Markers of early progressive renal decline in type 2 diabetes suggest different implications for etiological studies and prognostic tests development

Kidney Int. 2018 May;93(5):1198-1206. doi: 10.1016/j.kint.2017.11.024. Epub 2018 Feb 2.


To identify determinants of early progressive renal decline in type 2 diabetes a range of markers was studied in 1032 patients enrolled into the 2nd Joslin Kidney Study. eGFR slopes estimated from serial measurements of serum creatinine during 5-12 years of follow-up were used to define early renal decline. At enrollment, all patients had normal eGFR, 58% had normoalbuminuria and 42% had albuminuria. Early renal decline developed in 6% and in 18% patients, respectively. As determinants, we examined baseline values of clinical characteristics, circulating markers: TNFR1, KIM-1, and FGF23, and urinary markers: albumin, KIM-1, NGAL, MCP-1, EGF (all normalized to urinary creatinine) and the ratio of EGF to MCP-1. In univariate analysis, all plasma and urinary markers were significantly associated with risk of early renal decline. When analyzed together, systolic blood pressure, TNFR1, KIM-1, the albumin to creatinine ratio, and the EGF/MCP-1 ratio remained significant with the latter having the strongest effect. Integration of these markers into a multi-marker prognostic test resulted in a significant improvement of discriminatory performance of risk prediction of early renal decline, compared with the albumin to creatinine ratio and systolic blood pressure alone. However, the positive predictive value was only 50% in albuminuric patients. Thus, markers in plasma and urine indicate that the early progressive renal decline in Type 2 diabetes has multiple determinants with strong evidence for involvement of tubular damage. However, new, more informative markers are needed to develop a better prognostic test for such decline that can be used in a clinical setting.

Keywords: diabetes; diabetic nephropathy; microalbuminuria.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albuminuria / diagnosis
  • Albuminuria / etiology
  • Albuminuria / physiopathology
  • Biomarkers* / blood
  • Biomarkers* / urine
  • Blood Pressure
  • Chemokine CCL2 / urine
  • Creatinine / urine
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Diabetes Mellitus, Type 2 / urine
  • Diabetic Nephropathies / diagnosis
  • Diabetic Nephropathies / etiology*
  • Diabetic Nephropathies / physiopathology
  • Disease Progression
  • Early Diagnosis
  • Epidermal Growth Factor / urine
  • Female
  • Glomerular Filtration Rate
  • Hepatitis A Virus Cellular Receptor 1 / blood
  • Humans
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Receptors, Tumor Necrosis Factor, Type I / blood
  • Risk Assessment
  • Risk Factors
  • Time Factors


  • Biomarkers
  • CCL2 protein, human
  • Chemokine CCL2
  • HAVCR1 protein, human
  • Hepatitis A Virus Cellular Receptor 1
  • Receptors, Tumor Necrosis Factor, Type I
  • TNFRSF1A protein, human
  • Epidermal Growth Factor
  • Creatinine