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Updated: Mar 26, 2026

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Higher urine heat shock protein 70/creatinine ratio in type 1 diabetes mellitus
Alev Yilmaz1, Asuman Gedikbasi2, Zeynep Yuruk Yildirim1
1a Pediatric Nephrology Department, Istanbul Medical Faculty , Istanbul University , Istanbul , Turkey ;
Insights
Urine heat shock proteins (HSPs) are elevated in children with type 1 diabetes mellitus (T1DM), indicating progressive kidney damage. Urine heat shock protein 70 (uHSP70/Cr) levels increase over time, serving as a potential early biomarker for diabetic nephropathy.
Area of Science:
- Nephrology
- Endocrinology
- Biochemistry
Background:
- Type 1 diabetes mellitus (T1DM) can cause insidious progressive renal damage starting in childhood.
- Heat shock proteins (HSPs) are crucial in cellular responses to stress and damage.
- Early detection of renal injury in diabetic children is vital for timely intervention.
Purpose of the Study:
- To investigate if urine HSP levels increase in diabetic children over time.
- To determine if elevated urine HSPs indicate progressive renal injury in T1DM.
- To assess the potential of urine HSPs as early biomarkers for diabetic nephropathy.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) was used to measure urine HSP27, HSP40, HSP60, HSP70, and HSP90 levels.
- Measurements were taken from 33 T1DM patients and 24 healthy children over two consecutive years (2012 and 2013).
- Results were normalized to creatinine levels (uHSP/Cr) and analyzed for significant changes and predictive value.
Main Results:
- Urine HSP levels (HSP27/Cr, HSP40/Cr, HSP60/Cr, HSP70/Cr, HSP90/Cr) were significantly higher in diabetic children compared to controls in 2012.
- In 2013, urine HSP70/Cr levels significantly increased, while HSP60/Cr decreased, and others remained stable.
- Urine HSP70/Cr demonstrated high diagnostic accuracy (AUC 0.957) with 85% sensitivity and 96% specificity for predicting diabetic kidney damage.
Conclusions:
- Elevated urine HSP levels are present in children with T1DM, suggesting early renal stress.
- Increasing urine HSP70/Cr levels over time may signify progressive kidney damage in T1DM.
- Urine HSP70/Cr shows promise as a sensitive and specific non-invasive biomarker for early detection of diabetic nephropathy in children.
Abstract:
Insidious progressive renal damage caused by type 1 diabetes mellitus (T1DM) begins in childhood before it becomes manifest in adult ages. Heat shock proteins (HSPs) regulate the cell response to any hazardous factors to prevent cell structure. The aim of the study is to determine whether urine levels of HSPs increase in diabetic children with time and indicate a progressive renal injury in T1DM. Thirty-three patients with T1DM and 24 healthy children were enrolled in the study. Renal function was normal in all patients. Urine levels of HSP27, HSP40, HSP60, HSP70, and HSP90 were measured by enzyme-linked immunosorbent assay at two consecutive years (2012 and 2013). The results were evaluated as urine HSP/creatinine ratios (uHSP/Cr). Mean urine HSP27/Cr, HSP40/Cr, HSP60/Cr, HSP70/Cr, HSP90/Cr in patient group were significantly higher than in controls in 2012 (uHSP27/Cr 460.12 ± 217.64 versus 270.02 ± 136.83 pg/mgCr; uHSP40/Cr 180.89 ± 118.59 versus 99.44 ± 62.49 pg/mgCr; uHSP60/Cr 114.40 ± 64.91 versus 70.50 ± 43.70 pg/mgCr; uHSP70/Cr 41.17 ± 28.42 versus 16.47 ± 7.32 pg/mgCr; uHSP90/Cr 175.64 ± 102.22 versus 107.61 ± 75.85 pg/mgCr) (p < 0.05). In 2013, uHSP70/Cr level increased significantly (51.08 ± 27.72 pg/mgCr; p = 0.001), whereas uHSP60/Cr level decreased and uHSP27/Cr, uHSP40/Cr, uHSP90/Cr levels remained stable (p > 0.05). Area under the curve (AUC) for uHSP70/Cr (0.957) was significantly higher than the others. Using a cutoff 22.59 pg/mgCr for uHSP70/Cr to predict of diabetic damage, sensitivity and specificity were 85% and 96%, respectively. Our results suggest that uHSP70/Cr increases over time and may indicate early phases of progressive kidney damage in diabetic children.
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