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.

Proteomic signature associated with chronic kidney disease (CKD) progression identified by data-independent acquisition mass spectrometry

“…The Salford Kidney Study (SKS), is a longitudinal, prospectively collected, ongoing observational study with full ethical permission that has recruited and followed-up patients with non-dialysis dependent CKD (NDD-CKD) in the United Kingdom since March 2002 [ 25 , 28 ]. This large NDD-CKD cohort consists of > 3500 patients that have provided their informed consent when admitted to the nephrology inpatient centre at Salford Royal Hospital or referred to nephrology outpatient clinics [ 8 , 26 ]. The participants in the current study were ≥ 18 years at the time of consent with (eGFR) < 60 ml/min/1.73 m 2 who had not started renal replacement therapy (RRT).…”

Evaluation of a proteomic signature coupled with the kidney failure risk equation in predicting end stage kidney disease in a chronic kidney disease cohort

“…Firstly, our inclusion criteria focused solely on patients with linear progression within the rapid progression group. Non-linear decline is common, yet these patients often tend to have different phenotypes and outcomes, and as of yet the proteomic signature of this cohort has not been studied specifically [ 38 ]. Additionally, while we carried out internal validation of our findings, and data were analysed using fold-change analysis (which is not affected by overfitting), it is important to acknowledge that machine learning models developed in this study require further validation in independent external samples to demonstrate robustness and generalisability of the results, for clinical utilisation.…”

Predictors of decline in kidney function in the general population: a decade of follow-up from the Tehran Lipid and Glucose Study

“…In contrast, we also found that higher eGFR was a protective factor among CKD patients. Previous work shows that the lower eGFR, the higher the risk of CKD progression and incident ESKD among those with CKD [ 71 , 72 ].…”