Analysis of eGFR index category and annual eGFR slope association with adverse clinical outcomes using real-world Japanese data: a retrospective database study

Abstract

Objectives: Real-world clinical outcome data of patients with an above-normal estimated glomerular filtration rate (eGFR) and increasing eGFR over time (eGFR slope) are scarce. Although eGFR is commonly recorded, eGFR slopes are rarely used for adverse outcome risk categorisation in clinical practice. We investigated the association of above-normal/below-normal eGFR ranges and increasing/declining eGFR slopes with clinical outcomes in Japan.

Design: Observational cohort study.

Setting: Primary and acute care hospitals; 423 centres.

Participants: 57 452 patients aged ≥16 years with ≥3 eGFR values (latest available January 2013-December 2016) from the Japanese Medical Data Vision database were stratified into six index eGFR and six eGFR slope groups (slopes calculated using a linear mixed model).

Primary and secondary outcome measures: Time-to-event analyses of cardiovascular mortality, all-cause mortality (ACM), all-cause hospitalisation (ACH) and cardiovascular and major kidney events. eGFR and slope groups were analysed by Cox proportional hazard models with multivariable adjustment, using normal eGFR/little-to-no slope groups as reference.

Results: Higher risk of clinical outcomes was observed with declining eGFR slope groups versus the reference group; the HR (95% CI) for slope ≤-5 mL/min/1.73 m²/year: cardiovascular events 1.8 (1.4 to 2.2), ACH 1.8 (1.5 to 2.1), and ACM 2.8 (1.9 to 4.2) and was non-significant for kidney events 1.5 (0.9 to 2.5). A similar, but non-significant, pattern was observed with increasing slope groups (slope >3 mL/min/1.73 m²/year HR (95% CI): cardiovascular events 1.2 (0.9 to 1.5), ACH 1.1 (0.9 to 1.4) and ACM 1.5 (0.9 to 2.3)).Above-normal and below-normal eGFR groups were associated with poorer outcomes versus the reference group, but kidney events were associated with below-normal eGFR only.

Conclusion: Poorer clinical outcomes were observed not only for below-normal eGFR and declining eGFR slope groups but also for certain above-normal eGFR and increasing slope groups. eGFR and eGFR slope may, therefore, be useful for identifying patients at high risk of adverse clinical outcomes.

Keywords: acute renal failure; cardiology; nephrology; risk management.

Figure 1

Cohort selection. eGFR, estimated glomerular filtration rate; MDV, Medical Data Vision.

Figure 2

Risk of CV, mortality, hospitalisation and kidney outcomes by eGFR slope category. *Cox proportional hazard model for time-to-event, with outcome and slope categories as independent variables. †Cox proportional hazard model for time-to-event, adjusted for age, sex, medical history, BL type 2 diabetes status, BL ECI score, BL medication use and index eGFR value for the multivariate model, plus interaction terms for slope categories in the full model. Categories 2–6 (eGFR slopes: ≤−5, >−5 to ≤−3, >−3 to ≤−1,>1 to≤3,>3) were analysed by outcome, with Category 1 (slope >−1 to ≤1) as reference. ‡Statistically significant HRs. §Based on inpatient death data. ¶Stroke, chronic heart failure or myocardial infarction. **End-stage kidney disease, dialysis, acute kidney failure or kidney transplant. BL, baseline; CV, cardiovascular; ECI, Elixhauser Comorbidity Index; eGFR, estimated glomerular filtration rate; eGFRdec, eGFR decliner; eGFRinc, eGFR increaser; HR, hazard ratio.

Figure 3

Risk of CV, mortality, hospitalisation and kidney outcomes by index eGFR category. *Cox proportional hazard model for time-to-event, adjusted for age, sex, medical history, baseline type 2 diabetes status, baseline ECI score and baseline medication use. Categories 2–6 (index eGFR values of <15, ≥15 to<30, ≥30 to<60, ≥90 to<120, ≥120 to≤200) were analysed by outcome, with index eGFR Category 1 (index eGFR of ≥60 to<90) as reference. †Statistically significant HRs. ‡Based on inpatient death data. §Stroke, chronic heart failure or myocardial infarction. ¶End-stage kidney disease, dialysis, acute kidney failure or kidney transplant. **These HRs are not presented in the forest plot, as they are extremely high values and so would distort the other HRs in the plot. CV, cardiovascular; ECI, Elixhauser Comorbidity Index; eGFR, estimated glomerular filtration rate; HR, hazard ratio.