MAKE and MACE were common in predialysis CKD; lower baseline kidney function and albuminuria severity were associated with adverse kidney outcomes, whereas older age, diabetes mellitus, and lower baseline kidney function were associated with incident cardiovascular events, highlighting distinct renal and cardiovascular risk profiles.
Key Findings
Results
Major adverse kidney events and incident major adverse cardiovascular events were common over long-term follow-up in predialysis CKD.
Retrospective cohort of 263 adults with predialysis CKD followed for at least five years; median follow-up 2829 days.
MAKE occurred in 97 patients (36.9%), an incidence rate of 47.8 per 1000 person-years.
MACE occurred in 53 patients (20.2%), an incidence rate of 26.0 per 1000 person-years.
Patients with baseline dialysis, kidney transplantation, coronary artery disease, heart failure, stroke, or malignancy were excluded.
Results
Lower baseline eGFR was independently associated with higher risk of MAKE.
In multivariable Cox models, HR per 10 mL/min/1.73 m2 increase in eGFR was 0.84 (95% CI 0.72-0.98; p = 0.024).
MAKE was defined as chronic dialysis, kidney transplantation, or a ≥50% decline in baseline eGFR.
Results
Greater albuminuria severity was strongly and independently associated with MAKE, with a graded relationship.
Microalbuminuria versus normal albuminuria: HR 4.15 (95% CI 1.91-9.00; p < 0.001), approximately fourfold higher hazard.
Macroalbuminuria versus normal albuminuria: HR 7.73 (95% CI 4.01-14.90; p < 0.001), approximately eightfold higher hazard.
Results
Older age and diabetes mellitus were independently associated with higher risk of incident MACE.
Older age: HR per 10 years 1.52 (95% CI 1.12-2.06; p = 0.007).
Diabetes mellitus: HR 3.00 (95% CI 1.60-5.62; p < 0.001).
MACE comprised nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death.
Results
Higher baseline eGFR was associated with lower MACE risk in treatment-adjusted models.
HR per 10 mL/min/1.73 m2 was 0.76 (p = 0.032-0.037) across the treatment-adjusted models.
Separate multivariable Cox models were built for MAKE and MACE.
Results
Time-dependent SGLT2 inhibitor and ACE inhibitor/ARB use were not significantly associated with MAKE or MACE.
Treatment exposures were modeled as time-dependent covariates in Cox models.
SGLT2 inhibitor exposure occurred in 75 patients (28.5%).
The authors caution that treatment-related findings should be interpreted carefully given the limited exposure and observational design.
Results
Fine-Gray competing-risk sensitivity analyses gave results broadly consistent with the primary Cox analyses.
Fine-Gray competing-risk regression was performed as a sensitivity analysis.
Results were described as broadly consistent.
Conclusions
Renal and cardiovascular outcomes showed distinct risk profiles in predialysis CKD.
Kidney outcomes were driven by lower baseline eGFR and albuminuria severity.
Cardiovascular events were associated with older age, diabetes mellitus, and lower baseline eGFR.
What This Means
This study followed 263 adults with chronic kidney disease who were not yet on dialysis, for at least five years (median about 7.7 years). None had known heart disease, stroke, or cancer at the start. About 37% had a major kidney event (starting dialysis, receiving a kidney transplant, or losing at least half of their kidney function), and about 20% had a major cardiovascular event (heart attack, stroke, or cardiovascular death).
Kidney outcomes were mainly linked to how well the kidneys were working at the start and how much protein was leaking into the urine. People with moderate or heavy protein leakage had roughly four to eight times the risk of a kidney event compared with those with normal levels. Cardiovascular events, by contrast, were linked more to older age, diabetes, and lower kidney function at baseline. This research suggests that kidney and heart risks in CKD are driven by partly different factors.
The study did not find a significant link between use of SGLT2 inhibitors or ACE inhibitor/ARB drugs and either outcome. However, only 28.5% of patients took SGLT2 inhibitors, and this was an observational study at a single set of centers, so these results cannot show whether the drugs work or not. The findings mainly help identify who may be at higher risk.
Karaduru Avcı A, Inci A, Avcı R, Büyükokudan U, Sargin F, Koç L, et al.. (2026). Long-Term Major Adverse Kidney and Cardiovascular Events in Predialysis Chronic Kidney Disease: A Real-World Cohort Study.. Medicina (Kaunas, Lithuania). https://doi.org/10.3390/medicina62101957