Long-term Renal Function Research Articles

Arteriolar hyalinization at 0-hour biopsy predicts long-term graft function in deceased kidney transplantation.

Regarding the relationship between donor kidney quality and renal graft function after deceased kidney transplantation (KTx) following donation after cardiac death (DCD), the evaluation timing varies depending on the study. Evaluation of histology and changes in long-term renal graft function is limited. A retrospective single-center study included 71 recipients who underwent 0-hour biopsy for KTx from DCD. The recipients were divided into two groups to evaluate factors related to renal graft function (study1). The two groups were categorized as stable graft function and poor graft function with the change of estimated glomerular filtration rate (eGFR) after KTx. The recipients were then divided into four groups to assess whether the factors identified in study1 were related to the change in long-term renal graft function (study2). They were categorized as follows: Improved, Stable, Deteriorated, and Primary non-function with the change of eGFR after KTx. In study1, donor age ≥ 50 years (29.5% vs. 65.2%; p = 0.09), banff arteriolar hyalinosis (ah) score (0.66 ± 0.78 vs. 1.2 ± 1.0; p = 0.018), and presence of glomerulosclerosis (43.2% vs. 76.2%; p = 0.017) were significant risk factors for poor long-term graft function. When the recipients were divided into four groups, the severity of ah correlated well with changes in long-term renal function. We can predict the shift in long-term renal graft function after KTx from DCD according to the severity of ah by 0-hour biopsy.

Real-world observational study on the long-term effect of L-glutamine treatment on renal parameters of adult and pediatric patients with sickle cell disease.

Sickle cell disease (SCD) is a rare genetic blood condition affecting millions worldwide. Oxidative stress is a key player in the pathogenesis of SCD and its comorbid consequences. Renal function impairment is a common complication of SCD in both pediatric and adult patients with serious consequences leading to increased risk of mortality. In this observational real-world study, we are reporting the long-term (120 weeks) renal function in 10 patients treated with L-glutamine. Ten patients (4 pediatric and 6 adults), with confirmed diagnoses of SCD (HbSS genotype), were enrolled, these included four patients from Qatar with Arab Indian haplotype and six patients from French Guiana with African haplotype. All patients were treated with L-glutamine oral powder (~0.3 g/kg body weight, Endari®) twice daily for 120 weeks. Clinical events and laboratory parameters (renal function, hemoglobin, reticulocytes, and lactate dehydrogenase [LDH]) were measured at baseline, 48, and 120 weeks. The study showed that with L-glutamine treatment there were improvements in renal and hematological parameters with no vaso-occlusive crisis at both 48-and 120-week follow-up time points in all 10 patients. Improvements were seen in the albumin creatinine ratio (ACR) from baseline to 48 weeks (mean [Standard deviation SD] ACR: -4.19 [9.81] mg/g) and 120 weeks (mean [SD] ACR: -12.31 [21.09] mg/g). Mean (SD) increase in hemoglobin concentrations from baseline to 48 weeks and 120 weeks was 0.72 (1) g/dL and 1.41 (0.79) g/dL, respectively. Mean (SD) reticulocyte counts and LDH levels decreased from baseline to 48 weeks (mean [SD] change from baseline to 48 weeks, reticulocyte counts: -40.30 [101.58] × 109 cells/L; LDH levels: -259 [154.93] U/L) and 120 weeks (mean [SD] change from baseline to 120 weeks, reticulocyte counts: -58.30 [128.38] × 109 cells/L; LDH levels: -344.80 [274.63] U/L). This is one of the first studies that assessed the long-term renal outcomes in SCD using L-glutamine. L-glutamine improved the renal function in patients with SCD along with improvements in clinical outcomes and hemolysis, from 48 weeks and sustained through 120 weeks of treatment.

Development and validation of a novel fetal vesico-amniotic shunt, the vortex shunt.

Fetal lower urinary tract obstruction (LUTO) is a severe malformation associated with an up to 80% mortality risk as well as significant renal and pulmonary morbidity in survivors. Fetal vesico-amniotic shunts (VAS) bypass the bladder obstruction, improve amniotic fluid volume and enhance in-utero pulmonary development. VAS has been shown to reduce respiratory morbidity and mortality in the neonatal period without proven benefit on long-term renal and bladder function. Clinically available shunts are associated with an up to 80% dislodgement rate, leading to repeat invasive procedures which increase fetal and maternal risks. We developed a novel "Vortex" shunt, which incorporates enhanced fixation to reduce dislodgement, a one-way valve to optimize in-utero bladder function, and enhanced sonographic echogenicity that optimizes the accurate deployment. Following the validation of these characteristics in initial benchtop experiments we have moved to feasibility studies in the fetal lamb model. We hope that the Vortex shunt may ultimately facilitate shunt deployment, reduce dislodgement risk, improve neonatal morbidity and mortality, and decrease the significant healthcare expenditures associated with long-term morbidity in LUTO survivors. In this manuscript, we review the natural history of LUTO, the risks and benefits of clinically available fetal shunts, and our development and early validation experiments.

Short and long-term renal function changes with direct oral anticoagulants in elderly patients with atrial fibrillation

Abstract Background Atrial Fibrillation (AF) and chronic kidney disease (CKD) frequently coexist in elderly patient. Previous evidence showed that vitamin K antagonists (VKAs) may be associated with an accelerated decrease of estimated glomerular filtration rate (eGFR) compared to direct oral anticoagulants (DOACs). However, there is little evidence on DOACs in the elderly population and in real life settings; the evidence available to us comes from randomized clinical trials with younger populations. Purpose The main objective of this study was to investigate the medium to long term renal function changes in older AF patients treated with DOACs and VKAs. Methods Enrolled patients underwent 3 eGFR measurements during follow-up, and the between arms difference in eGFR lost over time was investigated by 1) the Linear Mixed Models (LMM) and 2) group-based trajectory model (GBTM) analyses. Analysis was done according to short-term (3.2 years) and long-term follow-up (6.7 years). During the study period 420 enrolled AF patients (77.0±6.0 years, 136 on VKAs and 284 on DOACs) underwent 1260 eGFR assessments. Results After a median follow-up of 4.9 years, in the whole sample eGFR decreased from 67.4±18.2 ml/min/1.73 m2 to 47.1±14.3 ml/min/1.73 m2, p<0.001. Patients on DOACs experienced a significantly lower eGFR decrease that those treated with VKAs (-21.3% vs -45.1%, p<0.001). The benefit of DOACs compared with VKAs was evident both in the short term (eGFR decline -6.6 (95% CI: -9.1 to -4.0) ml/min/1.73 m2 vs -19.9 (95% CI: -23.6 to -16.2) ml/min/1.73 m2 respectively) and in the long-term, (eGFR -13.5 (95% CI: -16.1 to -11.0) ml/min/1.73 m2 in DOACs group vs -34.2 (95% CI: -37.9 to -30.5) ml/min/1.73 m2), respectively). After stratifying our study population into 5 groups according to trajectories of renal function decline, from the first (lowest decline in eGFR) to the fifth (greatest decline in eGFR), the first trajectory consisted of 80% patients on DOACs therapy. Logistic regression showed that the group on DOACs therapy was 3.03- to 4.24-fold more likely to belong to the trajectory with less eGFR decline than the VKAs group. Conclusions In conclusion, DOACs were associated with less long term decline in renal function in elderly patients with AF compared with VKAs.

Harmful effect of repetitive intravenous iodinated contrast media administration on the long-term renal function of patients with early gastric cancer

This retrospective study investigated whether repetitive exposure to intravenous iodinated contrast media (ICM) affects long-term renal function in patients who undergo curative surgery for early gastric cancer (EGC) collected from the Korean Health Insurance and Review Assessment (HIRA) database. Patients diagnosed with gastric cancer between January 2010 and December 2013 underwent regular computed tomography (CT) scans to monitor for extragastric recurrence. Patients who already had chronic kidney disease (CKD) before cancer diagnosis or had undergone chemotherapy or repeated surgery were excluded. A nested case–control study design was chosen to analyze the effect of repetitive ICM exposure to long-term renal function by comparing patients who developed CKD 2 years after cancer diagnosis and patients who did not. Among 59,971 patients collected according to inclusion and exclusion criteria, 1021 were diagnosed with CKD 2 years after cancer diagnosis. Using 1:5 matching after adjusting for age, sex and date of cancer diagnosis, 5097 control patients were matched to 1021 CKD patients. Conditional logistic regression showed that the number of CTs taken using ICM slightly increased the odds of CKD (odds ratio, 1.080; 95% confidence interval (CI): 1.059, 1.100; P < 0.0001). Thus, the administration of ICM might contribute to chronic renal function impairment.

Surgery in Bilateral Wilms Tumor-A Single-Center Experience.

The treatment of bilateral Wilms tumors (BWT) involves curing the cancer, preserving long-term renal function, and maintaining a good quality of life. Established methods for achieving these goals include preoperative chemotherapy and nephron-sparing surgery (NSS). This study aimed to evaluate the experience of a single institution in treating patients with BWT. We analyzed cases of BWT treated at the Pediatric Oncology Institute-GRAACC-Federal University of São Paulo over a period of 35 years. Bleeding control was performed with manual compression of the renal parenchyma. Thirty-three patients were included in the study. Thirty cases were synchronous tumors. The mean age at diagnosis was 30.4 months (±22 m) and 66.7% were girls. The median follow-up period was 83 months. Neoadjuvant chemotherapy was the primary approach in most patients (87.9%), with a simultaneous upfront surgical approach performed in 84.8%. Most patients underwent bilateral NSS (70.4%). There were no early complications in this series, but 39.4% had clinical complications. The five-year survival rate was 76%. Therefore, it is clear that the surgical approach to BWT plays a crucial role in achieving good outcomes. However, it is difficult to standardize surgical techniques and technology may have the potential to enhance safety.

Tacrolimus and Diabetes in Kidney Transplantation: The Impact of Cyp3a5 Gene Polymorphism

To explore the correlation between single nucleotide polymorphisms (SNPs) of CYP3A4 rs2740574 and CYP3A5 rs776746 and post-transplant diabetes mellitus (PTDM) in Chinese renal allograft recipients treated with tacrolimus. A total of 244 patients treated with tacrolimus were included in this study, wherein DNA sequencing was detected through fluorescence in situ hybridization, and SNP genotyping was performed. Among the 244 patients, 44 (18%) developed PTDM. The PTDM group exhibited higher preoperative body mass index and fasting plasma glucose levels, with higher creatinine values one year after surgery. The CYP3A4 rs2740574 genotype was found to be unique in its homozygous AA form. For CYP3A5 rs776746, the genotypes were distributed as follows: 28 (11.5%) cases with AA, 101 (41.4%) cases with AG, and 115 (47.1%) cases with GG, respectively (P=.042). The AA genotype showed a statistically significant difference from both AG and GG genotypes. Furthermore, the A allele of CYP3A5 rs776746 was found to be associated with an increased risk for PTDM development. The occurrence of tacrolimus-related PTDM is associated with body mass index, fasting plasma glucose levels, and CYP3A5 genotype before renal transplantation. Post-transplant diabetes mellitus is correlated with unfavorable long-term renal graft function, whereas the expression of the CYP3A5 rs776746 gene is linked to an elevated risk of PTDM.

Association between fibrosis-related gene polymorphism and long-term allograft outcome in renal transplant recipients

BackgroundRenal allograft fibrosis is one of characteristic causes of long-term renal function loss. The purpose of our study is to investigate the association between fibrosis-related genes single nucleotide polymorphism (SNPs) and kidney function in 5 years after kidney transplantation.MethodsA total of 143 recipients were eligible for screening with 5-year follow-up information and SNP sequencing information from blood samples were included in this study. Minor Allele Frequency (MAF) and Hardy–Weinberg Equilibrium (HWE) analysis was conducted to identify tagger single-nucleotide polymorphisms (SNPs) and haplotypes. SNPs associated with the fifth year chronic kidney disease (CKD) staging were screened by SPSS and the “SNPassoc” package in RStudio and used for subsequent prediction model construction.ResultsA total of 275 renal transplant-related SNPs identified after target sequencing analysis. 64 Tagger SNPs were selected, and two SNPs (rs13969 and rs243849) were statistically significant for stage of CKD in 5 years. Finally, a model based on Gender, Age, rs1396, and rs243849 was constructed by multivariate linear regression analysis. Additionally, this model has a good performance in predicting uremia five years after kidney transplantation.ConclusionTwo SNPs (rs13969 and rs243849) were identified to be significantly associated with long-term renal allograft function. Based on this, a prediction model for long-term allograft function was established containing Gender, Age, rs1396, and rs243849. However, an independent cohort should be enrolled to validate the predicting performance.

Renin Inhibition and the Long-Term Renal Function in Patients With Hypertensive Emergency: A Retrospective Cohort Study.

The rehospitalization rate in a hypertensive emergency is high, indicating the necessity for optimizing its long-term management. The role of the renin-angiotensin system (RAS) blockade in this disorder remains uncertain. We conducted a retrospective analysis involving 20 admitted patients who received aliskiren, a direct renin inhibitor (DRI), for the management of hypertensive emergency associated with elevated plasma renin activity (PRA). We analyzed the changes in blood pressure (BP), kidney function, and RAS activity in the subacute and chronic phases. The use of DRI was associated with a marked reduction in PRA (median, from 25.0 to 1.2 ng/ml/h) and serum aldosterone levels (from 404 to 130 pg/ml) during the index admission. BP also decreased from 226/143 to 142/80 mm Hg. A comparison of clinical characteristics according to the renal function indicated that dialysis-dependent patients had higher aldosterone levels than non-dialysis-dependent patients at admission, despite comparable BP levels. After a median follow-up of 567 days in non-dialysis-dependent patients with DRI, eGFR levels were significantly increased from 14.3 to 23.1 ml/min/1.73 m2. PRA levels were consistently suppressed at 0.8 ng/ml/h. We found a significant correlation between the degree of PRA suppression and changes in eGFR (r = -0.58), indicating that the effective blockade of RAS is associated with the preservation of eGFR in the study subjects. DRI can successfully suppress PRA in patients with high-renin hypertensive emergency in both subacute and chronic phases. An efficient RAS blockade is associated with preserved renal function in these patients.

Oncological and functional outcome of robotic-assisted radical cystectomy with total intracorporeal stentless J-pouch neobladder reconstruction.

Robotic-assisted radical cystectomy (RARC) with neobladder reconstruction has gained popularity in recent years. We conducted a retrospective study of 17 consecutive patients who underwent RARC with totally intracorporeal J-pouch neobladder reconstruction without ureteral stent by a single experienced surgeon to evaluate perioperative, oncological and functional outcomes. The median follow-up duration was 32.8months (range: 17.4-59.0months), and the 2-year disease-free survival rate was 88.2%. Five out of 12 patients were totally continent, and none required more than one pad per day. The overall complication rate was 41.2%, and hydronephrosis was the most common adverse event. The renal function remained stable, and no long-term renal function impairment was detected. Our study suggests that RARC with totally intracorporeal J-pouch neobladder reconstruction without ureteral stent is a safe and feasible option for the treatment of muscle-invasive bladder cancer, with good oncological and functional outcomes.

Postoperative decline in renal function after rectal resection and all-cause mortality: a retrospective cohort study.

Fluid loss, dehydration and resultant kidney injury are common when a diverting ileostomy is formed during rectal cancer surgery, the consequences of which are unknown. The aim of this retrospective single-site cohort study is to evaluate the impact of sustained postoperative renal dysfunction after rectal resection on long-term renal impairment and survival. All patients with rectal adenocarcinoma undergoing resection between January 2003 and March 2017 were included, with follow-up to June 2020. The primary outcome was impact on long-term mortality attributed to a 25% or greater drop in estimated glomerular filtration rate (eGFR) following rectal resection. Secondary outcomes were the long-term effect on renal function resulting from the same drop in eGFR and the effect on long-term mortality and renal function of a 50% drop in eGFR. We also calculated the effect on mortality of a 1% drop in eGFR. A total of 1159 patients were identified. Postoperative reductions in eGFR of 25% and 50% were associated with long-term overall mortality with adjusted hazard ratios of 1.84 (1.22-2.77) (p = 0.004) and 2.88 (1.45-5.71) (p = 0.002). The median survival of these groups was 86.0 (64.0-108.0) months and 53.3 (7.8-98.8) months compared with 144.5 (128.1-160.9) months for controls. Long-term effects on renal function were demonstrated, with those who sustained a >25% drop in renal function having a 38.8% mean decline in eGFR at 10 years compared with 10.2% in controls. Persistent postoperative declines in renal function may be linked to long-term mortality. Further research is needed to assess causal relationships and prevention.

Preoperative Renal Parenchyma Volume as a Predictor of Kidney Function Following Nephrectomy of Complex Renal Masses

BackgroundThe von Hippel-Lindau disease (VHL) is a hereditary cancer syndrome with multifocal, bilateral cysts and solid tumors of the kidney. Surgical management may include multiple extirpative surgeries, which ultimately results in parenchymal volume loss and subsequent renal function decline. Recent studies have utilized parenchyma volume as an estimate of renal function prior to surgery for renal cell carcinoma; however, it is not yet validated for surgically altered kidneys with multifocal masses and complex cysts such as are present in VHL. ObjectiveWe sought to validate a magnetic resonance imaging (MRI)-based volumetric analysis with mercaptoacetyltriglycine (MAG-3) renogram and postoperative renal function. Design, setting, and participantsWe identified patients undergoing renal surgery at the National Cancer Institute from 2015 to 2020 with preoperative MRI. Renal tumors, cysts, and parenchyma of the operated kidney were segmented manually using ITK-SNAP software. Outcome measurements and statistical analysisSerum creatinine and urinalysis were assessed preoperatively, and at 3- and 12-mo follow-up time points. Estimated glomerular filtration rate (eGFR) was calculated using serum creatinine-based CKD-EPI 2021 equation. A statistical analysis was conducted on R Studio version 4.1.1. Results and limitationsPreoperative MRI scans of 113 VHL patients (56% male, median age 48 yr) were evaluated between 2015 and 2021. Twelve (10.6%) patients had a solitary kidney at the time of surgery; 59 (52%) patients had at least one previous partial nephrectomy on the renal unit. Patients had a median of three (interquartile range [IQR]: 2–5) tumors and five (IQR: 0–13) cysts per kidney on imaging. The median preoperative GFR was 70 ml/min/1.73 m2 (IQR: 58–89). Preoperative split renal function derived from MAG-3 studies and MRI split renal volume were significantly correlated (r = 0.848, p < 0.001). On the multivariable analysis, total preoperative parenchymal volume, solitary kidney, and preoperative eGFR were significant independent predictors of 12-mo eGFR. When only considering patients with two kidneys undergoing partial nephrectomy, preoperative parenchymal volume and eGFR remained significant predictors of 12-mo eGFR. ConclusionsA parenchyma volume analysis on preoperative MRI correlates well with renogram split function and can predict long-term renal function with added benefit of anatomic detail and ease of application. Patient summaryPrior to kidney surgery, it is important to understand the contribution of each kidney to overall kidney function. Nuclear medicine scans are currently used to measure split kidney function. We demonstrated that kidney volumes on preoperative magnetic resonance imaging can also be used to estimate split kidney function before surgery, while also providing essential details of tumor and kidney anatomy.

Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in patients with chronic kidney disease: a systematic review and meta-analysis.

Owing to the pharmacological mechanism, sodium-glucose cotransporter 2 inhibitors (SGLT2is) may be less effective in patients with reduced renal functions, but no systematic review or meta-analysis addressed chronic kidney disease (CKD) patients specifically. We aimed to assess the efficacy and safety of SGLT2is in CKD patients. We conducted a systematic review and meta-analysis of randomized controlled trials. Mean difference (MD) were pooled for the decline of glomerular filtration rate (eGFR) and change in urine albumin-to-creatinine ratio (uACR). Hazard ratio (HR) and rate ratio (RR) were pooled for composite of renal outcomes and adverse effects. Thirty articles were identified. Overall MD in rate of eGFR decline was 0.02 (P = 0.05), with a borderline significant difference favoring SGLT2is, while the change in uACR from baseline was - 141.34mg/g and hazard ratio of composite renal outcomes was 0.64 significantly favoring SGLT2is. Subgroup analyses showed that the long-term renal function, participants with baseline macroalbuminuria, and stage 4 CKD patients had significantly slower eGFR decline rate in SGLT2is compared to the placebo group. Risks of genital mycotic infection and ketoacidosis were significantly higher among the SGLT2is group than placebo. For CKD patients, no matter diabetic or non-diabetic, our study showed potential renoprotective effects favoring SGLT2is in overall and long-term phase, and in patients with macroalbuminuria or stage 4 CKD. However, only slight increased risk of adverse effects among the SGLT2is group is observed. Therefore, we concluded that in CKD patients, prescribing SGLT2is was safe and had renal benefits.

A new machine-learning model to predict long-term renal function impairment after minimally invasive partial nephrectomy: the Fundació Puigvert predictive model.

To provide a new model to predict long-term renal function impairment after partial nephrectomy (PN). Data of consecutive patients who underwent minimally invasive PN from 2005 to 2022 were analyzed. A minimum of 12 months of follow-up was required. We relied on a machine-learning algorithm, namely classification and regression tree (CART), to identify the predictors and associated clusters of chronic kidney disease (CKD) stage migration during follow-up. 568 patients underwent minimally invasive PN at our center. A total of 381 patients met our inclusion criteria. The median follow-up was 69 (IQR 38-99) months. A total of 103 (27%) patients experienced CKD stage migration at last follow-up. Progression of CKD stage after surgery, ACCI and baseline CKD stage were selected as the most informative risk factors to predict CKD progression, leading to the creation of four clusters. The progression of CKD stage rates for cluster #1 (no progression of CKD stage after surgery, baseline CKD stage 1-2, ACCI 1-4), #2 (no progression of CKD stage after surgery, baseline CKD stage 1-2, ACCI ≥ 5), #3 (no progression of CKD stage after surgery and baseline CKD stage 3-4-5) and #4 (progression of CKD stage after surgery) were 6.9%, 28.2%, 37.1%, and 69.6%, respectively. The c-index of the model was 0.75. We developed a new model to predict long-term renal function impairment after PN where the perioperative loss of renal function plays a pivotal role to predict lack of functional recovery. This model could help identify patients in whom functional follow-up should be intensified to minimize possible worsening factors of renal function.

Sparsentan: A First-in-Class Dual Endothelin and Angiotensin II Receptor Antagonist.

To provide an overview of the guidelines on the management of immunoglobulin A nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS), review the evidence for sparsentan, and discuss its place in therapy. A literature search was conducted using MEDLINE, EMBASE, and clinicaltrials.gov using the search terms "sparsentan" and "RE-021" up to the end of Jun 2023. English studies were included if they evaluated the pharmacology, pharmacokinetics, efficacy, and safety of sparsentan in human subjects. Information from the Food and Drug Administration (FDA) and manufacturer's monograph were also extracted. In comparison with irbesartan, sparsentan reduced urine protein-to-creatinine ratio (UPCR) in both IgAN (-49.8% vs -15.1% at interim 36 weeks) and FSGS (-44.8% vs -18.5% at 8 weeks). Hypotension and edema were the most common adverse events in the sparsentan groups. Hepatotoxicity appears to be comparable between sparsentan and irbesartan in short-term results. Sparsentan provides a new option for patients with IgAN who are otherwise at high risk of progressive kidney disease. Continued FDA approval is dependent on long-term study results on renal function decline and safety. Sparsentan reduces proteinuria in IgAN and FSGS, and has expedited approval by the FDA for IgAN in patients at risk of rapid disease progression, generally at urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g. Interim results from PROTECT and results from DUET showed promise for improving proteinuria in IgAN and FSGS. Long-term renal function benefit and safety data are pending.

Long-term ozone exposure is negatively associated with estimated glomerular filtration rate in Chinese middle-aged and elderly adults

Chronic kidney disease (CKD) is an inflammatory disease characterized by the deterioration of renal function, which imposes a significant burden on the healthcare system. In the recent decades, the ageing of the population and the increase of ozone pollution have accelerated. However, epidemiological associations between long-term ozone exposure and renal function in susceptible populations are understudied. In this study, we aimed to investigate the association of 1 y ozone exposure with renal function among the older adults in Xiamen City, China. We recruited 6024 eligible participants with a median age of 65.00 years, estimated their ozone exposure data, and collected questionnaires on demographic status and lifestyle factors as well as information on healthcare access. A generalized linear model was used to assess the association. An increase of 10 μg/m3 of 1 y ozone exposure was negatively associated with the estimated glomerular filtration rate (eGFR) [-3.12 (95% CI: −4.76, −1.48)]. The associations were stronger in men, non-smokers, and those with hypertension or T2DM. Clinical indicators of high-density lipoprotein, low-density lipoprotein, triglycerides, and total cholesterol were the main mediators to regulate the ozone-renal function association. Our results suggested that long-term ozone exposure is a potential risk factor for renal function in Chinese middle-aged and elderly adults.

Abstract 056: Pooled, 6-month Renal Safety And Blood Pressure Reductions Using The Symplicity Spyral Radiofrequency Renal Denervation Catheter

Background: Renal denervation (RDN) targets the sympathetic nervous system to lower blood pressure (BP). Impact on long-term renal function after RDN is less well known. We report 6-month renal safety and BP reductions after RDN from the largest database, using the latest generation, multi-electrode, radiofrequency (RF) Symplicity Spyral™ catheter. Methods: A broad spectrum of patients with hypertension were enrolled in the SPYRAL HTN Global Clinical Program (4 major studies; SPYRAL First-In-Man, SPYRAL HTN-OFF MED, -ON MED and Global SYMPLICITY Registry [GSR]). GSR is an all-comer registry for patients with uncontrolled hypertension, including chronic kidney disease (CKD), whereas patients enrolled in the SPYRAL HTN-OFF and -ON MED trials required to have OSBP ≥150 and &lt;180 mmHg and ODBP ≥90 mmHg. OFF MED patients were required to have a drug washout period prior to treatment and did not take drugs for the first 3 months. ON MED patients were on a stable 1-3 antihypertensive drug regimen for 6 months. All were treated with RF RDN using the Spyral catheter. We pooled reductions in office and 24-h ambulatory BP, safety outcomes include changes in the estimated glomerular filtration rate (eGFR) and renal artery stenosis incidence (&gt;70%, confirmed by angiography). Results: As of December 2022, 1,284 patients have received RF RDN with the Spyral catheter. Patients at baseline were 58±12yrs old, 37.6% female, 29.1% had type 2 diabetes, eGFR was 77.7±23.9mL/min/1.73m2, 20.7% had CKD stage 3 or higher, OSBP was 166±21mmHg and ASBP was 153±16mmHg. 6 months after RDN, OSBP changed by -14.8±22.1 (n=940; p&lt;0.001) and ASBP changed by -8.9±16.0 (n=678; p&lt;0.001). Significant diastolic BP reductions were also observed. eGFR changed by -2.0mL/min/1.73m2. There was no incidence of renal artery stenosis (&gt;70%). Conclusion: In this large, pooled population of patients receiving RF RDN using the Spyral catheter, there were significant and consistent BP reductions through 6 months. There was no incidence of renal artery stenosis, and eGFR change was consistent with the natural progression of the aging hypertensive population. These data highlight the safety and efficacy of RF RDN as an adjunctive therapy to antihypertensive drugs to treat high BP.

PE077 - Prediction of long-term renal function impairment after minimally invasive partial nephrectomy through a new CART-based model.

PE077 - Prediction of long-term renal function impairment after minimally invasive partial nephrectomy through a new CART-based model.

2nd Window NIR Imaging of Radiation Injury Mitigation Provided by Reduced Notch-Dll4 Expression on Vasculature.

Vascular endothelium plays a central role in the pathogenesis of acute and chronic radiation injuries, yet the mechanisms which promote sustained endothelial dysfunction and contribute to late responding organ failure are unclear. We employed 2nd window (> 1100nm emission) Near-Infrared (NIR) imaging using indocyanine green (ICG) to track and define the role of the notch ligand Delta-like ligand 4 (Dll4) in mediating vascular injury in two late-responding radiosensitive organs: the lung and kidney. Consomic strains of female Salt Sensitive or SS (Dll4-high) and SS with 3rd chromosome inherited from Brown Norway, SS.BN3 (Dll4-low) rats at ages 11-12weeks were used to demonstrate the impact of reduced Dll4 expression on long-term vascular integrity, renal function, and survival following high-dose 13Gy partial body irradiation at 42- and 90days post-radiation. 2nd window dynamic NIR fluorescence imaging with ICG was analyzed with physiology-based pharmacokinetic modeling and confirmed with assays of endothelial Dll4 expression to assess the role of endogenous Dll4 expression on radiation injury protection. We show that SS.BN3 (Dll4-low) rats are relatively protected from vascular permeability disruption compared to the SS (Dll4-high) strain. We further demonstrated that SS.BN3 (Dll4-low) rats have reduced radiation induced loss of CD31+ vascular endothelial cells, and increased Dll4 vascular expression is correlated with vascular dysfunction. Together, these data suggest Dll4 plays a key role in pathogenesis of radiation-induced vascular injury to the lung and kidney.

Longitudinal estimated glomerular filtration rate (eGFR) modeling in long-term renal function to inform clinical trial design in kidney transplantation.

Kidney transplantation is the preferred treatment for individuals with end-stage kidney disease. From a modeling perspective, our understanding of kidney function trajectories after transplantation remains limited. Current modeling of kidney function post-transplantation is focused on linear slopes or percent decline and often excludes the highly variable early timepoints post-transplantation, where kidney function recovers and then stabilizes. Using estimated glomerular filtration rate (eGFR), a well-known biomarker of kidney function, from an aggregated dataset of 4904 kidney transplant patients including both observational studies and clinical trials, we developed a longitudinal model of kidney function trajectories from time of transplant to 6 years post-transplant. Our model is a nonlinear, mixed-effects model built in NONMEM that captured both the recovery phase after kidney transplantation, where the graft recovers function, and the long-term phase of stabilization and slow decline. Model fit was assessed using diagnostic plots and individual fits. Model performance, assessed via visual predictive checks, suggests accurate model predictions of eGFR at the median and lower 95% quantiles of eGFR, ranges which are of critical clinical importance for assessing loss of kidney function. Various clinically relevant covariates were also explored and found to improve the model. For example, transplant recipients of deceased donors recover function more slowly after transplantation and calcineurin inhibitor use promotes faster long-term decay. Our work provides a generalizable, nonlinear model of kidney allograft function that will be useful for estimating eGFR up to 6 years post-transplant in various clinically relevant populations.