Chronic kidney disease (CKD) is a noncommunicable disease with increasing importance. Its pathophysiology interacts with cardiovascular (CV) and metabolic diseases, and extends to other neurological and respiratory disorders with clinically significant interplay. Despite its growing global burden, CKD remains underdiagnosed and undertreated. At a symposium in Hong Kong, a multidisciplinary panel highlighted the urgent need for earlier identification of CKD, integrated CV-kidney-metabolic (CKM) care, and timely implementation of guideline-directed medical therapy (GDMT) — including sodium-glucose cotransporter-2 inhibitors (SGLT2i; eg, dapagliflozin) — to slow progression toward kidney failure and reduce CKD-related complications.
Why kidney health can’t wait?
CKD affects an estimated 850 million people worldwide and is projected to become the fifth leading cause of premature death by 2040. In Hong Kong, nearly 500,000 adults have CKD, with diabetes as the leading cause of kidney failure, accounting for more than half of cases, and hypertension contributing to >10 percent. [Nat Rev Nephrol 2024;20:473-485; Lancet Reg Health West Pac 2025;64:101726; Hong Kong Med J 2024;30:332-336]
Recognizing the growing burden, the WHO adopted a landmark resolution on kidney health in 2025, formally acknowledging CKD as a noncommunicable disease of increasing global priority. Member states are urged to raise awareness of CKD, enhance prevention and early detection, improve access to affordable and quality treatment, and strengthen health systems for effective CKD management. [https://apps.who.int/gb/ebwha/pdf_ files/EB156/B156_(20)-en.pdf]
Spotting CKD early: eGFR and UACR as gold-standard tests
Global guidelines emphasize routine CKD screening in high-risk people, such as those with diabetes and hypertension, yet uptake remains suboptimal worldwide. According to a recent meta-analysis involving >29 million adults, only about one in five patients with diabetes and/or hypertension receives routine albuminuria testing in clinical practice. [Kidney Int 2024;105:S117-S314; BMC Nephrol 2025;27:18]
Accurate detection and management of CKD require both estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Combined assessment of eGFR and UACR is essential for diagnosis, risk stratification, and treatment planning. Declining eGFR together with increasing albuminuria synergistically amplifies the risk of progression to kidney failure and adverse CV outcomes, as highlighted in the Kidney Disease: Improving Global Outcomes (KDIGO) risk stratification heatmap. (Figure 1) [Kidney Int 2024;105:S117-S314]
Risk prediction can be further refined using the clinically validated Kidney Failure Risk Equation (KFRE), which integrates age, sex, eGFR, and UACR to estimate kidney failure risk and guide individualized decision-making and timely referral. [JAMA 2016;315:164-174]
“Early diagnosis is critical, as there are now effective treatments that can meaningfully change the trajectory of CKD and delay dialysis,” said Dr Winston Fung from the Department of Medcine & Therapeutics, Chinese University of Hong Kong. [Kidney Int 2020;97:226-232]
Timely GDMT for CKD matters
Effective treatment of CKD encompasses both indirect and direct strategies. Indirect management targets upstream drivers — most prominently diabetes and hypertension — to reduce renal and CV risk. However, controlling glycaemia and blood pressure alone is insufficient to slow CKD progression. CKD is characterized by ongoing, often irreversible structural and functional kidney damage that requires disease-specific therapy. [Kidney Int 2022;102:S1-S127; Kidney Int 2021;99:S1-S87; Int J Mol Sci 2021;22:10084]
Accordingly, major guidelines (eg, KDIGO, American Diabetes Association, European Society of Hypertension) emphasize timely initiation of GDMT for CKD, using agents with proven reno-and cardio-protective benefits. Renin-angiotensin-aldosterone system inhibitors (RAASi) remain the cornerstone of CKD management, particularly in patients with diabetic kidney disease or those with hypertension and albuminuria. The addition of SGLT2i represents a major advance in CKD care, providing robust cardiorenal protection beyond glycaemic control. [Kidney Int 2024;105:S117-S314; Diabetes Care 2023;46:1574-1586; Eur Heart J 2024;45:3912-4018; J Hypertens 2023;41:1874-2071]
In the landmark DAPA-CKD trial, dapagliflozin significantly reduced the risk of a composite outcome of sustained ≥50 percent decline in eGFR, kidney failure, or death from kidney or CV causes by 39 percent vs placebo (hazard ratio [HR], 0.61; 95 percent confidence interval [CI], 0.51–0.72; p<0.001). Importantly, these benefits were consistent in patients with (HR, 0.64; 95 percent CI, 0.52–0.79) or without diabetes (HR, 0.50; 95 percent CI, 0.35–0.72). All-cause mortality was also reduced by 31 percent with dapagliflozin vs placebo (HR, 0.69; 95 percent CI, 0.53–0.88; p=0.004). [N Engl J Med 2020;383:1436-1446]
Modelling based on DAPA-CKD data suggests that earlier initiation of dapagliflozin may provide greater kidney benefit, with a potential delay in kidney replacement therapy of up to 16 years (based on a between-group difference in eGFR decline of 1.92 mL/min/1.73 m2/year. (Figure 2) [N Engl J Med 2020;383:1436-1446]
The real-world OPTIMISE-CKD study showed that among CKD patients treated with dapagliflozin, eGFR trajectories/slopes, risks of cardiorenal events and all-cause mortality were comparable across UACR levels, supporting dapagliflozin’s broad applicability irrespective of baseline albuminuria or diabetes status. “Given the benefits of SGLT2i even in patients without albuminuria, these therapies can be initiated early [without waiting for the progression to severe proteinuria],” noted Dr Winston Fung. [Adv Ther 2024;41:1151-1167; Clin Kidney J 2024;17:sfae100]
These observations are supported by a meta-analysis of 10 trials, demonstrating that SGLT2i reduced the risk of CKD progression regardless of baseline eGFR, albuminuria or diabetes status. Another meta-analysis of six trials involving individuals with type 2 diabetes (T2D) at high CV risk or with CKD found that SGLT2i use was associated with a lower risk of serious hyperkalaemia without an increased risk of hypokalaemia. Given that hyperkalaemia can limit optimal use of RAASi in patients with T2D and CKD or heart failure, these findings may have implications for treatment optimization in this population. [JAMA 2026;335:233-244; Circulation 2022;145:1460-1470]
CKD’s links to respiratory and neurological conditions
Emerging evidence suggests that chronic respiratory diseases may contribute to CKD, potentially through systemic inflammatory mechanisms. For example, chronic obstructive pulmonary disease (COPD) induces the release of inflammatory mediators such as tumour necrosis factor-α, interleukin-6, and C-reactive protein, which are correlated with kidney tubular injury, glomerular damage, and CKD progression. [Front Public Health 2024;12:1494291]
In line with this, a retrospective local analysis found that hospitalization for acute exacerbations (HAE) of COPD — an indicator of severe disease — was associated with a higher risk of kidney progression or death vs non-HAE COPD (adjusted odds ratio [aOR], 2.380; 95 percent CI, 1.144–4.954; p=0.02). The HAE group also exhibited a more rapid decline in eGFR than the non-HAE group (-4.64 vs -2.40 mL/min/1.73 m2/year; p=0.025). Similarly, another analysis demonstrated that bronchiectasis exacerbators had worse long-term kidney progression-free survival vs non-exacerbators (aOR, 6.49; 95 percent CI, 5.47–7.69; p<0.001). [Respir Res 2024;25:36; Clin Respir J 2025;19:e70029]
CKD is also associated with cognitive decline, particularly vascular dementia. In the Framingham Offspring cohort, CKD was linked to a higher risk of vascular dementia (adjusted HR, 2.78; 95 percent CI, 1.16– 6.68; p=0.023). A meta-analysis reported that reduced eGFR (<60 mL/min/1.73 m2) was associated with poorer language and global cognitive performance. Similarly, the Japanese Suita study found that each 10 mL/min/1.73 m2 increase in eGFR reduced the odds of cognitive impairment by 4.8 percent, while a Swedish cohort study showed that lower baseline eGFR and faster decline (>2 mL/min/1.73 m2/year) were linked to increased dementia risk. [Nat Rev Nephrol 2025;21:536-552; Nephrol Dial Transplant 2024;39:1911-1922; BMC Med 2016;14:206; Hypertens Res 2024;47:672- 676; Neurology 2021;96:e2956-e2965]
Worsening kidney function is also linked to cerebrovascular events. In an Icelandic MRI study, rapid eGFR decline (>3 mL/ min/1.73 m2/year) was associated with incident subcortical infarcts (OR, 1.53; 95 percent CI, 1.05–2.22), while albuminuria was associated with cerebral microbleeds (OR, 1.42; 95 percent CI, 1.02–1.96). Furthermore, meta-analyses and biobank studies confirmed consistent associations with stroke and intracerebral haemorrhage. [Kidney Int 2018;94:608-615; Nephrol Dial Transplant 2015;30:1162-1169; JAMA Neurol 2022;79:911-918]
Conclusion
Timely diagnosis and intervention are the cornerstone of effective CKD management. Early detection using eGFR and UACR, along with prompt initiation of GDMT, is essential to slow CKD progression, reduce complications, and delay or prevent dialysis.
The above content is for medical education purposesupported by AstraZeneca (Hong Kong) Limited.
HK-12941 8 Jul 2026
