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Browsing by Subject "Glomerular filtration rate"
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Item Association of delayed cord clamping with acute kidney injury and two-year kidney outcomes in extremely premature neonates: a secondary analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT)(Research Square, 2024-07-19) Harer, Matthew; Zapata, Henry; Todurkar, Namrata; Favel, Kristen; Griffin, Russell; Starr, Michelle; Charlton, Jennifer; McAdams, Ryan; Askenazi, David; Kulkarni, Tapas; Menon, Shina; Mammen, Cherry; Pediatrics, School of MedicineBackground: Delayed cord clamping (DCC) occurs in most preterm births. Objective: Evaluate the association of DCC with acute kidney injury (AKI) and two-year kidney outcomes. Methods: Secondary analysis of the Preterm Erythropoietin Neuroprotection Trial of neonates born 240/7 to 276/7 weeks' gestation. AKI and two year kidney outcomes were compared in neonates with DCC (≥30 seconds after delivery) to those with early cord clamping (ECC) (<30 seconds after delivery). Results: The incidence and severity of AKI did not differ between the DCC and ECC groups (aOR 1.17 [95%CI 0.76-1.80]). At two years corrected age, DCC was associated with a 4.5-fold times increased adjusted odds of eGFR <90 mL/min/1.73m2. No significant associations were noted between DCC and albuminuria or elevated BP. Conclusions: DCC was not associated with decreased neonatal AKI, but was associated with higher adjusted odds of eGFR <90 mL/min/1.73m2 at two years.Item Estimation of glomerular filtration rate for drug dosing in patients with very high or low body mass index(Wiley, 2022) Donker, Erik M.; Bet, Pierre; Nurmohamed, Azam; Serné, Erik; Burchell, George Louis; Friedman, Allon N.; Bouquegneau, Antoine; Lemoine, Sandrine; Ebert, Natalie; Cirillo, Massimo; van Agtmael, Michiel A.; Bartelink, Imke H.; Medicine, School of MedicineAn accurate estimated glomerular filtration rate (eGFR) is essential in drug dosing. This study demonstrates the limitations of indexed (ml/min/1.73 m2 ) and de-indexed (ml/min) eGFR based drug dosing in patients with obesity or underweight. This systematic study aimed to determine the most appropriate approach to estimate the GFR for standardized eGFR based drug dosing in these patients. (Raw) data of 12 studies were selected to investigate the accuracy and bias of both the indexed and de-indexed estimations of the Modification of Diet in Renal Disease (MDRD) study equation and the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI), and of the Cockcroft-Gault (CG) in patients with obesity or underweight. Accuracy was calculated as the proportion of eGFR values within 30% of the measured GFR (P30) using an inert tracer (e.g., iohexol, inulin, 51 Cr-EDTA, or iothalamate clearance). An accuracy of at least 80% was considered acceptable. GFR values estimated with the CG, MDRD, and CKD-EPI differ significantly within a patient with obesity or underweight regardless of whether it is indexed or de-indexed. All studies, with two exceptions, show that all three equations are inaccurate for patients with underweight or class II obesity (P30: 55%-94%). De-indexing eGFR improves not or modestly the accuracy, and mostly remains below the 80% (P30: 62%-100%). CG was highly inaccurate in obese and underweight patients (P30: 7%-82%). Although these results show that CG is obsolete, the accuracy of MDRD and CKD-EPI is low in patients with obesity or underweight and de-indexing is not the solution. Better education and more accurate methods for appropriate drug dosing (e.g., measured GFR with inert tracer, therapeutic drug monitoring, or 24-h creatinine clearance) are recommended.Item Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes According to Baseline HbA1c and Insulin Use: An Analysis From the FIDELIO-DKD Study(American Diabetes Association, 2022) Rossing, Peter; Burgess, Ellen; Agarwal, Rajiv; Anker, Stefan D.; Filippatos, Gerasimos; Pitt, Bertram; Ruilope, Luis M.; Gillard, Pieter; MacIsaac, Richard J.; Wainstein, Julio; Joseph, Amer; Brinker, Meike; Roessig, Lothar; Scott, Charlie; Bakris, George L.; FIDELIO-DKD Investigators; Medicine, School of MedicineObjective: Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease trial. We explored whether baseline HbA1c level and insulin treatment influenced outcomes. Research design and methods: Patients with T2D, urine albumin-to-creatinine ratio (UACR) of 30-5,000 mg/g, estimated glomerular filtration rate (eGFR) of 25 to <75 mL/min/1.73 m2, and treated with optimized renin-angiotensin system blockade were randomly assigned to receive finerenone or placebo. Efficacy outcomes included kidney (kidney failure, sustained decrease ≥40% in eGFR from baseline, or renal death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite endpoints. Patients were analyzed by baseline insulin use and by baseline HbA1c <7.5% (58 mmol/mol) or ≥7.5%. Results: Of 5,674 patients, 3,637 (64.1%) received insulin at baseline. Overall, 5,663 patients were included in the analysis for HbA1c; 2,794 (49.3%) had baseline HbA1c <7.5% (58 mmol/mol). Finerenone significantly reduced risk of the kidney composite outcome independent of baseline HbA1c level and insulin use (Pinteraction = 0.41 and 0.56, respectively). Cardiovascular composite outcome incidence was reduced with finerenone irrespective of baseline HbA1c level and insulin use (Pinteraction = 0.70 and 0.33, respectively). Although baseline HbA1c level did not affect kidney event risk, cardiovascular risk increased with higher HbA1c level. UACR reduction was consistent across subgroups. Adverse events were similar between groups regardless of baseline HbA1c level and insulin use; few finerenone-treated patients discontinued treatment because of hyperkalemia. Conclusions: Finerenone reduces kidney and cardiovascular outcome risk in patients with CKD and T2D, and risks appear consistent irrespective of HbA1c levels or insulin use.Item Longer time to recovery from acute kidney injury is associated with major adverse kidney events in patients with cirrhosis(Wiley, 2023) Patidar, Kavish R.; Naved, Mobasshir A.; Kabir, Shaowli; Grama, Ananth; Allegretti, Andrew S.; Cullaro, Giuseppe; Asrani, Sumeet K.; Worden, Astin; Desai, Archita P.; Ghabril, Marwan S.; Nephew, Lauren D.; Orman, Eric S.; Medicine, School of MedicineBackground: In patients with cirrhosis and acute kidney injury (AKI), longer time to AKI-recovery may increase the risk of subsequent major-adverse-kidney-events (MAKE). Aims: To examine the association between timing of AKI-recovery and risk of MAKE in patients with cirrhosis. Methods: Hospitalised patients with cirrhosis and AKI (n = 5937) in a nationwide database were assessed for time to AKI-recovery and followed for 180-days. Timing of AKI-recovery (return of serum creatinine <0.3 mg/dL of baseline) from AKI-onset was grouped by Acute-Disease-Quality-Initiative Renal Recovery consensus: 0-2, 3-7, and >7-days. Primary outcome was MAKE at 90-180-days. MAKE is an accepted clinical endpoint in AKI and defined as the composite outcome of ≥25% decline in estimated-glomerular-filtration-rate (eGFR) compared with baseline with the development of de-novo chronic-kidney-disease (CKD) stage ≥3 or CKD progression (≥50% reduction in eGFR compared with baseline) or new haemodialysis or death. Landmark competing-risk multivariable analysis was performed to determine the independent association between timing of AKI-recovery and risk of MAKE. Results: 4655 (75%) achieved AKI-recovery: 0-2 (60%), 3-7 (31%), and >7-days (9%). Cumulative-incidence of MAKE was 15%, 20%, and 29% for 0-2, 3-7, >7-days recovery groups, respectively. On adjusted multivariable competing-risk analysis, compared to 0-2-days, recovery at 3-7 and >7-days was independently associated with an increased risk for MAKE: sHR 1.45 (95% CI 1.01-2.09, p = 0.042), sHR 2.33 (95% CI 1.40-3.90, p = 0.001), respectively. Conclusion: Longer time to recovery is associated with an increased risk of MAKE in patients with cirrhosis and AKI. Further research should examine interventions to shorten AKI-recovery time and its impact on subsequent outcomes.Item Measurement of glomerular filtration rate reveals that subcapsular injection of shear‐thinning hyaluronic acid hydrogels does not impair kidney function in mice(Wiley, 2022-03) Soranno, Danielle E.; Kirkbride-Romeo, Lara; Han, Daniel; Altmann, Christopher; Rodell, Christopher B.; Pediatrics, School of MedicineThe continued development of minimally invasive therapeutic implants, such as injectable hydrogels, necessitates the concurrent advancement of methods to best assess their biocompatibility via functional outcomes in vivo. Biomaterial implants have been studied to treat kidney disease; however, assessment of biocompatibility has been limited to biomarker and histological assessments. Techniques now exist to measure kidney function serially in vivo in murine studies via transcutaneous measurements of glomerular filtration rate (tGFR). In this study, adult male and female wild-type BalbC mice underwent right unilateral nephrectomy. The remaining solitary left kidney was allowed 4 weeks to recover via compensatory hypertrophy, after which subcapsular injection of either saline or shear-thinning hyaluronic acid hydrogel was performed. Serial tGFR measurements before and after treatment were used to assess the effect of hydrogel injection on kidney filtration. Urine and serum biomarkers of kidney function, and kidney histology were also quantified. Hydrogel injection did not affect kidney function, as assessed by tGFR. Results were in agreement with standard metrics of serum and urine biomarkers of injury as well as histological assessment of inflammation. The model developed provides a direct functional assessment of implant compatibility for the treatment of kidney disease and impact on kidney function.Item Percutaneous Renal Access: Surgical Factors Involved in the Acute Reduction of Renal Function(Mary Ann Liebert, Inc., 2016-02) Handa, Rajash K.; Johnson, Cynthia D.; Connors, Bret A.; Evan, Andrew P.; Lingeman, James E.; Liu, Ziyue; Department of Anatomy & Cell Biology, IU School of MedicineINTRODUCTION AND OBJECTIVE: Studies in patients and experimental animals have shown that percutaneous nephrolithotomy (PCNL) can acutely impair glomerular filtration and renal perfusion, but the factors contributing to this decline in renal function are unknown. The present study assessed the contribution of needle puncture of the kidney vs dilation of the needle tract to the acute decline in renal hemodynamic and tubular transport function associated with PCNL surgery. MATERIALS AND METHODS: Acute experiments were performed in three groups of anesthetized adult farm pigs: sham-percutaneous access (PERC), that is, no surgical procedure (n = 7); a single-needle stick to access the renal collecting system (n = 8); expansion of the single-needle access tract with a 30F NephroMax balloon dilator and insertion of a nephrostomy sheath (n = 10). The glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and renal extraction of para-amino hippurate (EPAH, estimates tubular organic anion transporter [OAT] activity) were assessed before and 1 to 4.5 hours after sham-PERC or PERC surgical procedures. RESULTS: Overall, GFR responses were similar in all three groups. Sham-treated PERC pigs showed no significant change in ERPF over the experimental observation period, whereas a single-needle stick to access the renal collecting system resulted in renal vasoconstriction (∼30% reduction in ERPF, p < 0.05). Dilation of the single-needle access tract to create the nephrostomy did not lead to a further decline in ERPF. PERC surgical procedure-mediated renal vasoconstriction was most evident at the 1-hour posttreatment time point. A reduction in EPAH was only observed in pig kidneys with a nephrostomy. CONCLUSIONS: Needle puncture of the kidney for percutaneous access to the renal collecting system is the major driving force for the renal vasoconstriction observed after PCNL surgery, whereas creation of the nephrostomy appears to be largely responsible for decreasing tubular OAT activity.Item The relationship between kidney function and body mass index before and after bariatric surgery in patients with chronic kidney disease(Elsevier, 2021) Fischer, Heidi; Weiss, Robert E.; Friedman, Allon N.; Imam, Talha H.; Coleman, Karen J.; Medicine, School of MedicineBackground: Improvements in kidney function post-bariatric surgery may be related to weight loss-independent effects. Objectives: To characterize the dynamic relationship between body mass index (BMI) and estimated glomerular filtration rate (eGFR) before and after bariatric surgery in patients with chronic kidney disease (CKD). Setting: Kaiser Permanente Southern California (KPSC) health system. Methods: We conducted an observational, retrospective cohort study of patients with CKD stage 3 or higher who received bariatric surgery at the KPSC health system between 2007-2015. Bariatric surgery procedures included primary Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) procedures. Outcomes consisted of mean trajectory estimates and correlations of BMI and eGFR taken between 2 years before and 3 years after surgery. Multivariate functional mixed models were used to estimate how BMI and eGFR trajectories evolved jointly. Results: A total of 619 RYGB and 474 SG patients were included in the final analytic sample. The measurements were available before surgery for a median time of 1.9 years for SG and 1.8 years for RYGB patients. Median follow-up times after surgery were 2.8 years for both SG and RYGB patients. The mean age at the time of surgery was 58 years; 77% of patients were women; 56% of patients were non-Hispanic White; the mean BMI was 44 kg/m2; 60% of patients had diabetes mellitus; and 84% of patients had hypertension. Compared to the presurgery eGFR declines, the postsurgery declines in eGFR were 57% slower (95% credible interval [CrI], 33%-81%) for RYGB patients and 55% slower (95% CrI, 25%-75%) for SG patients. The mean correlation between BMI and eGFR was negligible at all time points. Conclusion: Though bariatric surgery slowed declines in eGFR up to 3 years after surgery, changes in eGFR tracked poorly with changes in BMI. This study provides evidence that the kidney-related benefits of bariatric surgery may be at least partly independent of weight loss. Confirming this hypothesis could lead to mechanistic insights and new treatment options for CKD.