Glucose Metabolism, Insulin Resistance, and Renal Pathology in Non-Diabetic Chronic Kidney Disease

Abstract

Background: The relation between insulin resistance and atherosclerosis is widely recognized, but it remains unknown whether glucose metabolism/insulin resistance is related to renal pathology in humans. Methods: We quantitatively evaluated pathological changes in the glomeruli, tubulointerstitium, and vessels in renal biopsy specimens from 23 patients with non-diabetic chronic kidney disease (CKD), all of whom took a 75-gram oral glucose tolerance test. We correlated the renal pathological changes with fasting plasma glucose (FPG), fasting plasma insulin, 2-hour plasma glucose (2-h PG), 2-hour plasma insulin (2-h PI), homeostasis model assessment of insulin resistance (HOMA-IR), and body mass index. Results: HOMA-IR exceeded 1.73 in 11 patients (47.8%), and 2-h PI exceeded 64.0 µU/ml in 14 (60.9%). FPG significantly correlated with interstitial fibrosis (r = 0.532, p = 0.009). The significance was marginal in the correlation between FPG and tubular atrophy and arterio-arteriolosclerosis. Statistically significant correlation was also found between 2-h PG and arterio-arteriolosclerosis (r = 0.422, p = 0.04) and between HOMA-IR and interstitial fibrosis (r = 0.416, p = 0.04). Conclusion: Although precise mechanisms remain unknown, glucose metabolism/insulin resistance seem to play pathogenic roles in formation and progression of renal pathological changes, especially tubulointerstitial and vascular lesions, in non-diabetic CKD.

Postprandial hyperglycemia and hyperinsulinemia associated with renal arterio-arteriolosclerosis in chronic kidney disease

“…4 We showed earlier the association between glucose metabolism/insulin resistance and renal pathology; FPG and interstitial fibrosis; 2-h PG and renal arterio-arteriosclerosis; and HOMA-IR and interstitial fibrosis. 8 Among these pathological changes, renal arterio-arteriolosclerosis is important, because it is known to be related to renal function and prognosis. [9][10][11][12] However, whether clinical factors other than hypertension have an impact on renal arterioarteriolosclerosis remains to be elucidated.…”

“…Our previous study showed the association of glucose metabolism/insulin resistance with interstitial and intra-renal vascular changes, but not with glomerular changes. 8 Previous studies showed 'atypical' renal pathology in a substantial proportion of patients with type 2 diabetes mellitus: absent or mild glomerular changes with disproportionately severe tubulointerstitial injury and renal arterio-arteriolosclerosis. 32 Renal insufficiency with almost normal urinalysis can be a clinical manifestation of absent or mild glomerular changes with severe tubulointerstitial injury and renal arterio-arteriolosclerosis.…”

“…Of the patients included this study, 23 patients were included also in our previous study. 8 The ethical committee of our hospital approved this study.…”

“…Recently, we reported the association between renal pathological changes and indices of glucose metabolism/insulin resistance determined by 75 g oral glucose tolerance test in non-diabetic CKD patients. 8 This study included 23 patients, and showed significant correlation between fasting plasma glucose (FPG) and interstitial fibrosis; 2-h plasma glucose (2-h PG) and renal arterio-arteriolosclerosis; and HOMA-IR and interstitial fibrosis. To our knowledge, this was the first study showing the association between renal pathology and glucose metabolism/insulin resistance.…”

Serum Complement C3 Predicts Renal Arteriolosclerosis in Non-Diabetic Chronic Kidney Disease

“…, postprandial hyperglycemia, hyperinsulinemia 38,39) and serum adiponectin 5,6) contribute to the development of renal arteriolosclerosis. Furthermore, hypertriglyceridemia at the time of diagnosis has been shown as a risk factor for the progression of IgAN, and may play a role in the pathogenesis of glomerulosclerosis and arteriolosclerosis 40) .…”