Insulin resistance and the progression of IgA glomerulonephritis

Kaartinen, Kati; Syrjänen, Jaana; Pörsti, Ilkka; Harmoinen, Aimo; Pasternack, Amos; Huhtala, Heini; Niemelä, Onni; Mustonen, Jukka

doi:10.1093/ndt/gfl704

Cited by 36 publications

(23 citation statements)

References 17 publications

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“…As mentioned above, HOMA-IR was associated with the progression of IgA nephropathy. 7 In addition, increased levels of serum uric acid and triglyceride were associated with intra-renal vascular changes in IgA nephroptahy. 37,41 There is a possibility that the association between hyperglycemia/ hyperinsulinemia and renal arterio-arteriolosclerosis may depend on the type of glomerular disease.…”

Section: Discussionmentioning

confidence: 99%

“…For example, it has been reported that in a general non-diabetic population, higher fasting plasma insulin (FPI) accelerates age-related decline of renal function. 6 In patients with IgA nephropathy, Kaartinen et al 7 showed that higher FPI and homeostasis model assessment of insulin resistance (HOMA-IR) were associated with the progression of renal insufficiency. However, the effects of glucose metabolism/insulin resistance on human renal pathology remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2010

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Hypertension has an important function in the formation of renal arterio-arteriolosclerosis. However, renal arterioarteriolosclerosis is sometimes found in biopsy specimens of normotensive patients, which indicates unknown factors may contribute to renal arterio-arteriolosclerosis. In this study, we aimed to evaluate the effects of glucose metabolism/insulin resistance on renal arterio-arteriolosclerosis. Forty-eight patients with biopsy-proven non-diabetic chronic glomerular disease were included. Renal arterio-arteriolosclerosis was evaluated as the percentage of vessels showing hyaline changes or wall thickening. We correlated renal arterio-arteriolosclerosis with clinical parameters including indices obtained by 75 g oral glucose tolerance test. Of the 48 patients, 30 had hypertension. The results of univariate analysis showed significant association of renal arterio-arteriolosclerosis with hypertension, increased serum creatinine (S-Cr), hypertriglyceridemia, increased 2-h plasma glucose (PG) and increased 2-h plasma insulin (PI). In stepwise multiple regression analysis, hypertension (b¼0.344, P¼0.009), S-Cr (b¼0.287, P¼0.03) and 2-h PG (b¼0.274, P¼0.03) were independently associated with renal arterioarteriolosclerosis. Eleven of the 30 hypertensive patients did not have renal arterio-arteriolosclerosis. The hypertensive patients with renal arterio-arteriolosclerosis showed significantly higher 2-h PG (134 ± 25 vs. 106 ± 26 mg per 100 ml, P¼0.008) and higher 2-h PI (67.7 ± 34.9 vs. 48.3 ± 30.0 lU ml À1 , P¼0.04) compared with those without renal arterio-arteriolosclerosis, but the difference in S-Cr was not significant. Postprandial hyperglycemia and hyperinsulinemia may contribute to the formation of renal arterio-arteriolosclerosis independently of hypertension.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2010

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“…Other authors have reported that insulin resistance predicts cardiovascular death in patients on chronic HD [7]. Kaartinen et al [25] reported that plasma insulin level and HOMA-IR are associated with the progression of IgA nephropathy. Thus, insulin resistance in CKD is an issue of interest.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2008

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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.

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“…For instance, insulin resistance has been shown to predict ESRD in patients with mild renal impairment due to IgA nephritis (3). Furthermore, the opposite chain of events has also been observed; patients with ESRD without diabetes have been shown to develop insulin resistance in the later stage of the disease (3,4). Based on previous data, we hypothesized that reduced insulin sensitivity could be involved in the development of renal dysfunction via pathways that are not primarily mediated via increased glucose levels.…”

mentioning

confidence: 94%

“…However, lower insulin sensitivity has also been suggested to be associated with impaired renal function in individuals without overt diabetes (2). For instance, insulin resistance has been shown to predict ESRD in patients with mild renal impairment due to IgA nephritis (3). Furthermore, the opposite chain of events has also been observed; patients with ESRD without diabetes have been shown to develop insulin resistance in the later stage of the disease (3,4).…”

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confidence: 99%

Insulin Sensitivity Measured With Euglycemic Clamp Is Independently Associated With Glomerular Filtration Rate in a Community-Based Cohort

et al. 2008

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OBJECTIVE -To investigate the association between insulin sensitivity and glomerular filtration rate (GFR) in the community, with prespecified subgroup analyses in normoglycemic individuals with normal GFR.RESEARCH DESIGN AND METHODS -We investigated the cross-sectional association between insulin sensitivity (M/I, assessed using euglycemic clamp) and cystatin C-based GFR in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men [ULSAM], n ϭ 1,070). We also investigated whether insulin sensitivity predicted the incidence of renal dysfunction at a follow-up examination after 7 years.RESULTS -Insulin sensitivity was directly related to GFR (multivariable-adjusted regression coefficient for 1-unit higher M/I 1.19 [95% CI 0.69 -1.68]; P Ͻ 0.001) after adjusting for age, glucometabolic variables (fasting plasma glucose, fasting plasma insulin, and 2-h glucose after an oral glucose tolerance test), cardiovascular risk factors (hypertension, dyslipidemia, and smoking), and lifestyle factors (BMI, physical activity, and consumption of tea, coffee, and alcohol). The positive multivariable-adjusted association between insulin sensitivity and GFR also remained statistically significant in participants with normal fasting plasma glucose, normal glucose tolerance, and normal GFR (n ϭ 443; P Ͻ 0.02). In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function (GFR Ͻ50 ml/min per 1.73 m 2 ) during follow-up independently of glucometabolic variables (multivariable-adjusted odds ratio for 1-unit higher of M/I 0.58 [95% CI 0.40 -0.84]; P Ͻ 0.004).CONCLUSIONS -Our data suggest that impaired insulin sensitivity may be involved in the development of renal dysfunction at an early stage, before the onset of diabetes or prediabetic glucose elevations. Further studies are needed in order to establish causality.

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Insulin resistance and the progression of IgA glomerulonephritis

Abstract: Our results show that in addition to the known risk factors age, hypertension, proteinuria and hyperuricaemia, plasma insulin level and calculated HOMA-IR are associated with the progression of IgAGN.

Cited by 36 publications

References 17 publications

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

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

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

Insulin Sensitivity Measured With Euglycemic Clamp Is Independently Associated With Glomerular Filtration Rate in a Community-Based Cohort

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