The transition from the pre-ESRD to ESRD phase of CKD: much remains to be learned Original paper

What was reviewed?

This review article examines the transition from pre-ESRD to ESRD, a critical period in chronic kidney disease care when patients move from advanced kidney failure into dialysis-dependent end-stage renal disease. The authors synthesize emerging evidence showing that clinical instability, abrupt changes in kidney function, and cardiometabolic stressors strongly influence how patients fare after dialysis initiation. They assess observational and prospective cohort research, including studies linking volume overload, rapid eGFR decline, and blood pressure management with mortality risk. The review highlights major gaps in understanding this transition and emphasizes that events occurring before dialysis initiation can shape long-term ESRD outcomes. Although not a microbiome-focused review, the transition period aligns closely with shifts in systemic inflammation, immune activation, and gut-derived metabolite load, all of which are microbiome-relevant signatures clinicians increasingly monitor.

Who was reviewed?

The reviewed studies collectively involve adults with advanced CKD approaching dialysis initiation and incident ESRD patients captured in datasets such as USRDS, CHOICE, CDS, DOPPS, CRIC, MDRD, and AASK. These populations include diverse demographic and clinical profiles, though some datasets—such as VA health system records—over-represent older adults and men. Across cohorts, patients exhibit varying etiologies of CKD, comorbidity burdens, rates of kidney function decline, cardiovascular risk, and degrees of fluid overload. The review’s synthesis centers on individuals who experienced clinical events, hemodynamic fluctuations, and therapeutic changes immediately before dialysis, contextualizing how their pre-ESRD physiology affects ESRD survival trajectories.

Most important findings

Across the reviewed evidence, several key findings emerge regarding the transition from pre-ESRD to ESRD. Volume overload at dialysis initiation is associated with significantly increased mortality, highlighting congestion as a major physiologic stressor. Rapid or abrupt declines in eGFR—often linked with heart failure events—predict a threefold higher first-year ESRD mortality risk, underscoring the importance of early recognition of destabilization patterns. Strict blood pressure control during CKD does not alter time to kidney failure but is linked with reduced post-ESRD mortality, potentially due to lower cardiovascular disease burden at dialysis start. These findings collectively illuminate how pre-ESRD cardiometabolic stress maps onto outcomes after renal replacement therapy. From a microbiome perspective, volume overload, uremia, heart failure events, and systemic inflammation each correlate with amplified production or reduced clearance of gut-derived uremic toxins such as p-cresol sulfate and indoxyl sulfate—signatures that may serve as biomarkers of physiologic deterioration approaching ESRD.

Key implications

The review emphasizes that the pre-ESRD phase is not merely a precursor but a determinant of ESRD outcomes. Clinical instability—whether from fluid overload, cardiovascular events, or rapid renal decline—sets trajectories for survival during the early dialysis period. For clinicians, this highlights the need for proactive stabilization, refined timing of dialysis initiation, and closer monitoring of markers that reflect systemic inflammation and microbiome-derived toxin burden. The findings argue for integrated care models that span the CKD-to-ESRD continuum and for future research that incorporates microbiome signatures to better characterize metabolic stress during this transition.

Citation

Sharief S, Hsu C. The transition from the pre-ESRD to ESRD phase of CKD: much remains to be learned. Am J Kidney Dis. 2017;69(1):8-10. doi:10.1053/j.ajkd.2016.10.001