Crohn’s disease may promote inflammation in IgA nephropathy: a case–control study of patients undergoing kidney biopsy

Abstract

Intestinal immunity has been closely associated with the pathogenesis and progression of renal diseases, a relationship known as the “gut–kidney axis.” To determine the association between immunoglobulin A nephropathy (IgAN) and Crohn’s disease (CD), a clinico-pathological study was performed on patients who had IgAN with CD (CD-IgAN) and without CD (NOS-IgAN). We enrolled 29 patients diagnosed with IgAN via renal biopsy at the Tokyo Yamate Medical Center from 2009 to 2017. The patients were divided into CD-IgAN (n = 18) and NOS-IgAN (n = 11) and evaluated for clinical and pathological findings. IgA subclasses and galactose-deficient IgA1 (Gd-IgA1) were examined via immunohistochemistry using formalin-fixed paraffin-embedded sections from renal biopsy. Our results showed no significant difference in the extent of mesangial IgA subclasses or Gd-IgA1 deposition according to the presence or absence of CD. Pathologically, however, those with CD-IgAN had remarkably higher percentage of global glomerulosclerosis and extent of interstitial fibrosis and tubular atrophy (IF/TA) compared to those with NOS-IgAN. Moreover, the extent of macrophage infiltration in the glomerulus and interstitium was significantly higher in CD-IgAN than in NOS-IgAN. Clinically, the CD-IgAN group had significantly worse responsiveness to steroid treatment compared to the NOS-IgAN group. In conclusion, the similar immunological characteristics of deposited IgA molecules in the glomeruli between the CD-IgAN and NOS-IgAN groups might suggest their etiological similarity. However, a renal pathology showing advanced glomerular and tubulointerstitial sclerosis accompanying increased macrophage infiltration and highly resistant clinical features in patients with CD-IgAN suggests that some pathophysiological factors in CD, including abnormal intestinal immunity, may promote and activate the inflammatory process in IgAN via undetermined mechanisms.

Kidney Diseases Associated With Inflammatory Bowel Disease: Impact of Chronic Histologic Damage, Treatments, and Outcomes

“…Interestingly, a previous study described a remarkably higher percentage of glomerulosclerosis and a greater extent of interstitial fibrosis and tubular atrophy in IgAN associated with CD, together with a higher macrophage infiltration, suggesting that these patients may have a more aggressive clinical phenotype of IgAN. 32 Despite that, the optimal therapeutic approach of these patients remains to be elucidated. Moreover, although the novel targeted-release formulation of budesonide appears to be a promising therapeutic strategy for the management of both IBD and IgAN, 33 , 34 other generic forms of budesonide currently available for the treatment of IBD should also be compared in these patients.…”