Changes In Renal Function Research Articles

Peptide Receptor Radionuclide Therapy and clinical associations with renal and hematological toxicities and survival in patients with neuroendocrine tumors: an analysis from two U.S. medical centers

PurposeRenal and hematological toxicity are side effects and dose-limiting factors of Peptide Receptor Radionuclide Therapy (PRRT). We aimed to assess the changes in renal and hematological function and associations with survival in neuroendocrine tumor (NET) patients treated with PRRT.MethodsA retrospective cohort of 448 NET patients treated with either 177Lu-DOTATATE or 90Y-DOTATOC were followed for changes of renal and hematological function. Renal function was assessed by monitoring changes in serum creatinine, blood urea nitrogen and estimated glomerular filtration rate. Hematological function was determined by examining changes in white blood cell counts (WBC), platelet counts, and hemoglobin levels over time. Piecewise linear mixed effect models were applied to model the longitudinal repeated measurements of renal and hematological function. Overall survival (OS) and progression-free survival (PFS) were modelled using Cox proportional hazard regressions.ResultsOf the 448 PRRT treated patients, 335 received 177Lu-DOTATATE (74.78%) and 113 were treated with 90Y-DOTATOC (25.22%). Comparing patients treated with 177Lu-DOTATATE to those treated with 90Y-DOTATOC, renal function did not differ significantly prior to, during or after PRRT. Compared with patients treated with 90Y-DOTATOC, significantly decreased indicators of hematological function were observed in those treated with 177Lu-DOTATATE prior to and during PRRT treatment (WBC: estimate, -0.10, 95% CI, -0.15 to -0.05; P < 0.001; platelet count: estimate, -2.53, 95% CI, -3.83 to -1.24; P < 0.001), and no significant recovery was observed in hematological function post PRRT. Individuals who received 177Lu-DOTATATE tended to have a longer PFS (hazard ratio, 0.47, 95%CI: 0.28–0.79, P = 0.004) compared with 90Y-DOTATOC, but there was no difference in OS.ConclusionThere was no significant renal, but minor hematological toxicity, in patients treated with 177Lu-DOTATATE compared with 90Y-DOTATOC. Compared to 90Y-DOTATOC, 177Lu-DOTATATE appears to enhance PFS, but not OS. Treatment with 177Lu-DOTATATE may necessitate follow-up for hematological toxicity irrespective of other therapies prior to PRRT.

Glucagon receptor activation contributes to the development of kidney injury.

The underlying causes of diabetic kidney disease are still largely unknown. New insights into the contributing causes of diabetic nephropathy are important to prevent this complication. Hyperglycemia and hypertension are some of the risk factors for diabetic nephropathy. However, the incidence of diabetic nephropathy is increasing despite efforts to normalize blood glucose levels and blood pressure. Therefore, other factors should be investigated as causes of diabetic nephropathy. We investigated whether long-term increased plasma levels of glucagon contribute to the development of pathophysiological changes in kidney function as seen in patients with diabetic nephropathy. Using mouse models of chronic activation and inactivation of glucagon receptor signaling, we investigated whether glucagon is involved in changes in renal function, renal structure, and transcriptional changes. We found several histopathological changes in the kidney, such as thickening of the parietal layer of Bowman's capsule, glomerular mesangial cell expansion, and significant albuminuria in the mice with activated glucagon receptor signaling. Opposite effects on mesangial area expansion and the development of albuminuria were demonstrated in mice with glucagon receptor inactivation. RNA sequencing data revealed that transcription of genes related to fatty acid metabolism, podocytes, Na+-K+-ATPase, and sodium/glucose transport was significantly changed in mice with activated glucagon receptor signaling. These data implicate that glucagon receptor signaling is involved in the development of kidney injury, as seen in type 2 diabetes, and that glucagon receptor is a potential therapeutic target in the treatment of diabetes. NEW & NOTEWORTHY This study suggests that the glucagon receptor is a potential therapeutic target in the treatment of diabetic kidney disease. We show, in mice, that long-term treatment with a glucagon analog showed not only pathophysiological changes and changes in renal function but also transcriptional changes in the kidneys, whereas opposite effects were demonstrated in mice with glucagon receptor inactivation. Therefore, the use of glucagon in a treatment regimen requires investigation of possible metabolic and renal abnormalities.

Impact of smoking cessation on metabolic parameters and renal function in patients with and without diabetes mellitus

Backgroud and objectivesAs patients with diabetes are at a significantly higher risk of cardiovascular diseases than those without diabetes, it is important to gain a clinical understanding of the differential effects of smoking cessation on several risk factors between patients with and without diabetes. Materials and methodsPatients who participated in a smoking cessation program received an assessment of the outcomes of interest. The outcomes were changes in metabolic parameters and renal function from baseline to 6-month follow-up after the smoking cessation program. ResultA total of 1,954 patients joined the smoking cessation program, and 1,381 patients were in the smoking cessation failure (SCF) group and 573 were in the smoking cessation success (SCS) group. The decrease in HbA1c after smoking cessation was only observed in patients with diabetes. Smoking cessation was also associated with a significant decrease in LDL cholesterol in patients with diabetes. In terms of renal function, smoking cessation was associated with an improvement in eGFR, and the trend was similar in patients with and without diabetes. ConclusionSuccessful smoking cessation was associated with improvement in renal function. Moreover, it was associated with improvements in HbA1c and LDL cholesterol in patients with diabetes, despite significant weight gain.

Relationship between changes in renal function after acute phase of tafamidis administration and left ventricular diastolic function at mid-term follow-up in transthyretin cardiac amyloidosis

Abstract Background A large number of heart failure (HF) patients present with various degrees of renal dysfunction, known as cardio-renal syndrome. Renal impairment in HF patients is also associated with an independent risk factor for morbidity and mortality. Transthyretin (TTR) amyloidosis (ATTR) is characterized by disintegrated liver-derived TTR that accumulates as amyloid fibrils in the myocardium, leading to initially presenting as left ventricular (LV) hypertrophy and LV diastolic dysfunction. Although there is no proven therapy for patients with ATTR cardiomyopathy (ATTR-CM), tafamidis meglumine, a TTR stabilizer, has been associated with favorable outcomes. Although the kidneys are also an important organ where amyloid deposition occurs, the effect of tafamidis on renal function and its relationship to LV diastolic function is unclear. Purpose The purpose of this study was to investigate the relationship between changes in renal function after the acute phase of tafamidis administration and LV diastolic function at mid-term follow-up in patients with ATTR-CM. Methods We studied 56 patients with biopsy-proven ATTR-CM who were treated with tafamidis. All patients underwent blood examinations before and 45.6 ± 23.0 days after the acute phase of tafamidis administration. Echocardiography was performed before and 15.6 ± 9.8 months after the mid-term of tafamidis administration. The primary endpoint was defined as a composite of cardiovascular death or HF hospitalization for 5.0 years. Results Twelve patients had improved renal function as assessed by estimated glomerular filtration rate in the acute phase after tafamidis administration, while 44 patients deteriorated. In the group with improved renal function in the acute phase after tafamidis administration, pulsed-wave Doppler-derived early diastolic velocity from the septal mitral annulus (E’) and left atrial volume index (LAVI) tended to improve at mid-term follow-up compared to the non-improved group. (E’: 0.8 ± 1.7 cm/s vs. 0.2 ± 1.1 cm/s, p=0.127, LAVI: -8.7 ± 12.0 mL/m2 vs. 0.2 ± 16.8 mL/m2, p=0.093). Furthermore, Kaplan-Meier curve indicated that the occurrence of cardiovascular events for patients with improved renal function in the acute phase after tafamidis administration tended to be lower than those without (log-rank P=0.137). Conclusions The improvement of renal function in the acute phase after tafamidis administration was associated with the improvement of LV diastolic function at mid-term follow-up, leading to favorable outcome. Our findings may provide new insights for the management of patients with ATTR-CM.

Blood pressure and renal function changes in patients with severe chronic kidney disease undergoing radiofrequency renal denervation: 12 months outcomes from the Global SYMPLICITY Registry DEFINE

Abstract Background Radiofrequency renal denervation (RF RDN) lowers blood pressure (BP) in patients with uncontrolled hypertension (HTN). The impact of renal function on safety and efficacy of RDN is unknown. Purpose To assess BP and renal function in patients with HTN following RDN. Methods All patients treated with RF RDN (n=3332) from the observational Global SYMPLICITY Registry Denervation Findings in Real World (GSR DEFINE) were included. Patients were categorized into CKD stages by the corresponding estimated glomerular filtration rate (eGFR; mL/min/1.73m2): &amp;lt;45 (CKD stage 3b and higher; n=339), 45-59 (CKD stage 3a; n=467), ≥60 (CKD stage 2 and lower; n=2334). BP (office, 24h ambulatory BP), eGFR changes from baseline through 12 months were compared between groups. Comparisons between groups were made after adjusting for baseline BP and change in number of antihypertensive drug classes from baseline. Results At baseline, office systolic SBP (OSBP) in eGFR groups &amp;lt;45, 45-59, and ≥60 ml/min/1.73 m2 was: 164±25, 163±26 and 165±25 mmHg, respectively (p=0.083). 24-h ambulatory systolic BP (ASBP) was: 156±19, 153±20 and 154±19 mmHg, respectively (p=0.082). Mean eGFR was: 32.5±11.2, 53.6±4.4, and 86.8±18.6 ml/min/1.73 m2, respectively. A total of 1.1% of patients were on dialysis. Patients in eGFR group &amp;lt;45 ml/min/1.73 m2 were significantly older, had higher rates of ischemic heart disease, heart failure, diabetes, on more antihypertensive drug classes compared to higher eGFR groups. Patients were on 5.0±1.3, 4.6±1.3, and 4.5±1.4 antihypertensive drugs in eGFR &amp;lt;45, 45-59 and ≥60 ml/min/1.73 m2 groups, respectively (p&amp;lt;0.001). At 12 months, all had significant OSBP drop from baseline within the different eGFR groups (p&amp;lt;0.001). OSBP changed by -10.8±27.8, -10.5±25.9 and -14.7±26.6 mmHg in eGFR &amp;lt;45, 45-59 and ≥60 ml/min/1.73 m2 groups, respectively (adjusted p=0.095; Figure 1A). Similarly at 12 months, all patients had significant ASBP reductions from baseline across the eGFR groups (p&amp;lt;0.01). ASBP changed by -5.2±18.0, -6.9±18.8, and -8.5±18.8 mmHg in eGFR &amp;lt;45, 45-59 and ≥60 ml/min/1.73 m2 subgroups, respectively (adjusted p=0.16). At 12 months, eGFR did not significantly change from baseline in eGFR &amp;lt;45 and 45-59 ml/min/1.73 m2 groups (Figure 1B): 0.1±14.6 (p=0.92) and -0.6±12.8 ml/min/1.73 m2 (p=0.45), respectively. Estimated GFR changed from baseline by -5.6±15.5 ml/min/1.73 m2 in eGFR ≥60 ml/min/1.73 m2 group (p&amp;lt;0.001). Between group differences in eGFR changes were statistically significant (adjusted p&amp;lt;0.001), but by a numerically small difference. The no. of antihypertensive drug classes changed by -0.2±1.3, -0.1±1.0 and -0.1±1.0 in eGFR &amp;lt;45 and 45-59 ml/min/1.73 m2 groups, respectively. Conclusion Patients with uncontrolled HTN with different CKD severity including those with eGFR &amp;lt;45 ml/min/1.73 m2 had significant SBP reductions from baseline through 12 months, whilst renal function was preserved.Figure 1

Hemodynamic effects of intra-aortic balloon pump in patients with advanced heart failure and cardiogenic shock waiting heart transplant

Abstract Background The use of intra-aortic ballon pump (IABP) as a bridge therapy in patients with advanced heart failure (HF) and cardiogenic shock (CS) waiting heart transplant (HTx) remains under debate. IABP can be an available device to improve hemodynamic conditions of these patients until HTx. Purpose Evaluate the hemodynamic effects of IABP and its efficacy in patients with advanced HF and CS waiting HTx. Methods We retrospectively analyzed from a single center intensive care unit, between 2009 and 2020, patients with advanced HF with optimized intravenous drugs that required IABP placement before HTx. Changes in oxygen central venous saturation (ScvO2), arterial lactate, renal function, and use of vasoactive drugs before and 96 hours after IABP insertion were evaluated. Patients with acute myocardial infarction and implant of ventricular assist device before HTx were excluded. Results A total of 199 patients (mean age 46,5 ± 12 years) were included. Median time of IABP onset to HTx was 20 days. Mean left ventricle ejection fraction was 23,5 ± 5,9%, 53,7% of patients had moderate to severe right ventricular dysfunction and the most frequent etiology was Chagas disease (47,2%, n=94). Before the IABP placement, 97,47% of patients were using dobutamine, 19,29% milrinone, 58,08% nitroprusside and 17,7% norepinephrine. Clinical and laboratory data were compared before and 96 hours after IABP therapy. ScvO2 increased from 49,9% to 66,85% (p&amp;lt;0,001), lactate decreased from 21,91 mg/dl to 12,6 mg/dl (p&amp;lt;0,001), creatinine decreased from 2,04 mg/dL to 1,72 mg/dL (p=0,301) and urine output increased from 1690,12 mL/24h to 2193,12 mL/24h (p&amp;lt;0,001). These differences were maintained until the day before HTx. Use of nitroprusside increased from 58,08 to 63,59% (p=0,154), and the use of norepinephrine decreased from 17,7% to 6,63% (p&amp;lt;0,001). Conclusion IABP improves tissue perfusion, renal function, and hemodynamic status in patients with advanced HF and CS and can be an effective method of circulatory support as a bridge therapy to HTx.Laboratory data pre and post-IABPVasoactive Drugs pre and post-IABP

Effects of sodium-glucose cotransporter 2 inhibitors on pulmonary hemodynamics in chronic heart failure patients with a pulmonary artery pressure sensor

Abstract Background Approximately 50% of patients with chronic heart failure (HF), either with preserved or reduced left ventricular ejection fraction (LVEF), have secondary pulmonary hypertension, which results in poorer prognosis. In previous studies, sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown a reduction in cardiovascular death, HF hospitalization and pulmonary artery pressure (PAP) in patients with HF, regardless of LVEF, but exact mechanisms remain unclear. Purpose The main objective of this study is to analyse effects of SGLT2i on PAP in patients with chronic HF followed by a PAP sensor (CardioMEMS HF system). The secondary objective is to analyse effects in subgroups of LVEF. Methods We included chronic HF patients (regardless of LVEF) with previously implanted a PAP sensor, from July 2019 to February 2023. SGLT2i had been added in fourth position in patients with reduced LVEF, since they were previously on optimal HF treatment as chronic patients. Changes in PAP, renal function and N-terminal pro B-type natriuretic peptide (NTproBNP) were compared between two periods of time: "30 days before" and "30 days after" SGLT2i initiation. Patients were then classified in two groups: group 1 (LVEF ≤40%) and group 2 (LVEF &amp;gt;40%) and repeated same analyses. Results Overall, 61 patients were screened, and 17 finally were included, mean age 71.7 ± 9.6 years, 64.7% were men, mean LVEF was 49.4 ± 17.5%, 23.5% had ischaemic aetiology and 64.7% were in NYHA class III (Table 1). There were more men in group 1 than in group 2 (p=0.043), without other differences in basal characteristics between groups (Table 1). Dapagliflozin (10mg daily) was initiated in 14 patients (82.4%), 5 from group 1 and 9 from group 2 (p=1.000), and empagliflozin (10mg daily) in 3 patients (17.6%), 1 from group 1 and 2 from group 2 (p=1.000). Before SGLT2i, mean diastolic PAP (dPAP) was 17.3 ± 5.6 mmHg and median NTproBNP was 2841.5 (289-10515) pg/mL. SGLT2i significantly reduced dPAP; average dPAP ("30 days after" period) was 1.5 mmHg lower (95% CI, 0.26-2.74; p=0.021) compared to "30 days before" period (Figure 1). SGLT2i also reduced systolic PAP (-2.2 mmHg), mean PAP (-1.7 mmHg), NTproBNP (-183 pg/mL) and creatinine (-0.2 mg/dL), but not statistically significant. SGLT2i reduced PAP, NTproBNP and creatinine too in group 1 (6 patients), but did not achieve statistical significance. Reductions were as well observed in group 2 (11 patients), and SGLT2i significantly reduced dPAP (-2.04 mmHg) (95% CI, 0.31-3.77; p=0.025). Conclusions In patients with chronic HF and a PAP sensor, SGLT2i, added to previous HF treatment, significantly reduced dPAP. PAP reductions were observed regardless LVEF, but results were more robust in patients with LVEF &amp;gt;40%.Figure 1

Ponatinib exacerbate renal injury in systemic lupus erythematosus mouse model through PDGFR-PI3K/AKT pathway

Lupus nephritis (LN) is a common clinical complication of systemic lupus erythematosus (SLE). Proliferative lupus nephritis represents the gravest form of LN, and since effective drugs for its treatment are still lacking, tyrosine kinase inhibitors (TKIs) find extensive clinical utility due to their notable impact on suppressing cell proliferation and may serve as potential drugs for LN treatment. However, previous studies on the effects of TKI on LN have been controversial. Ponatinib, a third-generation TKI, lacks studies on its role in LN. This study aimed to investigate the impact of the ponatinib on LN. MRL/lpr mice were evaluated for renal function, autoimmune markers and histopathological changes after oral administration of ponatinib. RNA-seq analysis was performed to explore the molecular pathways involved in ponatinib-induced kidney injury. Ponatinib uniquely exacerbated renal damage in MRL/lpr mice, evidenced by a decline in renal function and acute pathological changes, without affecting lupus-related autoimmune markers. Differential expressed genes analysis and functional enrichment implicate ponatinib-induced renal damage in MRL/lpr mice associated with adiponectin. Furthermore, we verified ponatinib signaling the PI3K/AKT pathway through PDGFRα, potentially influencing high molecular weight adiponectin (HMW ADIPOQ) expression and exacerbating renal damage. In conclusion, this study demonstrates that ponatinib can up-regulate HMW ADIPOQ expression via the PI3K/AKT pathway by inhibiting PDGFRα phosphorylation, highlighting the potential nephrotoxic effects of ponatinib in lupus-prone mice, and underscoring the importance of monitoring renal function in systemic autoimmune diseases patients receiving ponatinib.

Blood concentration monitoring and renal function changes during gentamicin administration for infective endocarditis: a retrospective observational study

BackgroundEstablished guidelines for monitoring gentamicin blood concentration are lacking; therefore, we focused on improving pharmacological interventions and ensuring their safety. We aimed to optimize gentamicin administration for infective endocarditis (IE) treatment.MethodsThe study involved adult patients diagnosed with IE and treated with gentamicin from January 2014 to December 2022. Clinical presentation and drug therapy regimen were comprehensively evaluated. We performed a retrospective chart review of the frequency of gentamicin dose adjustments and changes in renal function while on gentamicin. In addition, we attempted to extract risk factors for renal impairment using univariate analysis.ResultsOn average, a 7.1% decline [changed to − 6.7 ± 20.4 (standard deviation) mL/min/1.73 m2] in the estimated glomerular filtration rate was observed after gentamicin administration, but it was statistically insignificant. Notably, 58% of patients required dosage adjustments, with a subset requiring multiple adjustments. Among the cases in which dosage adjustments were made, 61% were within the first week of treatment. There were no patients with gentamicin levels below the target peak concentration. Furthermore, no independent risk factors were identified in patients requiring dose reduction.ConclusionsDose adjustment was necessary in many cases after treatment initiation. The time to dose adjustment varied widely. These findings highlight the importance of consistent blood concentration monitoring in patients of all demographics, at least weekly, and underscore that routine peak concentration assessments may not be essential when a 3 μg/mL target is maintained. This study provides information on monitoring gentamicin blood level, which can improve IE treatment safety.

Intermittent Fasting Ameliorates Age-Induced Morphological Changes in Aged Albino Rat Kidney via Autophagy Activation and Reduction of Apoptosis and Inflammation

Abstract Aging is a biological process with gradual decrease of cell function. Kidneys are one of the organs with higher susceptibility to the development of age-dependent tissue damage. Intermittent fasting has several beneficial effects on age-related degenerative changes. The aim of this study was to investigate the possible beneficial effect of intermittent fasting in delaying age-related renal changes and the possible mechanisms of this effect. Thirty male albino rats were classified into three groups: control, adult rats aged 3 months; aged group, 15-month-old rats and maintained until the age of 18 months; and intermittent fasting-aged groups, 15-month-old rats maintained on intermittent fasting for 3 months. Kidneys were processed for histological and immunohistochemical study. Aging resulted in a significant reduction in renal function and significant several degenerative changes in renal corpuscles and tubules which showed abnormal histological structure with increased collagen deposition. Aging caused significant reduction in the expression of autophagic marker light chain 3 with increased expression of active caspase-3 and inducible nitric oxide synthase. Intermittent fasting significantly improved these age-related renal changes. Intermittent fasting effectively prevents age-related renal changes through the reduction of age-related oxidative stress, inflammation, apoptosis, and activation of autophagy.

Subchronic Toxicity of Ethanol Extract of Mangosteen Rind (Garcinia Mangostana L.) on Kidney Function in Wistar Rats

Mangosteen (Garcinia mangostana L.) is a fruit that possesses antioxidant, antibacterial, antihistamine, anti-inflammatory, and antidiabetic properties. Before this, an acute toxicity test was conducted on the ethanol extract of mangosteen rind. However, further testing is required, specifically the subchronic toxicity test, to identify any hazardous effects that may not have been found in the previous study. The objective of this study is to evaluate the amount of toxicity based on the mortality rate, alterations in the relative weight of the kidneys, and changes in renal function as shown by levels of urea and creatinine. This study is an experimental investigation that employs the Post-test Only Control Group Design methodology, with a sample of 40 rats. The rats were categorized into two groups: the control group and the treatment group. The treatment group was divided into three subgroups, each receiving a dosage of 250 mg/kg body weight. The doses were 500 milligrams per kilogram and 1000 milligrams per kilogram of body weight, respectively. The control group received simply water and feed. The duration of the treatment was 28 days. Observations were conducted over 28 days, which involved monitoring animal mortality. On the 29th day, a surgical procedure was carried out to assess the comparative weight of the kidneys and collect blood samples for analyzing the levels of urea and creatinine. The findings demonstrated no mortality in the test subjects, although there was an elevation in the relative mass of the kidneys and an increase in urea concentrations. The increase in urea levels was observed in female rats using the Kruskal–Wallis test (P = 0.019). The study was further conducted using the post-hoc Mann–Whitney test. Control female rats exhibited notable disparities when administered dosages of 250 mg/kgBW and 500 mg/kgBW. The repeated administration of an ethanolic extract derived from the peel of the mangosteen fruit had a detrimental impact on the functioning of the kidneys, as evidenced by a rise in urea concentrations. Keywords: mangosteen, toxicity test, subchronic, kidney

Use of Branched EVAR in Treatment of Juxtarenal Aortic Aneurysm and Essential Accessory Renal Artery: Another Tool on the Shelf? A Case Report.

We present the case of a 58-year-old male patient referred to our department from a smaller facility for further evaluation and treatment strategy regarding the choice between open or endovascular surgery. The patient was diagnosed with a 6cm asymptomatic juxtarenal aortic aneurysm and a 5mm diameter accessory renal artery (ARA) supplying the lower half of left kidney. Further diagnostic assessments indicated that the left ARA was perfusing over 40% of the left kidney. Given the patient's significant pre-existing medical conditions and elevated perioperative risk, the decision was made to proceed with minimally invasive endovascular surgery using a custom-made 5-branches stent graft (BEVAR). In the early postoperative period, the patient reported left flank pain. A subsequent CT scan identified a partial infarction in the left kidney due to the occlusion of an early small branch from the upper left renal artery. However, laboratory results showed no significant change in renal function compared to preoperative values. The patient was discharged 6 days post-surgery, with no additional complications observed during the early postoperative period. This case report demonstrates that BEVAR is acceptable technique with satisfactory early postoperative outcomes for treating juxtarenal aortic aneurysms with an accessory renal artery in patients who are high-risk candidates for open repair and anatomically unsuitable for FEVAR or Ch-EVAR procedures.

Effects of Catheter-Based Renal Denervation in Hypertension: A Systematic Review and Meta-Analysis.

Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes. We aimed to perform a comprehensive meta-analysis of all randomized, sham-controlled trials investigating RDN with first- and second-generation devices in hypertension. We searched MEDLINE and the Cochrane Library for eligible trials. Outcomes included both efficacy (24-hour and office systolic [SBP] and diastolic blood pressure [DBP]) and safety (all-cause death, vascular complication, renal artery stenosis >70%, hypertensive crisis) of RDN. We performed a study-level, pairwise, random-effects meta-analysis of the summary data. Ten trials comprising 2478 patients with hypertension while being either off or on treatment were included. Compared with sham, RDN reduced 24-hour and office systolic blood pressure by 4.4 mm Hg (95% CI, 2.7 to 6.1; P<0.00001) and 6.6 mm Hg (95% CI, 3.6 to 9.7; P<0.0001), respectively. The 24-hour and office diastolic blood pressure paralleled these findings (-2.6 mm Hg [95% CI, -3.6 to -1.5]; P<0.00001; -3.5 mm Hg [95% CI, -5.4 to -1.6]; P=0.0003). There was no difference in 24-hour and office systolic blood pressure reduction between trials with and without concomitant antihypertensive medication (P for interaction, 0.62 and 0.73, respectively). There was no relevant difference in vascular complications (odds ratio, 1.69 [95% CI, 0.57 to 5.0]; P=0.34), renal artery stenosis (odds ratio, 1.50 [95% CI, 0.06 to 36.97]; P=0.80), hypertensive crisis (odds ratio, 0.65 [95% CI, 0.30 to 1.38]; P=0.26), and all-cause death (odds ratio, 1.76 [95% CI, 0.34 to 9.20]; P=0.50) between RDN and sham groups. Change of renal function based on estimated glomerular filtration rate was comparable between groups (P for interaction, 0.84). There was significant heterogeneity between trials. RDN safely reduces ambulatory and office systolic blood pressure/diastolic blood pressure versus a sham procedure in the presence and absence of antihypertensive medication.

Quantifying preserved renal volume and function in patients undergoing standard partial nephrectomy vs. tumor enucleation for localized renal tumors

IntroductionRenal parenchymal volume loss from standard partial nephrectomy (SPN) is a significant prognosticator for postoperative renal function. Tumor enucleation (TE) minimizes parenchymal loss compared to SPN. Little is known regarding discrete changes in renal function associated with volume loss. We sought to quantify the differences between SPN and TE in preserving parenchymal volume and estimated glomerular filtration rate (eGFR). MethodsWe identified 420 patients who underwent robotic partial nephrectomy (SPN or TE) at our tertiary care center from 2009 to 2022. Parenchymal volumes were calculated using TeraRecon 3D reconstruction software from axial imaging performed preoperatively and within 6 months postoperatively. Renal volume preserved and renal function were evaluated with multivariable linear and logistic regression models. ResultsAt 1 year, eGFR was 7% lower in patients undergoing SPN compared to TE (P < 0.01). Across both SPN and TE, only volume of preserved parenchyma was predictive of eGFR and chronic kidney disease (CKD) progression (both P < 0.01). TE preserved more healthy parenchymal volume compared to SPN (median percentage 97.6% vs 89.2%; P < 0.001). Each 1% of volumetric loss corresponded to a 0.35% decrease in eGFR at 1 year postoperatively (P < 0.01). ConclusionsVolume of preserved renal parenchyma was the strongest factor associated with preserved eGFR and reduced odds of CKD progression. TE preserved more parenchyma than SPN, which translated to higher eGFR preservation at 1 year postoperatively.

Efficacy and Safety of Adding Empagliflozin to Liraglutide on Renal Function in Patients with Advanced-Stage Type 2 Diabetic Kidney Disease: A Randomized Controlled Trial.

The aim of this study was to investigate the additional effects of empagliflozin on liraglutide in patients with advanced-stage type 2 diabetic kidney disease. Forty-one patients were randomly assigned (1:1) to treatment with liraglutide alone during the first 6 months and subsequent treatment with liraglutide plus empagliflozin during the next 6 months (liraglutide plus empagliflozin group) (n = 20) or treatment with liraglutide alone for 12 months (liraglutide group) (n = 21). Liraglutide was administered subcutaneously once daily at a starting dose of 0.3 mg/day and up-titrated weekly by 0.3 mg to a maximum dose of 0.9 mg/day. Empagliflozin was administered orally at a dose of 10 mg once daily. The primary outcome was the change in renal function (estimated glomerular filtration rate) during the latter 6 months. Secondary outcomes were changes in body weight, systolic blood pressure, hemoglobin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, uric acid, blood glucose, hemoglobin A1c, and urine protein creatinine ratio during the latter 6 months. Empagliflozin significantly increased the hemoglobin concentration (from 12.9 ± 1.9 to 13.7 ± 1.9 g/dL; p<0.05) and decreased body weight (from 66.1 ± 12.9 to 64.5 ± 12.6 kg; p<0.05). No significant differences were observed between the groups for estimated glomerular filtration rate, systolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, uric acid, blood glucose, hemoglobin A1c, and urine protein creatinine ratio. Empagliflozin increased hemoglobin concentration and decreased body weight in patients with advanced-stage type 2 diabetic kidney disease who received liraglutide. However, empagliflozin did not provide short-term benefits with regard to renal function decline, urinary protein excretion, or glycemic control in these patients.

Porphyromonas gingivalis Induces Chronic Kidney Disease through Crosstalk between the NF-κB/NLRP3 Pathway and Ferroptosis in GMCs.

Porphyromonas gingivalis (P.gingivalis) is a gram-negative bacterium found in the human oral cavity and is a recognized pathogenic bacterium associated with chronic periodontitis and systemic diseases, including chronic kidney disease (CKD), but the roles and molecular mechanism of P.gingivalis in CKD pathogenesis are unclear. In this study, an animal model of oral P.gingivalis administration and glomerular mesangial cells (GMCs) cocultured with M1-polarized macrophages and P.gingivalis supernatant were constructed. After seven weeks of P.gingivalis gavaged, peripheral blood was collected to detect the changes in renal function. By collecting the teeth and kidneys of mice, H&E staining and IHC were used to analyze the expression of periodontal inflammatory factors in mice, PAS staining was used to analyze glomerular lesions. The supernatant of macrophages was treated with 5% P.gingivalis supernatant. H&E staining, IHC, Western blot and RT-PCR were applied to analyze renal inflammatory factors, macrophage M1 polarization, NF-κB, NLRP3 and ferroptosis changes in vitro. We found that oral P.gingivalis administration induced CKD in mice. P.gingivalis supernatant induced macrophage polarization and inflammatory factor upregulation, which triggered the activation of the NF-κB/NLRP3 pathway and ferroptosis in GMCs. By inhibiting the NF-κB/NLRP3 pathway and ferroptosis in GMCs, cell viability and the inflammatory response were partially alleviated in vitro. We demonstrated that P.gingivalis induced CKD in mice by triggering crosstalk between the NF κB/NLRP3 pathway and ferroptosis in GMCs. Overall, our study suggested that periodontitis can promote the pathogenesis of CKD in mice, which provides evidence of the importance of periodontitis therapy in the prevention and treatment of CKD. P.gingivalis promotes ferroptosis in kidneys and accelerates the progression of CKD through NF-κB/NLRP3 signaling pathway.

Metolazone Versus Chlorothiazide in Acute Heart Failure Patients With Diuretic Resistance and Renal Dysfunction: A Retrospective Cohort Study.

Guidelines recommend intravenous loop diuretics as first-line therapy for patients hospitalized with acute heart failure (AHF) and volume overload. Additional agents can be used for augmentation, but there is limited guidance on agent selection. The study objective was to determine if chlorothiazide or metolazone is associated with differences in diuretic efficacy or safety in loop diuretic-resistant patients with AHF and renal dysfunction (eGFR <45 mL/min/1.73 m²). We conducted a multicenter, retrospective cohort study of patients hospitalized with AHF and renal dysfunction who received metolazone or chlorothiazide in addition to intravenous loop diuretics. The primary end point was a comparison of 24-hour urine output (UOP) between the 24 hours before and after thiazide administration. Secondary and safety end points included weight change, requirement for vasopressors or inotropes, electrolyte abnormalities, and changes in renal function. A total of 221 patients were included. The mean daily diuretic doses were chlorothiazide 632 mg and metolazone 7 mg. The mean 24-hour UOP increased more among chlorothiazide-treated (from 1668 mL to 3826 mL) versus metolazone-treated patients (from 1672 mL to 2834 mL) ( P < 0.001) after the addition of the second diuretic. Statistically significant reductions in serum creatinine were observed in the chlorothiazide group following 72 hours of treatment ( P = 0.016). More hypomagnesemia was observed in the chlorothiazide group; no differences in other electrolytes or changes in weight were observed. Overall, chlorothiazide was associated with a greater increase in 24-hour UOP than metolazone without an excess of potassium or serum creatinine derangements. However, weight changes did not differ significantly between groups. Future prospective studies are needed to confirm potential differences in diuretic response and safety.

Reduced Rate of Anemia after Transcatheter Aortic Valve Replacement.

Background/Objectives: We sought to evaluate changes in hemoglobin level and renal function in patients 5-12 months after transcatheter aortic valve replacement (TAVR), and to examine possible relationships between these changes. Anemia is common in older people with severe aortic stenosis (AS). The two most common etiologies for anemia in this population are iron deficiency due to gastrointestinal blood loss and renal failure. Angiodysplasia in the gastrointestinal system is a feature of AS syndrome. Methods: We collected clinical data, including hemoglobin level and renal function before and 5-12 months after TAVR in 315 consecutive patients. To examine whether calculated clinical predictors such as EuroScore 2 are associated with the persistence of anemia after TAVR, we performed multivariable correlation analysis with post-TAVR anemia as the dependent variable. Results: The mean hemoglobin level increased significantly (from 11.76 to 12.16 g/dL, p < 0.0001) 5-12 months after TAVR, and the number of patients with anemia decreased significantly (from 67.5% to 53.9%, p < 0.0001). At 5-12 months following TAVR, a small reduction in estimated glomerular filtration rate was observed (from 60.05 ± 24.1 to 58.30 ± 24.50 mL/min, p = 0.024). The multivariable correlation analysis did not identify clinical predictors of persistent anemia. Conclusions: A significant increase in hemoglobin was observed 5-12 months after TAVR, despite a reduction in renal function. Our findings imply that gastrointestinal blood loss, which occurs in patients with severe AS, is significantly reduced following TAVR.

4-Octyl itaconate attenuates renal tubular injury in db/db mice by activating Nrf2 and promoting PGC-1α-mediated mitochondrial biogenesis

Objectives: The aim of this study was to investigate the mechanism of itaconate’s potential effect in diabetic kidney disease. Methods: Renal immune responsive gene 1 (IRG1) levels were measured in db/db mice and streptozotocin (STZ) + high-fat diet (HFD)-induced diabetic mice. Irg1 knockout mice were generated. db/db mice were treated with 4-octyl itaconate (4-OI, 50 mg/kg), a derivative of itaconate, for 4 weeks. Renal function and morphological changes were investigated. Ultrastructural alterations were determined by transmission electron microscopy. Results: Renal IRG1 levels were reduced in two diabetic models. STZ+HFD-treated Irg1 knockout mice exhibited aggravated renal tubular injury and worsened renal function. Treatment with 4-OI lowered urinary albumin-to-creatinine ratio and blood urea nitrogen levels, and restored renal histological changes in db/db mice. It improved mitochondrial damage, increased expressions of peroxisome-proliferator-activated receptor γ coactivator-1α (PGC-1α) and mitochondrial transcription factor A (TFAM) in the renal cortex of db/db mice. These were confirmed in vitro; 4-OI improved high glucose-induced abnormal mitochondrial morphology and TFAM expression in HK-2 cells, effects that were inhibited by PGC-1α silencing. Moreover, 4-OI reduced the number of apoptotic cells in the renal cortex of db/db mice. Further study showed that 4-OI increased renal Nrf2 expression and decreased oxidative stress levels in db/db mice. In HK-2 cells, 4-OI decreased high glucose-induced mitochondrial ROS production, which was reversed by Nrf2 silencing. Nrf2 depletion also inhibited 4-OI-mediated regulation of PGC-1α, TFAM, and mitochondrial apoptotic protein expressions. Conclusions: 4-OI attenuates renal tubular injury in db/db mice by activating Nrf2 and promoting PGC-1α-mediated mitochondrial biogenesis.

Association of Therapeutic Monitoring of Tacrolimus with Laboratory Markers of Kidney Function in Receptors of Kidney Allograft

Introduction: Kidney transplantation is the most commonly performed type of transplant in Brazil. Tacrolimus is one of the primary drugs used in post-transplant immunosuppressive therapy, and one of its main adverse effects is nephrotoxicity. Laboratory tests to assess renal function are of great importance in monitoring post-kidney transplant patients, helping to diagnose events indicative of graft dysfunction. Objective: !e present study aimed to evaluate the association between laboratory changes in renal function and blood levels of tacrolimus in post-kidney transplant patients. Methods: Observational, analytical and cross-sectional study. !e results of blood levels of tacrolimus and measurements of urea, creatinine and estimated Glomerular Filtration Rate (eGFR) were analyzed, as well as the sociodemographic data of kidney transplant recipients followed at a university hospital who underwent laboratory tests between months from January 2021 to July 2022 in a period close to 1 year after the transplant. !e variables analyzed in the research were collected from the patient's medical records and subsequently analyzed; the statistical analyses considered p &lt; 0.05. !e project was approved by the Ethics Committee of the Walter Cantídio University Hospital under opinion number 5,436,434 and CAAE number 57396622.1.0000.5045. Results: !e sample was mainly composed of males, mixed race, with an average age of 51.5 years (SD ± 12.5) and from cities in the interior of Ceará. Regarding the percentage of patients with laboratory changes, 50.62% (n = 45) showed changes in tacrolimus blood levels. 56.79% (n = 46) had changes in serum creatinine levels, 49.38% (n = 40) had changes in serum urea levels, and 59.26% (n = 48) had altered eGFR. !e correlation analyses suggested a low signi#cance between variations of the variables studied. Conclusion: !e results indicate no relationship between variations in tacrolimus blood concentrations and the appearance of changes in the results of classic renal biomarkers at the end of the #rst year post-transplant. However, it is necessary to carry out new studies to understand better the impact of changes in blood levels of tacrolimus on the renal function of renal allograft recipients.