Progression of incident chronic kidney disease: a danish nationwide population-based cohort study

Abstract Background and Aims The increasing global burden of kidney failure calls for targeted interventions to slow progression of chronic kidney disease (CKD). However, the understanding of progression from CKD stage G3 is limited. We aimed to characterise individuals with incident CKD stage G3 in Denmark and to examine CKD progression defined by three different measures. Method We conducted a nationwide, population-based cohort study using routinely collected individual-level data from national health and administrative databases in Denmark (population ∼5.9 million). Using creatinine tests performed in general practice and the outpatient hospital setting from 1 January 2017 to 31 December 2020, we included all adults in Denmark with incident CKD stage G3, based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria (≥2 creatinine measurements corresponding to an estimated glomerular filtration rate (eGFR) between 30-59 ml/min/1.73 m2 separated by ≥90 days). We used the 2009 CKD Epidemiology Collaboration Creatinine Equation for calculating eGFR. The three years leading up to the study period comprised a washout period to minimise inclusion of individuals with prevalent CKD. We explored CKD progression based on three outcome measures of different sensitivity, including 1) rapid CKD progression (decline in eGFR of ≥5 ml/min/1.73 m2/year, that is, for each eGFR measurement taken during follow-up, we considered this and the measurements taken in the prior year (requiring ≥3 eGFR measurements separated by ≥90 days)); 2) drop in GFR category (drop between GFR categories, 45–59 [G3a], 30–44 [G3b], 15–29 [G4], <15 [G5] ml/min/1.73 m2, accompanied by ≥25% drop in eGFR from baseline); and 3) kidney failure (≥2 eGFR measurements <15 ml/min/1.73 m2 separated by ≥90 days and/or kidney replacement therapy). The 1- and 3-year risks of CKD progression according to the three definitions and all-cause mortality were examined as cumulative incidences using the Aalen-Johansen method. Results We included 133,443 individuals with incident CKD stage G3. The median age at inclusion was 75 years (interquartile range (IQR): 69-82) and 55% were females with 59% having hypertension, 18% having diabetes and 10% having heart failure. The median eGFR at inclusion was 56 ml/min/1.73 m2 (IQR: 51-58) and the median number of eGFR measurements was 3 (IQR: 2-5) in the prior year. Among the 133,443 individuals with incident CKD stage G3, 48,997 (37%) fulfilled the criteria for rapid CKD progression at inclusion. Among the 84,446 individuals without rapid progression on the day of inclusion, the 1- and 3-year risks of rapid CKD progression were 25.0% (95% confidence interval (CI): 24.7-25.3) and 46.0% (95% CI: 45.6-46.4), respectively. The risk of a drop in GFR category was 6.9% (95% CI: 6.8-7.1) after 1 year and 16.6% (95% CI: 16.4-16.8) after 3 years. The risks of kidney failure/renal replacement therapy were 0.1% (95% CI: 0.1-0.1) and 0.3% (95% CI: 0.3-0.4) after 1 and 3 years, respectively. All-cause mortality was 6.8% (95% CI: 6.7-6.9) in the first year and the 3-year mortality was 18.1% (95% CI: 17.9-18.4) (Table 1). Conclusion This nationwide, population-based cohort study showed that a substantial proportion of individuals experienced rapid CKD progression in the 3 years following incident CKD stage G3, whereas the risk of drop in GFR category was considerably lower. Kidney failure within 3 years was rare, while all-cause mortality was relatively modest, taking the high average age into account. This highlights the potential for preventive interventions in patients at risk of rapidly deteriorating kidney function, who might benefit from regular monitoring and targeted treatment.