Expression of the intrarenal angiotensin receptor and the role of renin-angiotensin system inhibitors in IgA nephropathy.

The critical role of the intrarenal renin-angiotensin system (RAS) in the development of kidney disease has been well demonstrated in animal and cell-culture experiments, but evidence from human kidney tissues is lacking. In this study, we screened 438 patients with IgA nephropathy (IgAN) and analyzed their clinical characteristics. Renal biopsy revealed the expression of angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), and MAS receptor (MASR) in the tissues of 260 patients not treated with RAS inhibitors, 32 patients treated with angiotensin-converting enzyme inhibitors (ACEIs), and 89 patients treated with angiotensin receptor blockers (ARBs). The correlations in expression among these three receptors and the results of Oxford typing were analyzed, together with the ability of ACEIs and ARBs to reduce proteinuria and the effects of ARBs on AT1R and AT2R expression. The results showed significantly higher AT1R, AT2R, and MASR expression in the M1 group (mesangial score > 0.5) than in the M0 group (mesangial score < 0.5), significantly higher AT1R expression in the S1 group (presence of segmental glomerulosclerosis) than in the S0 group (absence of segmental glomerulosclerosis); AT1R expression in the C2 group (crescent formation > 25%) was significantly higher than in the C0 (crescent formation = 0) and C1 (crescent formation < 25%) groups. Patients treated with an ARB for < 6 months had significantly lower urinary protein levels than those taking these drugs for > 6 months. These findings imply that overexpression of AT1R on the mesangial cells of IgAN patients is associated with mesangial cell proliferation, glomerular segmental sclerosis, and crescent formation. In addition, long-term administration of ARB may decrease the efficacy of these medications in terms of reducing proteinuria.

Effects of adding Rheum officinale to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on renal function in patients with chronic renal failure: A meta-analysis of randomized controlled trials
.

OBJECTIVE: Rheum officinale is a traditional medicinal herb used widely in China to treat chronic renal failure, but the proof of evidence-based medicine is poor. This meta-analysis aims to assess the benefits of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) supplemented with Rheum officinale for delaying the progression of chronic renal failure. MATERIALS AND METHODS: The MEDLINE, EMBASE, Cochrane Library, SinoMed, Chinese National Knowledge Infrastructure, Wanfang, and VIP databases were searched to identify studies published before September 2016 that investigated the effects of ACEI/ARB plus the Chinese patented medicine Rheum (CPM-Rheum) compared to ACEI/ARB alone in lowering serum creatinine (SCr) and blood urea nitrogen (BUN) levels in chronic renal failure patients. Review Manager 5.3 was used to perform the meta-analysis. Fixed- and random-effects models were used to analyze the data. RESULTS: The meta-analysis included nine clinical trials. Comparisons of patients before and after treatment with ACEI/ARB plus CPM-Rheum or ACEI/ARB alone revealed that ACEI/ARB plus CPM-Rheum resulted in significantly greater reductions in SCr (short-term: weighted mean difference (WMD): 17.26, 95% confidence interval (CI): 7.28 - 27.24; long-term: WMD: 63.71, 95% CI: 51.01 - 76.41) and BUN (short-term: WMD: 1.70, 95% CI: 1.27 - 2.12; long-term: WMD: 3.98, 95% CI: 3.14 - 4.82) than ACEI/ARB alone. CONCLUSION: In patients with chronic renal failure, the addition of CPM-Rheum to ACEI/ARB significantly lowered both SCr and BUN, particularly after long-term administration. Thus, the combination of ACEI/ARB and CPM-Rheum may improve the treatment of patients with impaired renal function.
.

Complete remission in a patient with metastatic gastric cancer receiving tislelizumab combined with chemotherapy: a case report.

The prognosis for patients with advanced gastric cancer (AGC) is poor, with limited treatment options available due to the difficulty of resection. In recent years, chemotherapy and immunotherapy for AGC have shown promising efficacy. However, there is a controversy regarding the surgery of primary tumors and/or metastases in patients with stage IV gastric cancer after systematic therapy. Here, we present a 63-year-old retired female of AGC with supraclavicular metastasis with positive PD-L1 and tumor mutational burden-high (TMB-H). After receiving 8 cycles of capecitabine and oxaliplatin (XELOX) in combination with tislelizumab, the patient achieved complete remission (CR). No evidence of recurrence was identified during follow-up. To the best of our knowledge, this is the first case of AGC with supraclavicular metastasis who achieved CR after treatment with tislelizumab. The mechanism of CR was discussed by genomic and recent clinical studies. The results indicated that programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥5 may serve as a clinical indication and standard for chemo-immune combination therapy. In combination with other similar reports, patients with microsatellite instability-high/defective mismatch repair (MSI-H/dMMR), (TMB-H), and positive PD-L1 had better sensitivity to tislelizumab. The patient recovered successfully except for symptoms of gastrointestinal hemorrhage during treatment, which may be associated with the treatment cycle and age. Immunotherapy with tislelizumab has been well-established in the treatment of malignant melanoma, lung cancer, and clear-cell kidney cancer, but its efficacy and safety for esophageal and gastric cancers remain to be validated. The CR of our patient suggested the prospects of tislelizumab in the immunotherapy of gastric cancer. Additionally, a watch-and-wait (WW) method maybe offered for patients with AGC who achieved complete clinical remission (CCR) after immune combination therapy if the patient was older or in poor physical condition.