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Table 3 Associations between stage II biomarkers and renal outcomes

From: Biomarkers for the detection of renal fibrosis and prediction of renal outcomes: a systematic review

Reference Biomarker/cut off Patient Population Subjects N (%)* Definition of renal progression Follow up: Median (range) Mean (± SD) Point Estimate (95% CI; p-value) C-statistic or AUC/specificity/sensitivity Quality Score
Chen et al [29] Urine TGF-β > 569 ng/l Unilateral ureteral obstruction requiring percutaneous nephrostomy 45 (24) Non-functioning kidney group defined by no improvement in eGFR 3 months NR NR/82%/82% Fair (7)
Harris et al [30] Blood TGF- β Renal transplant recipients 100 (23) Biopsy proven chronic allograft nephropathy using Banff 97 5 years HR 1.7 (1.1-2.6; p = 0.008) NR/NR/NR Good (10)
Wong et al [31] Blood total TGF- β 1
Blood active TGF- β 1
Type II diabetes 102
179 (HC)
Doubling of serum creatinine 5 years Blood total TGF- β 1: OR 3.9 (2.1-7.3) Conventional predictors:a 0.75/NR/NR Fair (7)
Blood active TGF- β 1: NR Addition of total TGF-β1: 0.82/NR/NR
  Addition of active TGF-β1: 0.88/NR/NR
Addition of both active and total TGF- β 1: 0.96/NR/NR
Hsu et al [27] Blood MMP-2 Non diabetic patients referred for coronary angiography 251 (16) eGFR decline >25% from baseline 8.5 (±2.4) years HR 2.5 (1.2-5.1) NR/NR/NR Good (9)
Shi et al [28] Urine MMP-2 Chronic tubulointerstitial nephropathy 61
20 (HC)
Continuous outcome of eGFR decline 38 (11-54) months β coefficient
-0.1 ml/min/m2, (p = 0.05)
0.74 (p < 0.05)/NR/NR Fair (7)
Titan et al [32] Urine MCP-1 ≥ 52 ng/g Macroalbuminuric type II diabetes 56 (27) Composite outcome of risk of dialysis, or doubling of serum creatinine or deathb 30.7 (±10) months OR 11.0 (1.6–76.4; p = 0.02) 0.65 (p = 0.08)/NR/NR Fair (8)
Verhave et al [33] Urine MCP-1 ≥ 48 ng/mmol Diabetic nephropathy 83 The rate of eGFR decline as a continuous outcome 2.1 years β coefficient
-2.0 ml/min/m2 (p = 0.001)
NR/NR/NR Fair (7)
Ogliari et al [34] Blood donor MCP-1 > 66th percentile SPK recipients 77 Graft loss 87.4 (65.4–132.3) months HR 4.5 (1.2–16.8; p = 0.02) NR/NR/NR Poor (6)
Nadkarni et al [35] Urine MCP-1 (continuous and tertiles) Type II diabetes 380 (50) eGFR decline >40% from baseline 5 years OR (continuous) 2.3 (1.4-3.6)
OR (3rd vs. 1st tertile) 5.3 (2.2-12.7)
C-statistic Conventional predictors: c 0.70
Addition of MCP-1: 0.74
Fair (7)
  1. AUC area under the curve, CAN chronic allograft nephropathy, eGFR estimated glomerular filtration rate, HC Healthy controls, HR Hazard ratio, MMP-2 matrix metalloprotinease-2, MCP-1 monocyte chemoattractant protein-1, NR not reported, OR odds ratio, PIINP procollagen type III amino-terminal pro- peptide, SPK simultaneous pancreas kidney transplant, TGF-β Transforming growth factor-beta
  2. *N represents the total sample size and the percentage represents the percent of those with the outcome when available in the literature
  3. aConventional Predictors: sex, body mass index, age, duration of diabetes mellitus, hemoglobin A1c, eGFR(CKD-EPI), randomized treatment interventions, urinary albumin/creatinine ratio, and history of macrovascular and microvascular events. bDeath only occurred in two people, hence the composite outcome was mainly worsening of renal function and study was included in phase II. c Sex, body mass index, hemoglobin A1C, eGFR, fibrate intervention, Angiotensin converting enzyme inhibitors/angiotensin II receptor blockers, urine albumin-creatinine ratio, and cardiovascular disease history