Inhibition of ferroptosis ameliorates hypertensive nephropathy through p53/Nrf2/p21 pathway by Taohongsiwu decoction: Based on network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Hypertensive nephropathy (HN) is a complication of hypertension. Taohongsiwu decoction (THSWD) is used clinically but its application in the prevention and treatment of HN remains unelucidated. AIM OF STUDY: This study aims to explore the potential targets and molecular mechanisms of THSWD in the treatment of HN. MATERIALS AND METHODS: A network pharmacology approach was used to predict the components and targets of THSWD for treating HN. Animal experiments were performed to verify the network pharmacology findings. RESULTS: 205 targets were identified and regarded as potential targets of THSWD in HN treatment. Subsequently, we screened 17 hub genes and identified TP53 as the most critical one. KEGG enrichment analysis showed that p53 signaling pathway might play a significant role. In vivo experiments indicated that high-salt diets can lead to high blood pressure, kidney injury, inflammation, and fibrosis. Furthermore, the altered levels of biomarkers (Iron, malondialdehyde, catalase, ferritin, transferrin, Superoxide dismutase and Glutathione Peroxidase 4) provided evidence of ferroptosis. We found that the ferroptosis inhibitor ferrostatin-1 (Fer-1) and THSWD could significantly alleviate HN by suppressing ferroptosis. THSWD and Fer-1 treatment downregulated the protein and mRNA expression of p53, p21, RB, and CTNNB1, which were upregulated by high salt. Meanwhile, THSWD and Fer-1 reversed the downregulation of Nrf2 caused by high-salt diet. CONCLUSIONS: Our results suggested that THSWD attenuate HN induced by a high-salt diet through inhibiting ferroptosis via the p53/Nrf2/p21 pathway.

Effect of botanical drugs in improving symptoms of hypertensive nephropathy: Analysis of real-world data, retrospective cohort, network, and experimental assessment.

Background/aim: Hypertensive nephropathy (HN) is a common complication of hypertension. Traditional Chinese medicine has long been used in the clinical treatment of Hypertensive nephropathy. However, botanical drug prescriptions have not been summarized. The purpose of this study is to develop a prescription for improving hypertensive nephropathy, explore the evidence related to clinical application of the prescription, and verify its molecular mechanism of action. Methods: In this study, based on the electronic medical record data on Hypertensive nephropathy, the core botanical drugs and patients' symptoms were mined using the hierarchical network extraction and fast unfolding algorithm, and the protein interaction network between botanical drugs and Hypertensive nephropathy was established. The K-nearest neighbors (KNN) model was used to analyze the clinical and biological characteristics of botanical drug compounds to determine the effective compounds. Hierarchical clustering was used to screen for effective botanical drugs. The clinical efficacy of botanical drugs was verified by a retrospective cohort. Animal experiments were performed at the target and pathway levels to analyze the mechanism. Results: A total of 14 botanical drugs and five symptom communities were obtained from real-world clinical data. In total, 76 effective compounds were obtained using the K-nearest neighbors model, and seven botanical drugs were identified as Gao Shen Formula by hierarchical clustering. Compared with the classical model, the Area under the curve (AUC) value of the K-nearest neighbors model was the best; retrospective cohort verification showed that Gao Shen Formula reduced serum creatinine levels and Chronic kidney disease (CKD) stage [OR = 2.561, 95% CI (1.025-6.406), p < 0.05]. With respect to target and pathway enrichment, Gao Shen Formula acts on inflammatory factors such as TNF-α, IL-1ß, and IL-6 and regulates the NF-κB signaling pathway and downstream glucose and lipid metabolic pathways. Conclusion: In the retrospective cohort, we observed that the clinical application of Gao Shen Formula alleviates the decrease in renal function in patients with hypertensive nephropathy. It is speculated that Gao Shen Formula acts by reducing inflammatory reactions, inhibiting renal damage caused by excessive activation of the renin-angiotensin-aldosterone system, and regulating energy metabolism.

The Protective Effect of the Asystasia chelonoides Extracts on Hypertensive Nephropathy Rats.

BACKGROUND: Hypertensive nephropathy (HN) is one kind of kidney disorders caused by long-term uncontrolled hypertension, usually resulting in severe kidney damage, including inflammation and oxidative stress, no matter in cells or tissues, from patients with nephropathy. In recent years, nephropathy accompanied by hypertension is becoming one of the main causes for kidney replacement therapy, but few effective treatments have been reported for HN treatment. Asystasia chelonoides (AC) is a kind of plant with the effects of anti-inflammation, lowering blood pressure, and anti-oxidative stress. Still, the therapeutic effect of AC in HN rats is not clear. METHODS: To establish HN model by feeding high sugar and high fat diet spontaneously hypertensive rats. Blood measurement, HE staining, PAS staining and biochemical analysis and were used to assess the therapeutic effects of AC extracts and western blotting analyzed the underlying mechanisms of AC extracts treatment in the HN rat model. RESULTS: AC extracts could significantly lower systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) in HN rats; and reduce the expression of total protein (TP), blood urea nitrogen (BUN), microalbuminuria (MALB), creatinine (Cr), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) concentrations, and also could down-regulate expression of IL-6, MDA and AGEs, up-regulate the expression of SOD in HN rats; HE staining and PAS staining demonstrated that AC extracts could alleviate the histopathological changes in HN rats; western blotting demonstrated that AC extracts could up-regulate the expression of PPARγ and down-regulate the expression of TGFß1 and NF-кB in HN rats. CONCLUSION: The finding of the article demonstrated that AC extracts had the better therapeutic effect for HN, and provided the pharmacological evidences for AC extracts treatment for HN.

Efficacy of Huangqi Injection in the Treatment of Hypertensive Nephropathy: A Systematic Review and Meta-Analysis.

Background: Huangqi injection (HQI) is the extract of Astragalus membranaceus (Fisch.) Bunge, which is widely used in the treatment of a variety of diseases in China. It is supposed to be an important adjuvant therapy for hypertensive nephropathy. Objective: To evaluate the efficacy of HQI combined with antihypertensive drugs in the treatment of hypertensive nephropathy. Materials and Methods: We systematically searched China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wanfang Knowledge Service Platform (WanfangData), Chinese Biomedical Database (CBM), EMBASE, PubMed and Cochrane Library from their inception to April 23st, 2021. All studies were independently screened by two auditors according to the inclusion and exclusion criteria. Randomized controlled trials comparing HQI in combination with antihypertensive drugs vs. antihypertensive drugs alone were extracted. Results: The meta-analysis included 15 studies involving 1,483 participants.The effect of HQI combined with antihypertensive drugs is better than that of antihypertensive drugs alone in regulating hypertensive nephropathy for reducing 24-h urinary total protein (24 h UTP) [WMD=-0.29, 95% CI (-0.40, -0.18), P = 0.000], microalbuminuria (mALB) [WMD = -17.04, 95% CI (-23.14, -10.94), P = 0.000], serum creatinine (SCr) [WMD = -40.39, 95% CI (-70.39, -10.39), P = 0.008], systolic blood pressure (SBP) [WMD = -9.50, 95% CI (-14.64, -4.37), P = 0.000], diastolic blood pressure (DBP) [WMD = -4.588, 95% CI (-6.036, -3.140), P = 0.000], cystatin-C (Cys-c) [WMD = -0.854, 95% CI (-0.99, -0.72), P = 0.000], blood urea nitrogen (BUN) [WMD = -4.155, 95% CI (-6.152, -2.157), P = 0.000]. Conclusion: The combination of HQI and antihypertensive drugs is more efficient in improving the related indexes of patients with hypertensive nephropathy than using antihypertensive drugs alone, and a moderate dose of HQI (no more than 30 mL) may benefit more. However, the quality of the methodology is low and the number of samples is small, the results need to be confirmed by more stringent randomized controlled trials.

Traditional Chinese Medicine Injections Combined With Antihypertensive Drugs for Hypertensive Nephropathy: A Network Meta-Analysis.

Background: Hypertension, a risk factor for cardiovascular events, is often associated with chronic kidney disease. This is called hypertensive nephropathy (HN), which negatively affects physical fitness and body mass, leading to economic burden. Traditional Chinese medicine injections (TCMIs) are common traditional Chinese-patent medicine preparations in China. There was a lack of evidence to prove which TCMIs combine with ADs (TCMIs+ADs) may be a therapeutic option for HN. Thus, we systematically reviewed the efficacy and safety of various TCMIs + ADs in patients with HN. Methods: We conducted a comprehensive search of PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and VIP information resource integration service platform databases for relevant Chinese- and English-language randomized controlled trials (RCTs) published from database inception until May 2021. Literature screening, data extraction, and quality assessment was performed by two reviewers independently but using the same criteria. We performed the effect modeling to analyze the data for all outcomes and ranked each intervention using the P-score. Furthermore, sensitivity analysis, meta-regression, and funnel plots were used to test the stability, heterogeneity, and publication bias, respectively. Results: We included 69 RCTs with 6373 patients and including six TCMIs + ADs. Network analysis indicated that the ginkgo leaf extract and dipyridamole combined with ADs (GLED + ADs) was the most efficacious in terms of 24-h urinary protein excretion [mean difference (MD) = -0.70, 95% confidence interval (CI): -0.82 to -0.58; P-score = 1] and systolic blood pressure (MD = -12.95, 95% CI: -21.03 to -4.88; P-score = 0.88), whereas the salvianolate combined with ADs (SA + ADs) showed the highest effectiveness for diastolic blood pressure (MD = -6.88, 95% CI: -10.55 to -3.21; P-score = 0.9). Based on the combined P-score of network meta-analysis results (88% and 85.26%) and sensitivity analysis results (72% and 71.54%), the biplots showed that the GLED + ADs was the most efficacious intervention in all TCMIs + ADs for primary outcomes, followed by the SA + ADs and sodium tanshinone IIA sulfonate combined with ADs (STS + ADs). There was no significant difference in terms of safety between TCMIs + ADs and ADs alone. Conclusion: Of all the TCMIs + ADs, GLED + ADs, SA + ADs, and STS + ADs may demonstrate a higher efficacy than ADs alone for HN. Weighing with the potential benefits and limitations in methodology, potential heterogeneity and outcomes, we should use various TCMIs with caution in clinical practice. Nevertheless, additional high-quality RCTs are warranted and future research should focus on the clinical value of core outcomes to confirm the effectiveness and safety of TCMIs for HN. Systematic Review Registration: clinicaltrials.gov, identifier CRD42020205358.

Qian Yang Yu Yin Granule Improves Renal Injury of Hypertension by Regulating Metabolic Reprogramming Mediated by HIF-1α/PKM2 Positive Feedback Loop.

Protection against hypoxia injury is an important therapeutic strategy for treating hypertensive nephropathy. In this study, the effects of Qian Yang Yu Yin granule (QYYY) on spontaneously hypertensive rats fed with high salt diet and HEK293T cells exposed to hypoxia were investigated. After eight weeks' treatment of QYYY, blood pressure, serum creatinine, serum cystatin C, blood urea nitrogen, urinary ß2-microglobulin, urinary N-acetyl-ß-glucosaminidase, and urinary microalbumin were assessed. The changes of hypoxia-inducible factor-1α (HIF-1α), pyruvate kinase M2 (PKM2), glucose transport 1 (GLUT1), lactate dehydrogenase A (LDH-A), connective tissue growth factor (CTGF), transforming growth factor-ß1 (TGF-ß1), ATP, lactate, pyruvate, and pathology were also assessed in vivo. HEK293T cells pre-treated with QYYY and/or HIF-1α over expressing cells were cultured in a three gas hypoxic incubator chamber (5% CO2, 1% O2, 94% N2) for 12 h and then the expressions of HIF-1α, PKM2, GLUT1, LDH-A, CTGF, TGF-ß1, ATP, lactate, and pyruvate were detected. Our results showed that QYYY promoted the indicators of renal inflammation and fibrosis mediated by HIF-1α/PKM2 positive feedback loop in vivo and vitro. Our findings indicated that QYYY treated hypertensive nephropathy by regulating metabolic reprogramming mediated by HIF-1α/PKM2 positive feedback loop.

Mechanism of herbal medicine on hypertensive nephropathy (Review).

Hypertensive nephropathy is the most common complication of hypertension, and is one of the main causes of end­stage renal disease (ESRD) in numerous countries. The basic pathological feature of hypertensive nephropathy is arteriolosclerosis followed by renal parenchymal damage. The etiology of this disease is complex, and its pathogenesis is mainly associated with renal hemodynamic changes and vascular remodeling. Despite the increased knowledge on the pathogenesis of hypertensive nephropathy, the current clinical treatment methods are still not effective in preventing the development of the disease to ESRD. Herbal medicine, which is used to relieve symptoms, can improve hypertensive nephropathy through multiple targets. Since there are few clinical studies on the treatment of hypertensive nephropathy with herbal medicine, this article aims to review the progress on the basic research on the treatment of hypertensive nephropathy with herbal medicine, including regulation of the renin angiotensin system, inhibition of sympathetic excitation, antioxidant stress and anti­inflammatory protection of endothelial cells, and improvement of obesity­associated factors. Herbal medicine with different components plays a synergistic and multi­target role in the treatment of hypertensive nephropathy. The description of the mechanism of herbal medicine in the treatment of hypertensive nephropathy will contribute towards the progress of modern medicine.

[Network Meta-analysis of Huoxue Huayu Chinese medicine injections on hypertensive nephropathy].

To assess the clinical efficacy of Huoxue Huayu Chinese medicine injections on hypertensive nephropathy by using Network Meta-analysis method. The relative randomized controlled trials(RCTs) of Huoxue Huayu Chinese medicine injections on hypertensive nephropathy were retrieved from CNKI, WanFang, VIP, SinoMed, PubMed, Cochrane Library and Web of Science in November 2019. Two researchers independently conducted literature screening, data extraction and quality evaluation. The data was analyzed by RevMan 5.3, Stata 15.1, ADDIS 1.16.8 software. Finally, 4 518 patients in 50 RCTs were included, involving 5 kinds of Huoxue Huayu Chinese medicine injections. The five Chinese medicine injections were Breviscapine Injection, Danhong Injection, Sodium Tanshinone Ⅱ_A Sulfonate Injection, Ginkgo Dipyridamole Injection, and Salvianolate Injection. Meta-analysis showed that, in terms of renal function protection, urine protein quantification and serum creatinine of each Chinese medicine injections combined with conventional Western medicine group, except Salvianolate Injection combined with conventional Western medicine group, was significantly lower than those of the conventional Western medicine treatment group. Ginkgo Dipyridamole Injection combined with conventional Western medicine had the best effect in reducing urine protein, and Danhong Injection combined with conventional Western medicine had the best effect in reducing serum creatinine. In terms of blood pressure control, the blood pressure of each Chinese medicine injections combined with conventional Western medicine group, except Breviscapine Injection combined with conventional Western medicine group, was significantly lower than that of conventional Western medicine treatment group. Salvianolate Injection combined with conventional Western medicine had the best effect in reducing blood pressure. In terms of safety, no serious adverse reactions were found in all studies. The five kinds of Huoxue Huayu Chinese medicine injections combined with conventional Western medicine had significantly advantages in the treatment of hypertensive nephropathy. Ginkgo Dipyridamole Injection combined with conventional Western medicine is most likely to be the optimal therapy. However, limited by the quantity and quality of the documents included, the conclusion of this study still needs to be verified by more high-quality, multi-center and large-sample RCT.

Danhong Injection for the Treatment of Hypertensive Nephropathy: A Systematic Review and Meta-Analysis.

OBJECTIVE: Danhong Injection (DHI) has been widely used to treat various diseases in China for many years. The objective of this systematic review was to evaluate the efficacy of DHI combined with antihypertensive drugs for treatment of hypertensive nephropathy. METHODS: Seven databases were searched from inception to September 21st, 2019. Randomized controlled trials comparing DHI combined with antihypertensive drugs versus antihypertensive drugs alone were extracted. The primary outcome was microalbuminuria (mALB). Secondary outcomes included systolic blood pressure (SBP), diastolic blood pressure (DBP), and serum creatinine (SCr). RESULTS: Fifteen studies were included in the meta-analysis, which indicated that DHI combined with antihypertensive drugs has advantages compared with antihypertensive drugs alone for reducing mALB [weighted mean difference (WMD) = -12.86, 95% confidence interval (CI) (-14.72, -11.0), P < 0.01], lowering SBP [WMD = -2.84, 95% CI (-4.56, -1.12), P = 0.001] and DBP [WMD = -2.38, 95% CI (-4.34, -0.43), P = 0.017], and decreasing SCr [WMD = -40.45, 95% CI (-55.69, -25.21), P < 0.01]. CONCLUSION: The combination of DHI with antihypertensive drugs appears to be more effective than antihypertensive drugs alone for treatment of hypertensive nephropathy. A moderate duration (≤4 weeks) of DHI administration is reasonable, and longer treatment with DHI should be avoided, according to the results of subgroup analysis.

Qian Yang Yu Yin Granule protects against hypertension-induced renal injury by epigenetic mechanism linked to Nicotinamide N-Methyltransferase (NNMT) expression.

ETHNOPHARMACOLOGICAL RELEVANCE: Qian Yang Yu Yin Granule (QYYY) is a Chinese herbal formulation. It is used to treat hypertensive nephropathy for decades in China, but it is unknown that the exact mechanism of QYYY on hypertensive nephropathy. AIMS OF STUDY: The present study was to elucidate its epigenetic mechanism of QYYY on hypertensive nephropathy. MATERIALS AND METHODS: In the current study, HEK293T cells' proliferation induced by Ang II was chosen to observe epigenetic mechanisms of QYYY on renal damage. The cell proliferation was examined by MTT assays and ethynyldeoxyuridine analysis. Cell cycle analysis was performed. After treatment with QYYY, expression of Nicotinamide N-methyltransferase (NNMT), sirtuin1(SIRT1), S-adenosylhomocysteine(SAH), histone H3K4 methylation, and cortactin acetylation(acetyl-cortactin,ac-cortactin) were further investigated by western-blotting and real time PCR. DNA methylation was detected by ELISA. The study also observed the changes of SIRT1, SAH, H3K4 methylation, acetyl-cortactin when NNMT over-expressed by lentivirus transfection. Angiotensin II(Ang II) induced renal damage in spontaneously hypertensive rats(SHR). After eight weeks treatment of QYYY, blood pressure, serum and urine creatinine, and urinary microalbumin(mAlb) were assessed. The concentration of N1 -methylnicotinamide were detected by liquid chromatography with tandem mass spectrometry. The protein of NNMT, ac-cortactin, H3K3me3 were also assessed in vivo. RESULTS: QYYY inhibited HEK293T cells' proliferation, down-regulated the expression of NNMT, SAH, acetyl-cortactin and DNA methylation, up-regulated the expression of SIRT1, histone H3K4 trimethylation(H3K4me3). Over-expression of NNMT increased the expression of SAH and acetyl-cortactin, and reduced the expression of SIRT1 and H3K4me3. The study also demonstrated that QYYY promoted urinary creatinine excretion and reduced serum creatinine and urinary mAlb in SHR. QYYY decreased the concentration of N1 -methylnicotinamide in Ang II group. QYYY decreased the protein of NNMT, ac-cortactin and increased H3K4me3 in vivo. CONCLUSION: The results showed that QYYY alleviated renal impairment of SHR and inhibited HEK293T cells' proliferation induced by Ang II through the pathway of epigenetic mechanism linked to Nicotinamide N-Methyltransferase (NNMT) expression, including histone methylation, DNA methylation and acetyl-cortactin. This study unveiled a novel molecular mechanism by which QYYY controlled the progression of hypertensive nephropathy.

The Combination of Scutellaria baicalensis Georgi and Sophora japonica L. ameliorate Renal Function by Regulating Gut Microbiota in Spontaneously Hypertensive Rats.

Chronic kidney disease (CKD) is becoming a notable health concern globally. The combination of Scutellaria baicalensis Georgi (SB) and Sophora japonica L. (SJ) has been demonstrated to have anti-hypertensive effects and improve kidney injury clinically. This study aimed to explore the renal protective effect of the combination of SB and SJ against CKD and clarify the potential mechanisms. Male spontaneously hypertensive rats (SHR) were used to induce hypertensive nephropathy and were treated with SB or SJ separately or in combination for 15 weeks, and an antibiotic group was used for a rescue experiment. Blood pressure, serum or urine biochemical markers, serum inflammation factors, short-chain fatty acids (SCFAs), indoxyl sulfate (IS), and oxidative stress indicators were assessed. Western blot analysis was performed to determine the expression of intestinal tight junction proteins, including occludin and ZO-1. The mRNA expression of the SCFAs receptors olfactory 78 (Olfr78) and G protein-coupled receptor 41 (GPR41) was determined by quantitative real-time PCR. Gut microbiota profiles were established via high-throughput sequencing of the V3-V4 region of the bacterial 16S rRNA gene. SB and SJ significantly ameliorated the severity of renal injury induced by hypertension. The combination also decreased the ratio of Firmicutes/Bacteroidetes, increased the relative abundance of Lactobacillus, and reduced that of Clostridiaceae. The intestinal barrier was improved, and the change in dominant bacteria reduced IS accumulation and further inhibited oxidative stress activation in kidneys. SB and SJ increased SCFAs production, inhibited inflammatory factor release, and regulated blood pressure by decreasing the expression of Olfr78 and increasing that of GPR41, then alleviated kidney damage. This research demonstrated the positive effects of SB and SJ in a rat model of hypertensive nephropathy, indicated that the treatment of SB and SJ by improving the intestinal barrier function, increasing SCFAs, reducing inflammation, decreasing IS, and inhibiting oxidative stress reactions.

Naringenin Ameliorates Renovascular Hypertensive Renal Damage by Normalizing the Balance of Renin-Angiotensin System Components in Rats.

Background: Naringenin, a member of the dihydroflavone family, has been shown to have a protective function in multiple diseases. We previously demonstrated that naringenin played a protective role in hypertensive myocardial hypertrophy by decreasing angiotensin-converting enzyme (ACE) expression. The kidney is a primary target organ of hypertension. The present study tested the effect of naringenin on renovascular hypertensive kidney damage and explored the underlying mechanism. Methods and Results: An animal model of renovascular hypertension was established by performing 2-kidney, 1-clip (2K1C) surgery in Sprague Dawley rats. Naringenin (200 mg/kg/day) or vehicle was administered for 10 weeks. Blood pressure and urinary protein were continuously monitored. Plasma parameters, renal pathology and gene expression of nonclipped kidneys were evaluated by enzyme-linked immunosorbent assay, histology, immunohistochemistry, real-time polymerase chain reaction, and Western blot at the end of the study. Rats that underwent 2K1C surgery exhibited marked elevations of blood pressure and plasma Ang II levels and renal damage, including mesangial expansion, interstitial fibrosis, and arteriolar thickening in the nonclipped kidneys. Naringenin significantly ameliorated hypertensive nephropathy and retarded the rise of Ang II levels in peripheral blood but had no effect on blood pressure. 2K1C rats exhibited increases in the ACE/ACE2 protein ratio and AT1R/AT2R protein ratio in the nonclipped kidney compared with sham rats, and these increases were significantly suppressed by naringenin treatment. Conclusions: Naringenin attenuated renal damage in a rat model of renovascular hypertension by normalizing the imbalance of renin-angiotensin system activation. Our results suggest a potential treatment strategy for hypertensive nephropathy.

Efficacy and Safety of Sodium Tanshinone IIA Sulfonate Injection on Hypertensive Nephropathy: A Systematic Review and Meta-Analysis.

Background: Sodium tanshinone IIA sulfonate (STS) injection, the extractive of traditional Chinese medicine Danshen, is supposed to be a supplementary treatment in hypertensive nephropathy. Objectives: To evaluate the efficacy and safety of STS in treatment of hypertensive nephropathy. Methods: We systematically searched China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wan-fang database, Chinese Biomedicine Database (CBM), PubMed, Embase, Web of Science, and Cochrane Library from their inception to December 2018. All studies were screened by two reviewers according to the inclusion and exclusion criteria independently. The Cochrane Collaboration's risk tool was used to assess the methodological quality of the included studies. Reviewer Manager 5.3 was employed for statistical analysis. Results: Sixteen trials involving 1,696 patients were included. The meta-analysis results indicated a combination of STS and angiotensin receptor blockers (ARBs) was more effective than ARB monotherapy in modulating hypertensive nephropathy, as represented by improved estimated glomerular filtration rate (eGFR) [mean difference (MD) = 6.87, 95% CI (4.47, 9.28), P < 0.00001] and reduced 24 h urinary protein [MD = -0.23, 95% CI (-0.27, -0.19), P < 0.00001], serum creatinine (SCr) [MD = -21.74, 95% CI (-24.11, -19.38), P < 0.00001], cystatin-C [MD = -0.16, 95% CI (-0.24, -0.07), P = 0.0003], urinary immunoglobulin G (IgG) [MD = -0.85, 95% CI (-1.11, -0.59), P < 0.00001], and urinary transferrin [MD = -0.61, 95% CI (-1.04, -0.17), P = 0.007]. In addition, the combination therapy had better control in systolic blood pressure (SBP) [MD = -6.53, 95% CI (-8.19, -4.87), P < 0.00001] and diastolic blood pressure (DBP) [MD = -4.14, 95% CI (-5.69, -2.59), P < 0.00001]. Only three trials reported adverse events, and no adverse drug reactions were observed. Conclusions: STS combined with ARBs had a stronger effect on improving renal function in patients with primary hypertensive nephropathy than ARB monotherapy. The combination therapy also provided auxiliary hypotensive effects. Further large-scale, multicenter, and rigorously designed randomized controlled trials (RCTs) should be conducted to confirm our findings.

Risk factors for pulmonary hypertension in patients receiving maintenance peritoneal dialysis

We investigated the risk factors for pulmonary hypertension (PH) in patients receiving maintenance peritoneal dialysis (MPD). A group of 180 end-stage renal disease patients (124 men and 56 women; mean age: 56.43±8.36) were enrolled in our study, which was conducted between January 2009 and June 2014. All of the patients received MPD treatment in the Dialysis Center of the Second Affiliated Hospital of Soochow University. Clinical data, laboratory indices, and echocardiographic data from these patients were collected, and follow-ups were scheduled bi-monthly. The incidence and relevant risk factors of PH were analyzed. The differences in measurement data were compared by t-test and enumeration data were compared with the χ2 test. Among the 180 patients receiving MPD, 60 were diagnosed with PH. The remaining 120 were regarded as the non-PH group. Significant differences were observed in the clinical data, laboratory indices, and echocardiographic data between the PH and non-PH patients (all P<0.05). Furthermore, hypertensive nephropathy patients on MPD showed a significantly higher incidence of PH compared with non-hypertensive nephropathy patients (P<0.05). Logistic regression analysis showed that the proportion of internal arteriovenous fistula, C-reactive protein levels, and ejection fraction were the highest risk factors for PH in patients receiving MPD. Our study shows that there is a high incidence of PH in patients receiving MPD and hypertensive nephropathy patients have an increased susceptibility to PH.