Baseline liver function tests and full blood count indices and their association with progression of chronic kidney disease and renal outcomes in Aboriginal and Torres Strait Islander people: the eGFR follow- up study

Abstract

Background Determination of risks for chronic kidney disease (CKD) progression could improve strategies to reduce progression to ESKD. The eGFR Study recruited a cohort of adult Aboriginal and Torres Strait Islander people (Indigenous Australians) from Northern Queensland, Northern Territory and Western Australia, aiming to address the heavy CKD burden experienced within these communities. Methods Using data from the eGFR study, we explored the association of baseline liver function tests (LFTs) (alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), bilirubin and albumin) and full blood count (FBC) indices (white blood cell and red blood cell counts and haemoglobin) with annual eGFR decline and renal outcomes (first of 30% decline in eGFR with a follow-up eGFR < 60 mL/min/1.73 m2, initiation of renal replacement therapy, or renal death). Comparisons of baseline variables across eGFR categories were calculated using analysis of variance and logistic regression as appropriate. Linear and multivariable regression models were used to estimate the annual change in eGFR for changes in FBC indices and LFTs. Cox proportional hazard models were used to estimate the hazard ratio for developing renal outcome for changes in baseline FBC indices and LFTs. Results Of 547 participants, 540 had at least one baseline measure of LFTs and FBC indices. The mean age was 46.1 (14.7) years and 63.6% were female. The median follow-up was 3.1 (IQR 2.8–3.6) years. Annual decline in eGFR was associated with low serum albumin (p < 0.001) and haemoglobin (p = 0.007). After adjustment for age, gender, urine albumin/creatinine ratio, diabetes, BMI, CRP, WHR, alcohol consumption, cholesterol and triglycerides, low serum albumin (p < 0.001), haemoglobin (p = 0.012) and bilirubin (p = 0.011) were associated with annual decline in eGFR. Renal outcomes were inversely associated with serum albumin (p < 0.001), bilirubin (p = 0.012) and haemoglobin (p < 0.001) and directly with GGT (p = 0.007) and ALP (p < 0.001). Other FBC indices and LFTs were not associated with annual decline in eGFR or renal outcomes. Conclusions GGT, ALP, bilirubin, albumin and haemoglobin independently associate with renal outcomes. Contrary to findings from other studies, no association was found between renal outcomes and other FBC indices. These findings may help focus strategies to prevent disease progression in this high-risk population.

Interaction of Serum Alkaline Phosphatase and Folic Acid Treatment on Chronic Kidney Disease Progression in Treated Hypertensive Adults

“…Multiple previous studies have reported that ALP is associated with increased risk of mortality in CKD patients, despite whether they were dialysis-dependent ( Fan et al, 2017 ; Zhan et al, 2019 ) or non-dialysis dependent patient ( Taliercio et al, 2013 ; Sumida et al, 2018 ). To date, however, only two small studies ( Yamazoe et al, 2016 ; Majoni et al, 2020 ) have investigated the association between serum ALP and renal outcomes. One study conducted in Japan ( Yamazoe et al, 2016 ), reported that the risk of worsening renal function during hospitalization increased by 69 and 95%, respectively, in patients in ALP tertile 2 (203–278 IU/L) and tertile 3 (>278 IU/L), compared with those in tertile 1 (<203 IU/L), among 972 patients with acute decompensated heart failure, and who were not on hemodialysis or peritoneal dialysis.…”

Low Albumin, Low Bilirubin, and High Alfa-Fetoprotein Are Associated with a Rapid Renal Function Decline in a Large Population Follow-Up Study

“…First, a low albumin level was associated with a rapid renal function decline. Several studies have reported associations between lower serum albumin concentrations and kidney function decline, risk of incident CKD, and progression to ESRD [ 13 , 25 , 26 , 27 ]. Potential mechanisms for hypoalbuminemia include decreased supply of amino acids, impaired liver synthesis, increased renal loss, and increased tissue catabolism or distributional problems [ 28 ].…”

“…A prospective observational study reported an association between low bilirubin concentration and the composite of a two-fold increase in serum creatinine or ESRD requiring dialysis in Japanese patients with stages 3–5 CKD [ 12 ]. Nevertheless, some studies have reported opposite findings [ 13 , 34 , 35 ]. Majoni et al reported that a high bilirubin concentration was associated with a faster annual decline in eGFR but better renal outcomes in an Australian population [ 13 ].…”

“…Nevertheless, some studies have reported opposite findings [ 13 , 34 , 35 ]. Majoni et al reported that a high bilirubin concentration was associated with a faster annual decline in eGFR but better renal outcomes in an Australian population [ 13 ]. A cross-sectional study conducted in the United States also demonstrated associations between a high bilirubin concentration and low eGFR and increased albuminuria in healthy adults [ 34 ].…”

“…This supports the emerging evidence that high bilirubin may protect against a decline in renal function [ 11 , 12 ]. However, high bilirubin was associated with better renal outcomes but faster annual decline in renal function in an Australian study [ 13 ].…”