Renal function decline and optimized planning for kidney replacement therapy

Abstract

Chronic Kidney disease (CKD) is an increasing health problem world-wide, and the prevalence increases with age. CKD is a life-threatening condition, with high risk of cardiovascular disease and mortality. Patients with advanced CKD often need Kidney Replacement Therapy, (KRT), this includes transplantation, dialysis or conservative care. Education and follow-up of patients with advanced CKD is often referred to as predialysis care. This increases patient knowledge and enables more individualized treatment choices. Research on the natural course, and prognosis of CKD is necessary to be able to offer our patients best possible care. This thesis studies the influence of kidney progression rate on prognosis, planning for KRT, vascular access and patient survival.

All studies were observational cohort studies. Patients were included from the Swedish Renal Registry, (SRR), SRR-CKD, SRR-Access and Stockholm CREAtinin Measurement (SCREAM) during 2005-2020.

Study I described the impact of progression rate and age on the absolute risk for KRT and death. We used an unselected nephrology- referred CKD population, (n=8,771) with at least two creatinine measurements within a year. We used competing risk models and compared fast to slow progressors with regard to outcomes. Fast progression was associated to increased KRT risk in all ages and CKD stages, but the prognosis was affected by the age and eGFR of the patient.

Study II studied the progression rate following access creation, comparing Arteriovenous (AV) to peritoneal dialysis (PD) access placement in patients with severe CKD. Data were collected at 100 days before and after surgery, (n=744). We used linear mixed models with random intercept and slope. Access surgery was associated to a slower progression rate, but without any significant differences in AV compared to PD accesses. This study emphasizes the importance of predialysis care, but the need for dialysis remains the main determinant for access creation.

Study III compared the influence of open surgical versus endovascular intervention for AV access thrombosis on time to access abandonment and next intervention, (n=904). We also compared several categories of each intervention. The outcome; time to access abandonment were described in Kaplan-Mayer curves and compared with log-rank statistics. There was a statistically significant benefit of endovascular intervention on both short- and long-term access survival, albeit small in absolute terms.

Study IV evaluated the use of Kidney Failure Risk Equation, (KFRE) versus eGFR15 as a threshold for optimized timing of AV access creation. We used cumulative incidences to describe the outcomes of KRT, death and test diagnostics. KFRE>40% had superior specificity and positive predictive value compared to eGFR15 and were superior to predict KRT initiation and death.

To summarize, an individualized predialysis care considering progression rate and age is important to optimize the plan for future care. We found no evidence of a specific effect of AV access creation on the eGFR decline, and endovascular methods for vascular access thrombosis were shown to increase the proportion of people with a functioning access after 3-6 months. The use of KFRE>40% could be a valuable tool to improve the proportion of patients starting hemodialysis with a working access.