Biomarkers of rapid chronic kidney disease progression in type 2 diabetes

Abstract

Here we evaluated the performance of a large set of serum biomarkers for the prediction of rapid progression of chronic kidney disease (CKD) in patients with type 2 diabetes. We used a case-control design nested within a prospective cohort of patients with baseline eGFR 30-60 ml/min per 1.73 m(2). Within a 3.5-year period of Go-DARTS study patients, 154 had over a 40% eGFR decline and 153 controls maintained over 95% of baseline eGFR. A total of 207 serum biomarkers were measured and logistic regression was used with forward selection to choose a subset that were maximized on top of clinical variables including age, gender, hemoglobin A1c, eGFR, and albuminuria. Nested cross-validation determined the best number of biomarkers to retain and evaluate for predictive performance. Ultimately, 30 biomarkers showed significant associations with rapid progression and adjusted for clinical characteristics. A panel of 14 biomarkers increased the area under the ROC curve from 0.706 (clinical data alone) to 0.868. Biomarkers selected included fibroblast growth factor-21, the symmetric to asymmetric dimethylarginine ratio, β2-microglobulin, C16-acylcarnitine, and kidney injury molecule-1. Use of more extensive clinical data including prebaseline eGFR slope improved prediction but to a lesser extent than biomarkers (area under the ROC curve of 0.793). Thus we identified several novel associations of biomarkers with CKD progression and the utility of a small panel of biomarkers to improve prediction.

Urine biomarkers of tubular injury do not improve on the clinical model predicting chronic kidney disease progression

“…Some prior studies did not capture information regarding albuminuria 16 or did not have albuminuria measurements concurrent with the biomarkers measurements 17, 18 or did not analyze albuminuria beyond a dichotomous 17 or semi-quantitatively fashion. 18 eGFR was usually not modeled flexibly (e.g.…”

Association between circulating fibroblast growth factor 21 and mortality in end-stage renal disease

“…Two other studies in ESRD patients on dialysis showed that the FGF21 levels were about 15-fold higher in chronic HD patients and about 8-fold higher in peritoneal dialysis patients than in normal subjects [12, 37]. Furthermore, prospective cohort studies in type 2 diabetes have shown that the circulating FGF21 level is a marker of rapid CKD progression, remaining significant even after adjustment for the baseline glomerular filtration rate [14, 15]. This result suggests that elevated FGF21 levels might reflect the processes that are causally related to renal dysfunction in type 2 diabetes patients, although reduced renal clearance is suggested as a major cause of FGF21 elevation [10, 23].…”

“…Indeed, end-stage renal disease (ESRD) patients receiving dialysis showed 8- to 15-fold higher circulating FGF21 levels than normal subjects [9, 12], and circulating FGF-21 levels were inversely correlated with the residual renal function in peritoneal dialysis patients [13]. Furthermore, the FGF21 level is an independent biomarker of rapid CKD progression in patients at early stages of diabetic nephropathy [14, 15]. Recent studies showed that the circulating FGF21 level predicts the rates of cardiovascular events and mortality in patients with type 2 diabetes [16, 17] and coronary artery disease [18].…”

Assessment of Urine Proteomics in Type 1 Primary Hyperoxaluria

“…7–10 Table 1 identifies targeted urine PROs in this investigation that were significantly different between the cohorts and/or within the PH1 cohort, and data from the literature regarding Ur-PROs from healthy individuals, CKD, acute kidney injury (AKI), stone formers, and in calculi matrices.…”