Novel Biomarkers for change in renal function in people with
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Diabetes is a major risk factor for renal function decline and failure. The availability of multiplex panels of biochemical markers provides the opportunity to identify novel biomarkers that can better predict changes in renal function than routinely available clinical markers.

Adding up to 16 biomarkers to routinely measured clinical risk factors improves the prediction of annual change in eGFR in people with dysglycemia.

The concentration of 239 biochemical markers was measured in stored serum from participants in the biomarker substudy of Outcome Reduction With Initial Glargine Intervention (ORIGIN) trial. Repeated-measures mixed-effects models were used to compute the annual change in eGFR (measured as mL/min/1.73 square metre/year) for the 7,482 participants with a recorded baseline and follow-up eGFR.

Linear regression models using forward selection were used to identify the independent biomarker determinants of the annual change in eGFR after accounting for baseline HbA1c, baseline eGFR, and routinely measured clinical risk factors. The incidence of the composite renal outcome (i.e., renal replacement therapy, renal death, renal failure, albuminuria progression, doubling of serum creatinine) and death within each fourth of change in eGFR predicted from these models was also estimated.

Results: During 6.2 years of median follow-up, the median annual change in eGFR was −0.18 mL/min/1.73 m square/year. Fifteen biomarkers independently predicted eGFR decline after accounting for cardiovascular risk factors, as did 12 of these plus 1 additional biomarker after accounting for renal risk factors. Every 0.1 mL/min/1.73 m square predicted annual fall in eGFR predicted a 13% higher mortality.

These analyses show that the addition of up to 16 biochemical markers to routinely measured clinical markers clearly improves the ability to predict the decline in eGFR in middle-aged and older patients with either early diabetes or prediabetes who have additional cardio- vascular risk factors. They also show that the 15 biomarkers that were identified after accounting for previously identified clinical cardiovascular risk factors included 12 of the 13 that were identified after accounting for previously identified clinical renal risk factors. Despite the clear improvement in the prediction of eGFR, the addition of these biomarkers to clinical cardiovascular or renal risk factors only slightly improved the ability to predict death and a renal composite outcome during >6 years of follow-up.