Estimating GFR and the Effects of AKI on Progression of Chronic Kidney Disease

Chronic kidney disease (CKD) is a common health problem with a high prevalence in the elderly and is associated with high mortality rates and co-morbidity. CKD guidelines recommend that diagnosis and staging of CKD be based on estimated glomerular filtration rate (eGFR). Estimating GFR requires estimating equations using the variables gender, race and age and body surface area based on serum creatinine levels. The commonly recommended and used equations are the Modification of Diet in Renal Disease (MDRD) study and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations but these have not yet been validated in elderly people, who are at significant risk of developing CKD. The numbers of patients with progressive CKD is reportedly low with only a small proportion of patients reaching end-stage renal disease (ESRD). This study set out to find out why there is such a disproportion in the high prevalence of CKD and the low incidence of ESRD patients. Many patients die before they reach ESRD but prevalence studies have shown that mortality rates alone do not account for these numbers. I hypothesised that the methods used to estimate GFR underestimate renal function in elderly people causing an overestimate in CKD prevalence. This study firstly set out to assess the accuracy of the MDRD and CKD-EPI equations in an elderly Caucasian population against measured GFR across a wide range of renal function. The study demonstrated both equations perform fairly accurately in the elderly population with a tendency to slightly over-estimate GFR. This study has validated the use of these estimating equations in an elderly Caucasian population disproving my first hypothesis.

If the CKD prevalence data is a fair estimate and only a small proportion progress then the answer may lie in how CKD progresses. There are several known factors that influence CKD progression including GFR and albuminuria category, cause of renal disease and hypertension. Some of these risk factors are modifiable and need to be identified and managed in order to impact on long term outcomes including death, cardiovascular events and disease progression. Acute kidney injury (AKI) is also rising in incidence and is complicated by high mortality rates, increased risk of cardiovascular events and more recently CKD progression. Little is known about the impact of more minor episodes occurring in the community on renal outcome.

The second part of this study examined the relationship of multiple episodes of community AKI with CKD progression in a population of patients with CKD stage 3-5 referred to renal services. In this observational study, patterns of CKD progression were assessed and multiple AKI events were recorded. This study demonstrated a clear relation between multiple AKI events and CKD progression however only low eGFR at referral, diabetes and albuminuria were independent risk factors associated with disease progression. During the study it emerged that there were two patterns of CKD progression. In comparison to the more commonly assumed linear decline, the more common pattern was a stepwise progressive pattern characterised by accelerated rates of decline followed by a period of stability. Multiple AKI events were significantly more common in the stepwise progressive group suggesting AKI may have an important role as a promoter of CKD progression. This study suggests that community AKI is a modifiable risk factor that needs identifying at early stages in order to minimise risk of poor outcomes including CKD progression.