitutes clinical inertia that must be managed appropriately29. The WHO has recently recommended monitoring the proportion of diabetes patients with DKD in healthcare facilities, which should be considered in our health clinic settings to ensure optimal patient and programme monitoring14.
From a public health standpoint, the high DKD burden should alert health policymakers and programme managers about the substantial financial costs and adverse health outcomes associated with the disease, such as frailty, ESKD, reduced quality of life, and premature deaths1. The problem will only be magnified if more Malaysians develop diabetes, and if diabetes control remains unattainable among existing patients, more of them will end up having ESKD20. Around 106,000 dialysis patients are projected in Malaysia by the year 204030, and the relative high share of ESKD health expenditure in the public sector will stress the financing mechanism of the disease31. Therefore, primary, secondary, and tertiary prevention of diabetes must be optimised to tackle the diabetes epidemic in Malaysia. This effort is consistent with the National Action Plan for Healthy Kidneys 2018–2025, a strategic plan to decrease CKD burdens in the country32.
Established risk factors for DKD can be divided into non-modifiable and modifiable risk factors1,5. Our study findings are consistent with increasing age, male sex, ethnicity, and long duration of diabetes as non-modifiable factors associated with DKD1,5. Previous studies reported ethnic differences with Asian, Hispanic, and indigenous Australians tend to have a higher prevalence of DKD than Caucasians1. Further, Asian participants were found to have the highest proteinuria compared to Hispanic, African, Caucasian, and other ethnic groups26. The reasons for ethnic variations in DKD are complex and multifactorial1. The factors include genetic factors and developmental programming, age of T2D onset, lifestyle factors, socioeconomic disadvantages, access to and uptake of care, inadequate screening rates, and poorer attainment of treatment targets1.
Our multi-ethnic populations in Malaysia confer an advantage in observing ethnic variations in the prevalence of DKD. However, it is unclear why the Malay ethnicity is more likely to be associated with DKD. Further research is recommended to investigate the underlying reasons for the observed ethnic differences in Malaysia.
Obesity, hypertension, poor glycaemic control, poor blood pressure control, and lipid abnormalities are known modifiable risk factors for DKD, and our study again showed consistent findings1,5. These results further emphasise the crucial need to optimise body weight and control metabolic targets among T2D patients. However, most of our patients with DKD did not achieve HbA1c, intensified BP, or intensified LDL-cholesterol goals. This is alarming because inadequate metabolic control can lead to the progression of DKD to ESKD1. Moreover, poor control of these risk factors will increase the competing risk of premature mortality, mainly due to cardiovascular diseases1.
We also found that diabetic retinopathy, diabetic foot ulcer, nontraumatic lower-extremity amputation, ischaemic heart disease, stroke, insulin, antiplatelet agents, and higher numbers of antihypertensive agents were associated with DKD. All these factors are proxies for more severe diabetes conditions and are clinically logical to be related to DKD. Similar associations have been reported in other epidemiological studies among patients with T2D in Singapore, Thailand, Hong Kong, and Italy25,28,33,34. Interestingly, we found that underweight patients were independently associated with DKD; the adjusted odds ratio was even higher than that for obesity. A Korean nationwide cohort study reported that the underweight BMI category was an independent risk factor for ESKD among patients with diabetes35. Moreover, those with weight loss > 10% had the fastest decline in kidney function35. Some plausible mechanisms include sarcopenia and oxidative DNA damage associated with weight loss35.
We acknowledge missing data as a limitation in this registry-based study. We noted that a higher proportion of patients selected for this study and those included in the regression analysis were females, in the younger age category, and of Malay ethnicity, and this could cause selection bias and distort the actual prevalence of DKD in this study. As increasing age and male sex are established non-modifiable risk factors for DKD1,5, our study sample could have pulled the DKD prevalence downwards. In other words, the actual prevalence of DKD among T2D patients in Malaysia could be higher if more males and older patients were included. In contrast, since we found that the Malay ethnicity was more likely to have DKD, a higher proportion of Malay patients could have pushed the prevalence upwards. Nevertheless, our current prevalence estimate is still valid based on available real-world clinical data, with the prevalence falling between the range reported worldwide and similar to our neighbouring countries in Singapore and Thailand5,25,28.
This study has other limitations. The cross-sectional design disallows any causal inference between DKD and the associated factors. Measurement errors can occur because of the lack of standardisation mechanisms between health clinics across Malaysia. Nevertheless, the data reflect real-world clinical scenarios. Besides that, the analysis was limited to the data available in the National Diabetes Registry. Uncaptured information, such as socioeconomic disadvantages, family history of DKD, previous episodes of acute kidney injury, and inflammatory markers, all associated with DKD, could not be investigated in this study5. We were also unable to quantify the level of albuminuria as the details were not captured in the database. Our study definition of DKD was based on a single positive reading of albuminuria, a decreased GFR, or both with no repeated measurement typically taken 3 months apart to confirm the chronic nature of CKD18. Nevertheless, our results are still valid with similar definitions employed in other cross-sectional studies with no repeated measures to determine CKD or DKD prevalence25,28,36,37. Finally, the study population was confined to T2D patients in public health clinics; hence, the results cannot be generalised to patients treated in hospitals and those with type 1 diabetes.
To our best knowledge, this nationwide study is among the first to report the prevalence of DKD and its associated factors among patients with T2D in Malaysia. Real-world clinical information offers the added advantage of depicting the actual situations in the field. Our results have established a baseline prevalence of DKD among T2D patients in Malaysia, which may aid in monitoring the WHO indicator for DKD14. This study uncovers a high prevalence of DKD with important clinical and public health implications, as discussed above. We hope the results will help inform policymaking and the development of clinical practice guidelines in the country. This study also benefitted from the multi-ethnic population in Malaysia. The observed ethnic differences in the prevalence of DKD may provide an impetus for new studies on kidney complications among multi-ethnic diabetes patients to improve clinical outcomes.
In summary, DKD is highly prevalent among T2D patients in Malaysia. Increasing age, male sex, Malay ethnic group, longer duration of diabetes, overweight, obesity, hypertension, diabetic retinopathy, diabetic foot ulcer, nontraumatic lower-extremity amputation, ischaemic heart disease, stroke, insulin, higher numbers of antihypertensive agents, antiplatelet agents, poorer HbA1c control, higher systolic BP, non-achievement of triglyceride target, and non-attainment of HDL-cholesterol goal are independent factors associated with DKD. Clinicians, program managers, and health policymakers should target these modifiable factors to manage DKD and prevent its progression to ESKD.
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- Source: https://www.nature.com/articles/s41598-024-57723-6