Trypanosoma cruzi and hematospermia,

Liraglutide promotes autophagy by regulating the AMPK/mTOR pathway in a rat remnant kidney model of chronic renal failure Abstract Background We aimed to determine whether the glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide (LRG) could ameliorate renal function through promoting autophagy via regulating the AMPK/mTOR pathway in a rat remnant kidney model of chronic renal failure. Methods Rats were divided into four groups (n = 10 per group) as follows: (1) sham, (2) nephrectomy (NPX), (3) LRG control (LRG control), and (4) LRG treatment (LRG). Except for rats in the sham group, all rats underwent 5/6 nephrectomy surgery to establish a remnant kidney model of chronic renal failure. In addition, rats in LRG group received LRG as a subcutaneous injection at a dose of 10 mg/kg (once daily) for 4 consecutive weeks, whereas rats in the LRG control group received treatment similar to that of rats in the LRG group, except saline was used instead of LRG. After 4 weeks of treatment, serum creatinine (Scr), blood urea nitrogen (BUN), and urinary albumin excretion were determined. Immunofluorescence assay, immunoprecipitation assay, and Western blot analysis were performed to evaluate the AMPK/mTOR pathway expression of proteins. Results Nephrectomized rats (including rats in the NPX, LRG control, and LRG groups) showed higher levels of the Scr, BUN, and urinary albumin excretion, as well as down-regulation of GLP-1R, LC3-II, and AMPK phosphorylation, and up-regulation of mTOR phosphorylation when compared with rats in the sham group. However, those changes were blocked by liraglutide. Conclusion Liraglutide may promote autophagy through regulating the AMPK/mTOR pathway to exert renoprotective effects in a rat remnant kidney model of chronic renal failure.

The impact of dyslipidemia and oxidative stress on vasoactive mediators in patients with renal dysfunction Abstract Hyperlipidemia and oxidative stress are indispensable features of chronic kidney disease (CKD) that favor the development of atherogenic plaques and cardiovascular disease (CVD). A number of vasoactive mediators including proprotein convertase subtilisin–kexin type 9 (PCSK9), endothelin-1, nitric oxide, and angiotensin II have fundamental roles in the pathophysiology of atherosclerotic events; moreover, their levels are affected by dyslipidemia and oxidative stress due to renal dysfunction. Therefore, therapeutic measures aimed at correcting dyslipidemia and alleviating oxidative stress could potentially protect against CVD in CKD patients. In this review, we discuss the relation between dyslipidemia, oxidative stress, and vasoactive mediators as well as the available treatment options against these disturbances in CKD patients.

A novel method for pain control: infiltration free local anesthesia technique (INFLATE) for transrectal prostatic biopsy using transcutaneous electrical nerve stimulation (TENS) Abstract Purpose To describe a novel method for the control of pain during prostate biopsies, infiltration free local anesthesia technique (INFLATE) for transrectal prostatic biopsies with no further needle insertions for local anesthetic infiltration. Methods A total of 138 men with elevated prostate-specific antigen levels and/or abnormal digital rectal examination findings were included in the study. Of the patients, 73 were assigned to the INFLATE group and 65 to the TRUS-PNB group. Demographic data, PSA levels, findings of digital rectal examinations, and multiparametric prostatic magnetic resonance imaging were recorded. In the INFLATE group, a two-channel TENStem eco basic device with two electrodes was used for pain control during the biopsy. For the TRUS-PNB group, 60 mg lidocaine gel was given intrarectally in addition to infiltration of a prilocaine and bupivacaine mixture (5 mL of 2% prilocaine + 5 mL of 0.25% bupivacaine). Pain perception was assessed using a linear numeric rating scale. Results The mean ages, BMIs, prostate volumes, and PSA levels were similar between the two groups (p > 0.05). Of the 56 participants with prostate adenocarcinoma, 28 were in the INFLATE group, and 28 were in the TRUS-PNB group with a 40.6% overall cancer detection rate. The mean preoperative and post-operative pain scores during probe insertion, biopsy and post-biopsy were similar between the groups (p > 0.05). Conclusion The results of the study confirmed that INFLATE for transrectal prostate biopsy using a TENS device could safely and effectively be used for pain control with the advantage of two fewer needle attempts with no increase in significant complications.

Systemic immune-inflammation index, serum albumin, and fibrinogen impact prognosis in castration-resistant prostate cancer patients treated with first-line docetaxel Abstract Purpose To evaluate the prognostic value of pretreatment plasma systemic immune-inflammation index (SII), albumin, and fibrinogen levels in metastatic castration-resistant prostate cancer (mCRPC) patients treated with first-line docetaxel and to screen out the patients with the greatest risk for poor prognosis. Methods The plasma SII, albumin, and fibrinogen levels were examined before treatment and analyzed with patient clinicopathological parameters and overall survival (OS). The survival analysis was performed using the Kaplan–Meier method, and prognostic factors were assessed using the Cox proportional hazard regression model. Results The incidences of elevated SII level, hypoproteinemia, and hyperfibrinogenemia were 52.51%, 25.14%, and 27.93%, respectively. SII level was associated with neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) (P < 0.001). Albumin level was found closely correlated with ECOG PS (P = 0.006), PLR (P = 0.042), and hemoglobin (P = 0.009), but not other parameters. Elevated plasma fibrinogen level was significantly associated with Eastern Cooperative Oncology Group performance status (ECOG PS) (P = 0.009), visceral metastases (P < 0.001), and PLR (P = 0.001). In multivariate Cox regression model, visceral metastases SII (HR 2.133, 95% CI 1.163–3.913; P = 0.014), albumin (HR 0.540, 95% CI 0.307–0.949; P = 0.032), and fibrinogen (HR 1.888, 95% CI 1.069–3.335; P = 0.029) were further confirmed to be the independent prognostic factors for OS. Of the three target parameters, we found that patients with none abnormalities of the three parameters showed the best prognosis, and patients with at least any two abnormalities of them showed markedly worse prognosis than patients with any one abnormalities of the three parameters (P < 0.001). Conclusions Pretreatment SII, albumin, and fibrinogen are independent prognostic factors in mCRPC patients treated with first-line docetaxel. Moreover, the combined use of SII, albumin, and fibrinogen levels may help us to identify the high-risk populations for treatment decisions.

Efficacy and safety of the new antiviral agents for the treatment of hepatitis C virus infection in Egyptian renal transplant recipients Abstract Purpose Hepatitis C virus (HCV) infection in kidney transplant recipients (KTRs) is common and can impact on patient and graft survival rates. The efficacy and safety of direct-acting antivirals (DAAs) to treat genotype-4 HCV-infected KTRs have not been fully established. Methods A prospective, single-arm, single-center study was conducted at Mansoura Urology/Nephrology Center (Mansoura University, Egypt). 114 HCV RNA(+) genotype 4 KTRs were enrolled in this study after a hepatology consultation and consented to start treatment with interferon-free DAAs. A sofosbuvir-based regimen was given to 109 recipients that had creatinine clearance (Crcl) of > 30 mL/min/1.73 m2. Ritonavir-boosted paritaprevir/ombitasvir was prescribed to five recipients with Crcl < 30 mL/min/1.73 m2. Results The mean age of the cohort was 45.2 ± 11.2 years; most were male. The mean duration with a transplant was 14.2 ± 3.5 years, with different immunosuppressive regimens, mostly based on calcineurin inhibitors. A rapid virological response (RVR), i.e., clearance of viral load, was achieved in 100% at 4 weeks after starting treatment. All patients had a sustained virological response (SVR) at 12 and 24 weeks posttreatment, with one exception. During DAA therapy serum creatinine increased in 12 patients. In three, this was concomitant with elevated calcineurin inhibitor and sirolimus trough levels. Graft biopsies were performed in 8 of these 12 patients: these revealed an acute rejection in 4 cases (acute cellular rejection grade-1A: n = 2, and grade-1B: n = 2). The rejection episodes occurred at 4–6 weeks after starting treatment. Conclusion DAAs were highly efficacious and safely treated genotype-4 HCV-infected KTRs and had no significant adverse effects on graft function/survival.

The gut microbiota and its relationship with chronic kidney disease Abstract Chronic kidney disease (CKD) is a worldwide health problem, because it is one of the most common complications of metabolic diseases including obesity and type 2 diabetes. Patients with CKD also develop other comorbidities, such as hypertension, hyperlipidemias, liver and cardiovascular diseases, gastrointestinal problems, and cognitive deterioration, which worsens their health. Therapy includes reducing comorbidities or using replacement therapy, such as peritoneal dialysis, hemodialysis, and organ transplant. Health care systems are searching for alternative treatments for CKD patients to mitigate or retard their progression. One new topic is the study of uremic toxins (UT), which are excessively produced during CKD as products of food metabolism or as a result of the loss of renal function that have a negative impact on the kidneys and other organs. High urea concentrations significantly modify the microbiota in the gut also, cause a decrease in bacterial strains that produce anti-inflammatory and fuel molecules and an increase in bacterial strains that can metabolize urea, but also produce UT, including indoxyl sulfate and p-cresol sulfate. UT activates several cellular processes that induce oxidative environments, inflammation, proliferation, fibrosis development, and apoptosis; these processes mainly occur in the gut, heart, and kidney. The study of the microbiota during CKD allowed for the implementation of therapy schemes to try to reduce the circulating concentrations of UT and reduce the damage. The objective of this review is to show an overview to know the main UT produced in end-stage renal disease patients, and how prebiotics and probiotics intervention acts as a helpful tool in CKD treatment.

Treatment of asymptomatic hyperuricemia complicated by renal damage: a controversial issue Abstract The prevalence of asymptomatic HUA is increasing year after year. HUA is a risk factor for the occurrence and development of renal diseases. However, the role of urate-lowering therapy in asymptomatic HUA complicated by renal damage is still controversial. In some experiments, the treatment of asymptomatic HUA complicated by renal damage may delay the progression of kidney damage. In addition, there is increasing evidence, suggesting that elevated serum uric acid is an independent risk factor for kidney disease. However, in other studies, uric acid-lowering therapy did not improve renal function, and uric acid levels could not be used as an independent predictor for CKD development. Further experimental studies are needed to determine the starting threshold and target value of asymptomatic HUA complicated by renal damage. At the same time, confirmation of the benefits of urate-lowering therapy for kidneys requires studies with larger samples and high-quality RCTs.

The effect of trimetazidine on preventing contrast-induced nephropathy after cardiac catheterization Abstract Purpose Trimetazidine has been shown to prevent the risk of contrast-induced nephropathy (CIN) in patients with renal dysfunction undergoing percutaneous coronary intervention (PCI). However, the effect of trimetazidine on CIN in unselected patients is unknown. We aimed to evaluate the effect of trimetazidine on preventing CIN in unselected patients treated with PCI. Methods 2154 consecutive patients were enrolled and divided into the trimetazidine (n = 529) and non-trimetazidine group (n = 1625). Patients in the trimetazidine group received trimetazidine 20 mg thrice daily starting at least 24 h before the procedure and continuing until discharge. The primary outcome was CIN. Results CIN was observed in 197 (9.2%) patients. The incidence of CIN was similar between two groups (9.1% vs. 9.2%, P = 0.947). After adjusting for other potential risk factors, trimetazidine did not significantly reduce the risk of CIN (OR = 0.70, 95% CI 0.46–1.08, P = 0.104). The results remained similar when using the alternate definitions of CIN and different subgroup analysis based on diabetes or chronic kidney disease. In additional, no significant difference between two groups was found with respect to in-hospital major adverse clinical events (1.89% vs. 1.66%, P > 0.05). Conclusions Trimetazidine did not exert significant renal protective effect on preventing CIN and in hosptial major adverse clinical events in unselected patients undergoing PCI.

Total testosterone density predicts high tumor load and disease reclassification of prostate cancer: results in 144 low-risk patients who underwent radical prostatectomy Abstract Objectives The aim of this study is to evaluate the association between total testosterone density (TTD), defined as the ratio of serum TT to prostate volume (PV), and high tumor load (HTL) in low-risk prostate cancer (PCA) patients who underwent radical prostatectomy. Materials and methods Tumor load was defined as the percentage of prostate volume invaded by cancer (PPI-PCA) in the surgical specimen. Pathologic features including tumor upgrading, upstaging or positive surgical margins in the specimen defined unfavorable disease (UD). PSA, TT, PSA density (PSAD), TTD, percentage of biopsy positive cores (BPC), PV and body mass index (BMI). The association of factors with the risk UD and HTL was evaluated by statistical methods. Results The cohort included 144 consecutive low-risk PCA patients. Overall, 104 patients (72.2%) had at least one feature indicating UD. TTD was associated with BMI, TT, PSA, PV and PPI-PCA ≥ 20% defined as HTL. A higher PPI-PCA was associated with an increased risk of UD with a fair discriminant power (area under the curve, AUC = 0.775; p < 0.0001). Patients with PPI-PCA > 20% were considered the study group versus patients with a PPI-PCA < 20% (control group). BPC, PSAD and TTD were independently associated with the risk of HTL (PPI-PCA ≥ 20%) with receiver-operating characteristics (ROC) curves indicating the same discriminant power for BPC (AUC = 0.628; p = 0.013), PSAD (AUC = 0.611; p = 0.032) and TTD (AUC = 0.610; p = 0.032). Conclusions Among low-risk PCA patients, TTD is associated with the risk of HTL, which is an independent predictor of UD and should be evaluated in the management of these patients.