A hierarchical kidney outcome using win statistics in patients with heart failure from the DAPA-HF and DELIVER trials.

Win statistics offer a new approach to the analysis of outcomes in clinical trials, allowing the combination of time-to-event and longitudinal measurements and taking into account the clinical importance of the components of composite outcomes, as well as their relative timing. We examined this approach in a post hoc analysis of two trials that compared dapagliflozin to placebo in patients with heart failure and reduced ejection fraction (DAPA-HF) and mildly reduced or preserved ejection fraction (DELIVER). The effect of dapagliflozin on a hierarchical composite kidney outcome was assessed, including the following: (1) all-cause mortality; (2) end-stage kidney disease; (3) a decline in estimated glomerular filtration rate (eGFR) of ≥57%; (4) a decline in eGFR of ≥50%; (5) a decline in eGFR of ≥40%; and (6) participant-level eGFR slope. For this outcome, the win ratio was 1.10 (95% confidence interval (CI) = 1.06-1.15) in the combined dataset, 1.08 (95% CI = 1.01-1.16) in the DAPA-HF trial and 1.12 (95% CI = 1.05-1.18) in the DELIVER trial; that is, dapagliflozin was superior to placebo in both trials. The benefits of treatment were consistent in participants with and without baseline kidney disease, and with and without type 2 diabetes. In heart failure trials, win statistics may provide the statistical power to evaluate the effect of treatments on kidney as well as cardiovascular outcomes.

Effects of empagliflozin in patients with chronic kidney disease from Japan: exploratory analyses from EMPA-KIDNEY.

BACKGROUND: EMPA-KIDNEY assessed the effects of empagliflozin 10 mg once daily vs. placebo in 6609 patients with chronic kidney disease (CKD) at risk of progression, including 612 participants from Japan. METHODS: Eligibility required an estimated glomerular filtration rate (eGFR) of ≥ 20 < 45; or ≥ 45 < 90 ml/min/1.73m2 with a urinary albumin-to-creatinine ratio (uACR) of ≥ 200 mg/g. The primary outcome was a composite of kidney disease progression (end-stage kidney disease, a sustained eGFR decline to < 10 ml/min/1.73m2 or ≥ 40% from randomization, or renal death) or cardiovascular death. In post-hoc analyses, we explored the effects of empagliflozin in participants from Japan vs. non-Japan regions, including additional models assessing whether differences in treatment effects between these regions could result from differences in baseline characteristics. RESULTS: Japanese participants had higher levels of albuminuria and eGFR than those from non-Japan regions. During a median of 2.0 year follow-up, a primary outcome occurred in 432 patients (13.1%) in the empagliflozin group and in 558 patients (16.9%) in the placebo group (hazard ratio [HR], 0.72, 95% confidence interval [95%CI] 0.64-0.82; P < 0.0001). Among the participants from non-Japan regions, there were 399 vs. 494 primary outcomes (0.75, 0.66-0.86), and 33 vs. 64 (0.49, 0.32-0.75; heterogeneity p = 0.06) in Japan. Results were similar when models explicitly considered treatment interactions with diabetes status, categories of eGFR/uACR, and recruitment in Japan (heterogeneity p = 0.08). Safety outcomes were broadly comparable between the two groups, and by Japanese status. CONCLUSIONS: Empagliflozin safely reduced the risk of "kidney disease progression or cardiovascular death" in patients with CKD, with consistent effects in participants from Japan.

Anticoagulation for Patients With Concomitant Atrial Fibrillation and End-Stage Renal Disease: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Concomitant atrial fibrillation and end-stage renal disease is common and associated with an unfavorable prognosis. Although oral anticoagulants have been well established to prevent thromboembolism, the applicability in patients under long-term dialysis remains debatable. The study aimed to determine the efficacy and safety of anticoagulation in the dialysis-dependent population. METHODS AND RESULTS: An updated network meta-analysis based on MEDLINE, EMBASE, and the Cochrane Library was performed. Studies published up to December 2022 were included. Direct oral anticoagulants (DOACs, dabigatran, rivaroxaban, apixaban 2.5/5 mg twice daily), vitamin K antagonists (VKAs), and no anticoagulation were compared on safety and efficacy outcomes. The outcomes of interest were major bleeding, thromboembolism, and all-cause death. A total of 42 studies, including 3 randomized controlled trials, with 185 864 subjects were pooled. VKAs were associated with a significantly higher risk of major bleeding than either no anticoagulation (hazard ratio [HR], 1.47; 95% CI, 1.34-1.61) or DOACs (DOACs versus VKAs; HR, 0.74 [95% CI, 0.64-0.84]). For the prevention of thromboembolism, the efficacies of VKAs, DOACs, and no anticoagulation were equivalent. Nevertheless, dabigatran and rivaroxaban were associated with fewer embolic events. There were no differences in all-cause death with the administration of VKAs, DOACs, or no anticoagulation. CONCLUSIONS: For dialysis-dependent populations, dabigatran and rivaroxaban were associated with better efficacy, while dabigatran and apixaban demonstrated better safety. No anticoagulation was a noninferior alterative, and VKAs were associated with the worst outcomes.

Combination of Fushengong decoction with Western medicine on patients with chronic renal failure: An observational study.

Chronic renal failure (CRF) causes a reduction in glomerular filtration rate and damage to renal parenchyma. Fushengong decoction (FSGD) showed improvement in renal function in CRF rats. This study aims to analyze the differentially expressed proteins in CRF patients treated with Western medicine alone or in combination with FSGD. Sixty patients with CRF recruited from Yongchuan Traditional Chinese Medicine Hospital affiliated to Chongqing Medical University were randomly assigned into control (treated with Western medicine alone) and observation groups (received additional FSGD treatment thrice daily for 8 weeks). The clinical efficacy and changes in serum Bun, serum creatinine, Cystatin C, and transforming growth factor beta 1 (TGF-ß1) before and after treatment were observed. We employed isotope relative labeling absolute quantification labeling and liquid chromatography-mass spectrometry to identify differentially expressed proteins and carried out bioinformatics Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Patients in the observation group showed greater clinical improvement and lower levels of serum Bun, serum creatinine, Cyc-c, and TGF-ß1 than the control group. We identified 32 differentially up-regulated and 52 down-regulated proteins in the observation group. These proteins are involved in the blood coagulation system, protein serine/threonine kinase activity, and TGF-ß, which are closely related to the pathogenesis of CRF. Protein-protein-interaction network analysis indicated that candidate proteins fibronectin 1, fibrinogen alpha chain, vitronectin, and Serpin Family C Member 1 were in the key nodes. This study provided an experimental basis suggesting that FSGD combined with Western medicine could significantly improve renal function and renal fibrosis of CRF patients, which may be through the regulation of fibronectin 1, fibrinogen alpha chain, vitronectin, Serpin Family C Member 1, TGF-ß, and the complement coagulation pathway (see Graphical abstract S1, Supplemental Digital Content, http://links.lww.com/MD/L947).

[Pituitary disorders in patients with end-stage chronic renal failure].

Disorders in the kidneys lead to disturbance of homeostasis. As the glomerular filtration rate decreases, the metabolism of numerous biologically active substances, including pituitary hormones, decreases. The article presents an overview of pituitary dysfunction in patients with chronic kidney disease (CKD) and discusses the possible reasons of the pathogenetic mechanisms. Particular focus is being given to the assessment of changes in the concentration of pituitary hormones in patients with end-stage chronic kidney disease (CKD) and discusses the pathogenetic mechanisms of their formation. Particular attention is paid to the assessment of changes in the concentration of pituitary hormones in patients receiving renal replacement therapy (RRT). CKD leads to an increase in the level of prolactin, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Concentrations of growth hormone (GH), isulin-like growth factor-1 (IGF-1), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH) and vasopressin may remain within normal values or increase in this group of patients. RRT does not reduce the levels of prolactin, LH, FSH, while the concentration of growth hormone, IGF-1, TSH tends to normalize. The content of ACTH and vasopressin may remain unchanged or decrease. Kidney transplantation in most cases corrects hormonal disorders. Correction of hormonal changes can improve the clinical outcome and quality of life of patients with end stage CKD.

Renal Metabolomics Study and Critical Pathway Validation of Shenkang Injection in the Treatment of Chronic Renal Failure.

To reveal the mechanism of Shenkang injection (SKI) in the treatment of chronic renal failure, and verify the key pathway. In this work, an untargeted metabolomics approach was performed by LC-MS coupled with multivariate statistical analysis to provide new insights into therapeutic mechanism of SKI. Hematoxylin-eosin (H&E) Staining and Immunohistochemistry were used to evaluate the effects of drug treatment, Western blot was used to verify the critical pathway. Then, a total of 44 potential biomarkers of chronic renal failure (CRF) were identified and reversed regulation, including 2,8-dihydroxypurine, 5-methoxytryptophan, uric acid, acetylcarnitine, taurine, etc. Mainly concerned with arginine and proline metabolism, purine metabolism, histidine metabolism, etc. Pathological examination showed that the renal interstitium of SKI group was significantly improved, with fewer inflammatory cells and thinner vascular walls compared with the model group. Immunohistochemical results showed that the expression of α-smooth muscle actin (α-SMA) was decreased, and the expression of E-cadherin was increased in CRF model group, and the two indicators were reversed regulation in SKI injection, indicating that the degree of fibrosis was relieved. Critical signaling pathway phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and nuclear factor-kappaB (NF-κB) protein expressions were significantly inhibited. This study was the first to employ metabolomics to elucidate the underlying mechanisms of SKI in chronic renal failure. The results would provide some support for clinical application of traditional Chinese medicines in clinic.

Valacyclovir Neurotoxicity in Patients with End-Stage Renal Disease: Two Cases Reviewed.

Purpose: The objective of this case series is to highlight different manifestations of valacyclovir associated neurotoxicity (VAN) and demonstrate the importance of adjusting medication appropriately in patients with end-stage renal disease (ESRD) on hemodialysis to prevent these complications. Summary: Valacyclovir is a medication used to treat herpes zoster infection, commonly known as shingles. Valacyclovir is renally cleared and can accumulate in patients with renal dysfunction leading to severe side effects due to the prolonged half-life. VAN is a common adverse effect in patients with underlying kidney disease, that can be easily prevented if valacyclovir is properly dosed. This case series details the clinical outcomes of two elderly patients who were prescribed valacyclovir at six-times the recommended dose based on their renal function. Failure to reduce the dose of valacyclovir resulted in severe neurological and physical manifestations that required hospital admission and emergent hemodialysis. Conclusion: This case series details the importance of adjusting valacyclovir dose based on renal function. In patients with ESRD, the half-life of valacyclovir can be up to 14 hours, therefore hemodialysis should be utilized in severe cases of neurotoxicity to improve rapid excretion of the drug and promote rapid recovery from VAN.

The arsenic-lowering effect of inulin-type prebiotics in end-stage renal disease: a randomized crossover trial.

Background: Circulatory imbalance of trace elements is frequent in end-stage renal disease (ESRD), leading to a deficiency of essential elements and excess of toxic elements. The present study aimed to investigate whether inulin-type fructans (ITFs) could ameliorate the circulatory imbalance by modulating gut microbiota and regulating the absorption and elimination of trace elements. Methods: Peritoneal dialysis patients were enrolled in a randomized crossover trial, undergoing interventions with ITFs (10 g d-1) and maltodextrin (placebo) over a 9-month period (with a 3-month washout). The primary outcomes included essential elements Mn, Fe, Co, Cu, Zn, Se, Sr, and Mo and potential toxic elements V, Cr, Ni, As, Cd, Ba, Tl, Pb, Th, and U in plasma. Secondary outcomes included the gut microbiome, short chain fatty acids (SCFAs), bile acids (BAs), and daily removal of trace elements through urine, dialysate and feces. Results: Among the 44 participants initially randomized, 29 completed the prebiotic, placebo or both interventions. The daily dietary intake of macronutrients and trace elements remained consistent throughout the study. The administration of 10 g d-1 ITFs significantly reduced plasma arsenic (As) by 1.03 µg L-1 (95%CI: -1.74, -0.33) (FDR-adjusted P = 0.045) down from the baseline of 3.54 µg L-1 (IQRs: 2.61-4.40) and increased the As clearance rate by urine and dialysis (P = 0.033). Positive changes in gut microbiota were also observed, including an increase in the Firmicutes/Bacteroidetes ratio (P = 0.050), a trend towards higher fecal SCFAs (P = 0.082), and elevated excretion of primary BAs (P = 0.035). However, there were no significant changes in plasma concentrations of other trace elements or their daily removal by urine, dialysis and feces. Conclusions: The daily administration of 10 g d-1 ITFs proved to be effective in reducing the circulating retention of As but demonstrated to be ineffective for other trace elements in ESRD. These sentences are ok to include but as "The clinical trial registry number is ChiCTR-INR-17013739 (https://www.chictr.org.cn/showproj.aspx?proj=21228)".

Efficacy and safety of direct oral anticoagulants vs vitamin K antagonists in patients with atrial fibrillation and end-stage renal disease on hemodialysis: A systematic review and meta-analysis.

BACKGROUND: The prevalence of atrial fibrillation (AF) in individuals with end-stage renal disease (ESRD) on chronic hemodialysis is increasing. The optimal anticoagulant choice in this population is unclear since these patients were excluded from the pivotal randomized controlled trials (RCTs) of direct oral anticoagulants (DOACs) vs. vitamin K antagonists (VKAs) in the general AF population. We aimed to assess the efficacy and safety of DOACs vs. VKAs in patients with AF and ESRD on chronic hemodialysis through a systematic review and meta-analysis of all available evidence. PATIENTS/METHODS: We performed a systematic search in MEDLINE and Scopus for RCTs or observational studies of patients with AF and ESRD on chronic hemodialysis who were treated with DOACs or VKAs. The outcomes of interest included ischemic stroke, the composite of ischemic stroke or systemic embolism, major bleeding, gastrointestinal bleeding, minor bleeding events and all-cause mortality. RESULTS: Among 397 studies identified from the literature search, six studies (three RCTs and three observational studies) were included in the meta-analysis. Compared with VKA-treated patients, those treated with DOACs had similar risk of ischemic stroke (RR:0.76, 95% CI:0.41-1.41), ischemic stroke or systemic embolism (RR:0.65, 95% CI:0.38-1.10), major bleeding (RR:0.79, 95% CI:0.49-1.28) and all-cause death (RR:0.79, 95% CI:0.56-1.12). The risk of gastrointestinal bleeding was lower in DOAC- vs VKA-treated patients in three eligible observational studies (RR:0.73, 95% CI: 0.54-0.99, I2 = 79%) but this was not confirmed in two eligible RCTs (RR:0.69, 95% CI: 0.33-1.43, I2 = 0%). CONCLUSIONS: Among AF patients with ESRD on chronic hemodialysis, the risk of ischemic stroke, ischemic stroke or systemic embolism, minor bleeding, major bleeding, and all-cause mortality is similar in patients treated with DOACs compared to VKAs. Given that the meta-analysis of RCTs on gastrointestinal bleeding did not confirm the results of the meta-analysis of the observational studies, it cannot be concluded that gastrointestinal bleeding is lower among DOAC-treated patients. PROTOCOL REGISTRATION: PROSPERO CRD42023391966.

The therapeutic effect of wine-processed Corni Fructus on chronic renal failure in rats through the interference with the LPS/IL-1-mediated inhibition of RXR function.

ETHNOPHARMACOLOGICAL RELEVANCE: Corni Fructus, derived from the fruit of Cornus officinalis Sieb. et Zucc, is a widely utilized traditional Chinese medicine (TCM) with established efficacy in the treatment of diverse chronic kidney diseases. Crude Corni Fructus (CCF) and wine-processed Corni Fructus (WCF) are the main processed forms of Corni Fructus. Generally, TCM is often used after processing (paozhi). Despite the extensive use of processed TCM, the underlying mechanisms of processing for most TCMs have been unclear so far. AIM OF THE STUDY: In this study, an integrated strategy combined renal metabolomics with proteomics was established and investigated the potential processing mechanisms of CCF or WCF on chronic renal failure (CRF) models. MATERIALS AND METHODS: Firstly, the differences in biochemical parameters and pathological histology were compared to evaluate the effects of CCF and WCF on CRF model rats. Then, the tissue differential metabolites and proteins between CCF and WCF on CRF model rats were screened based on metabolomics and proteomics technology. Concurrently, a combined approach of metabolomics and proteomics was employed to investigate the underlying mechanisms associated with these marker metabolic products and proteins. RESULTS: Compared to the MG group, there were 27 distinct metabolites and 143 different proteins observed in the CCF-treatment group, while the WCF-treatment group exhibited 24 distinct metabolites and 379 different proteins. Further, the integration interactions analysis of the protein and lipid metabolite revealed that both WCF and CCF improved tryptophan degradation and LPS/IL-1-mediated inhibition of RXR function. WCF inhibited RXR function more than CCF via the modulation of LPS/IL-1 in the CRF model. Experimental results were validated by qRT-PCR and western blotting. Notably, the gene expression amount and protein levels of FMO3 and CYP2E1 among 8 genes influenced by WCF were higher compared to CCF. CONCLUSION: The results of this study provide a theoretical basis for further study of Corni Fructus with different processing techniques in CRF. The findings also offer guidance for investigating the mechanism of action of herbal medicines in diseases employing diverse processing techniques.

Antihypertensive treatment of end-stage renal disease patients on hemodialysis does not alter circulating ACE and ACE2 activity and angiotensin peptides.

Cardiovascular diseases (CVD) are the main causes of death in hemodialysis patients, representing a public health challenge. We investigated the effect of different antihypertensive treatments on circulating levels of renin-angiotensin system (RAS) components in end-stage renal disease (ESRD) patients on hemodialysis. ESRD patients were grouped following the prescribed antihypertensive drugs: ß-blocker, ß-blocker+ACEi and ß-blocker+AT1R blocker. ESDR patients under no antihypertensive drug treatment were used as controls. Blood samples were collected before hemodialysis sessions. Enzymatic activities of the angiotensin-converting enzymes ACE and ACE2 were measured through fluorescence assays and plasma concentrations of the peptides Angiotensin II (Ang II) and Angiotensin-(1-7) [Ang-(1-7)] were quantified using mass spectrometry (LC-MS/MS). ACE activity was decreased only in the ß-blocker+ACEi group compared to the ß-blocker+AT1R, while ACE2 activity did not change according to the antihypertensive treatment. Both Ang II and Ang-(1-7) levels also did not change according to the antihypertensive treatment. We concluded that the treatment of ESRD patients on hemodialysis with different antihypertensive drugs do not alter the circulating levels of RAS components.

ß2-Adrenergic receptor agonists as a treatment for diabetic kidney disease.

We have previously shown that the long-acting ß2-adrenergic receptor (ß2-AR) agonist formoterol induced recovery from acute kidney injury in mice. To determine whether formoterol protected against diabetic nephropathy, the most common cause of end-stage kidney disease (ESKD), we used a high-fat diet (HFD), a murine type 2 diabetes model, and streptozotocin, a murine type 1 diabetes model. Following formoterol treatment, there was a marked recovery from and reversal of diabetic nephropathy in HFD mice compared with those treated with vehicle alone at the ultrastructural, histological, and functional levels. Similar results were seen after formoterol treatment in mice receiving streptozotocin. To investigate effects in humans, we performed a competing risk regression analysis with death as a competing risk to examine the association between Veterans with chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD), who use ß2-AR agonists, and Veterans with CKD but no COPD, and progression to ESKD in a large national cohort of Veterans with stage 4 CKD between 2011 and 2013. Veterans were followed until 2016 or death. ESKD was defined as the initiation of dialysis and/or receipt of kidney transplant. We found that COPD was associated with a 25.6% reduction in progression from stage 4 CKD to ESKD compared with no COPD after adjusting for age, diabetes, sex, race-ethnicity, comorbidities, and medication use. Sensitivity analysis showed a 33.2% reduction in ESKD in Veterans with COPD taking long-acting formoterol and a 20.8% reduction in ESKD in Veterans taking other ß2-AR agonists compared with those with no COPD. These data indicate that ß2-AR agonists, especially formoterol, could be a treatment for diabetic nephropathy and perhaps other forms of CKD.NEW & NOTEWORTHY Diabetic nephropathy is the most common cause of ESKD. Formoterol, a long-acting ß2-adrenergic receptor (ß2-AR) agonist, reversed diabetic nephropathy in murine models of type 1 and 2 diabetes. In humans, there was an association with protection from progression of CKD in patients with COPD, by means of ß2-AR agonist intake, compared with those without COPD. These data indicate that ß2-AR agonists, especially formoterol, could be a new treatment for diabetic nephropathy and other forms of CKD.

Safety and effectiveness of remdesivir for the treatment of COVID-19 patients with end-stage renal disease: A retrospective cohort study.

BACKGROUND: Remdesivir has been used to treat severe coronavirus 2019 (COVID-19); however, its safety and effectiveness in patients remain unclear. This study aimed to investigate the safety and effectiveness of remdesivir in patients with COVID-19 with end-stage renal disease (ESRD). METHODS: This retrospective study used the Chang Gung Research Database (CGRD) and extracted data from 21,621 adult patients with COVID-19 diagnosed between April 2021 and September 2022. The patients were divided into groups based on their remdesivir use and the presence of ESRD. The adverse effects of remdesivir and their outcomes were analyzed after propensity score matching. RESULTS: To compare the adverse effects of remdesivir, propensity scores were used for one-to-one matching between patients with and without ESRD treated with remdesivir (N = 110). There were no statistically significant differences in heart rates, blood glucose levels, variations in hemoglobin levels before and after remdesivir use, or liver function between the two groups after remdesivir use. A comparison was made between patients with ESRD using remdesivir and those not using remdesivir after propensity score matching (N = 44). Although a shorter length of stay (LOS), lower intensive care unit (ICU) admission rate, and lower intubation rate were noted in the ESRD group treated with remdesivir, the difference was not statistically significant. CONCLUSION: Remdesivir is safe for use in patients with COVID-19 and ESRD; no increased adverse effects were noted compared with patients without ESRD. However, the effectiveness of remdesivir use in patients with COVID-19 and ESRD remains uncertain.

Protective effect of activated charcoal against progression of chronic kidney disease: A randomized clinical study.

Chronic kidney disease (CKD) is a non-reversible and progressive disease affecting the kidneys, significantly impacting global public health. One of the complications of chronic kidney disease is impaired intestinal barrier function, which may allow harmful products such as urea to enter the bloodstream and cause systemic inflammation. This study aimed to investigate whether supplementation with activated charcoal could reduce uremic toxins in patients with end-stage renal disease (ESRD). The study was a randomized clinical trial conducted at the Dialysis Center of al Diwaniyah Medical Hospital in the Diwaniyah Governorate. Eighty-two patients with ESRD on regular hemodialysis were enrolled, with 15 patients receiving oral supplementation with activated charcoal in addition to standard care and 13 patients receiving only standard care. Blood samples were collected at baseline and after eight weeks, and several biomarkers were measured, including estimated glomerular filtration rate (eGFR), creatinine, urea, phosphorus, albumin, and indoxyl sulfate. The results showed a significant reduction in both serum urea and serum phosphorus levels after eight weeks of oral-activated charcoal treatment. However, the other biomarkers were not affected by the treatment. In conclusion, the use of oral-activated charcoal for eight weeks in Iraqi patients undergoing maintenance hemodialysis improved urea and phosphorus levels.

Cardiometabolic comorbidities in autosomal dominant polycystic kidney disease: a 16-year retrospective cohort study.

BACKGROUND: Autosomal-dominant polycystic kidney disease (ADPKD) is the most prevalent hereditary kidney disease and the fourth leading cause of end-stage renal disease (ESRD) requiring renal replacement therapy (RRT). Nevertheless, there is a paucity of epidemiological research examining the risk factors and survival on RRT for ADPKD. Thus, we aimed to investigate the cumulative effects of cardiometabolic comorbidities, including hypertension (HTN), type 2 diabetes mellitus (DM), and dyslipidemia (DLP) to clinical outcomes in ADPKD. METHODS: We identified 6,142 patients with ADPKD aged ≥ 20 years from 2000 to 2015 using a nationwide population-based database. HTN, DM, and DLP diagnoses before or at the time of ADPKD diagnosis and different combinations of the three diagnoses were used as the predictors for the outcomes. Survival analyses were used to estimate the adjusted mortality risk from cardiometabolic comorbidities and the risk for renal survival. RESULTS: Patients with ADPKD who developed ESRD had the higher all-cause mortality (HR, 5.14; [95% CI: 3.88-6.80]). Patients with all three of the diseases had a significantly higher risk of entering ESRD (HR:4.15, [95% CI:3.27-5.27]), followed by those with HTN and DM (HR:3.62, [95% CI:2.82-4.65]), HTN and DLP (HR:3.54, [95% CI:2.91-4.31]), and HTN alone (HR:3.10, [95% CI:2.62-3.66]) compared with those without any three cardiometabolic comorbidities. CONCLUSIONS: Our study discovered the cumulative effect of HTN, DM, and DLP on the risk of developing ESRD, which reinforces the urgency of proactive prevention of cardiometabolic comorbidities to improve renal outcomes and overall survival in ADPKD patients.

Treatment of diabetic kidney disease. A network meta-analysis.

BACKGROUND: Diabetic kidney disease (DKD) is a health burden of rising importance. Slowing progression to end stage kidney disease is the main goal of drug treatment. The aim of this analysis is to compare drug treatments of DKD by means of a systemic review and a network meta-analysis. METHODS: We searched Medline, CENTRAL and clinicaltrials.gov for randomized, controlled studies including adults with DKD treated with the following drugs of interest: single angiotensin-converting-enzyme-inhibitor or angiotensin-receptor-blocker (single ACEi/ARB), angiotensin-converting-enzyme-inhibitor and angiotensin-receptor-blocker combination (ACEi+ARB combination), aldosterone antagonists, direct renin inhibitors, non-steroidal mineralocorticoid-receptor-antagonists (nsMRA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i). As primary endpoints, we defined: overall mortality and end-stage kidney disease, as secondary endpoints: renal composite outcome and albuminuria and as safety endpoints: acute kidney injury, hyperkalemia and hypotension. Under the use of a random effects model, we computed the overall effect estimates using the statistic program R4.1 and the corresponding package "netmeta". Risk of bias was assessed using the RoB 2 tool and the quality of evidence of each pairwise comparison was rated according to GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: Of initial 3489 publications, 38 clinical trials were found eligible, in total including 42346 patients. Concerning the primary endpoints overall mortality and end stage kidney disease, SGLT2i on top of single ACEi/ARB compared to single ACEi/ARB was the only intervention significantly reducing the odds of mortality (OR 0.81, 95%CI 0.70-0.95) and end-stage kidney disease (OR 0.69, 95%CI 0.54-0.88). The indirect comparison of nsMRA vs SGLT2i in our composite endpoint suggests a superiority of SGLT2i (OR 0.60, 95%CI 0.47-0.76). Concerning safety endpoints, nsMRA and SGLT2i showed benefits compared to the others. CONCLUSIONS: As the only drug class, SGLT2i showed in our analysis beneficial effects on top of ACEi/ARB treatment regarding mortality and end stage kidney disease and by that reconfirmed its position as treatment option for diabetic kidney disease. nsMRA reduced the odds for a combined renal endpoint and did not raise any safety concerns, justifying its application.

The efficacy and safety of direct-acting antiviral regimens for end-stage renal disease patients with HCV infection: a systematic review and network meta-analysis.

Background: Hepatitis C virus (HCV) infection is an independent risk factor associated with adverse outcomes in patients with end-stage renal disease (ESRD). Due to the wide variety of direct-acting antiviral regimens (DAAs) and the factor of renal insufficiency, careless selection of anti-hepatitis C treatment can lead to treatment failure and safety problems. The integrated evidence for optimized therapies for these patients is lacking. This study would conduct comparisons of different DAAs and facilitate clinical decision-making. Methods: We conducted a systematic literature search in multiple databases (PubMed, Ovid, Embase, Cochrane Library, and Web of Science) up to 7 August 2023. Study data that contained patient characteristics, study design, treatment regimens, intention-to-treat sustained virologic response (SVR), and adverse event (AE) data per regimen were extracted into a structured electronic database and analyzed. The network meta-analysis of the estimation was performed by the Bayesian Markov Chain Monte Carlo methods. Results: Our search identified 5,278 articles; removing the studies with duplicates and ineligible criteria, a total of 62 studies (comprising 4,554 patients) were included. Overall, the analyses contained more than 2,489 male individuals, at least 202 patients with cirrhosis, and no less than 2,377 patients under hemodialysis. Network meta-analyses of the DAAs found that receiving ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (R) plus dasabuvir (DSV), glecaprevir (G)/pibrentasvir (P), and sofosbuvir (SOF)/ledipasvir (LDV) ranked as the top three efficacy factors for the HCV-infected ESRD patients. Stratified by genotype, the G/P would prioritize genotype 1 and 2 patients with 98.9%-100% SVR, the SOF/DCV regimen had the greatest SVR rates (98.7%; 95% CI, 93.0%-100.0%) in genotype 3, and the OBV/PTV/R regimen was the best choice for genotype 4, with the highest SVR of 98.1% (95% CI, 94.4%-99.9%). In the pan-genotypic DAAs comparison, the G/P regimen showed the best pooled SVR of 99.4% (95% CI, 98.6%-100%). DAA regimens without Ribavirin or SOF showed the lowest rates of AEs (49.9%; 95% CI, 38.4%-61.5%) in HCV-infected ESRD patients. Conclusion: The G/P could be recommended as the best option for the treatment of pan-genotypic HCV-infected ESRD patients. The OBV/PTV/R plus DSV, SOF/Velpatasvir (VEL), SOF/Ledipasvir (LDV), and SOF/DCV would be reliable alternatives for HCV treatment with comparable efficacy and safety profiles. Systematic review registration: https://www.crd.york.ac.uk/prospero/#searchadvanced, PROSPERO: CRD42021242359.

[A Case of Mycobacterium abscessus Identified by Suspicious Gram Staining in the Blood Culture of a Patient with Chronic Renal Failure]. / Kronik Böbrek Yetmezlikli Hastanin Kan Kültüründe Süpheli Gram Boyamasi ile Tanimlanan Mycobacterium abscessus Olgusu.

Mycobacterium abscessus (M.abscessus), which is from the group of non-tuberculosis mycobacteria and is widely found in the natural environment, has been reported with increasing frequency as the causative agent of various infections; especially in the lower respiratory tract and in immuncompromised people. In this report, a case of M.abscessus, which developed tubular adenoma, pancytopenia and sepsis on the basis of chronic renal failure (CRF) was diagnosed by suspecting the causative agent in the Gram stain examination prepared from blood culture, was presented. A 49-year-old patient with CRF, who had complaints of weight loss, weakness, and loss of appetite for the last six months, admitted to the emergency department with a 7-8-day history of severe diarrhea and fever. Besides other tests, as the white blood cell count was 1.6 x 103/µl, neutrophil count was 80.6%, hemoglobin was 9.3 g/ dl and the platelet value was 36 x 103/µl in the blood samples, the patient was first taken into internal medicine service and then to the intensive care unit with a preliminary diagnosis of hypotension and sepsis. Meropenem and teicoplanin were started with the preliminary diagnosis of peritonitis in the internal medicine service. In addition to other tests, on the fifth day of antibiotic treatment, two consecutive sets of blood cultures were taken and sent to the microbiology laboratory. A positive signal was obtained from two aerobic blood culture samples at 42 and 45 hours of incubation in the BacT/Alert device. No bacteria were observed in the Gram staining of these samples and Erhlich Ziehl Neelsen (EZN) staining was performed because the structures considered as dye residues were noted as a result of the examination. Acid-fast bacteria were observed in the EZN-stained slide examination, and a panic report was given to the clinician. The patient died shortly after the notification was made in the evening hours. On culture plates inoculated after a positive signal, at the end of two days of aerobic incubation at 37 °C, small smooth S colonies grew on chocolate and sheep blood agar. Growing bacteria were detected as positive by EZN staining and identified as M.abscessus with 99.9% confidence by MALDI-TOF MS. After the bacterium was named as M.abscessus, the isolates were sent to the tuberculosis central laboratory of Süreyyapasa Chest Diseases and Thoracic Surgery Hospital for molecular typing. After DNA extraction from the growing colonies and polymerase chain reaction (PCR), they were typed using the GenoType NTM-DR (Hain Lifescience GmbH, Germany) kit and identified as M.abscessus, consistent with the MALDITOF MS result. After the species level identification, the erm, rrl (clarithromycin, azithromycin), and rrs (kanamycin, amikacin, and gentamicin) genes were investigated in the isolate, and it was determined that the bacteria were resistant to macrolides and sensitive to aminoglycosides. In the clinic, it should be noted that, non-tuberculous mycobacteria may play a role as an agent in immunocompromised people. On the other hand, it should be considered that non-tuberculosis bacteria may be the causative agent, with gram-positive bacilli appearing as stain residues or pale staining in Gram stains made from samples of such patients. As in this case, if the agent is seen as dye residue in blood culture Gram staining samples, it may be life-saving to suspect the agent and to report the result to the clinician accurately and quickly after EZN staining.