Changes In Renal Function Research Articles

Changes in renal function in patients with hypertension and chronic obstructive pulmonary disease according to retrospective analysis of medical records

Background. Hypertension determines both the social and economic component of the impact on the health of the population with a tendency to a significant increase in this pathology rate. Another common disease that can be prevented and treated is a chronic obstructive pulmonary disease (COPD). The concept of comorbidity implies the formation of relationships and interactions due to the common pathogenetic mechanisms, namely chronic inflammation, oxidative stress, and endothelial dysfunction. Hypertension is both a cause and a consequence of chronic kidney disease (CKD) and contributes to its progression. Patients with COPD have a higher risk of comorbidities. Aim. To study the dynamics of renal function and frequency of CKD development in patients with hypertension and COPD based on the retrospective analysis of case reports and outpatient medical records. Materials and methods. According to the criteria of inclusion and exclusion from the study, 188 patients were selected, which were divided into three groups by the clinical diagnosis: group 1 consisted of 64 patients with hypertension, group 2 — 58 patients with hypertension and chronic obstructive pulmonary disease, and group 3 — 66 patients with chronic obstructive pulmonary disease. The average age of patients with hypertension was 61.0 (57.0; 72.0) years, patients with hypertension and COPD — 62.3 (11.5), the average age of patients with COPD — 58.5 (55.0; 62.00). The physical examination, the laboratory tests of blood and urine were analyzed in all patients by studying the case reports and outpatient medical records. The obtained results were processed using biostatistical methods (Statistica v.6.1). Results. Important significance between the frequency of anemia in patients was not found, but there was a tendency to increase in anemia frequency in hypertensive patients — 14.1 % and in the comorbidity of hypertension and COPD — 8.6 %. The lowest incidence of anemia was recorded in patients with COPD and was 7.6 %. The level of total cholesterol in the respective groups did not differ statistically and was equal to 4.8 (4.2; 5.3), 4.7 (4.0; 5.4), and 5.3 (4.5; 5.9) mmol/l. The highest values ​​of total blood cholesterol were determined in patients with hypertension and chronic obstructive pulmonary disease. The highest level of blood creatinine was determined in patients with hypertension and COPD, and the lowest — in patients with COPD. Thus, the patients with hypertension had the lowest GFR and the patients with COPD had the highest one. Conclusions. COPD has a tightening effect on the renal function of patients with hypertension and leads to an increase in blood creatinine levels with statistical significance. Also, in the group of patients with hypertension and comorbid pathology, a higher incidence of anemia was registered than in the group of patients with COPD. But, in turn, the filtration function of the kidneys, which was determined by GFR, was the lowest in hypertension.

Mechanical support for the failing single ventricle after Fontan

Mechanical support for the failing single ventricle after Fontan

Long-term follow-up of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab: post-marketing surveillance in Japan.

All Japanese patients with paroxysmal nocturnal hemoglobinuria (PNH) treated with eculizumab were enrolled in post-marketing surveillance (PMS) between June 2010 and August 2019 to assess the long-term effectiveness and safety of eculizumab. The reduction in intravascular hemolysis, the change in hemoglobin (Hb) level, and the change in renal function were assessed to determine the effectiveness of eculizumab. The types and frequencies of adverse events (AEs) were assessed to determine its safety. A total of 632 patients were enrolled and the median treatment duration was 3.6years. Treatment with eculizumab significantly reduced lactate dehydrogenase (LDH) levels and significantly increased Hb levels. These changes were maintained for up to 5years of treatment. An estimated glomerular filtration rate ≥ 60ml/min/1.73m2 and higher LDH level at baseline were associated with increases in Hb levels during eculizumab treatment. The overall incidence of any AE was 69.92/100 patient-years. Hemolysis was the most common AE (6.43/100 patient-years). The incidence of infection-related AEs was 20.57/100 patient-years, and included meningococcal infection in three patients (0.12/100 patient-years). This long-term follow-up of patients with PNH demonstrated the sustained effectiveness of eculizumab and supports its well-established safety profile.

Irreversible electroporation in renal tumours: A systematic review of safety and early oncological outcomes.

We review the safety and early oncological outcomes of irreversible electroporation (IRE), a novel non-thermal ablation technique, in small renal masses (SRMs). Following PROSPERO registration (CRD42020197943), a systematic search of MEDLINE, EMBASE and SCOPUS databases according to PRISMA guidelines was performed. Critical appraisal of the included studies was performed using the Newcastle-Ottawa Scale. Of 224 articles screened, 10 met the inclusion criteria. In total, 83 patients were identified. Except for one cohort study (n = 41), the remaining studies were case series of n < 10. Follow up was <12 months in 7/10 articles (range 3–34 months). About 10/10 articles reported safety outcomes. There were no 30-day mortalities. The most frequently reported adverse events were transient haematuria (11/83) and asymptomatic perirenal haematomas (7/83). About 62/63 patients with reported length of stay were discharged within 24 h. No significant long-term changes in renal function were reported. About 7/10 articles reported oncological outcomes. Only one article assessed histopathological outcomes, whilst the remaining studies used cross-sectional imaging modalities to assess efficacy, recurrence or disease progression. About 4/7 patients with histopathology outcomes, showed complete response (CR). About 43/55 patients with radiological outcomes showed CR. No mortalities were reported due to SRMs. These initial findings support IRE as safe and feasible in managing SRMs. However, results from larger studies with longer follow-up are needed to evaluate oncological outcomes and compare these with other ablation methods.

Association between protein intake and changes in renal function among Japanese community-dwelling older people: The SONIC study.

AimThe aim of this study was to clarify the association between dietary protein intake and decline in the estimated glomerular filtration rate (eGFR) among Japanese older adults.MethodsWe used the data of the Septuagenarians, Octogenarians and Nonagenarians Investigation with Centenarians (SONIC) study, an ongoing narrow‐age range cohort study: 69–71 years, 79–81 years and 89–91 years. The outcome variable, change in eGFR, was estimated from serum creatinine measured at the baseline and 3‐year follow up, and the exposure variable, protein intake, was calculated using the brief‐type self‐administered diet history questionnaire at the baseline. Associations between eGFR change and protein intake were determined by multiple linear regression analysis.ResultsThe mean eGFR change per year was −1.89 mL/min/1.73 m2. The mean protein intake was 1.50 g/kg/day. The results of this study showed that there was no significant association between protein or animal protein intake and change in eGFR per year in the entire population of participants, including the very elderly, but there was a significant positive association in those whose renal function fell into chronic kidney disease stage G3 or G4.ConclusionsProtein intake among community‐dwelling older adults was not associated with lower eGFR, and for older chronic kidney disease patients, protein and animal protein intakes were more beneficial in maintaining eGFR. The results provide evidence that protein intake should not be restricted for older patients with chronic kidney disease, including the very elderly. Geriatr Gerontol Int 2022; 22: 286–291.

Renal Denervation Prevents Atrial Arrhythmogenic Substrate Development in CKD.

In patients with chronic kidney disease (CKD), atrial fibrillation (AF) is highly prevalent and represents a major risk factor for stroke and death. CKD is associated with atrial proarrhythmic remodeling and activation of the sympathetic nervous system. Whether reduction of the sympathetic nerve activity by renal denervation (RDN) inhibits AF vulnerability in CKD is unknown. Left atrial (LA) fibrosis was analyzed in samples from patients with AF and concomitant CKD (estimated glomerular filtration rate [eGFR], <60 mL/min per 1.73 m2) using picrosirius red and compared with AF patients without CKD and patients with sinus rhythm with and without CKD. In a translational approach, male Sprague Dawley rats were fed with 0.25% adenine (AD)-containing chow for 16 weeks to induce CKD. At week 5, AD-fed rats underwent RDN or sham operation (AD). Rats on normal chow served as control. After 16 weeks, cardiac function and AF susceptibility were assessed by echocardiography, radiotelemetry, electrophysiological mapping, and burst stimulation, respectively. LA tissue was histologically analyzed for sympathetic innervation using tyrosine hydroxylase staining, and LA fibrosis was determined using picrosirius red. Sirius red staining demonstrated significantly increased LA fibrosis in patients with AF+CKD compared with AF without CKD or sinus rhythm. In rats, AD demonstrated LA structural changes with enhanced sympathetic innervation compared with control. In AD, LA enlargement was associated with prolonged duration of induced AF episodes, impaired LA conduction latency, and increased absolute conduction inhomogeneity. RDN treatment improved LA remodeling and reduced LA diameter compared with sham-operated AD. Furthermore, RDN decreased AF susceptibility and ameliorated LA conduction latency and absolute conduction inhomogeneity, independent of blood pressure reduction and renal function. In an experimental rat model of CKD, RDN inhibited progression of atrial structural and electrophysiological remodeling. Therefore, RDN represents a potential therapeutic tool to reduce the risk of AF in CKD, independent of changes in renal function and blood pressure.

Evaluation of the effect of simultaneous hybrid coronary revascularization on postoperative bleeding and renal function: A comparison study with minimally invasive direct off-pump coronary artery bypass grafting in patients with multivessel coronary artery disease

ObjectivesThe present study sought to compare postoperative bleeding and renal function in patients with multivessel coronary artery disease undergoing simultaneous hybrid coronary revascularization (HCR) and minimally invasive direct off-pump coronary artery bypass grafting (MIDCABG). MethodsThe study retrospectively collected the data of 594 consecutive patients who underwent simultaneous HCR and 351 patients who underwent MIDCABG with planned staged HCR (MIDCABG first, then elective percutaneous coronary intervention) in Fuwai Hospital from June 2007 to December 2020. A total of 317 pairs of patients who were matched in a 1:1 ratio with propensity score matching were enrolled in this study. Bleeding and changes in renal function were compared between the 2 groups. ResultsCompared with patients who underwent MIDCABG, patients who underwent simultaneous HCR had significantly greater chest tube drainage on the day of the operation (492.7 ± 282.4 mL vs 441.0 ± 261.9 mL; P = .023), but no significant difference was detected in the total amount during the postoperative period (788.8 ± 458.9 mL vs 753.3 ± 409.8 mL; P = .74). The differences in re-exploration for bleeding (0.3% vs 1.6%; P = .13), blood transfusion (18.9% vs 16.4%; P = .13), acute kidney injury (23.3% vs 18.6%; P = .53), and in-hospital major adverse cardiovascular and cerebrovascular events (including all-cause death, myocardial infarction, stroke, and repeated revascularization) (2.5% vs 1.9%; P = .67) between the 2 groups did not reach statistical significance. ConclusionsCompared with MIDCABG, simultaneous HCR (MIDCABG first, instant percutaneous coronary intervention) did not increase postoperative bleeding or the incidence of acute kidney injury.

Estimated glomerular filtration rate in Korean patients exposed to long-term lithium maintenance therapy

BackgroundLithium-induced nephrotoxicity has long been debated. However, it has been rarely explored in Asian populations. The aim of the present study was to assess the effect of lithium maintenance therapy on estimated glomerular filtration rate (eGFR) in Korean patients diagnosed with a psychiatric illness.MethodsThis was a single-centered, retrospective study that included patients treated with lithium or comparator drug (valproate) in Samsung Seoul Medical Center between November 1994 and July 2020. Patients diagnosed with ICD codes F20-33 who had ≥ 6 months of exposure to lithium or valproate were included. Patients had to have ≥ 1 baseline and ≥ 2 post-baseline eGFR data with post-baseline data having an interval of at least 30 days. Chronic kidney disease (CKD) was defined as CKD stage 3 (eGFR < 60 mL/min/1.732). To be considered as CKD, the threshold had to be met at two consecutive post-baseline measurements. Those treated with both lithium and valproate, diagnosed with CKD stages 3–5, diagnosed with a renal disease, or received kidney transplantation were excluded.ResultsA total of 766 patients were included (242 treated with lithium and 524 with valproate). Two (0.8%) in the lithium group and 8 (1.5%) in the valproate group developed CKD stage 3. None developed CKD stages 4–5. Median yearly eGFR change was − 1.3 mL/min/1.732 (IQR: − 6.8, 1.7) for the lithium group and − 1.1 mL/min/1.732 (IQR: − 4.5, 1.5) for the valproate group, showing no significant difference between the two groups (p = 0.389). The rate of decline was more rapid for those with CKD in both groups. eGFR values of lithium and valproate groups did not show significant differences during a follow-up duration of 15 years or more. A significant negative correlation between baseline eGFR and yearly eGFR change was identified in a linear regression analysis.ConclusionsIn Korean patients, treatment with lithium did not increase the risk of developing CKD compared to treatment with valproate. Prevalence of CKD was lower than those previously reported in western populations. Low baseline eGFR showed significant correlation with changes in renal function.

POS-444 EFFECT OF AVACOPAN, A SELECTIVE C5A RECEPTOR INHIBITOR, ON KIDNEY FUNCTION IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS

Patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis and renal disease have a poor prognosis. The effect of avacopan, an oral C5a receptor inhibitor, on renal function is described. The ADVOCATE Phase 3 trial randomized patients to receive avacopan or prednisone taper on a background of either cyclophosphamide (followed by azathioprine) or rituximab. Primary endpoints were remission at Week 26 and sustained remission at Week 52. Secondary objectives included evaluation of kidney function. At Week 52, the difference in eGFR recovery in patients with eGFR <60 mL/min/1.73 m2and/or urinary abnormalities at baseline between avacopan and prednisone treatment groups was 5.5 mL/min/1.73 m2(95% CI [1.4, 9.6], p<0.01) (Figure 1A ). Improvement in eGFR with avacopan was most prominent in patients with eGFR <30 mL/min/1.73 m2at baseline, when by week 52, the least squares mean (LSM) increase in eGFR was 13.7 (avacopan group) vs. 8.2 mL/min/1.73 m2(prednisone group) (p<0.01) (Figure 1B) . Among patients with CKD Stage 4 at baseline: in the avacopan group (n=52), 26 (50%) improved 1 stage and 3 (5.8%) improved 2 stages; in the prednisone group (n=48), 21 (44%) improved 1 stage and 1 (2.1%) improved 2 stages (p=0.32). Avacopan was also associated with more rapid reduction in proteinuria and hematuria. Urinary albumin:creatinine ratio improved 40% within the first 4 weeks of treatment with avacopan vs. no change in the prednisone group (difference -40, 95% CI [-53, -22]). Figure 1. Change in Renal Function Through Week 52 In ADVOCATE, patients with ANCA-associated vasculitis in the avacopan group had greater recovery of kidney function compared to patients in the prednisone group, especially among patients with CKD Stage 4 and those with eGFR <60 mL/min/1.73 m2and/or urinary abnormalities at baseline.

Predictive factors for renal function deterioration during palliative first-line chemotherapy for metastatic colorectal cancer.

85 Background: Effective first-line therapy is a key determinant of treatment outcomes and should be selected after considering both clinical factors and biological markers in metastatic colorectal cancer (mCRC). Considering the increased number of cancer patients with old age and their chronic diseases, it is essential to select a therapeutic agent by evaluating the toxicity that may occur due to long-term chemotherapy. This study assessed changes in renal function for 1 year in patients diagnosed with mCRC during chemotherapy and analyzed the factors and effect of each chemotherapy regimen on renal function. Methods: We retrospectively investigated patients with mCRC treated with palliative 1st line chemotherapy at our institution from 2015 to 2020. According to the common 1st line treatment regimen, we divided into 4 groups; FOLFOX/FOLFIRI with bevacizumab/cetuximab. We checked the baseline renal function and 3, 6, 9 and 12 months after the start of chemotherapy. The change in estimated glomerular filtration rate (△eGFR) was calculated as [(eGFR at each time point) - (eGFR at baseline)/(eGFR at baseline) X 100]. The clinical factors such as age, gender, chronic disease, BMI (body mass index), disease status, baseline proteinuria, and 1st line chemotherapy regimen were evaluated. Proteinuria was detected on urine dipstick protein ≥ 1+. Additionally, predictors for ΔeGFR ≤ −30% at each time points after therapy initiation were evaluated using multivariate logistic regression analysis. Results: Among 466 mCRC patients, the median eGFR values at baseline was 95.4 ml/min/1.73m2. The median eGFR at 6 months after chemotherapy initiation were significantly lower than baseline (88.3 ml/min/1.73m2, p &lt; 0.001). As 1 year, patients with more than 30% worsening of renal function was observed in 27.6 % in FOLFIRI + bevacizumab, 26.3 % in FOLFOX + bevacizumab, 6.6 % in FOLFIRI + cetuximab, and 4.7 % in FOLFOX + cetuximab group. The FOLFIRI + bevacizumab was an independent predictor for ΔeGFR ≤ −30% at 6 months (odds ratio (OR) 1.94, 95% confidence interval (CI) 1.05-3.47, p = 0.034) along with old age (≥ 65 years, OR 2.18, 95% CI 1.29-3.68, p = 0.004) and BMI (p = 0.012). Additionally, FOLFIRI + bevacizumab regimen causes more proteinuria (46.4%) than other chemotherapy regimens. Conclusions: Deterioration of renal function was more common with FOLFIRI + bevacizumab than other combination regimen. Old age, BMI were also associated decreasing eGFR. These results will be helpful to be suggested as important consideration when selecting the 1st line chemotherapy regimen for mCRC.

The efficacy and safety of canagliflozin in the treatment of patients with early diabetic nephropathy.

This study aimed to observe the efficacy and safety of canagliflozin in the treatment of patients with early diabetic nephropathy (DN) and investigate its effect in reducing urinary protein levels. A total of 132 patients with DN and normal renal function (estimated glomerular filtration rate >60 ml/min/1.73 m2) combined with urine albumin/creatinine ratio (UACR) no less than 30 mg/g were selected and randomly divided into a control group and an observation group, with 66 cases in each group. Irbesartan treatment was administered to the control group based on conventional treatment, while a combination of canagliflozin and irbesartan was given to the observation group based on conventional treatment. The changes in blood glucose, blood pressure, body weight, renal function, and urinary protein were observed in both groups. Compared with the control group, patients in the observation group showed a significant decrease in blood glucose, blood pressure, body weight, and urinary protein starting at week 4 of treatment and continuing until the end of the experiment at week 24 (all P<0.05). Within the observation group, blood glucose, blood pressure, body weight, and urinary protein decreased significantly with 24 weeks of treatment compared with those before the experiment (P<0.01). Patients in the observation group experienced a mild decrease in renal function at week 4, but the function began to gradually recover by week 8 and had returned to the baseline by the end of the study (P<0.05). In conclusion: canagliflozin has good efficacy and safety in the treatment of early DN. It also lowers urinary protein levels and blood glucose.

Changes in Renal Function in Patients with Recurrence of Atrial Arrhythmia after an Initial Catheter Ablation.

Background Impaired renal function and atrial fibrillation (AF) can form a vicious cycle. Although there have been reports on improved renal function in patients who undergo successful AF ablation, renal function in patients with recurrence of AF has not been studied separately. We explored the changes in renal function in recurrent AF patients after catheter ablation with mild renal dysfunction and the influencing factors. Methods We retrospectively recruited nonvalvular AF (NVAF) patients with mildly impaired renal function admitted for catheter ablation and readmitted due to recurrence of AF. The estimated glomerular filtration rate (eGFR) was calculated before the index procedure and during readmission. △eGFR was defined as the difference between eGFR readmission and eGFR baseline. The same calculation applied for △CHA2DS2-VASc score. The primary endpoint was improved renal function (△eGFR >0) after AF catheter ablation in patients with atrial arrhythmia recurrence. Results A total of 132 NVAF patients were included in this study. The mean eGFR at readmission was significantly increased compared with the eGFR at baseline before the index ablation procedure (81.5 ± 1.1 vs. 78.0 ± 0.7 ml/min/1.73 m2, P < 0.001). The multivariable Cox regression analysis showed that a lower △CHA2DS2-VASc score (HR: 0.42, P=0.003) and paroxysmal recurrent atrial arrhythmia (HR: 2.97, P=0.001) were associated with better renal function. Conclusion In NVAF patients with mildly impaired renal function, even those with recurrence after the initial catheter ablation, we observed improvements in renal function, which was associated with a lower △CHA2DS2-VASc score and paroxysmal recurrent arrhythmia.

Changes in renal function increase the need for advanced ventilatory support and increase the risk of mortality in critically ill patients with COVID-19.

In addition to respiratory failure, another important outcome presented by patients hospitalized with coronavirus disease 2019 (COVID-19) is renal failure, which is related to increased severity of infection and a greater risk of mortality. Severity is often represented by the need for respiratory and/or life support, which can range from oxygen therapy to invasive mechanical ventilation. This study aimed to determine the association between the degree of renal and inflammatory impairment in patients with the need for advanced respiratory support and mortality. Included in the present study were 79 critically ill patients with COVID-19 on different days, who required a nasal cannula and/or orotracheal intubation. Data from laboratory tests, arterial blood gases and information on their clinical evolution were collected. The results obtained showed that the biochemical markers of renal function, as well as the inflammatory markers and the partial pressure of carbon dioxide, were significantly increased in patients who succumbed to the infection. Similarly, these markers were higher amongst patients who required increased respiratory assistance.

Renal Function after Nephrectomy: To Examine any Differences Between Kidney Cancer and Kidney Donation

Objective: To evaluate renal function after radical nephrectomy (RN) and donor nephrectomy (DN), and the differences in changes and identify factors that lead to chronic renal failure. Material and Methods: A retrospective review of patients diagnosed with renal cell carcinoma, who received RN and donors of living kidney transplantation. Kidney function in both groups was measured before and after surgery. We assessed the donors’ kidney functions using an estimated Glomerular filtration rate (eGFR), through a Modification of Diet in Renal Disease (MDRD) formula [GFR = 186 x serum creatine-1.154 age-0.203 x 0.742 (if the patient was female). Kidney function after surgery was evaluated at 1, 3, 6 and 12 months. Rates of renal function decline were analyzed compared with baseline.Results: A total of 249 patients were included in the study, 50 in the DN group and 199 in the RN group. The mean eGFRs before surgery were 68.6 ml/min/1.73m2 and 88.8 ml/min/1.73m2 in the RN and DN groups, respectively. During the first year postoperatively, renal function in the RN and DN groups decreased by approximately 25.6% and 27.2% from baseline, respectively.Conclusion: Renal function after surgery declined after both RN and DN, but the pattern of changes in renal function was different between the groups, possibly due to the patients in the DN group being younger and healthier. There were no differences in percentage of change in eGFR between the groups at the 1 year follow up.

Haematological, renal, and hepatic function changes among Rayong oil spill clean-up workers: a longitudinal study.

The Rayong oil spill incident of 2013 leaked over 50,000 barrels of crude oil into the Gulf of Thailand. This study assessed trends and changes in the haematological, renal, and hepatic indices among the Rayong oil spill clean-up workers 5years after the spill. Haematological, renal, and hepatic indices measured for 570 oil spill clean-up workers at baseline and annually during 5-year follow-ups were analysed. Haemoglobin (Hb), haematocrit (Hct), white blood cell (WBC) count, red blood cell (RBC) count, and platelet count for haematological function, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) for hepatic function, and creatinine (Cr) and blood urea nitrogen (BUN) for renal function were assessed. The longitudinal measures of haematological, renal and hepatic indices were analysed using analysis of variance for repeated measures. The generalised estimating equations (GEE) were used to assess trends of these indices and associated factors, including exposure level. Increasing trends were observed per year for WBC (0.52 ± 0.03 × 103 cells/μL), Cr (0.01 ± 0.00mg/dL), platelet (0.31 × 103 μL per year), and BUN (0.24 ± 0.03mg/dL). Decreasing trends of aspartate aminotransferase (AST) were observed (1.54 ± 0.21IU/L per year). Clean-up workers with high exposure to the oil spill had a significantly higher average of WBC and lower average of BUN than low-exposure and unknown-exposure workers. Gender and age were significantly associated with creatinine changes. Results of this study show the differences between baseline and follow-up haematological, renal, and hepatic indices and trends of these indices. The long-term changes in the indices in this study show worsening renal functions after oil spill and possibility of cardiovascular effects. These findings contribute to expanding knowledge on the long-term health effects of oil spills.

Efficacy and Safety of Switching to Dolutegravir/Lamivudine Versus Continuing a Tenofovir Alafenamide-Based 3- or 4-Drug Regimen for Maintenance of Virologic Suppression in Adults Living With Human Immunodeficiency Virus Type 1: Results Through Week 144 From the Phase 3, Noninferiority TANGO Randomized Trial.

Switching to dolutegravir/lamivudine (DTG/3TC) was noninferior to continuing tenofovir alafenamide (TAF)-based regimens for maintaining virologic suppression at week 48 of the TANGO study. Here we present week 144 outcomes (efficacy, safety, weight, and biomarkers). TANGO is a randomized (1:1, stratified by baseline third agent class), open-label, noninferiority phase 3 study. Virologically suppressed (>6 months) adults with human immunodeficiency virus type 1 (HIV-1) switched to once-daily DTG/3TC or continued TAF-based regimens. A total of 741 participants received study treatment (DTG/3TC, n = 369; TAF-based regimen, n = 372). At week 144, the proportion of participants with an HIV-1 RNA level ≥50 copies/mL (primary end point, Snapshot; intention-to-treat-exposed population) after switching to DTG/3TC was 0.3% (1 of 369) versus 1.3% (5 of 372) for those continuing TAF-based regimens, demonstrating noninferiority (adjusted treatment difference, -1.1 [95% confidence interval, -2.4 to .2), with DTG/3TC favored in the per-protocol analysis (adjusted treatment difference, -1.1 [-2.3 to -.0]; P = .04). Few participants met confirmed virologic withdrawal criteria (none in the DTG/3TC and 3 in the TAF-based regimen group), with no resistance observed. Drug-related adverse events were more frequent with DTG/3TC (15%; leading to discontinuation in 4%) than TAF-based regimens (5%; leading to discontinuation in 1%) through week 144, but rates were comparable after week 48 (4%; leading to discontinuation in 1% in both groups). Changes from baseline in lipid values generally favored DTG/3TC; no clinical impact on renal function and comparable changes in inflammatory and bone biomarkers across groups were observed. Switching to DTG/3TC demonstrated noninferior and durable efficacy compared with continuing TAF-based regimens in treatment-experienced adults with HIV-1, with good safety and tolerability, and no resistance through 144 weeks.

Podocyte protection by Angptl3 knockout via inhibiting ROS/GRP78 pathway in LPS-induced acute kidney injury

Acute kidney injury (AKI) caused by sepsis has a high incidence and poor prognosis. Thus, novel strategies that minimize AKI are urgently needed. In our previous research, we found that angiopoietin-like protein 3 (Angptl3) knockout exerts protective effects on kidney injury in adriamycin nephropathy. However, the role of Angptl3 in the pathogenesis of AKI is largely unclear. This study aimed to explore the renal protective effects and molecular mechanisms of Angptl3 knockout in lipopolysaccharide (LPS)-induced AKI in mice. B6;129S5 mice were injected intraperitoneally with 10 mg/kg of LPS to induce AKI. Then, the changes in renal function, podocyte apoptosis, inflammatory factors (tumor necrosis factor-α, TNF-α; interleukin-6, IL-6; and interleukin-1β, IL-1β), reactive oxygen species (ROS), and endoplasmic reticulum (ER) stress were measured. The mechanism of Angptl3 in the apoptosis of podocytes was also investigated. Results showed that Angptl3 knockout significantly alleviated the renal dysfunction and apoptosis of podocytes induced by LPS. Angptl3 knockout was associated with the (1) downregulation of Bax and upregulation of Bcl-2; (2) amelioration of the abnormal expression of nephrin, podocin, and CD2AP; (3) reduced ER stress; (4) reduced secretions of TNF-α, IL-6, and IL-1β; and (5) regulation of Bax expression via the ROS-related ER stress pathway. Our findings revealed that Angptl3 knockout alleviated the apoptosis of podocytes by regulating the ROS/GRP78 signaling pathway.

Evaluation of Changes in Renal Function of Pregnant Women with Preeclampsia in Al-Jabal Al-Akhdar

Evaluation of Changes in Renal Function of Pregnant Women with Preeclampsia in Al-Jabal Al-Akhdar

Gastrodin Pretreatment Alleviates Renal Ischemia-Reperfusion Injury

Introduction: This study aimed to investigate the possible effect of gastrodin in renal ischemia-reperfusion injury (IRI) and the mechanisms. Methods: Forty-eight male Sprague Dawley rats were randomly divided into 3 groups: sham-operated group, saline-treated IRI group, and gastrodin-treated IRI group. Gastrodin or 0.9% saline (300 mg/kg/day) was intragastrically administrated for 8 days before operation. We analyzed renal function and histological change. The malondialdehyde level, antioxidant enzymes’ activities, and markers of inflammation and apoptosis were measured. Statistical analysis was performed using 1-way analysis of variance (ANOVA) or Kruskal-Wallis ANOVA on ranks. Results: Gastrodin pretreatment improved IRI-induced renal dysfunction and histologic injury. Mechanistically, gastrodin reversed the elevation of malondialdehyde level and the reduction of antioxidant enzymes’ activities. Gastrodin also reduced the elevated myeloperoxidase activity, TNF-α and IL-1β levels, and the activation of p38 MAPK. Moreover, gastrodin-treated rats exhibited a dramatic reduction in renal tubular apoptosis, along with a decrease in caspase-3 activation and an increase in the Bcl-2/Bax ratio. Conclusion: Gastrodin pretreatment may alleviate renal IRI via the amelioration of oxidative injury, inflammatory response, and renal tubular apoptosis.

Safety and long-term outcomes of early liver transplantation for pediatric methylmalonic acidemia patients.

LT is a treatment option for MMA patients, but renal function impairment is one of the long-term concerns. The aim of this study was to evaluate the outcomes of early LT in these patients. A total of 11MMA mut-type patients (including 10mut0 cases and 1mut-case) who received LT in our institute were reviewed. Their metabolic profiles were compared between the pre/post-transplant periods. Their immunosuppressant and renal function changes after transplantation were assessed. After a mean follow-up of 97.5±38.4months, there were two deaths, and the actual survival rate was 81.8%. Their metabolic profiles had improved (mean blood ammonia level 366.8±105.5 vs. 53.1±17.4μg/dl, p<.001; C3/C2 ratio 2.68±0.87 vs. 0.73±0.22, p=.003; mean urine MMA level 920.5±376.6 vs. 196.2±85.4, p=.067), and hospital stays were decreased (78.8±74.5 vs. 7.4±7.0days/year, p=.009) after transplantation. The mean age at transplant was 1.81±2.02years old, and nine of these patients received LT before the age of 1.5years old (early LT). Under prospective immunosuppressant dose reduction, three of these early LT patients discontinued the drug and were sustained for more than 5years. Most of the patients had a preserved renal function, and no patient is currently on dialysis. In addition to the improvement in the metabolic parameters, early LT in MMA patients may allow for a dose reduction of the immunosuppressant, and the patient's renal function could be preserved in the long term.