Kidney Tubular Biomarkers in Type 1 Diabetes - Longitudinal Analysis of 2 Cohorts.

INTRODUCTION

Kidney tubular biomarker trends may provide insight into tubulointerstitial pathology that is not evident through measurement of glomerular filtration rate (GFR) and albumin excretion rate (AER).

METHODS

We examined longitudinal changes in tubular biomarkers in 2 type 1 diabetes (T1D) cohorts, namely the Renin-Angiotensin System Study (RASS, = 283), including adults with normal GFR and AER and the Preventing Early Renal Loss in Diabetes Study (PERL, = 530), including adults with albuminuria and/or rapid loss of estimated GFR (eGFR). The measurements included plasma kidney injury molecule-1 (KIM-1), soluble tumor necrosis factor receptor 1 (sTNFR1), arginine-citrulline ratio, urine epidermal growth factor (EGF), uromodulin (UMOD), and a tubular secretion score reflecting urinary clearances of 8 proximal tubular secreted molecules.

RESULTS

At baseline, RASS participants' mean age was 30 years and 47% were male, with mean diabetes duration of 11 years, hemoglobin A1c (HbA1c) of 8.6%, iohexol-based measured GFR (iGFR) of 128 ml/min per 1.73 m, and AER of 6 μg/min. PERL participants' mean age was 51 years and 66% were male, with mean diabetes duration of 35 years, HbA1c of 8.2%, iGFR of 68 ml/min per 1.73 m, and AER of 285 μg/min. Tubular biomarkers changed significantly over time as follows: KIM-1 of +5.7 pg/ml/yr, sTNFR1 of +14.2 pg/ml/yr, arginine-citrulline ratio of -0.03 units/yr, and EGF of -0.30 μg/d/yr in RASS; KIM-1 of +7.5 pg/ml/yr, sTNFR1 of +75.0 pg/ml/yr, UMOD of -3.4 mg/d/yr, and tubular secretion score of -0.53 units/yr in PERL. Higher baseline HbA1c and AER were associated with more rapid worsening of select tubular biomarkers in both RASS and PERL.

CONCLUSION

Tubular biomarkers significantly worsen over time in T1D, potentially reflecting progression of tubulointerstitial pathology.