Impact of Obesity on IgA Nephropathy: Comparative Ultrastructural Study between Obese and Non-Obese Patients

Abstract

Background: The pathological role of obesity in the progression of glomerular lesions has rarely been studied in primary glomerular diseases. The purpose of this study is to investigate the influence of non-diabetic obesity on clinicopathological findings in IgA nephropathy. Methods: 74 patients with biopsy-proven IgA nephropathy were retrospectively divided into two groups according to the criteria for obesity in Japan: non-obese group (group N: n = 50) with BMI <25 kg/m², and obese group (group O: n = 24) with BMI ≥25 kg/m². Clinical and pathological data at the time of renal biopsy were analyzed. Moreover, the outcome of proteinuria in patients treated with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARB) was evaluated in different groups after a 1-year follow-up. Results: Urinary protein excretion was significantly greater in the obese group compared to normal-weight patients (p < 0.05). There was no significant difference in the prevalence of hypertension and hyperlipidemia. By light microscopy, the obese group showed significantly larger glomerular size (p < 0.0001). On the other hand, the severity of mesangial matrix expansion and crescent formation revealed no difference between the two groups. By electron microscopy, glomerular basement membrane (GBM) thickness was significantly increased in obese patients (p < 0.001). Among 61 patients who were followed up for 1 year in our institute, 15 patients were treated with ACE-I or ARB without steroids. ACE-I or ARB treatment without steroids tended to reduce proteinuria in the obese patients, but this change did not achieve statistical significance. Conclusions: In IgA nephropathy, obesity induces not only glomerular enlargement but also ultrastructural modification of GBM, which would contribute to increase proteinuria.

Current Therapy for IgA Nephropathy

“…Finally, renal prognosis is worse in obese IgAN patients, 13,14 possibly related to superimposed obesity-related renal changes. 15 Nonsurgical weight loss can indeed lead to a reduction of proteinuria. 16 In terms of histologic parameters (Figure 2), the IgAN Oxford classification 17,18 may offer important advances by providing evidence that not only chronic fibrotic changes, particularly glomerulosclerosis and tubulointerstitial fibrosis, but also mesangial and endocapillary hypercellularity predict prognosis.…”

Scope and mechanisms of obesity-related renal disease

“…[8] [10] [11] [12] [13] Increased glomerular size may be a manifestation of processes that promote cell proliferation and matrix synthesis (see below). Additionally, the link of glomerulomegaly and sclerosis may reflect the limited capacity of mature podocytes to divide.…”

“…In obese patients with IgAN, GBM was ~25% thicker despite similar HgbA1c to the non obese. [12] Thicker GBM was also seen in biopsies from patients with benign nephrosclerosis related to essential hypertension and patients with ORG, with no data on glucose, though triglycerides and cholesterol were higher in the obese. [15] Another series found thicker GBM in obese patients, as well as direct correlation with HgbA1c in the normal range.…”

The Fatty Kidney: Obesity and Renal Disease

“…Obesity, thus, fuels the typical hyperfiltration of patients with significant reductions of renal mass. The detrimental effect of obesity, when superimposed in other renal diseases, has been scarcely investigated, with the exception of IgA nephropathy [8] . Several studies have shown a significant worse renal outcome among obese patients with this disease.…”