Inhibitory role of dietary protein restriction on the development and expression of immune-mediated antitubular basement membrane-induced tubulointerstitial nephritis in rats.

Abstract

The protective effect of dietary protein restriction on the development and expression of immune-mediated interstitial nephritis was evaluated in Brown Norway rats with anti-tubular basement membrane disease. In the first series of experiments, pair-fed rats received low protein (LP) (3% casein) or normal protein (NP) (27% casein), normocaloric diets. After 6 wk, each group was immunized with renal tubular antigen in adjuvant to produce anti-tubular basement membrane antibody (aTBM-Ab) and tubulointerstitial nephritis. The kidneys harvested from NP rats after four more weeks on the diet had histologically more severe interstitial disease than the LP rats (histologic severity, NP = 3.1±0.2 vs. LP = 1.1±03; P < 0.001), and serum creatinine values were concordantly different (NP = 1.34±0.02 vs. LP = 0.82±0.03). Titers of aTBM-Ab were similar in both groups, while the T cell-mediated immune response, as measured by delayed-type hypersensitivity (DTH), was nonspecifically impaired in LP rats when compared with the NP group. Admixture cotransfers of LP plus NP cells failed to demonstrate active suppression as an explanation for the depressed DTH in LP rats. The therapeutic role of dietary protein restriction was also examined in rats with established aTBM disease. In these experiments, rats were first immunized and fed NP diets for 4 wk (histologic severity = 3.0±0.2; creatinine = 1.78±0.02), and then were divided into two groups and followed for six more weeks on either LP or NP diets. LP rats, under these conditions, developed less disease than those fed NP diet (histologic severity; NP = 3.2±03 vs. LP = 1.4±0.2; P < 0.001), and serum creatinine values were concordantly different (NP = 1.92±0.05 vs. LP = 0.97±0.02). Again, the titers of aTBM-Ab in both LP and NP groups were similar. These data collectively suggest that LP diet has a protective effect both on the development and extent of tubulointerstitial nephritis that is perhaps, in part, related to the selective abrogation of effector T cell immunity.

New-Onset Acute Interstitial Nephritis Post-SARS-CoV-2 Infection and COVID-19 Vaccination: A Panoramic Review

“…It was well known that drugs were the most common cause of AIN, especially NSAIDs [ 47 ], and currently, the most widely accepted mechanism of drug-induced AIN was the cell-mediated type IV hypersensitivity theory. However, the exact pathophysiological mechanism remained to be elucidated [ 48 ].…”

“…Molecular mimicry: some structures of vaccines or adjuvants may be homologous to human proteins, and exposure to vaccines triggers antigenic epitopes of cross-reactive antibodies and thus disrupts immune tolerance. The figure refers to the pathogenesis of AIN by Sanchez-Alamo B et al [ 48 ] …”

Protein-Restricted Diets and Progression of Renal Failure

“…Agus et al [55] have demonstrated that protein restriction exhibits a protective ef fect in experimental immune interstitial ne-phritis. A low protein diet (corresponding to 0.4 g/kg/day for humans) retarded the devel opment of IN and ameliorated the extent of established immunologic disease in rats.…”