Adverse outcomes associated with rapid linear and non-linear patterns of chronic kidney disease progression

Abstract

Background: Patients with rapidly declining renal function face the dual threat of end-stage renal disease (ESRD) and mortality prior to ESRD. What is less well characterised is whether the pattern of the renal trajectory, linear or non-linear, unmasks subgroups of rapidly progressing patients that face adverse outcomes in a differential manner.

Methods: An individual eGFR slope was applied to all outpatient estimated glomerular filtration rate (eGFR) values for each patient in the Salford Kidney Study from 2002 to 2018 who had at least 2 years follow-up, ≥4 eGFR values and baseline eGFR 15 to < 60 ml/min/1.73m². Rapid progression was defined as an annual eGFR slope of ≤ - 3 ml/min/1.73m²/yr and patients were categorised as linear or non-linear progressors based on the nature of their eGFR-time graphs. A Fine-Gray competing risk hazard model was used to determine factors associated with progression to ESRD and with mortality prior to ESRD. Cumulative incidence function curves highlighted differences in outcomes between linear and non-linear patients.

Results: There were 211 rapidly deteriorating patients with linear eGFR trajectories and 61 rapid non-linear patients in the study cohort. Factors associated with ESRD included younger age, male gender, lower baseline eGFR and higher serum phosphate, whilst older age, history of myocardial infarction and anaemia predicted mortality prior to ESRD. Over a median follow-up of 3.7 years, linear progressors reached ESRD sooner whilst those with non-linear progression faced significantly higher rates of mortality prior to ESRD.

Conclusions: Patients with rapid eGFR decline have high rates of adverse outcomes that are differentially expressed in those progressing linearly and non-linearly as a result of differing phenotypic profiles. Consequently, addressing individual risk factor profiles is important to deliver optimal personalised patient care.

Keywords: CKD; Chronic kidney disease; ESRD; End-stage renal disease; Linear; Non-linear; Progression.

Fig. 1

Assembling the study cohort. Abbreviations: SKS (Salford Kidney Study)

Fig. 2

Examples of eGFR-time graphs of linear and non-linear progressors in the study cohort. Graphs A to C highlight examples of rapid linear progression, whilst graphs D to F show rapid non-linear eGFR trajectory

Fig. 3

Cumulative incidence functions for ESRD and death prior to ESRD compared between linear and non-linear progressors. Abbreviations: ESRD (end-stage renal disease)

Fig. 4

1-Kaplan-Meier curves for probability of survival from the composite outcome of either ESRD or death prior to ESRD compared between linear and non-linear progressors