Characteristics and negative impacts of pleural effusion in hospitalized patients undergoing maintenance hemodialysis.

BACKGROUND: Hospitalized patients on maintenance hemodialysis often develop pleural effusion (PE). The prognosis of these patients is likely to be affected by the PE. This study examined the characteristics of PE, identified risk factors for its development, and explored its negative effects. METHODS: In this retrospective study, we analyzed medical records of 1,077 patients who underwent maintenance hemodialysis between October 2014 and January 2022. According to the chest computed tomography (CT) imaging results, patients were categorized into two groups: PE and non-PE. A definitive diagnosis of PE was made after a nephrologist, a pulmonary physician, and a radiologist reviewed the case. RESULTS: Of the 1,077 patients, 343 (31.85%) were diagnosed with PE. These patients had a mean age of 55.28±15.21 years old and 61.47% of them were men. There were 77.84% patients with PE resulting from heart failure, and 82.02% of these patients had bilateral effusions. The occurrence of PE was associated with cardiovascular disease, clinic-systolic blood pressure (SBP), chest tightness, leg edema, and pro-brain natriuretic peptide (pro-BNP). PE patients had a poorer survival rate than patients without PE (unadjusted hazard ratio [HR]: 4.17; 95% CI: 3.12-5.57). The survival rates of patients with small PE did not differ from those with moderate to large PE. Similarly, no difference was found in survival between the bilateral PE and unilateral PE groups, as well as between the heart failure and non-heart failure groups. CONCLUSIONS: Hospitalized patients undergoing maintenance hemodialysis have a high incidence of PE. PE (even a small amount) is an risk factor for increased mortality. These poor prognostic features should be noted by physicians and managed accordingly.

Increased thromboxane/prostaglandin receptors contribute to high glucose-induced podocyte injury and mitochondrial fission through ROCK1-Drp1 signaling.

Excessive mitochondrial fission in podocytes serves as a central hub for the pathogenesis of diabetic nephropathy (DN), and the thromboxane/prostaglandin receptor (TP receptor) plays a potential role in DN. However, regulation of the TP receptor during mitochondrial dynamics disorder in podocytes remains unknown. Here, we firstly reported novel mechanistic details of TP receptor effects on mitochondrial dynamics in podocytes under diabetic conditions. Expression of the TP receptor was significantly upregulated in podocytes under diabetic conditions both in vivo and in vitro. S18886 attenuated podocyte mitochondrial fission, glomerular injury and renal dysfunction in diabetic mice. Furthermore, inhibition of the TP receptor by both genetic and pharmacological methods dramatically reduced mitochondrial fission and attenuated podocyte injury induced by high glucose through regulating dynamin-related protein 1 (Drp1) phosphorylation and its subsequent translocation to mitochondria. In contrast, TP receptor overexpression and application of TP receptor agonist U46619 in these podocytes showed the opposite effect on mitochondrial fission and podocyte injury. Furthermore, treatment with Y27632, an inhibitor of Rho-associated kinase1 (ROCK1), significantly blunted more fragmented mitochondria and reduced podocyte injuries in podocytes with TP receptor overexpression or after U46619 treatment. Finally, pharmacological inhibition of Drp1 alleviated excessive mitochondrial fragmentation and podocyte damage in TP receptor overexpressing podocytes. Our data suggests that increased expression of the TP receptor can occur in a human cultured podocyte cell line and in podocytes derived from streptozotocin (STZ)-induced diabetic mice, which contributes to mitochondrial excessive fission and podocyte injury via ROCK1-Drp1 signaling.

Nomogram predicting the risk of three-year chronic kidney disease adverse outcomes among East Asian patients with CKD.

BACKGROUND: Chronic kidney disease (CKD) is a common health challenge. There are some risk models predicting CKD adverse outcomes, but seldom focus on the Mongoloid population in East Asian. So, we developed a simple but intuitive nomogram model to predict 3-year CKD adverse outcomes for East Asian patients with CKD. METHODS: The development and internal validation of prediction models used data from the CKD-ROUTE study in Japan, while the external validation set used data collected at the First People's Hospital of Foshan in southern China from January 2013 to December 2018. Models were developed using the cox proportional hazards model and nomogram with SPSS and R software. Finally, the model discrimination, calibration and clinical value were tested by R software. RESULTS: The development and internal validation data-sets included 797 patients (191 with progression [23.96%]) and 341 patients (89 with progression [26.10%]), respectively, while 297 patients (108 with progression [36.36%]) were included in the external validation data set. The nomogram model was developed with age, eGFR, haemoglobin, blood albumin and dipstick proteinuria to predict three-year adverse-outcome-free probability. The C-statistics of this nomogram were 0.90(95% CI, 0.89-0.92) for the development data set, 0.91(95% CI, 0.89-0.94) for the internal validation data set and 0.83(95% CI, 0.78-0.88) for the external validation data-set. The calibration and decision curve analyses were good in this model. CONCLUSION: This visualized predictive nomogram model could accurately predict CKD three-year adverse outcomes for East Asian patients with CKD, providing an easy-to-use and widely applicable tool for clinical practitioners.

Rituximab for the treatment of idiopathic membranous nephropathy with nephrotic syndrome: a systematic review and meta-analysis

Background/aim: This meta-analysis comprehensively investigated the efficacy and safety of rituximab (RTX) in patients with idiopathic membranous nephropathy (IMN). Materials and methods: We searched the MEDLINE, EMBASE and Cochrane Registry of Controlled Trials databases from January 2000 to January 2020. Studies evaluating the efficacy and safety of RTX in the treatment of IMN with nephrotic syndrome (NS) were included. Results: Nine studies (total of 357 patients) were included in the meta-analysis. The pooled complete response and overall response (OR) rates at 12 months were 13.2% [95% con fidence interval (CI), 0.09­0.18] and 60% (95% CI, 0.48­0.72), and those at 24 months were 27.8% (95% CI, 0.22­0.34) and 66% (95% CI, 0.6­0.72), respectively. The pooled OR rates for the low-, standard-, and high-dose groups were 39.3%, 64%, and 60%, respectively, and those for the first-line and second-line groups were 58% and 54%, respectively. Conclusion: Treatment of IMN with RTX has comparable efficacy to other immunosuppressive treatments (ISTs). RTX has the advantages of no requirement for steroids and lower rates adverse event and relapse rates. Patients who relapse or are resistant to other IST agents also respond to RTX. RTX-based regimens and other B-cell-targeted therapies may represent the future of IMN therapy.

Comparative efficacy of different renin angiotensin system blockade therapies in patients with IgA nephropathy: a Bayesian network meta-analysis of 17 RCTs.

BACKGROUND: IgA nephropathy (IgAN) is still one of the most prevalent forms of primary glomerulonephritis globally. However, no guidelines have clearly indicated which kinds of renin angiotensin system blockade therapies (ACEIs or ARBs or their combination) in patients with IgAN result in a greater reduction in proteinuria and a better preservation of kidney function. Thus, we conducted a Bayesian network analysis to evaluate the relative effects of these three therapy regimens in patients with IgAN. METHODS: The protocol was registered in PROSPERO with ID CRD42017073726. We comprehensively searched the PubMed, the Cochrane Library, Embase, China Biology Medicine disc, WanFang and CNKI databases for studies published since 1993 as well as some grey literature according to PICOS strategies. Pairwise meta-analysis and Bayesian network analysis were conducted to evaluate the effect of different regimens. RESULTS: Seventeen randomized controlled trials (RCTs) involving 1,006 patients were analyzed. Co-administration of ACEIs and ARBs had the highest probability (92%) of being the most effective therapy for reducing proteinuria and blood pressure, but ACEIs would be the most appropriate choice for protecting kidney function in IgAN. CONCLUSION: The combination of ACEIs and ARBs seems to have a significantly better antiproteinuric effect and a greater reduction of blood pressure than ACEI or ARB monotherapy in IgAN. ACEIs appear to be a more renoprotective therapy regimen among three therapies.

Gut Microbiota Profile in Adult Patients with Idiopathic Nephrotic Syndrome.

BACKGROUND: Increasing evidences have reported gut microbiota dysbiosis in many diseases, including chronic kidney disease and pediatric idiopathic nephrotic syndrome (INS). There is lack evidence of intestinal microbiota dysbiosis in adults with INS, however. Here, we to address the association between the gut microbiome and INS. METHODS: Stool samples of 35 adult INS patients and 35 healthy volunteers were collected. Total bacterial DNA was extracted, and the V4 regions of the bacterial 16S ribosomal RNA gene were sequenced. The fecal microbiome was analyzed using bioinformatics. The correlation analysis between altered taxa and clinical parameters was also included. RESULTS: We found that microbial diversity in the gut was reduced in adult patients with INS. Acidobacteria, Negativicutes, Selenomonadales, Veillonellaceae, Clostridiaceae, Dialister, Rombousia, Ruminiclostridium, Lachnospira, Alloprevotella, Clostridium sensu stricto, Megamonas, and Phascolarctobacterium were significantly reduced, while Pasteurellales, Parabacteroides, Bilophila, Enterococcus, Eubacterium ventriosum, and Lachnoclostridium were markedly increased in patients with INS. In addition, Burkholderiales, Alcaligenaceae, and Barnesiella were negatively correlated with serum creatinine. Blood urea nitrogen levels were positively correlated with Christensenellaceae, Bacteroidales_S24.7, Ruminococcaceae, Ruminococcus, and Lachnospiraceae_NK4A136, but were negatively correlated with Flavonifractor_plautii and Erysipelatoclostridium_ramosum. Enterobacteriales, Enterobacteriaceae, Porphyromonadaceae, Escherichia/Shigella, Parabacteroides, and Escherichia_coli were positively correlated with albumin. Proteinuria was positively correlated with Verrucomicrobia, Coriobacteriia, Thermoleophilia, Ignavibacteria, Coriobacteriales, Nitrosomonadales, Coriobacteriaceae, and Blautia, but was negatively correlated with Betaproteobacteria, Burkholderiales, and Alcaligenaceae. CONCLUSION: Our findings show compositional alterations of intestinal microbiota in adult patients with INS and correlations between significantly altered taxa and clinical parameters, which points out the direction for the development of new diagnostics and therapeutic approaches targeted intestinal microbiota.

Comparative proteinuria management of different angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for normotensive patients with CKD: a Bayesian network meta-analysis.

BACKGROUND: Both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are blood pressure-lowering agents, but they are also being used to control proteinuria in early chronic kidney disease (CKD) patients. However, clinically, some patients present merely proteinuria without hypertension. No guidelines pointed out how to select treatments for proteinuria in normotensive patients. Thus, we conducted a Bayesian network analysis to evaluate the relative effects of different kinds of ACEI or ARB or their combination on proteinuria and blood pressure reduction. METHODS: The protocol was registered in PROSPERO with ID CRD42017073721. A comprehensive literature database query was carried out systematically according to PICOS strategies. The primary outcome was reduction in proteinuria, and the secondary outcomes were eGFR reduction and blood pressure reduction. Random-effects pairwise and Bayesian network meta-analyses were used to estimate the effect of different regimens. RESULTS: A total of 14 RCTs with 1,098 patients were included in the analysis. All treatment strategies of ACEI, ARB or their combination had significantly greater efficacy in reducing proteinuria than placebo in normotensive CKD patients. The combination therapy of olmesartan+temocapril had the highest probability (22%) of being the most effective treatment to reduce proteinuria in normotensive CKD patients. Olmesartan and lisinopril ranked second (12%), and temocapril ranked third (15%) but reduced blood pressure less than placebo. For IgA nephropathy, the combination therapy of olmesartan+temocapril also had the highest probability (43%) of being the best antiproteinuric treatment, while enalapril had the highest probability (58%) of being the best antiproteinuric therapy for diabetic nephropathy. CONCLUSIONS: The combination therapy of olmesartan plus temocapril appeared to be the most efficacious for reducing proteinuria in normotensive CKD patients and IgA nephropathy, but the clinical application should be balanced against potential harms. Temocapril can be an option when practitioners are searching for more proteinuria reduction but less blood pressure variation. In normotensive diabetic nephropathy, monotherapy with the ACEI enalapril seems to be the most efficacious intervention for reducing albuminuria. Future studies are required to give a more definitive recommendation.

Effect of the Combination of Hemodialysis and Hemoperfusion on Clearing Advanced Glycation End Products: A Prospective, Randomized, Two-Stage Crossover Trial in Patients Under Maintenance Hemodialysis.

Advanced glycation end products (AGEs) are protein-bound uremic toxins and are elevated in patients with the end-stage of renal disease. The present study sought to develop an effective method to remove the circulating AGEs from patients using the combination of hemodialysis (HD) and hemoperfusion (HP). Thirty-six patients undergoing maintenance HD for 3 months were randomly divided into two groups. Patients in Group 1 received HD, followed by the combined HP + HD treatment once, whereas patients in Group 2 were first treated with HP + HD and then they received the HD treatment alone. Patients treated with HD alone did not alter higher levels of serum AGEs. In contrast, patients treated with the combined HP + HD exhibited significantly lower levels of serum AGEs and TNF-α. Results from this study demonstrate that the combination of HD + HP treatment may be an effective and better approach to remove the protein-bound uremic toxins and inflammatory cytokines.

Capsaicin induces reflex scratching in inflamed skin.

We investigated whether capsaicin induces itching in skin with existing inflammation. We induced skin inflammation by intradermal injection of complete Freund's adjuvant (CFA) in the neck of mice. Four days later, we injected capsaicin in the same area and counted the number of scratching bouts for 30 min. We examined potential effects on pain in parallel experiments in which CFA and capsaicin were intradermally injected into hind paws. We used the time spent licking the hind paws during the 15 min after capsaicin injection as an estimate of pain. Capsaicin injection into the skin pretreated with CFA, but not into healthy skin, induced scratching. The scratching behavior was reduced by pretreatment with naloxone or capsazepine, selective antagonists for transient receptor potential vanilloid receptor-1 (TRPV1), but not morphine or mepyramine, selective antagonists for histamine 1 receptor. In animals injected with capsaicin into the hind paws, licking behavior was significantly inhibited via a µ-receptor-dependent mechanism. Our results show that TRPV1 activation, which normally induces pain, evokes an itch-related response in the presence of inflammation. This model may be interesting for future studies to explore the mechanism of a painful stimuli-induced itch observed under pathological conditions.