Renal Adverse Effects of Tenofovir Containing Regimens in HIV-Infected Children and Adolescents in North India.

OBJECTIVE: To study the prevalence of abnormal renal functions among children living with HIV (CLHIV) receiving tenofovir disoproxil fumarate (TDF) containing antiretroviral therapy (ART). METHODS: A prospective, observational study was conducted among CLHIV aged 10 years to 21 years attending the pediatric HIV clinic. We included CLHIV weighing ≥ 30 kg who had been receiving TDF-containing regimens for at least 6 months, with estimated glomerular filtration rate (eGFR) > 60 ml/min/m2 at enrolment and for whom baseline laboratory parameters were available before starting ART. Clinical and laboratory parameters like serum creatinine, serum phosphate, urinary protein and glucose estimation, CD4 count and viral load were noted from records. The mean change in serum creatinine, estimated glomerular filtration rate (eGFR), creatinine clearance, serum phosphate, and presence of urinary glucose and protein by dipstick were assessed at 3- and 12-months follow-up. RESULTS: We enrolled 70 patients with mean (SD) age 14.99 (2.45) years who had been receiving TDF-based ART for a mean (SD) duration of 14.60 (12.80) months. At 3-months and 12-months follow-up, 32.85% and 41.42% patients, respectively, had eGFR below 90 mL/min/1.73m2, while 4.2% and 2.8% patients, respectively, had eGFR between 50-60 mL/min/1.73m2. One patient had creatinine clearance below 50 mL/min/1.73m2. Four patients had hypophosphatemia at the first and last follow-up respectively, and five patients had proteinuria. There was no statistically significant change in CD4 counts, serum potassium, or serum uric acid during study duration. CONCLUSION: TDF-containing ART regimen is associated with decreased eGFR, creatinine clearance and proteinuria.

Terlipressin for hepatorenal syndrome.

PURPOSE OF REVIEW: The definition and diagnostic criteria of hepatorenal syndrome-acute kidney injury (HRS-AKI) has undergone recent changes. A major vasoconstrictor, terlipressin, has recently been approved as pharmacotherapy for HRS-AKI in the United States. The purpose of this review is to familiarize the readers with these new diagnostic criteria of HRS-AKI, and how best to use terlipressin. RECENT FINDINGS: Terlipressin is effective either as bolus dosing or continuous infusion and can achieve reversal of HRS-AKI in approximately 40% of patients. Continuous infusion allows lower daily dose with equal efficacy and less side effects but not an approved mode of administration in the United States. Response to terlipressin in the randomized controlled trials was defined as repeat reduction of serum creatinine to less than 1.5 mg/dl. Newer studies will likely require response to treatment to be defined as a repeat serum creatinine to be less than 0.3 mg/dl from baseline. Terlipressin use is associated with ischemic side effects and potential for respiratory failure development. SUMMARY: Careful patient selection and close monitoring are necessary for its use. Response to terlipressin with HRS-AKI reversal is associated with improved outcomes with better survival and less requirement for renal replacement therapy.

Nivolumab + Tacrolimus + Prednisone ± Ipilimumab for Kidney Transplant Recipients With Advanced Cutaneous Cancers.

PURPOSE: Cancer-related mortality rates among kidney transplant recipients (KTR) are high, but these patients have largely been excluded from trials of immune checkpoint inhibitors because of immunosuppression and risk of treatment-related allograft loss (TRAL). We conducted a prospective clinical trial testing nivolumab (NIVO) + tacrolimus (TACRO) + prednisone (PRED) ± ipilimumab (IPI) in KTR with advanced cutaneous cancers. METHODS: Adult KTR with advanced melanoma or basal, cutaneous squamous, or Merkel cell carcinomas were eligible. Immunosuppression was standardized to TACRO (serum trough 2-5 ng/mL) + PRED 5 mg once daily. Patients then received NIVO 480 mg IV once every 4 weeks. The primary composite end point was partial or complete (tumor) response (CR) or stable disease per RECIST v1.1 without allograft loss at 16W. Patients with progressive disease (PD) could receive IPI 1 mg/kg IV + NIVO 3 mg/kg once every 3 weeks × 4 followed by NIVO. Donor-derived cell-free DNA (dd-cfDNA) levels were measured approximately once every 2 weeks as a potential predictor of allograft rejection. RESULTS: Among eight evaluable patients, none met the trial's primary end point. All eight patients experienced PD on NIVO + TACRO + PRED; TRAL occurred in one patient. Six patients then received IPI + NIVO + TACRO + PRED. Best overall responses: two CR (one with TRAL) and four PD (one with TRAL). In total, 7 of 8 pre-NIVO tumor biopsies contained a paucity of infiltrating immune cells. In total, 2 of 5 on-NIVO biopsies demonstrated moderate immune infiltrates; both patients later experienced a CR to IPI + NIVO. In 2 of 3 patients with TRAL, dd-cfDNA elevations occurred 10 and 15 days before increases in serum creatinine. CONCLUSION: In most KTR with advanced skin cancer, TACRO + PRED provides insufficient allograft protection and compromises immune-mediated tumor regression after administration of NIVO ± IPI. Elevated dd-cfDNA levels can signal treatment-related allograft rejection earlier than rises in serum creatinine.

Tangshen formula improves diabetic nephropathy in STZ-induced diabetes rats fed with hyper-methionine by regulating the methylation status of kidney.

BACKGROUND: The objective of this study was to examine and analyze differential methylation profiles in order to investigate the influence of hyper-methioninemia (HM) on the development of diabetic nephropathy (DN). Male Wistar rats, aged eight weeks and weighing 250-300 g, were randomly assigned into four groups: a control group (Healthy, n = 8), streptozocin-induced rats (STZ group, n = 8), HM + STZ group (n = 8), and the Tangshen Formula (TSF) treatment group (TSF group, n = 8). Blood glucose levels and other metabolic indicators were monitored before treatment and at four-week intervals until 12 weeks. Total DNA was extracted from the aforementioned groups, and DNA methylation landscapes were analyzed via reduced representative bisulfite sequencing. RESULTS: Both the STZ group and HM + STZ group exhibited increased blood glucose levels and urinary albumin/creatinine ratios in comparison with the control group. Notably, the HM + STZ group exhibited a markedly elevated urinary albumin/creatinine ratio (411.90 ± 88.86 mg/g) compared to the STZ group (238.41 ± 62.52 mg/g). TSF-treated rats demonstrated substantial reductions in both blood glucose levels and urinary albumin/creatinine ratios in comparison with the HM + STZ group. In-depth analysis of DNA methylation profiles revealed 797 genes with potential therapeutic effects related to TSF, among which approximately 2.3% had been previously reported as homologous genes. CONCLUSION: While HM exacerbates DN through altered methylation patterns at specific CpG sites, TSF holds promise as a viable treatment for DN by restoring abnormal methylation levels. The identification of specific genes provides valuable insights into the underlying mechanisms of DN pathogenesis and offers potential therapeutic targets for further investigation.

Voriconazole plus flucytosine is not superior to amphotericin B deoxycholate plus flucytosine as an induction regimen for cryptococcal meningitis treatment.

BACKGROUND: The efficacy and side effects of voriconazole plus 5-flucytosine (Vori + 5-FC) versus amphotericin B deoxycholate plus 5-flucytosine (AmBd + 5-FC) as an induction treatment for cryptococcal meningitis are unknown. METHODS: Forty-seven patients treated with Vori + 5-FC and 92 patients treated with AmBd + 5-FC were included in the current study after propensity score matching (PSM) at a ratio of 1:2. Two-week laboratory test results and 90-day mortality were compared between the two groups. RESULTS: After 2 weeks of induction treatment, the CSF Cryptococcus sterile culture rate was 57.1% in the Vori + 5-FC group and 76.5% in the AmBd + 5-FC group (p = .026). No difference was found in the normalization of CSF indicators (glucose, total protein, intracranial pressure and India ink sterile rate) between the two groups. Both the Vori + 5FC regimen and AmBd + 5-FC regimen obviously decreased haemoglobin concentrations, platelet counts and serum potassium levels (all p ≤ .010). Notably, the Vori + 5FC regimen did not influence serum creatinine levels (p = .263), while AmBd + 5FC increased serum creatinine levels (p = .019) after 2-week induction treatment. The Vori + 5-FC group and AmBd + 5-FC group had similar 90-day cumulative survival rates (89.9% vs. 87.8%, p = .926). CONCLUSION: The Vori + 5-FC regimen was associated with low 2-week CSF sterile culture and was not superior to AmBd + 5-FC as induction therapy in terms of the 90-day cumulative survival rate of CM patients.

Study of hispidulin in the treatment of uric acid nephropathy based on NF-κB signaling pathway.

Uric acid nephropathy (UAN) is caused by purine metabolism disorders. UAN rat models were established in SD rats. The modeling rats received different doses of hispidulin (10, 20, 50 mg/mL). Febuxostat was applied as the positive drug. Serum creatinine, uric acid (UA), and cystatin-C (cys-C), neutrophil gelatinase-associated lipocalin (NGAL), IL-1ß, IL-8, TNF-α, and IL-6 in rats were detected. HE staining was done to assess kidney injury. UAN rats possessed prominent levels of serum creatinine, UA, cys-C, and NGAL, which all reduced after hispidulin treatment in a dose-dependent manner. HE staining determined the improvement of kidney injury after treatment, which was comparable to the efficacy of febuxostat. Hispidulin inhibited the release of IL-1ß, IL-8, TNF-α, and IL-6 in UAN rats. Hispidulin enhanced autophagy in UAN rats, presenting as ascending LC3II/I ratio and downregulated P62. The increasing trend of inflammasome-related proteins of NLRP3 and Caspase-1 was changeovered by hispidulin. The activation of NF-kB signaling was intercepted by hispidulin in UAN rats. Hispidulin can effectively improve renal function injury caused by UAN in rats. The mechanism may be related to the inhibition of inflammatory response induced by autophagy and activation of NF-κB pathway.

[The efficiency of pre-administration of a peptide mimicking the spatial structure of erythropoietin -chain B in modeling experimental post-contrast acute kidney injury].

AIM: To study the efficiency of pre-administration of a peptide mimicking the spatial structure of erythropoietin -chain B in modeling experimental post-contrast acute kidney injury. MATERIALS AND METHODS: In this study, an experimental model of post-contrast acute kidney injury was created using a non-steroidal anti-inflammatory drug, a nitric oxide synthase inhibitor, and injection of iopromide to mature male mice. After 48 hours, a comprehensive assessment of the concentration of creatinine, urea, glomerular filtration rate, the ratio of urea/albumin in the serum, as well as the level of proteinuria and interleukin 6 in the urine was carried out. RESULTS: A peptide mimicking the spatial structure of erythropoietin -chain B, administered at a dose of 100 g/kg 30 minutes before modeling of pathologic process, contributes to a significant decrease in creatinine and urea concentrations by 2.5 and 1.8 times, respectively, with an increase in glomerular filtration rate 4.4 times. In addition, in the group with pharmacological correction, there was a significant decrease in the ratio of urea/albumin by 2.2 times, a decrease in the level of proteinuria by 61.9% and a decrease in the concentration of pro-inflammatory interleukin-6 in the urine by 2.1 times. CONCLUSION: Thus, the preliminary administration of a peptide that mimics the spatial structure of the erythropoietin -chain B helps to reduce the severity of post-contrast acute kidney injury in the experiment, due to anti-inflammatory properties.

Comparison of Metabolic Effects of Three Different Treatment Combinations with Retrospective Real-life Data in People Living with HIV.

INTRODUCTION: Comorbidities are increasing in people living with HIV (PLHIV), and different treatment options have advantages and disadvantages. It is important to compare information from real-life treated cases. The aim of this study was to retrospectively evaluate the data on efficacy and clinical and laboratory findings during different antiretroviral therapies. METHODS: Retrospective file data of 47 PLHIV using Dolutegravir and Lamivudine (3TC/DTG), Tenofovir Alafenamide Emtricitabine and Elvitegravir Cobicistat (EVG/c/TAF/FTC) and Tenofovir Disoproxil Fumarate and Emtricitabine and Efavirenz (EFV/FTC/TDF) were analyzed. Data of the patients at baseline and 12 months after antiretroviral therapy (ART) were compared. RESULTS: About 47 PLHIV were included in the study. Of the patients, 22 (46.8%) were in the 3TC/DTG group, 19 (40.4%) in the EVG/c/TAF/FTC, and 6 (12.8%) in the EFV/FTC/TDF group. After 12 months of treatment, BMI, HIV-RNA, CD4, WBC, hemoglobin, MCV, PDW, RDW, platelet count, creatinine, eGFR, HDL, AST, glucose values of the 3TC/DTG group were significantly different (p<0.05). After 12 months of treatment, BMI, HIV-RNA, CD4 count, MCV, creatinine, eGFR, HDL, LDL, TG, TC, AST, and HOMA-IR values of the EVG/c/TAF/FTC treatment group were significantly different (p<0.05). After 12 months of treatment, HIV RNA, total bilirubin, and LDL values in the EFV/FTC/TDF treatment group were statistically different (p<0.05). CONCLUSION: All treatment groups showed a decrease in HIV-RNA and an increase in CD4 at the end of one year. While CD4 elevation is lower in EFV recipients than in integrase inhibitor (INSTI) recipients, weight gain is higher in INSTI recipients. While the lipid profile was more positively affected in the 3TC/DTG group, lipid profiles were more negatively affected in the EVG/c/TAF/FTC group, although liver and kidney functions were preserved.

Predictors of HbA1c treatment response to add-on medication following metformin monotherapy: a population-based cohort study.

Evidence on the influence of patient characteristics on HbA1c treatment response for add-on medications in patients with type 2 diabetes (T2D) is unclear. This study aims to investigate the predictors of HbA1c treatment response for three add-on medications (sulfonylureas (SU), dipeptidyl peptidase-4 (DPP-4) and sodium-glucose cotransporter-2 (SGLT-2) inhibitor) in metformin monotherapy treated patients with T2D. This retrospective cohort study was conducted using the electronic health record data from six primary care clinics in Singapore. A total of 9748 adult patients with T2D on metformin monotherapy receiving SU, DPP-4 or SGLT-2 add-on were 1:1 propensity score matched to patients receiving other add-on medications. Patient demographics, laboratory results, diabetes related complications, comedications, and treatment response at two endpoints (HbA1c reduction ≥ 1% at 6th month, HbA1c goal attainment < 7% at 12th month) were examined. Multiple logistic regression analyses were used to identify patient characteristics associated with the treatment responses. After matching, there were 1073, 517, and 290 paired cohorts of SU, DPP-4 and SGLT-2 respectively. Besides baseline HbA1c, patients with longer hypertension disease duration and higher cholesterol HDL were associated with better treatment response to SU medication add-on. Lower estimated glomerular filtration rate (eGFR), and angiotensin-II receptor medications were associated with better treatment response to DPP-4 add-on. Lower cholesterol HDL, higher creatinine serum, absence of renal complications and beta-blockers medications were associated with better treatment response to SGLT-2 add-on. The cholesterol HDL, creatinine serum, eGFR, hypertension disease duration, angiotensin-II receptors and beta-blockers class of medications can influence the HbA1c treatment response for SU, DPP-4 and SGLT-2 add-on medications. Knowing the patients' characteristics that influence treatment response can assist in guiding clinical decisions when selecting the appropriate add-on medication, ultimately helping to prevent the development of diabetes-related complications.

Neurological and Psychiatric Aspects of Biological Markers for the Provision of Medical Care to Patients with Spinal Muscular Atrophy 5q.

BACKGROUND: Spinal muscular atrophy (SMA) is a rare genetic disorder, in which, for the common childhood onset forms, loss of function of the SMA 5q gene leads to disability and death before adulthood. Symptomatic treatment focusses on respiratory and nutritional support, and physical therapy, but there is little consideration of psychiatric manifestations of SMA. The aim of this study was to explore blood biomarker levels, electromyography (EMG) data, and clinical manifestations, including psychiatric impairments, in patients with SMA 5q. Our objectives were twofold: First, to assess the clinical relevance of standard biomarkers, i.e., creatinine, creatine kinase (CK), and lactate dehydrogenase (LDH) levels, and second, to obtain data supporting the development of an effective prognostic algorithm for the course of this disease. RESULTS: We analyzed retrospective data from 112 medical records of 58 registered patients (2008-2022) with SMA. At the time of last registration, the 58 patients had a mean age 38.4 years [13.68; 55.0], of whom 32 (52%) were female. The subgroup of 21 pediatric patients had a mean age 12.32 years [6.57; 13.93], of whom 14 (24%) were girls. The ICD-10 diagnoses were as follows: G12.0 (n=7, 12%, children), G12.1 (n=14, 24% children; n=29, 50% adults), G12.8 (n=6, 10% adults), G12.9 (n=2, 1% adults). The archival data on psychiatric status indicated emotional lability (n=6, 10.3%), fatigue (n=10, 17.2%), and tearfulness (n=3, 5.2%) in some patients. There were no significant subgroup differences in serum creatinine and CK levels, but there were significant differences in LDH levels between the G12.0, G12.1, G12.8, and G12.9 subgroups. Among the serum biomarkers, only LDH levels showed significant differences among the subgroups of SMA 5q patients; higher levels in the G12.1, G12.8, and G12.9 groups compared to the G12.0 (infantile) group related to age, weight, gender, and level of physical activity. Data on psychiatric status were insufficient to identify group differences and associations with biomarker levels. Likewise, longitudinal data on repeat hospitalizations did not indicate associations with biomarker levels. CONCLUSIONS: Creatinine, CK, and LDH levels were insufficient for monitoring and predicting the course of SMA. Further prospective research is needed to elaborate the weak relationships between CK levels, the dynamics of the clinical presentation, and therapeutic interventions, and to investigate psychiatric co-morbidities in SMA 5q patients.

Efficacy and Safety of Esaxerenone in Hypertensive Patients with Diabetes Mellitus Undergoing Treatment with Sodium-Glucose Cotransporter 2 Inhibitors (EAGLE-DH).

INTRODUCTION: The EAGLE-DH study assessed the efficacy and safety of esaxerenone in hypertensive patients with diabetes mellitus receiving sodium-glucose cotransporter 2 (SGLT2) inhibitors. METHODS: In this multicenter, open-label, prospective, interventional study, esaxerenone was started at 1.25 or 2.5 mg/day and could be gradually increased to 5 mg/day on the basis of blood pressure (BP) and serum potassium levels. Oral hypoglycemic or antihypertensive medications prior to obtaining consent was continued. Data were evaluated in the total population and creatinine-based estimated glomerular filtration rate (eGFR) subcohorts (eGFR ≥ 60 mL/min/1.73 m2 [G1-G2 subcohort] and 30 to < 60 mL/min/1.73 m2 [G3 subcohort]). RESULTS: In total, 93 patients were evaluated (G1-G2, n = 49; G3, n = 44). Morning home systolic/diastolic BP values (SBP/DBP) were significantly reduced from baseline to week 12 (- 11.8 ± 10.8/- 5.1 ± 6.3 mmHg, both P < 0.001) and week 24 (- 12.9 ± 10.5/- 5.7 ± 6.3 mmHg, both P < 0.001). Similar results were observed in both eGFR subcohorts. The urinary albumin-to-creatinine ratio significantly decreased from baseline to week 24 in the total population (geometric percentage change, - 49.1%, P < 0.001) and in both eGFR subcohorts. The incidences of treatment-emergent adverse events (TEAEs) and drug-related TEAEs were 45.2% and 12.9%, respectively; most were mild or moderate. Serum potassium levels increased over the first 2 weeks of esaxerenone treatment, gradually decreased by week 12, and remained constant to week 24. One patient in the G1-G2 subcohort had serum potassium levels ≥ 5.5 mEq/L. No patients had serum potassium ≥ 6.0 mEq/L. CONCLUSION: Esaxerenone effectively lowered BP, was safe, and showed renoprotective effects in hypertensive patients with diabetes mellitus receiving treatment with SGLT2 inhibitors. Esaxerenone and SGLT2 inhibitors did not interfere with either drug's efficacy and may reduce the frequency of serum potassium elevations, suggesting they are a compatible combination. CLINICAL TRIAL REGISTRATION: jRCTs031200273.

Effects of Coriandrum sativum on distant organ inflammation and apoptosis due to liver ischemia/reperfusion injury.

Liver ischemia/reperfusion (IR) often affects distant organs, such as small intestine, kidney, and lung. Coriandrum sativum (CS) has an antioxidant and anti-inflammatory effect on liver damage. The aim of this study was to investigate the anti-inflammatory and antiapoptotic effects of CS extract on small intestine, lung, and kidney after the liver IR injury. Small intestine, lung, and kidney tissues were evaluated and scored in terms of cell degeneration, inflammation, and congestion, as well as caspase-3 (Cas-3) and cluster of differentiation 31 (CD31) immunostainings were carried out. Renal enzymes, creatinine and urea levels were measured biochemically in serum. After IR, a decrease in villi size, diffuse degeneration, epithelial cell shedding and extensive congestion in the capillaries were observed. Meanwhile, the number of degenerated villi and congestion decreased in the IR+CS group. Due to IR, increased congestion was detected in the interalveolar septum of the lungs and in the capillaries between the kidney tubules. It was also observed that the positively stained cells with Cas-3 and CD31 were increased in the lung, kidney, and small intestine tissues of the IR group, and decreased in the IR+CS group. Kidney enzymes, urea and creatinine levels were significantly increased in the IR group and decreased in the IR+CS group. In conclusion, it was observed that liver IR caused changes in distant organs, especially in the small intestine, lung, and kidneys. Damaging effects of IR as well as apoptosis and inflammation were found to be decreased in the groups treated with CS.

Role of Biomarkers in the Management of Immune-Checkpoint Inhibitor-Related Myocarditis.

PURPOSE OF REVIEW: Immune checkpoint inhibitor (ICI)-related myocarditis poses a major clinical challenge given its non-specific presentation, rapid progression, and high mortality rate. Here, we review the role of blood-based biomarkers in the clinical management of patients with ICI-related myocarditis. RECENT FINDINGS: Myocardial injury, its unique pattern, and the co-occurrence with myositis are defining features of ICI-related myocarditis. Non-cardiac biomarkers, specifically creatinine phosphokinase, precedes the symptomatic presentation and is highly sensitive for diagnosing ICI-related myocarditis, making them useful screening biomarkers. Combined elevations in cardiac troponins and non-cardiac biomarkers improve the confidence of an ICI myocarditis diagnosis. High troponin and creatinine phosphokinase levels are strongly associated with severe outcomes. We propose biomarker-based algorithms for the monitoring and diagnosis of ICI-related myocarditis. Biomarkers, such as cardiac troponins and creatine phosphokinase, can be used in combination in the monitoring, diagnosis, and prognostication of patients with ICI-related myocarditis.

Adjustment of creatinine clearance for carboplatin dosing in Calvert's formula and clinical efficacy for lung cancer.

BACKGROUND: The Cockcroft-Gault formula is commonly used as a substitute for glomerular filtration rate (GFR) in Calvert's formula for carboplatin dosing, where adjusting serum creatinine measured using the enzymatic method with 0.2 mg/dL has been suggested in Japan. However, the effects of these adjustments on efficacy in patients with non-small-cell lung cancer remain unknown. METHODS: We conducted a post hoc analysis of the PREDICT1 study (CJLSG1201), a multicenter prospective observational trial of carboplatin-pemetrexed. Glomerular filtration rate values in Calvert's formula were back-calculated from the administered dosages of carboplatin and the reported value of the target area under the curve. We estimated the serum creatinine adjustments and divided the patients into crude and adjusted groups. RESULTS: Patients in the crude group (N = 169) demonstrated similar efficacy to those in the adjusted group (N = 104) in progression-free survival (PFS) and overall survival (OS) (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.76-1.35; p = 0.916 vs. HR, 0.87; 95% CI, 0.65-1.17; p = 0.363), with higher grade 3-4 hematologic toxicity. Among patients aged ≥75 years, the crude group (N = 47) showed superior efficacy compared with the adjusted group (N = 17) in PFS and OS (HR, 0.37; 95% CI, 0.20-0.69; p = 0.002 vs. HR, 0.43; 95% CI, 0.23-0.82; p = 0.010). CONCLUSIONS: Serum creatinine adjustment may be associated with similar efficacy compared to the crude serum creatinine value. In older patients, the adjustment should be cautiously applied owing to the potential for reduced efficacy.

Efficacy and safety of long-acting cabotegravir versus oral tenofovir disoproxil fumarate-emtricitabine as HIV pre-exposure prophylaxis: A systematic review and meta-analysis.

WHO guidelines recommend daily oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) for pre-exposure prophylaxis (PrEP) of HIV in people at high risk of HIV infection. However, due to social, psychological and other reasons, the compliance with daily oral TDF-FTC in real life is low. Long-acting cabotegravir is currently the only long-acting drug approved by the U.S. Food and Drug Administration (FDA) for HIV PrEP. Due to the long dosing interval (8 weeks), long-acting cabotegravir has low compliance requirements for people at high risk of HIV infection. We aimed to discuss the feasibility of long-acting cabotegravir to replace TDF-FTC as HIV PrEP based on efficacy and safety analyses. Randomized controlled trials were retrieved, and R software was used for meta-analysis after data extraction. and discussion: Results of the meta-analysis showed that compared with TDF-FTC, long-acting cabotegravir was associated with a lower risk of HIV infection (HR = 0.22, 95% CI: 0.08-0.59, p < 0.01), less decreased creatinine clearance (RR = 0.96, 95% CI: 0.93-0.99, p < 0.01), but more tolerated injection sites adverse events (p < 0.01). No statistically significant differences were found between long-acting cabotegravir and oral placebo in non-injection-related adverse events (creatine phosphokinase, headache, nasopharyngitis, upper respiratory tract infection and gastroenteritis) (p > 0.05). Long-acting cabotegravir has a manageable safety profile and is more effective than TDF-FTC in preventing HIV infection. Interestingly, decreased creatinine clearance occurred less frequently with long-acting cabotegravir than with TDF-FTC. Long-acting cabotegravir is very promising to replace TDF-TFC in the future, which requires more large-sample, high-quality RCTs to verify.

Effects of Shenkang Decoction on Creatinine and Blood Urea Nitrogen in Chronic Renal Failure Hemodialysis Patients: A Randomized Controlled Trial.

Objective: To explore the clinical effect of Shenkang Decoction in chronic renal failure (CRF) patients with hemodialysis (HD). Methods: From November 2020 to December 2021, a total of 160 patients with CRF, who received HD, were included as the research objects, and they were divided into a reference group and a treatment group by random number table method (80 cases in each group). The former group was given basic drug treatment, and the latter group was given Shenkang decoction treatment at the same time as basic drug treatment. The renal function indexes, Traditional Chinese Medicine (TCM) syndrome scores, nutritional status, dialysis adequacy, treatment efficiency, and adverse reactions, were compared between the two groups. Results: After treatment, the patients in the treatment group had lower levels of creatinine and blood urea nitrogen, lower TCM syndrome scores, and higher levels of various nutritional status indicators than the reference group (p < 0.05). After treatment, the effective rate of the treatment group was higher compared with the reference group (p < 0.05). There was no significant difference between the two groups of dialysis adequacy index (p > 0.05). No adverse reaction was found in the two groups of patients in routine urine, blood, stool, liver, and kidney function tests, and electrocardiogram monitoring. Conclusions: Shenkang decoction applied to CRF and HD patients can significantly improve clinical symptoms and renal function, maintain a good nutritional status and little impact on dialysis adequacy, and improve life quality with significant curative effect, high safety, and little adverse reactions.

Impact of periodontal treatment on inflammatory oxidative stress in chronic kidney disease subjects: An interventional clinical trial.

PURPOSE: To evaluate the role of improvement in inflammatory oxidative stress by periodontal therapy (NSPT) in chronic kidney disease (CKD) subjects. METHODS: 50 stable subjects of CKD (stage III-IV) and having chronic periodontitis were enrolled for the present study. Group A (control group) subjects who did not receive NSPT and Group B (test group) subjects who received NSPT. Oral hygiene instructions were given to both groups, malondialdehyde (MDA) in gingival crevicular fluid (GCF) and serum, albumin creatinine ratio (ACR), urine protein creatinine ratio (UPCR), pocket depth (PD), clinical attachment loss (CAL), plaque index (PI), gingival index (GI), Interleukin 1-beta (IL-1ß), high sensitivity C-reactive protein (hs-CRP) in serum were assessed at baseline and 6 months. RESULTS: There was a significant difference observed in PD, CAL, PI, GI and MDA-GCF, hs-CRP, IL-1ß in serum following NSPT in the test group compared to the control group at 6 months follow up. Within the limitations of the study, the results revealed that NSPT can be used as an effective method to reduce inflammatory oxidative stress in CKD subjects and improve renal health. Further well-designed longitudinal trials with larger sample size and longer follow ups are needed. CLINICAL SIGNIFICANCE: The non-surgical periodontal intervention showed statistically significant improvement on oxidative and inflammatory stress markers in gingival crevicular fluid and serum in subjects suffering from chronic kidney disease which suggests that periodontal treatment may be beneficial for these subjects.

Impact of magnesium sulfate therapy in improvement of renal functions in high fat diet-induced diabetic rats and their offspring.

The role of magnesium sulfate (MgSO4) administration to prevent diabetic nephropathy (DN) by reducing insulin resistance (IR) and the relationship of this action with gender and the expression of NOX4 and ICAM1 genes in the parents and their offspring were studied. Males and females rat, and their pups were used. Type 2 diabetes induced by high-fat diet (HFD) administration and a low dose of streptozotocin. Animals were divided into the: non-treated diabetic (DC), the diabetic group received insulin (Ins), and the diabetic group received MgSO4. Two groups of parents received just a normal diet (NDC). Following each set of parents for 16 weeks and their pups for 4 months, while eating normally. We assessed the amount of water consumed, urine volume, and blood glucose level. The levels of glucose, albumin, and creatinine in the urine were also measured, as well as the amounts of sodium, albumin, and creatinine in the serum. Calculations were made for glomerular filtration rate (GFR) and the excretion rates of Na and glucose fractions (FE Na and FE G, respectively). The hyperinsulinemic-euglycemic clamp was done. NOX4 and ICAM1 gene expressions in the kidney were also measured. MgSO4 or insulin therapy decreased blood glucose, IR, and improved GFR, FE Na, and FE G in both parents and their offspring compared to D group. MgSO4 improved NOX4 and ICAM1 gene expressions in the parents and their offspring compared to D group. Our results indicated that MgSO4 could reduce blood glucose levels and insulin resistance, and it could improve kidney function.

A 600 mg of fixed-dose linezolid in renally impaired patients versus 15 mg/kg intermittent dose-optimized vancomycin in renally non-impaired patients: A single centre retrospective analysis for adult patients with hospital-acquired pneumonia due to methicillin-resistant Staphylococcus aureus.

OBJECTIVES: Both linezolid and vancomycin are approved by USFDA and IDSA guidelines for the management of nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA) in clinical practice. Baseline creatinine clearance is the criterion for prescribing vancomycin or linezolid for hospital-acquired pneumonia in our institution. However, patients with renal function impairment are far more difficult to manage in intensive care. Thus, the objectives of the study were to compare the clinical efficacy and safety of 600 mg of fixed-dose linezolid with intermittent dose-optimised vancomycin in hospital-acquired pneumonia due to MRSA and to evaluate parameters of clinical cure. METHODS: Analysis of a review of patients' charts. Patients with creatinine clearance <80 ml/min received 600 mg linezolid/12 h (n = 139, LN cohort), and patients with creatinine clearance ≥80 ml/min received intravenous 15 mg/kg vancomycin/12 h for 1-2 weeks consecutively or 3 weeks in case of bacteremia (n = 152, VC cohort) for management of hospital-acquired pneumonia due to MRSA. RESULTS: A 59% of patients from the LN cohort and 47% of patients from the VC cohort were clinically cured. Administration of systemic steroids (p = 0.0412) and ≥ 80 ml/min creatinine clearance (p = 0.0498) were the independent parameters for the clinical cure of patients. Nephrotoxicity was higher among patients of the VC cohort than the LN cohort (p = 0.0464). Treatment failed in 41% of patients from the LN cohort and in 53% of patients from the VC cohort (p = 0.0200). CONCLUSIONS: A 600 mg of fixed-dose linezolid is an ideal alternative to intermittent dose-optimised vancomycin for better clinical outcomes for patients with hospital-acquired pneumonia due to MRSA, especially for patients with renal impairment.

Efficacy and safety of tacrolimus versus mycophenolate mofetil as induction treatment and low-dose tacrolimus as treatment for lupus nephritis: a meta-analysis.

OBJECTIVE: The purpose of this study was to compare the efficacy and safety of tacrolimus and mycophenolate mofetil (MMF) as induction therapy and low-dose tacrolimus as treatment for lupus nephritis (LN). METHODS: Meta-analysis of randomized controlled trials (RCTs) was conducted to compare the efficacy and safety of tacrolimus and MMF as induction therapy for LN. We systematically reviewed RCTs and prospective cohort studies with a tacrolimus dose of 3 mg daily and performed a meta-analysis of the efficacy and safety of tacrolimus as an induction treatment for LN in comparison to MMF. RESULTS: The inclusion criteria were satisfied by eight studies (five RCTs and three prospective cohort studies) with a total of 408 individuals (289 for tacrolimus vs. MMF and 119 for low-dose tacrolimus). Tacrolimus and MMF had similar complete remission rates (odds ratio [OR] 1.028; 95% confidence interval [CI] 0.589-1.796; p = 0.922). The partial remission rate did not differ between the tacrolimus and MMF groups (OR 1.400; 95% CI 0.741-2.646; p = 0.300). Tacrolimus and MMF showed no differences in proteinuria, serum albumin, serum creatinine, creatinine clearance, renal Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), or extra-renal SLEDAI. The incidence of infection, severe infection, leukopenia, and hyperglycemia did not differ between the tacrolimus and MMF groups. However, herpes zoster infection was significantly less common in the tacrolimus group (OR 0.137; 95% CI 0.034-0.546; p = 0.005), whereas serum creatinine elevation was significantly higher in the tacrolimus group than in the MMF group (OR 8.148; 95% CI 1.369-48.50; p = 0.021). At 3 mg/d, tacrolimus was shown to be safe, well tolerated, and offered therapeutic benefits in all investigations. CONCLUSION: Tacrolimus was comparable to MMF in terms of effectiveness and safety as an induction therapy for LN, with the exception of a reduced risk of herpes zoster infection and a rise in serum creatinine. In individuals with LN, 3 mg/d tacrolimus was proven to be efficacious and safe.