Changes In Renal Function Research Articles

Different kinetics of NT-proBNP and sST2 highlight different therapeutic pathways of sacubitril/valsartan

Abstract Funding Acknowledgements Type of funding sources: None. Background N-terminal pro-B-type natriuretic peptide (NT-proBNP) and soluble interleukin 1 receptor-like 1 ST2 (sST2) are biomarkers used to grade heart failure with reduced ejection fraction (HFrEF) severity. Both are potential targets of HFrEF treatment, but the first is associated with the patient’s hemodynamic status, while the second is more indicative of the inflammatory status and of myocardial fibrosis. Purpose The aim of this study was to assess the kinetics of these biomarkers after treatment with sacubitril/valsartan in HFrEF. Methods We analyzed blood samples of HFrEF patients at baseline (before sacubitril/valsartan treatment), after 1, 2, 3 months (respectively after a month taking the 24/26 – 49/51 – 97/103mg b.i.d. doses), and 6 months after the maximum tolerated dose was reached (end-study). Results We obtained samples from 72 HFrEF patients (age 64.0±10.5, 83% males) (Table 1). NT-proBNP and sST2 values progressively and significantly reduced up to 37% and 16%, respectively, with a greater reduction for NT-proBNP (p<0.001). Specifically, NT-proBNP reduced from 1144 [593-2586] to 743 [358-1524] pg/mL and sST2 from 27.3 [20.5-35.0] to 23.1 [15.9-30.7] ng/mL, p for trend <0.001 in both cases). The reduction of the two biomarkers over time occurred with statistically significant different kinetics: deferred for sST2 and faster for NT-proBNP (Figure 1). No significant changes in renal function and potassium levels were recorded. Conclusions These findings suggest that, in HF patients, sacubitril/valsartan effects on the cardiovascular system share a double pathway: a first, hemodynamic, faster pathway and a second, non-hemodynamic anti-inflammatory, delayed one. Both likely contribute to the sacubitril/valsartan benefits in HFrEF.Table 1Figure 1

Predictors and Long-Term Prognostic Significance of Acute Renal Function Change in Patients Who Underwent Surgical Aortic Valve Replacement.

There are few reports on short-term changes in renal function after surgical aortic valve replacement, and data are scarce regarding its impact on long-term outcomes. This is a retrospective study of patients who underwent isolated aortic valve replacement between 2009 and 2020 in four medical centers. Patients with end-stage renal disease were excluded. Renal function was assessed based on short-term changes. Multivariable regression models were used to identify predictors of improvement/deterioration. Cox proportional hazard models were used to assess survival trends. The study included 2402 patients, with a mean age of 69.3 years and a mean eGFR of 82.3 mL/min/1.73 m2. Short-term improvement rates were highest in stage 4 (24.4%) and stage 3 (16.8%) patients. Deterioration rates were highest in stage 1 (38.1%) and stage 2 (34.8%) patients. Deterioration in the chronic kidney disease stage was associated with a higher ten-year mortality (p < 0.001, HR 1.46); an improved stage trended toward improved survival (p = 0.14, HR 0.722). Patients with stage 3 and 4 kidney disease tended to remain stable or improve in the short term after aortic valve replacement while patients at stages 1 and 2 were at increased risk of deteriorating.

Evaluation of Renal Function and Stent Durability Following Resonance Stent Placement for Benign Disease.

Introduction: The metal-based Resonance stent (RS) has traditionally been placed in patients with malignant ureteral obstruction; as such, the long-term utility of RS among patients with benign ureteral obstruction (BUO) remains underinvestigated. Methods: We retrospectively reviewed our database for patients with BUO who underwent RS placement between 2010 and 2020. The impact of chronic RS placement on renal function was evaluated by estimated serum creatinine-based glomerular filtration rate (eGFR), furosemide renal scan, and CT-based renal parenchymal volume measurement. The number of and reason for RS stent exchanges during the follow-up period, incidence of encrustation, and the average indwell time were recorded. A cost analysis of placing the RS vs a polymeric stent was performed. Results: Among 43 RS patients with BUO, at a mean follow-up of 26 months, there was no change in eGFR (p = 0.99), parenchymal volume (p = 0.44), or split renal function of the stent-bearing side on renal scan (p = 0.48). The mean RS indwell time was 9.7 months. Eleven patients (26%) underwent premature stent replacement (6 cases) or removal (5 cases). Stents in 9 patients (32%) were encrusted, of which 4 (44%) required laser lithotripsy. Overall, 25 patients (58%) and 12 patients (28%) had a mean stent indwell time of ≥6 months and ≥12 months, respectively. Placing an RS resulted in a 52%, 37%, and 5.6% cost reduction compared with a regular polymeric stent placement, where it was exchanged every 6, 4, or 3 months, respectively. Conclusions: RS deployment in the patient with a BUO results in cost-effective maintenance of renal function and of renal parenchymal volume at a mean follow-up of 2 years; however, only 28% of patients fulfilled the 1-year criterion for RS indwell time.

Renal function changes in patients with subclinical hyperthyroidism: a novel postulated mechanism

BackgroundSubclinical hyperthyroidism (SCH) is found to be associated with renal dysfunction. Hyperthyroidism is a well-known cause of secondary systolic hypertension. However, the effect of SCH on the kidney and its vasculature is still unknown.AimTo assess the presence of renal function changes and renal vasodysfunction in SCH patients and their relation to hypertension.MethodsThe study included 321 patients with SCH and 80 healthy matched controls. Laboratory investigations included thyroid function tests, anti-TSH receptor antibody (TRAb), creatinine, estimated glomerular filtration rate (eGFR), serum osmolarity (S. Osmol), urine osmolarity (U. Osmol), Fractional Excretion of Sodium (FeNa), Fractional Excretion of Potassium (FeK), copeptin (CPP), and aldosterone/renin ratio (ARR). Ultrasound for the thyroid gland, echocardiography, total peripheral resistance (TPR), flow-mediated dilatation (FMD), and Renal Arterial distensibility (RAD) was also done.ResultsSerum creatinine was significantly lower while eGFR was significantly higher in SCH patients compared to euthyroid subjects (mean 0.59 ± 0.11 mg/dl Vs mean 0.8 ± 0.1 mg/dl, p = 0.001 and mean 128.28 ± 14.69 ml/min/1.73m2 Vs mean 100.49 ± 14.9 ml/min/1.73m2, p = 0.013, respectively). The TPR and FMD showed a significant decrease in SCH group compared to controls (mean 975.85 ± 159.33 mmHg.min/L Vs mean 1120.24 ± 135.15 mmHg.min/L, p = 0.045 and mean 7.03 ± 4.02% Vs mean 13.48 ± 4.57%, p = 0.003, respectively). RAD was significantly higher in hypertensive SCH patients compared to normotensive SCH patients (mean 17.82 ± 2.46 mmHg Vs mean 11.98 ± 3.21 mmHg, p = 0.001).ConclusionSCH patients showed vascular resistance reduction. Alterations in thyroid hormones and blood pressure could be the driving mechanisms for the change in renal functions in patients with SCH.

Efficacy and safety of 1 L polyethylene glycol plus ascorbic acid for bowel preparation in elderly: comparison with oral sulfate solution.

Recently, 1 L of polyethylene glycol (PEG) plus ascorbic acid (Asc) has been introduced in Korea as a colonoscopy preparation agent. Data on its efficacy and safety in older adults have been limited. We aimed to evaluate the safety and efficacy of 1 L PEG/Asc in older adults by comparing it with oral sulfate solution (OSS). A prospective multicenter randomized study was conducted with subjects aged ≥ 65 years who underwent colonoscopy. The participants were randomized to receive 1 L PEG/Asc or OSS. The primary endpoint was successful bowel preparation, defined as total Boston Bowel Preparation Scale ≥ 6, and ≥ 2 at each segment. Patient satisfaction, adverse events, and renal function changes were compared between the groups. Among the 106 patients, 104 were finally included in the analysis. Overall, successful bowel preparation was achieved in 96.2% of both 1 L PEG/Asc and OSS groups. The satisfaction scores for taste, total amount ingested, overall feeling, and willingness to repeat the same regimen were not significantly different between the groups. Adverse events of moderate or higher severity occurred in 16 and 10 cases in the 1 L PEG/Asc and OSS group, respectively. There were no significant changes in electrolyte levels or renal function from baseline. The successful bowel preparation rate was > 90% in both groups without severe adverse effects and significant changes in renal function. As a new low-dose preparation regimen for colonoscopy in older adults, 1 L PEG/Asc, is as effective and safe as OSS.

Renoprotective Effect of Chrysanthemum coronarium L. Extract on Adenine-Induced Chronic Kidney Disease in Mice.

Chronic kidney disease (CKD) gradually leads to loss of renal function and is associated with inflammation and fibrosis. Chrysanthemum coronarium L., a leafy vegetable, possesses various beneficial properties, including anti-oxidative, anti-inflammatory, and antiproliferative effects. In this study, we investigated the renoprotective effect of Chrysanthemum coronarium L. extract (CC) on adenine (AD)-induced CKD in mice. CKD was induced by feeding mice with an AD diet (0.25% w/w) for 4 weeks. Changes in renal function, histopathology, inflammation, and renal interstitial fibrosis were analyzed. The adenine-fed mice were characterized by increased blood urea nitrogen, serum creatinine, and histological changes, including inflammation and fibrosis; however, these changes were significantly restored by treatment with CC. Additionally, CC inhibited the expression of the inflammatory markers, monocyte chemoattractant protein-1, interleukins-6 and -1β, intercellular adhesion molecule-1, and cyclooxygenase 2. Moreover, CC suppressed the expression of the fibrotic markers, type IV collagen, and fibronectin. Furthermore, CC attenuated the expression of profibrotic genes (tumor growth factor-β and α-smooth muscle actin) in AD-induced renal injury mice. Thus, our results suggest that CC has the potential to attenuate AD-induced renal injury and might offer a new option as a renoprotective agent or functional food supplement to manage CKD.

Gender disparities in patients with aortoiliac disease requiring open operative intervention

ObjectivePeripheral artery disease is known to affect males and females in different proportions. Disparate surgical outcomes have been quantified after endovascular aortic aneurysm repair, arteriovenous fistula creation, and treatment of critical limb ischemia. The aim of this study is to objectively quantify the sex differences in outcomes in patients undergoing open surgical intervention for aortoiliac occlusive disease. MethodsPatients were identified in the aortoiliac occlusive disease Vascular Quality Initiative database who underwent aorto-bifemoral bypass or aortic thromboendarterectomy as determined by Current Procedural Terminology codes between 2012 and 2019. Patients with a minimum of 1-year follow-up were included. Risk differences (RDs) by sex were calculated using a binomial regression model in 30-day and 1-year incidence of mortality and limb salvage. Additionally, incidence of surgical complications including prolonged length of stay (>10 days), reoperation, and change in renal function (>0.5 mg/dl rise from baseline), were recorded. Inverse probability weighting was used to standardize demographic and medical history characteristics. Multivariate logistic regression models were employed to conduct analyses of the before mentioned clinical outcomes, controlling for known confounders. ResultsOf 16,218 eligible patients from the VQI data during the study period, 6538 (40.3%) were female. The mean age, body mass index, and race were not statistically different between sexes. Although there was no statistically significant difference detected in mortality between males and females at 30 days postoperatively, females had an increased crude 1-year mortality with an RD of 0.014 (95% confidence interval, 0.01-0.02; P value < .001. Males had a higher rate of a postoperative change in renal function with an RD of −0.02 (95% confidence interval, −0.03 to −0.01; P < .001). ConclusionsAlthough there was no sex-based mortality difference at 30 days, there was a statistically significant increase in mortality in females after open aortoiliac intervention at 1 year based on our weighted model. Male patients are statistically significantly more likely to have a decline in renal function after their procedures when compared with females. Postoperative complications including prolonged hospital stay, reoperation, and wound disruption were similar among the sexes, as was limb preservation rates at 1 year. Further studies should focus on elucidating the underlying factors contributing to sex-based differences in clinical outcomes following aortoiliac interventions.

The effect of a ketogenic diet on weight loss in CKD: a randomized controlled trial in obese stage G1-3a CKD patients.

This study describes a multicentre randomized controlled trial comparing the effects of a ketogenic diet with a low-energy standard diet containing 0.8g/kg/day on weight loss and metabolic alterations in adult patients with mild-to-moderate non-diabetic chronic kidney disease (CKD) and mild-to-severe obesity. The study is being conducted to understand the impact of the ketogenic diet on weight loss in these patients, as the existing evidence on the ketogenic diet's effect in CKD patients is limited and inconclusive. The study will enrol mild-to moderate adult CKD patients (Stages G1-3a) with albumin to creatinine ratio ≥200mg/g, without diabetes, with obesity (body mass index ≥30kg/m2), and stable body weight and estimated glomerular filtration rate from at least 3months. The primary outcome will be weight loss at 6months, and secondary outcomes will include adherence to prescribed dietary regimens, body composition changes, changes in standardized blood pressure measurements, metabolic parameters, lipid profile, liver profile, mineral bone disease biomarkers, and changes in renal function and albuminuria. The findings of this study will contribute to a better understanding of the potential benefits and risks of the ketogenic diet in CKD patients with obesity. The results will help guide future research on the ketogenic diet and renal health.

Radiation nephropathy: Mechanisms of injury and recovery in a murine model

BackgroundRadiation nephropathy (RN) can be a severe late complication for patients treated with radiotherapy (RT) targeting abdominal and paraspinal tumors. Recent studies investigating the mechanisms of RT-mediated injury in the kidney have demonstrated that RT disrupts the cellular integrity of renal podocytes leading to cell death and loss of renal function. AimTo determine if RT-induced renal dysfunction is associated with alterations in podocyte and glomerular function, and whether RT-induced podocyte alterations were associated with changes in the glomerular basement membrane (GBM). MethodsC57BL/6 mice were treated with focal bilateral X-irradiation using a single dose (SD) of 4 Gy, 10 Gy, or 14 Gy or fractionated dosing (FD) of 5x6Gy or 24x2Gy. Then, 10–40 weeks after RT parameters of renal function were measured, along with glomerular filtration rate (GFR) and glomerular histology, as well as ultrastructural changes in GBM by transmission electron microscopy. ResultsRT treatment resulted in persistent changes in renal function beginning at 10 weeks with little recovery up to 40 weeks post RT. Dose dependent changes were seen with increasing SD but no functional sparing was evident after FD. RT-induced loss of renal function was associated with expansion of the GBM and significant increases in foot process width, and associated with significant reduction in GFR, podocyte loss, and renal fibrosis. ConclusionFor the first time, these data show that expansion of the GBM is one consequence of radiation injury, and disarrangement of the GBM might be associated with the death of podocytes. These data shed new light on the role podocyte injury and GBM in RT-induced renal dysfunction.

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

Objective: Atrial Fibrillation (AF) and chronic kidney disease frequently coexist in the elderly. Warfarin-like drugs (WLDs) may be associated with a relatively greater decrease of estimated glomerular filtration rate (eGFR) as compared to direct oral anticoagulants (DOACs), but there is no evidence on the medium- and long-term changes. To further elucidate this issue in elderly patients with AF, we investigated the renal function deterioration in the two groups of the study (DOACs or WLDs). Patients and Methods: A total of 420 AF patients were enrolled (mean age: 77.0 ± 6.0 years; 136 on WLDs and 284 on DOACs). These patients underwent three eGFR measurements during the follow-up period. The between-arms difference of eGFR decline over time was investigated by Linear Mixed Models and group-based trajectory model analyses. Results: In the whole study cohort, after a median follow-up of 4.9 years (interquartile range: 2.7-7.0 years), eGFR decreased from 67.4 ± 18.2 to 47.1 ± 14.3mL/min/1.73m2 (p < 0.001). Remarkably, patients on DOACs experienced a significantly smaller eGFR decline than WLDs patients (-21.3% vs. -45.1%, p < 0.001) and this was true both in the medium-term (-6.6 vs. -19.9mL/min/1.73m2) and in the long-term (-13.5 versus -34.2mL/min/1.73m2) period. After stratification into five subgroups according to trajectories of renal function decline over time, logistic regression showed that DOACs patients had from 3.03 to 4.24-fold greater likelihood to belong to the trajectory with less marked eGFR decline over time than WLDs patients. Conclusion: Elderly patients with AF on treatment with DOACs had a relatively smaller decline of eGFR over time compared to those on treatment with WLDs. This is consistent with what was partly reported in the literature.

A Placebo-Controlled, Double-Blind Clinical Investigation to Evaluate the Efficacy of a Patented Trigonella foenum-graecum Seed Extract “Fenfuro®” in Type 2 Diabetics

Background Trigonella foenum-graecum (Fenugreek) is an extensively researched phytotherapeutic for the management of Type 2 diabetes without any associated side effects. The major anti-diabetic bioactive constituents present in the plant are furostanolic saponins, which are more abundantly available in the seed of the plant. However, the bioavailability of these components depends on the method of extraction and hence formulation of the phytotherapeutic constitutes a critical step for its success. Objective The present study reports the efficacy of a novel, patented fenugreek seed extract, Fenfuro®, containing significant amount of furostanolic saponins, in an open-labelled, two-armed, single centric study on a group of 204 patients with Type 2 diabetes mellitus over a period of twelve consecutive weeks. Results Administration of Fenfuro® in the dosage of 500 mg twice daily along with metformin and/or sulfonylurea-based prescribed antidiabetic drug resulted in a reduction of post-prandial glucose by more than 33% along with significant reduction in fasting glucose, both of which were greater than what resulted for the patient group receiving only Metformin and/or Sulfonylurea therapy. Fenfuro® also resulted in reduction in mean baseline HOMA index from 4.27 to 3.765, indicating restoration of insulin sensitivity which was also supported by a significant decrease in serum insulin levels by >10% as well as slight reduction in the levels of C-peptide. However, in the case of the Metformin and/or Sulfonylurea group, insulin levels were found to increase by more than 14%, which clearly indicated that drug-induced suppression of glucose levels instead of restoration of glucose homeostasis. Administration of the formulation was also found to be free from any adverse side effects as there were no changes in hematological profile, liver function and renal function. Conclusion The study demonstrated the promising potential of this novel phytotherapeutic, Fenfuro®, in long-term holistic management of type-2 diabetes.

Longitudinal Estimated Glomerular Filtration Rate Trajectories in Children with Type 1 Diabetes

Although children with type 1 diabetes (T1D) are at risk for developing diabetic kidney disease (DKD), clinical practice guidelines do not uniformly recommend routine serum creatinine (SCr) monitoring, and data describing changes in renal function from diagnosis are lacking. As part of a quality improvement initiative, the Diabetes Clinic at British Columbia Children’s Hospital in Vancouver, Canada, implemented routine serum SCr monitoring. This study describes estimated glomerular filtration rate (eGFR) trajectories and prevalence of decreased eGFR, hypertension, and albuminuria and their relationship to patterns of nephrology referral in a cohort of children aged ≤18 years (n = 307) with T1D recruited between December 2016 and February 2019. Annualized eGFR (ml/min/1.73 m2 per year) was calculated using the CKiD U25 formula and categorized as declining (&lt;−3), stable (−3 to +3), and inclining (&gt;+3). eGFR was categorized as normal (≥90), mildly decreased (60 to &lt;90), and chronic kidney disease (CKD, &lt;60). In this cohort, 54% were male; the median age at diagnosis and duration of T1D was 6.2 years and 6.9 years, respectively. Over a median follow-up of 2.3 years, declining, stable, and inclining trajectories were observed in 33%, 32%, and 35%, respectively. During their follow-up, 32% had mildly decreased eGFR, elevated blood pressures (≥90th percentile), and/or abnormal urine albumin-creatinine ratios (≥2 mg/mmol), with &lt;10% referred for nephrology assessment. Twenty-three percent of subjects had an eGFR &lt;90; this subgroup was more highly represented in the declining trajectory group (vs. stable and inclining). Logistic regression analysis found female sex and higher baseline eGFR to be associated with a declining eGFR trajectory. In conclusion, these data challenge the commonly held paradigm that renal function remains stable in childhood T1D and supports systematic monitoring of renal function in children with T1D, as well as collaboration across disciplines, particularly endocrinology and nephrology, to provide evidence-based individualized care.

Simulation of Vancomycin Exposure Using Trough and Peak Levels Achieves the Target Area under the Steady-State Concentration-Time Curve in ICU Patients.

The therapeutic drug monitoring (TDM) of vancomycin (VCM) in critically ill patients often results in the estimated area being under the concentration-time curve (AUC) values that deviate from individual observations. In this study, we investigated the factors influencing the achievement of the target AUC of VCM at steady-state in critically ill patients. We retrospectively collected data from patients treated with VCM in an intensive care unit (ICU). Multivariate analysis was used to adjust for significant factors with p < 0.05 and identify new factors affecting the achievement of the target AUC at steady-state for VCM. Among the 113 patients included in this study, 72 (64%) were in the 1-point group (trough only), whereas 41 (36%) were in the 2-point group (trough/peak). The percentage of patients achieving the target AUC at the follow-up TDM evaluation was significantly higher in the two-point group. Multivariate analysis showed that being in the 2-point group and those with a 20% or more increase (or decrease) in creatinine clearance (CCr) were both significantly associated with the success rate of achieving the target AUC at the follow-up TDM. Novel findings revealed that in patients admitted to the ICU, changes in renal function were a predictor of AUC deviation, with a 20% or more increase (or decrease) in CCr being an indicator. We believe the indicators obtained in this study are simple and can be applied clinically in many facilities. If changes in renal function are anticipated, we recommend an AUC evaluation of VCM with a two-point blood collection, close monitoring of renal function, and dose adjustment based on reanalyzing the serum concentrations of VCM.

Transcutaneous measurement of renal function in two rodent models of obstructive nephropathy

ObjectiveGlomerular filtration rate (GFR) is a key indicator of renal function. In both clinical practice and pre-clinical research, serum levels of endogenous filtration markers, such as creatinine, are often used to estimate GFR. However, these markers often do not reflect minor changes in renal function. In this study, we therefore set out to evaluate the applicability of transcutaneous GFR (tGFR) measurements to monitor the changes in renal function, as compared to plasma creatinine (pCreatinine), in two models of obstructive nephropathy, namely unilateral ureteral obstruction (UUO) or bilateral ureteral obstruction followed by release (BUO-R) in male Wistar rats.ResultsUUO animals showed a significant reduction in tGFR compared to baseline; whereas pCreatinine levels were not significantly changed. In BUO animals, tGFR drops 24 h post BUO and remains lower upon release of the obstruction until day 11. Concomitantly, pCreatinine levels were also increased 24 h after obstruction and 24 h post release, however after 4 days, pCreatinine returned to baseline levels. In conclusion, this study revealed that the tGFR method is superior at detecting minor changes in renal function as compared to pCreatinine measurements.

Semi-physiological Enriched Population Pharmacokinetic Modelling to Predict the Effects of Pregnancy on the Pharmacokinetics of Cytotoxic Drugs.

As a result of changes in physiology during pregnancy, the pharmacokinetics (PK) of drugs can be altered. It is unclear whether under- or overexposure occurs in pregnant cancer patients and thus also whether adjustments in dosing regimens are required. Given the severity of the malignant disease and the potentially high impact on both the mother and child, there is a high unmet medical need for adequate and tolerable treatment of this patient population. We aimed to develop and evaluate a semi-physiological enriched model that incorporates physiological changes during pregnancy into available population PK models developed from non-pregnant patient data. Gestational changes in plasma protein levels, renal function, hepatic function, plasma volume, extracellular water and total body water were implemented in existing empirical PK models for docetaxel, paclitaxel, epirubicin and doxorubicin. These models were used to predict PK profiles for pregnant patients, which were compared with observed data obtained from pregnant patients. The observed PK profiles were well described by the model. For docetaxel, paclitaxel and doxorubicin, an overprediction of the lower concentrations was observed, most likely as a result of a lack of data on the gestational changes in metabolizing enzymes. For paclitaxel, epirubicin and doxorubicin, the semi-physiological enriched model performed better in predicting PK in pregnant patients compared with a model that was not adjusted for pregnancy-induced changes. By incorporating gestational changes into existing population pharmacokinetic models, it is possible to adequately predict plasma concentrations of drugs in pregnant patients which may inform dose adjustments in this population.

238-OR: Changes In Renal Function after Islet Transplantation in a Single-Centre Cohort in Canada over 20 Years

Islet transplantation (ITx) is an established treatment for recurrent, severe hypoglycemia in type 1 diabetes, but requires lifelong immunosuppression (IS) which can be nephrotoxic. We examined long term changes in renal function after ITx, through estimated GFR (eGFR), in a single centre cohort followed for up to 20 years. We used data from adults undergoing islet after kidney or ITx alone (94%) at the University of Alberta Hospital between March 11 1999 and Oct 1 2019 with &amp;gt;1 year of follow up. IS included tacrolimus and sirolimus/mycophenolate, balancing side effects with graft and renal function. We calculated individuals mean CKD EPI eGFR (ml/min/1.73m2) at baseline (≤1y pre transplant), 6m and yearly timepoints across follow up. We assessed the overall slope/year of eGFR against time from first transplant in 3 time periods; ≤1y, 1-5y and 5-20y, using mixed effects models. We also compared slopes between subjects with preserved (&amp;gt;60, n=217) vs. reduced (&amp;lt;60, n=38) eGFR at baseline. We included 255 adults (42% M) followed for 88.3m [50.2, 144.9] (median [IQR]). Whole cohort eGFR declined over follow up, most rapidly in the first year; -28.3 [-31.8, -24.5], with slower decline later post transplant 1-5y; -2.9 [-3.5, -2.3] and 5-20y; -1.2 [-1.4, -1.04]. Those with preserved baseline eGFR experienced steeper decline across all time phases as compared to those with reduced eGFR, with the steepest decline ≤1y post transplant (-29.8 [-33.8, -25.9], -18.3 [-27.8, -8.9], p=0.027). Between 5-20y post transplant renal function continued to decline slowly in those with preserved baseline eGFR but was stable in those with reduced baseline eGFR, (-1.4 [-1.6, -1.2], 0.2 [-0.3, 0.7] p&amp;lt;0.001). Nine (3.5%) developed ESRD. Initiation of IS associates with a rapid decline in eGFR the first year post ITx, with minimal decline beyond 5y. With careful IS management, rates of eGFR decline are not greater in those with reduced baseline eGFR. Effective IS regimens without nephrotoxicity remain an important goal. Disclosure A.L.J.Carr: None. A.Shapiro: n/a. P.A.Senior: Advisory Panel; Novo Nordisk Canada Inc., Consultant; Novo Nordisk Canada Inc., Bayer Inc., Viatris Inc., Vertex Pharmaceuticals Incorporated, ViaCyte, Inc., Insulet Corporation. B.A.Marfil-garza: None. Y.Ling: None. R.A.Oram: Consultant; Janssen Research &amp; Development, LLC, Research Support; Randox R &amp; D. A.Lam: None. B.L.Anderson: None. D.O'gorman: None. T.Kin: None. D.Bigam: None.

874-P: Effect on Renal Function of SGLT2i Treatment in Hospitalized Patients with Type 2 Diabetes—A Real-World Study

Background: SGLT2-I use is expanding greatly; however, temporary treatment hold is recommended in high risk states for kidney failure. Hospitalization is often associated with such risk, so the present study aimed to evaluate the effect on kidney function of SGLT2-I treatment in-hospital. Methods: This retrospective case-control study conducted in internal medicine patients included only those treated with SGLT2-I for &amp;gt;24 hours, and creatinine level was tested up to 48 hours before the start of treatment and after the end. Change in renal function was determined per eGFR (CKD-EPI formula). Factors most influencing in-hospital renal function were identified using backward regression. Results: Among 186 patients included, 66.7% (124) were male, mean age 66.4±8.3 years. Main reasons for hospitalization were atherosclerotic CVD 23.7% (44), heart failure 17.2% (32), and infectious disease 15.6% (29). Median in-hospital SGLT2-I use was three days (interquartile range 2-5 days) and 73.1% (144) received SGLT2-I before hospitalization. Prior eGFR was not low in most participants: in 65.1% (121) &amp;gt;60 ml/min/1.73 m2, and in only 13.4% &amp;lt;45. A high correlation was found between eGFR before and after treatment (r=0.8, p&amp;lt;0.001), with no drop in eGFR for the majority; however in 21% (39) it declined &amp;gt;10%, in 11.3% (21) &amp;gt;20%, in 4.8% (9) &amp;gt;30%, and in only 2.7% (5) &amp;gt;40%. The following factors were found to be significantly associated with a decrease in eGFR both &amp;gt;20% and &amp;gt;30%, including in-hospital initiation of SGLT2-I, in-hospital furosemide treatment, a background of insulin treatment, and age &amp;gt;70 years. In 93 patients treated with SGLT2-I prior to hospitalization and who did not receive in-hospital furosemide, none had a drop in eGFR &amp;gt;30% and only two &amp;gt;20%. Summary: In-hospital SGLT-2 treatment in type 2 diabetes is likely very safe from a renal standpoint in those treated pre-admission with SGLT2-I and not receiving furosemide. Disclosure A.Bashkin: None. E.Kruzel-davila: None. I.Tzfoni: None.

1082-P: Safety of SGLT2 Inhibitors in Heart Transplant Recipients

Objective: The safety of SGLT2 inhibitor (SGLT2I) use in patients receiving heart transplants is unknown. We aimed to evaluate key measures of safety after initiation of SGLT2I in a cohort of heart transplant recipients. Methods: Patients in the University of Colorado Health system who received a heart transplant between 1991 and 2022 were included if an SGLT2I was prescribed post-transplant and continued for at least 1 month. Number of urinary tract infections (UTI), urogenital yeast infections (UGI), and ED visits and hospital admissions for skin and soft tissue infections (SSTI) and euglycemic DKA (eDKA) were collected by chart review for the duration of SGLT2I use. Vital signs and lab values were collected at baseline, 3 months, and 6 months after SGLT2I initiation. Least squared means and mean differences were extracted from a random intercept mixed model with an unstructured covariance matrix for each variable. Results: Forty-six (46) patients met criteria for analysis. Mean age was 56.1 years, 80.4% had DM, and 84.8% had CKD at the time of SGLT2I initiation. Mean time on SGLT2I was 15 months (range 1-91 months). Three patients (6.5%) developed UTI and one developed UGI. Three (6.5%) had ED visits and admissions for SSTI: 1 had a post-surgical scalp infection and 2 had lower extremity cellulitis (1 led to hallux gangrene and amputation). No patients developed eDKA. Seven patients (15.2%) discontinued their SGLT2I: 2 for UTI and 1 each for hypotension, cost, fatigue, dialysis, and unspecified. Thirty-six (36) patients with adequate data over time were included in the analysis to assess change in vital signs and labs. There were no statistically significant changes from baseline to 3 months or 6 months after SGTL2I initiation for weight, BMI, SBP, DBP, Cr, eGFR, serum Na or serum K. Conclusions: In this sample of heart transplant recipients on SGLT2I, there were few urogenital and SSTI infections, no eDKA, and no significant change in renal function or electrolytes, which adds support for the safety of SGLT2I in this population. Disclosure S.Zahalka: None. C.C.Low wang: Research Support; Dexcom, Inc., Virta Health Corp., CellResearch Corporation. P.Choksi: None. H.M.Lawler: None. L.Grau: None. T.Jensen: Other Relationship; Somalogic.

Based on functional and histopathological correlations: is diffusion kurtosis imaging valuable for noninvasive assessment of renal damage in early-stage of chronic kidney disease?

To evaluate the potential of 3T magnetic resonance diffusion kurtosis imaging (DKI) in assessing the renal damage in early-stage of chronic kidney disease (CKD) patients with normal or slightly changed functional index, using histopathology as reference standard. 49 CKD patients and 18 healthy volunteers were recruited in this study. CKD patients were divided into two groups based on estimated glomerular filtration rate (eGFR): Study group I (eGFR ≥ 90ml/min/1.73m2 [n = 20]) and Study group II (eGFR < 90ml/min/1.73m2 [n = 29]). DKI was performed in all participants. The DKI parameters (mean kurtosis [MK], mean diffusivity [MD], fractional anisotropy [FA]) of renal cortex and medulla were measured. The differences of parenchymal MD, MK and FA values among the different groups were compared. The correlations between DKI parameters and clinicopathological characteristics were assessed. Diagnostic performance of DKI to assess renal damage in early-stage of CKD was analyzed. The cortex MD and MK showed significant difference among three groups (P < 0.05): trend of cortex MD: Study group II < Study group I < control group; trend of cortex MK: control group < Study group I < Study group II. The cortex MD and MK and medulla FA were correlated with eGFR and Interstitial fibrosis/Tubular atrophy score (0.3 < r < 0.5). Cortex MD and MK yielded an AUC of 0.752 for differentiating healthy volunteers from CKD patients with eGFR ≥ 90ml/min/1.73 m2. DKI shows potential in non-invasive and multi-parameter quantitative assessment of renal damage in early-stage of CKD patients and provide additional information for changes in renal function and histopathology.

Mitochondrial homeostasis: a potential target for delaying renal aging.

Mitochondria, which are the energy factories of the cell, participate in many life activities, and the kidney is a high metabolic organ that contains abundant mitochondria. Renal aging is a degenerative process associated with the accumulation of harmful processes. Increasing attention has been given to the role of abnormal mitochondrial homeostasis in renal aging. However, the role of mitochondrial homeostasis in renal aging has not been reviewed in detail. Here, we summarize the current biochemical markers associated with aging and review the changes in renal structure and function during aging. Moreover, we also review in detail the role of mitochondrial homeostasis abnormalities, including mitochondrial function, mitophagy and mitochondria-mediated oxidative stress and inflammation, in renal aging. Finally, we describe some of the current antiaging compounds that target mitochondria and note that maintaining mitochondrial homeostasis is a potential strategy against renal aging.