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Updated: Jun 22, 2026

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Insulin resistance is a risk factor for the progression of chronic kidney disease
H Kobayashi1, G Tokudome, Y Hara
1Hypertension Research Unit, Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine.
Objective:
Insulin resistance may contribute to the pathogenesis of hypertension and progressive chronic kidney disease (CKD), however, few clinical studies have explored the role of insulin resistance in predicting the deterioration of renal function in CKD patients.
Materials And Methods:
Enrolled in the study were non-diabetic hypertensive patients with CKD Stage 3. Insulin resistance was assessed by a homeostasis model assessment of insulin resistance (HOMA-R) measured at the entry to the study. Patients were followed for 3 years and comparisons of renal and metabolic parameters were made in conjunction with HOMA-R between entry and the end of the study period. The insulin-resistant (IR) group was defined as patients with HOMA-R 2.0 and more, and the insulin-sensitive (IS) group as those with HOMA-R < 2.0.
Results:
Blood pressure in both groups was equally controlled below 130/80 mmHg throughout the observation period. The degree of insulin resistance HOMA-R and immunoreactive insulin (IRI) remained unchanged in the IS group, however, both were ameliorated in the IR group (HOMA-R, from 3.4 +/- 1.5 - 3.0 +/- 1.1, p = 0.022 and IRI, from 14.4 +/- 6.1 microU/ml - 12.6 +/- 6.8 microU/ml, p = 0.012). Creatinine clearance (CCr) and estimated glomerular filtration rate (e-GFR) decreased and serum creatinine (Cr) concentration increased in all patients. The decline in CCr calculated as the slope of the reciprocal of serum Cr concentration (1/Cr) was greater in the IR group (0.007 +/- 0.004 (1/Cr/dl/mg/month) than in the IS group (0.003 +/- 0.002 (1/Cr/dl/mg/month), p < 0.001). Linear regression analysis showed that the slope of 1/Cr was negatively correlated with HOMA-R, IRI, BMI, respectively. Furthermore, stepwise regression analysis showed that the independent variables to explain the decline in renal function were HOMA-R and IRI.
Conclusion:
Insulin resistance is a significant risk factor for the deterioration of renal function in hypertensive non-diabetic patients with CKD.
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