Browsing by Subject "Nephritis"

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    Inhibition of periostin expression protects against the development of renal inflammation and fibrosis
    (American Society of Nephrology, 2014-08) Mael-Ainin, Mouna; Abed, Ahmed; Conway, Simon J.; Dussaule, Jean-Claude; Chatziantoniou, Christos; Department of Pediatrics, IU School of Medicine
    Increased renal expression of periostin, a protein normally involved in embryonic and dental development, correlates with the decline of renal function in experimental models and patient biopsies. Because periostin has been reported to induce cell differentiation, we investigated whether it is also involved in the development of renal disease and whether blocking its abnormal expression improves renal function and/or structure. After unilateral ureteral obstruction in wild-type mice, we observed a progressive increase in the expression and synthesis of periostin in the obstructed kidney that associated with the progression of renal lesions. In contrast, mice lacking the periostin gene showed less injury-induced interstitial fibrosis and inflammation and were protected against structural alterations. This protection was associated with a preservation of the renal epithelial phenotype. In vitro, administration of TGF-β to renal epithelial cells increased the expression of periostin several-fold, leading to subsequent loss of the epithelial phenotype. Furthermore, treatment of these cells with periostin increased the expression of collagen I and stimulated the phosphorylation of FAK, p38, and ERK 42/44. In vivo delivery of antisense oligonucleotides to inhibit periostin expression protected animals from L-NAME-induced renal injury. These data strongly suggest that periostin mediates renal disease in response to TGF-β and that blocking periostin may be a promising therapeutic strategy against the development of CKD.
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    Referral and Evaluation for Kidney Transplantation among Patients with Lupus Nephritis-Related End-Stage Kidney Disease
    (Sage, 2024) McPherson, Laura; Plantinga, Laura C.; Howards, Penelope P.; Kramer, Michael; Pastan, Stephen O.; Patzer, Rachel E.; Surgery, School of Medicine
    Objective: For the majority of patients with lupus nephritis-related end-stage kidney disease (LN-ESKD), kidney transplant is associated with better outcomes than dialysis. Access to kidney transplant requires an initial referral to a transplant center and medical evaluation prior to waitlisting. The study's objective was to examine access to these early steps in the kidney transplant process among patients with LN-ESKD. Methods: Adults who began treatment for ESKD in the Southeast, Northeast, New York, or Ohio River Valley U.S. regions from 1/1/2012 to 12/31/2019, followed through 6/30/2021, were identified from the United States Renal Data System. Referral and evaluation start data were collected from 28 of 48 transplant centers across these regions. The exposure was primary cause of ESKD (LN-ESKD vs other-ESKD). The outcomes were referral and evaluation start at a transplant center. Cox models quantified the association between LN-ESKD (vs other-ESKD) and referral and evaluation start. Results: Among 192,318 patients initiating treatment for ESKD, 0.4% had LN-ESKD. Over half (58%) of LN-ESKD patients were referred before study end, and among those referred, 66% started the evaluation. In adjusted analyses, patients with LN-ESKD were referred (HR: 1.09, 95% CI: 0.99, 1.19) and started the transplant evaluation (HR: 1.13, 95% CI: 1.00, 1.28) at a higher rate than patients with other-ESKD. Among referred patients with LN-ESKD, the median time from ESKD start to referral was 2.9 months (IQR: <1 to 11.7 months), which is similar to patients with other-ESKD (median 2.6 months, IQR: <1 to 8.8 months). Conclusions: Among incident patients with ESKD, having a primary diagnosis of LN-ESKD versus other-ESKD is associated with higher rates of early transplant access outcomes. Despite this, patients with LN-ESKD (vs other-ESKD) are less likely to be preemptively referred (i.e., referred prior to ESKD start) for kidney transplant. While providers may no longer be delaying the early steps in the kidney transplantation process among this patient population, there is still room for improvement in the rates of preemptive referral. Access to kidney transplant referral prior to ESKD could result in increased transplant rates and better transplant outcomes for patients with LN-ESKD.