Renal Clearance Rate Research Articles

Pharmacokinetics and safety of pirfenidone in individuals with chronic kidney disease (CKD) stage G2 and G3a: a single-dose, Phase I, Bridging study.

Pirfenidone is an inhibitor of transforming growth factor-beta 1 (TGF-β1) and is being developed for the treatment of diabetic kidney disease (DKD). We assessed the pharmacokinetics (PK) and safety of a single dose of pirfenidone in individuals with CKD stages G2/G3a. In this phase I bridging study, patients with CKD stages G2 or G3a, aged 18-70 years, with a body mass index of 18-26 kg/m2, and glomerular filtration rate (eGFR) ranging from 45 to 89 ml/min/1.73m2, received a single oral dose of 400 mg pirfenidone capsules 30 minutes after a standard breakfast. The pharmacokinetic parameters of the two groups were measured and compared after blood and urine collection. The co-primary endpoints were the area under the plasma concentration-time curve from time zero to 36 hours (AUC0-36) and the maximum observed plasma concentration (Cmax) of pirfenidone. Safety was a secondary endpoint. The trial has been registered on ClinicalTrials.gov (ChiCTR2300077297). A total of 20 subjects participated in this study. There were no significant differences between the control group and the patient group (CKD stages G2/G3a) in terms of plasma Cmax, the time to reach the maximum observed concentration (Tmax), and elimination half-life(t1/2). However, the Vz/F of the patient group (CKD G2 stage) was significantly higher than that of the control group. Renal accumulation rate, renal clearance rate (CLr), and urine drug concentration also showed no significant differences. No severe adverse events occurred during the trial. These results indicate that the PK and safety of pirfenidone are not influenced by renal function. Individuals with renal impairment may not require dose adjustments.

Effects of Sodium-Glucose Cotransporter 2 Inhibitors in Diabetic and Non-Diabetic Patients with Advanced Chronic Kidney Disease in Peritoneal Dialysis on Residual Kidney Function: In Real-World Data.

Background and Objectives: Peritoneal dialysis (PD) is a renal replacement therapy modality in which the dialysis dose can be individually adapted according to the patients' residual kidney function (RKF). RKF is a crucial factor for technique and patient survival. Pharmacological strategies aimed at slowing the loss of RKF in patients on PD are limited. Therefore, we aimed to assess the potential effects and safety of sodium-glucose cotransporter 2 (SGLT-2) inhibitors on the preservation of RKF in patients with and without type 2 diabetes mellitus (T2DM) on PD during an average follow-up of 6 months. Materials and Methods: In this retrospective observational, single-center study on real-world data, we included patients from the Peritoneal Dialysis Unit of the Hospital General Universitario de Ciudad Real, who started treatment with SGLT-2 inhibitors during the period from December 2022 to December 2023. Data on analytical and clinical parameters, RKF, and peritoneal membrane transport function were retrospectively collected at months 0, 3, and 6. Results: Out of 31 patients in our unit, 16 prevalent patients initiated treatment with SGLT-2 inhibitors (13 empagliflozin and 3 dapagliflozin). A total of 62.5% were male and the mean age was 67.3 years. The baseline peritoneal ultrafiltration was higher in the non-diabetic patient (NDMP) group than in the diabetic patient (DMP) group. However, the residual diuresis volume, 24 h residual renal clearance rate of urea in urine, and 24 h proteinuria were higher in the DMP group than in the NDMP group. At the sixth month, patients in both groups preserved RKF and diuresis, with a trend towards a non-significant reduction in proteinuria and blood pressure. Only two patients of the DMP group presented adverse effects. Conclusions: The use of SGLT-2 inhibitors in our sample of patients with and without T2DM on PD appears to be safe and effective to preserve RKF.

Treatment of ureteropelvic junction obstruction in patients with renal calculi via laparoscopic pyeloplasty and flexible vacuum-assisted ureteral access sheath ureteroscopy: a multicenter retrospective observational study

BackgroundUreteropelvic junction obstruction (UPJO) is a common obstructive disease of the urinary tract. UPJO patients commonly exhibit coexistent renal calculi. The main aim of therapy is to relieve the obstruction and remove the stones at the same time.MethodsThis retrospective study included 110 patients diagnosed with UPJO coexisting with multiple renal calculi at Shanxi Bethune Hospital and the First Hospital of Shanxi Medical University between March 2016 and January 2022. Patients were divided according to the methods used for dealing with UPJO and renal calculi. In Group A, patients underwent traditional open pyeloplasty and pyelolithotomy. In Group B, patients underwent percutaneous nephrolithotomy first and then laparoscopic pyeloplasty. In Group C, patients underwent flexible cystoscopy to remove stones and then laparoscopic pyeloplasty. In Group D, patients underwent flexible vacuum-assisted ureteral access sheath (FV-UAS)assisted flexible ureteroscopy (f-URS) and underwent laparoscopic pyeloplasty. The stones were broken up using a holmium laser. The pyeloplasty success rate, stone clearance rate, operation time, bleeding amount, complication occurrence rate, postsurgical pain, length of stay, and hospitalization cost were compared between the groups. The follow-up period was at least 2 years.ResultsThe use of f-URS and the FV-UAS, significantly increased the renal stone clearance rate and significantly reduced the complication incidence and operation time in UPJO patients with multiple coexisting renal calculi.ConclusionsLaparoscopic pyeloplasty combined with f-URS and FV-UAS is safe and effective for treating UPJO in patients complicated by renal caliceal stones.Trial registrationRetrospectively registered.

Absorbed dose coefficients for pediatric differentiated thyroid cancer patients undergoing radioiodine therapy

The escalating incidence of differentiated thyroid cancer (DTC) in pediatric patients and the resultant growing use of radioactive iodine (RAI) reinforce the need to evaluate radiation exposure to normal tissues and radiation-induced health risks in pediatric patients undergoing RAI therapy. In the current study, we calculated absorbed dose coefficients (i.e. absorbed dose per unit activity administered, mGy MBq−1) specific for pediatric patients with localized DTC undergoing RAI therapy following total thyroidectomy for use in epidemiological studies. We first modified previously-published biokinetic models for adult thyroid cancer patients to achieve a reasonable agreement with iodine biokinetics observed in pediatric patients or design principles addressed in the International Commission on Radiological Protection (ICRP) reference age-specific biokinetic models. We then combined the biokinetic models in conjunction with S values derived from ICRP reference pediatric voxel phantoms. The absorbed dose coefficients for pediatric patients were overall greater than those for adults with a ratio (pediatric/adult) up to 11.6 and rapidly decreased with increasing age. The sensitivity analysis showed that the renal clearance rate and S values may have the greatest impact on the absorbed dose coefficients with the rank correlation coefficients ranging from −0.53 to −0.82 (negative correlations) and from 0.51 to 0.80 (positive correlations), respectively. The results of the current study may be utilized in clinical or epidemiological studies to estimate organ-specific radiation absorbed doses and radiation-associated health risks among pediatric thyroid cancer patients.

Transitioning from a mobile to on-site extracorporeal shockwave lithotripsy service: Is it worth it?

Objectives: The aim of this study was to compare the efficiency and effectiveness of a previous mobile versus current on-site lithotripsy service at a tertiary referral centre. Methods: Patient demographics, stone properties and service provision data were collected; retrospectively for mobile extracorporeal shockwave lithotripsy service (mESWL) between December 2017 and December 2018, and prospectively for on-site extracorporeal shockwave lithotripsy service (osESWL) between March 2019 and March 2020. Results: The overall stone clearance rate for mESWL was 57.1% (68/119) and 79.2% (164/207) for osESWL ( p < 0.01). The overall osESWL ureteric stone clearance was 86.5% (77/89). The renal stone clearance rate with osESWL was greater than mESWL; 73.7% (87/118) versus 55.9% (62/111), p < 0.01. Waiting time for osESWL treatment to renal calculi was significantly lower than mESWL (35 versus 47 days), p < 0.01. To achieve stone clearance, mESWL required a larger proportion (25/111, 22.5%) of additional procedures compared to osESWL (16/118, 13.6%), p = 0.08. There was no significant difference in complication rates with mESWL versus osESWL. Over 5 years, there was a projected cost saving of £627,030 with osESWL compared to £158,660 with mESWL. Conclusion: With increased treatment capacity, higher stone clearance rate and shorter waiting times, the on-site lithotripter delivers a better service compared to a visiting mobile lithotripter. Furthermore, it may cut costs in the long term. Level of evidence: Not applicable.

Cholesterol-Conjugated Supramolecular Multimeric siRNAs: Effect of siRNA Length on Accumulation and Silencing In Vitro and In Vivo.

Conjugation of small interfering RNA (siRNA) with lipophilic molecules is one of the most promising approaches for delivering siRNA in vivo. The rate of molecular weight-dependent siRNA renal clearance is critical for the efficiency of this process. In this study, we prepared cholesterol-containing supramolecular complexes containing from three to eight antisense strands and examined their accumulation and silencing activity in vitro and in vivo. We have shown for the first time that such complexes with 2'F, 2'OMe, and LNA modifications exhibit interfering activity both in carrier-mediated and carrier-free modes. Silencing data from a xenograft tumor model show that 4 days after intravenous injection of cholesterol-containing monomers and supramolecular trimers, the levels of MDR1 mRNA in the tumor decreased by 85% and 68%, respectively. The in vivo accumulation data demonstrated that the formation of supramolecular structures with three or four antisense strands enhanced their accumulation in the liver. After addition of two PS modifications at the ends of antisense strands, 47% and 67% reductions of Ttr mRNA levels in the liver tissue were detected 7 days after administration of monomers and supramolecular trimers, respectively. Thus, we have obtained a new type of RNAi inducer that is convenient for synthesis and provides opportunities for modifications.

Effect of sodium-glucose type 2 cotransporter inhibitors on cardiac structure and function in patients with normal ejection fraction

Abstract Introduction Sodium-glucose cotransporter inhibitors (SGLT2i) have proven a reduction in cardiovascular events in diabetic patients with and without heart failure (HF), as well as in non-diabetic patients with heart failure with reduced and preserved ejection fraction (EF). The mechanisms underlying this benefit are not well known, with contradicting data on the changes that SGLT2i produce on cardiac function and structure. Methods Between October 2020 and October 2021, 31 diabetic patients without prior history of SGLT2i use with normal EF (>50%), glycated hemoglobin <6.5%, renal clearance rate of >60 ml/min/1.73 m2 and sinus rhythm were prospectively included. In all of them, SGLT2i were started. At inclusion and 6-months follow-up, different clinical, ECG, analytical and echocardiographic (standard, 3D and speckle tracking) variables were recorded. Results The average age of our population was 66.4 years (±8.4). 90% were male, 71% were hypertensive, 77.4% were dyslipidemic, 22.6% were obese and 87.1% were current or former smokers. 77.4% of patients had a history of ischemic heart disease, and 10% had vascular disease in other territories. At the time of inclusion, 80.6% of the population was treated with ACEI or ARB, 54.8% with beta-blockers, 29% with diuretics, and 93.5% with statins. After an average follow-up period of 6.6 months (±0.8), medication had to be withdrawn in 5 patients (in 3 of them due to repeated genital or urinary infections, and in 2 of them because of patient choice). An average reduction of 0.89 mm (±0.24, p = 0.001) in myocardial thickness was observed, as well as a reduction in the 3D-estimated left ventricle mass of 9.9 g/m2 (±4.5, p = 0.03), and in the E/é ratio of 1.4 (±4.5, p = 0.02). An increase in absolute left ventricle global longitudinal strain (LVGLS) of 0.74 (±0.35, p = 0.05) was observed, as well as an increase in isovolumetric relaxation time (IVRT) of 9.8 ms (±4.8, p = 0.05). An increase in LA strain and indexed volume was noted, although differences did not achieve statistical significance. No relevant differences in LV dimensions and volumes were observed, as well as in the evaluated RV parameters (picture 1). Conclusions It is necessary to understand the mechanism underlying the clinical benefit of these drugs. This will allow us to better understand its effect in patients with HF. Our data shows that the use of SGLT2i is associated with cardiac improvements, both structural (myocardial mass) and functional (IVRT, LVGLS, E/e'), in a population of patients with normal EF.

A-126 Evaluation of NMR-based GFR Estimation in Dosing of High-dose Methotrexate

Abstract Background The cytotoxic agent methotrexate (MTX) is mainly used in oncology and rheumatology. MTX is 80%–90% excreted unchanged in the urine, thus, impaired renal excretion because of kidney disease leads to accumulation and prolonged exposure, with a consequent increased risk of myelosuppressive and other toxic adverse effects. Direct kidney damage from MTX crystal precipitation and tubular injury may also occur. Therefore, precise and accurate measurement of renal function prior to MTX administration is of paramount importance to determine accurate dosing and to minimize such adverse risks. Commonly used estimated glomerular filtration rate (eGFR) equations perform poorly in patients with cachexia and at later stages of life—the typical oncology patient. Here we evaluate the feasibility of applying the recently introduced nuclear magnetic resonance (NMR)-based GFR equation (GFRNMR) using creatinine, cystatin C, myo-inositol, and valine, in oncology patients receiving high-dose MTX. Methods A series of residual sera from patients scheduled to receive high-dose MTX infusion for oncological indications were collected from two sites: n = 52 sera from the University Hospital Regensburg (Regensburg, Germany), at four time points (t0h, t24h, t42h, and t48h), and n = 10 cross-sectionally from the Mayo Clinic (MN). Standard drug-monitoring trough levels were used as a reference. Serum was prepared and NMR-measured in five replicates for all samples. GFRNMR was compared with the current standard GFR equations: i) CKD-EPI2021Cr (creatinine) and ii) CKD-EPI2021CrCys (creatinine and cystatin-C). Coefficient of determination for linear regression, kappa coefficient for categorical regression and bootstrapped confidence intervals were calculated. Results MTX was shown not to increase the GFRNMR failure rate or affect the intra-assay precision of GFRNMR. When monitoring eGFR during high-dose MTX treatment, MTX affected GFR according to the RIFLE criteria for AKI in 13 cycles in 9 patients; 1/13 were classified as ‘risk’ (creatinine increased 1.5-fold) and 1/13 were classified as ‘injury’ (creatinine increased 2.0-fold). Using MTX clearance as a surrogate for measured GFR, GFRNMR was shown to reflect the MTX plasma clearance constant k more accurately (using a fitting function c = c0*e−kt) with r = 0.758 (95% CI 0.36–0.92, P = 0.004) compared to CKD-EPI2021Cr (r = 0.401, 95%CI −0.19–0.78, P = 0.176) and CKD-EPI2021CrCyc (r = 0.632, 95% CI 0.12–0.88). Conclusion The robustness of GFRNMR test results is not affected by HD-MTX treatment. Compared to standard eGFR equations, GFRNMR is more closely associated with MTX renal clearance rates and may therefore be a novel method to improve the accuracy of MTX dosing in the future.

Enigma of Intramuscular Triamcinolone Acetonide (Kenalog®) Efficacy.

Triamcinolone acetonide is a glucocorticosteroid used in standard clinical practice for its anti-inflammatory properties. Although it can be given via different routes of administration, the intramuscular route is unique compared with other corticosteroids-its effects remain potent over a longer period of time. We summarize the existing literature on the pharmacokinetic and pharmacodynamic mechanisms of intramuscular triamcinolone acetonide (Kenalog®). The fascinating nature of the purported efficacy of triamcinolone acetonide may be attributed to differing binding mechanisms, low solubility in blood, a low renal clearance rate, and various metabolites and other yet defined effects on skin. The enigma of the purported efficacy of triamcinolone acetonide may lie in the fact that it has a unique nature of having a long-term effect on dermatologic disease using a seemingly low dose compared with other routes of administration and other corticosteroids. Possible reasons for this may be binding differences at the intramuscular site, low solubility due to acetonide esters, a slow rate of absorption from the injected site, and a low renal clearance rate. There is still much to be learned about its mechanism of action, which may be of clinical and therapeutic significance.

Comparative pharmacokinetics of six bioactive components of Shen-Wu-Yi-Shen tablets in normal and chronic renal failure rats based on UPLC-TSQ-MS/MS

Ethnopharmacological relevanceShen-Wu-Yi-Shen tablets (SWYST), a Chinese patent medicine consisting of 12 herbal medicines, was formulated by a famous TCM nephrologist, Zou Yunxiang. It is clinically used to improve the symptoms of nausea, vomiting, poor appetite, dry mouth and throat, and dry stool in patients with chronic renal failure (CRF) accompanied by qi and yin deficiency, dampness, and turbidity. SWYST can reduce urea nitrogen, blood creatinine, and urinary protein loss, and increase the endogenous creatinine clearance rate. However, little is known about its pharmacokinetics. Aim of studyTo compare the pharmacokinetics of six bioactive components after oral administration of SWYST in normal and adenine-induced CRF rats. Materials and methodsA method based on ultra-performance liquid chromatography coupled with a triple-stage quadrupole mass spectrometer (UPLC-TSQ-MS/MS) was developed and validated to determine the six bioactive compounds (albiflorin, paeoniflorin, plantagoguanidinic acid, rhein, aloe-emodin, and emodin) in rat plasma. Rat plasma samples were prepared using protein precipitation. Chromatography was performed on an Agilent Eclipse Plus C18 column (3.0 × 50 mm, 1.8 μm) using gradient elution with a mobile phase composed of acetonitrile and water containing 0.1% (v/v) formic acid, while detection was achieved by electrospray ionization MS under the multiple selective reaction monitoring modes. After SWYST administration, rat plasma was collected at different time points, and the pharmacokinetic parameters of six analytes were calculated and analyzed based on the measured plasma concentrations. ResultsThe UPLC-TSQ-MS/MS method was fully validated for its satisfactory linearity (r ≥ 0.9913), good precisions (RSD <11.5%), and accuracy (RE: -13.4∼13.1%), as well as acceptable limits in the extraction recoveries, matrix effects, and stability (RSD <15%). In normal rats, the six analytes were rapidly absorbed (Tmax ≤ 2 h), and approximately 80% of their total exposure was eliminated within 10 h. Moreover, in normal rats, the AUC0-t and Cmax of albiflorin, plantagoguanidinic acid, and rhein exhibited linear pharmacokinetics within the dose ranges, while that of paeoniflorin is non-linear. However, in CRF rats, the six analytes exhibited reduced elimination and significantly different AUC or Cmax values. These changes may reflect a decreased renal clearance rate or inhibition of drug-metabolizing enzymes and transporters in the liver and gastrointestinal tract caused by CRF. ConclusionsA sensitive UPLC-TSQ-MS/MS method was validated and used to investigate the pharmacokinetics of SWYST in normal and CRF rats. This is the first study to investigate the pharmacokinetics of SWYST, and our findings elucidate the causes of their different pharmacokinetic behaviors in CRF rats. Furthermore, the results provide useful information to guide further research on the pharmacokinetic-pharmacodynamic correlation and clinical application of SWYST.

Emerging and Legacy Perfluoroalkyl Substances in Breastfed Chinese Infants: Renal Clearance, Body Burden, and Implications.

Human breast milk is a primary route of exposure to perfluoroalkyl substances (PFAS) in infants. To understand the associated risks, the occurrence of PFAS in human milk and the toxicokinetics of PFAS in infants need to be addressed. We determined levels of emerging and legacy PFAS in human milk and urine samples from Chinese breastfed infants, estimated renal clearance, and predicted infant serum PFAS levels. In total, human milk samples were collected from 1,151 lactating mothers in 21 cities in China. In addition, 80 paired infant cord blood and urine samples were obtained from two cities. Nine emerging PFAS and 13 legacy PFAS were analyzed in the samples using ultra high-performance liquid chromatography tandem mass spectrometry. Renal clearance rates () of PFAS were estimated in the paired samples. PFAS serum concentrations in infants ( year of age) were predicted using a first-order pharmacokinetic model. All nine emerging PFAS were detected in human milk, with the detection rates of 6:2 Cl-PFESA, PFMOAA, and PFO5DoDA all exceeding 70%. The level of 6:2 Cl-PFESA in human milk () ranked third after PFOA () and PFOS (). The estimated daily intake (EDI) values of PFOA and PFOS exceeded the reference dose (RfD) of recommended by the U.S. Environmental Protection Agency in 78% and 17% of breastfed infant samples, respectively. 6:2 Cl-PFESA had the lowest infant (), corresponding to the longest estimated half-life of 49 y. The average half-lives of PFMOAA, PFO2HxA, and PFO3OA were 0.221, 0.075, and 0.304 y, respectively. The of PFOA, PFNA, and PFDA were slower in infants than in adults. Our results demonstrate the widespread occurrence of emerging PFAS in human milk in China. The relatively high EDIs and half-lives of emerging PFAS suggest potential health risks of postnatal exposure in newborns. https://doi.org/10.1289/EHP11403.

Renal clearance of graphene oxide: glomerular filtration or tubular secretion and selective kidney injury association with its lateral dimension

BackgroundRenal excretion is one of the major routes of nanomaterial elimination from the body. Many previous studies have found that graphene oxide nanosheets are excreted in bulk through the kidneys. However, how the lateral size affects GO disposition in the kidneys including glomerular filtration, active tubular secretion and tubular reabsorption is still unknown.ResultsThe thin, two-dimensional graphene oxide nanosheets (GOs) was observed to excrete in urine through the kidneys, but the lateral dimension of GOs affects their renal clearance pathway and renal injury. The s-GOs could be renal excreted via the glomerular filtration, while the l-GOs were predominately excreted via proximal tubular secretion at a much faster renal clearance rate than the s-GOs. For the tubular secretion of l-GOs, the mRNA level of basolateral organic anion transporters Oat1 and Oat2 in the kidney presented dose dependent increase, while no obvious alterations of the efflux transporters such as Mdr1 and Mrp4 mRNA expression levels were observed, suggesting the accumulation of l-GOs. During the GO renal elimination, mostly the high dose of 15 mg/kg s-GO and l-GO treatment showed obvious kidney injuries but at different renal compartment, i.e., the s-GOs induced obvious glomerular changes in podocytes, while the l-GOs induced more obvious tubular injuries including necrosis of renal tubular epithelial cells, loss of brush border, cast formation and tubular dilatation. The specifically tubular injury biomarkers KIM1 and NGAL were shown slight increase with mRNA levels in l-GO administrated mice.ConclusionsThis study shows that the lateral size of GOs affected their interactions with different renal compartments, renal excretion pathways and potential kidney injuries.

In Vitro Properties and Pharmacokinetics of Temporarily PEGylated Onc72 Prodrugs.

The favorable properties of antimicrobial peptides (AMPs) to rapidly kill pathogens are often limited by unfavorable pharmacokinetics due to fast degradation and renal clearance rates. Here, a prodrug strategy linking proline-rich AMP Onc72 to polyethylene glycol (PEGs) with average molecular weights of 5 and 20kDa via a peptide linker containing a protease cleavage site is tested for the first time in vivo. Onc72 is released from these 5k- and 20k-prodrugs in mouse serum with half-life times (t1/2 ) of 8 and 14h, respectively. Importantly, PEGylation protects Onc72 from proteolytic degradation providing a prolonged release of Onc72, balancing the degradation of free Onc72, and leading to relatively stable Onc72 concentrations and high antibacterial activities. The prodrugs are not hemolytic on human erythrocytes and show only slight cytotoxic effects on human cell lines indicating promising safety margins. When administered subcutaneously to female CD-1 mice, the prodrugs elimination t1/2 are 66min and ≈5.5h, respectively, compared to 43min of free Onc72. The maximal Onc72 plasma levels are obtained ≈1 and ≈8h postadministration, respectively. In conclusion, the prodrugs provide extended elimination t1/2 and a constant release of Onc72 in mice, potentially limiting adverse effects and increasing efficacy.

An Observational Pilot Study on Supine Percutaneous Nephrolithotomy: Initial Experience at a Single-Centre.

Objective To assess the surgical outcome of supine percutaneous nephrolithotomy (PCNL) in patients with co-morbidities. Materials and methods We retrospectively reviewed the data of 15 patients who underwent supine PCNL at our centre from September 2019 to May 2021. Preoperatively, a complete examination of the patients, along with biochemical and radiological investigations, was done. The data, which included patient demographics, comorbidities, complexity of renal calculi, complications, and stone clearance rate, were collected from the patients' medical records. Results Patients aged between 31 and 70 years were included in the study. The mean (SD) BMI was 26.01 (2.31). Twelve patients (80%) were overweight with a BMI of 25.3 to 29.3 kg/m2. The most common comorbidities were diabetes (33.3%) and hypertension (26.7%). In our study, six patients were American Society of Anesthesiologists (ASA) grade 3 (40%), followed by grade 2 in five patients (33.3%), grade 4, and grade 1 in two patients (13.3%) each. The Guy's Stone score was one in nine patients (60%) and two in six patients (40%). Complete clearance was achieved in 13 (86.7%) patients. Two patients (13.3%) had a stone clearance of more than 80%. Data analysis showed that 14 patients (93.3%) had no perioperative complications. Postoperative abdominal distension was noted in one patient (6.7%), which was managed conservatively (Clavien-Dindo grade 1). We did not encounter any cases of organ injury following supine PCNL. Postoperatively, none of our patients received blood transfusions. Conclusion Our study shows that supine PCNL is a good surgical option, especially for high-risk patients with good stone clearance and low complication rates.

Impact of baseline renal function on the efficacy and safety of different Anticoagulants in Atrial Fibrillation Patients – A cohort study

BackgroundVitamin K antagonists and different direct oral anticoagulants (DOACs) have different renal clearance rates. However, the impact of different stages of chronic renal impairment on the efficacy and safety of warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban in atrial fibrillation (AF) patients remains unclear.MethodsThis study enrolled AF patients from the Chang Gung Research Database. The study endpoints included thromboembolic events, major/fatal bleeding, gastrointestinal (GI) bleeding and intracranial hemorrhage (ICH). The risks of time to study endpoints between groups were compared using a Cox proportional hazards regression model with adjustment.ResultsThis study enrolled 3525 patients with moderate renal impairment (30 ≤ creatinine clearance (CrCl) < 60 mL/min), 2846 patients with mild renal impairment (60 ≤ CrCl < 90 mL/min) and 1153 patients with CrCl ≥ 90 mL/min. Over the 3.3 ± 0.9 years follow-up period, the cumulative thromboembolic events rates and the cumulative event rates of major/fatal bleeding and ICH did not differ among the warfarin and different DOAC groups at different stages of chronic renal impairment. The annual incidences of thromboembolic events, major/fatal bleeding, GI bleeding, and ICH were similar among the warfarin and different DOAC groups at different stages of renal impairment.ConclusionThere did not appear to be major differences in bleeding or thromboembolic risk compared to warfarin in AF patients across a range of degree of renal failure when appropriate dose reductions of the DOACs are made.

Anatrophic Nehphrolithotomy: Preservation of Renal Function and Stone Clearance Rate

Aim: To assess the outcomes of anatrophic nephrolithotomy in terms of stone clearance and change in renal function. Study design: Observational study Place and duration of study: Department of Urology Sindh Institute of Urology &amp; Transplantation, Karachi from 1st January 2016 to 31st December 2021. Methodology: Fifty patients who underwent anatrophic nephrolithotomy from were enrolled. Outcomes were measured in terms of stone clearance, change in pre and post procedure eGFR, serum creatinine and differential renal function on renal scan (MAG-3 scan). Results: There were 30 (60%) males and 20 (40%) females with mean age was 5.96±13.09 years. Post-operative serum creatinine and eGFR were compared with pre-operative values and no statistically significant difference observed. Comparison of pre-operative and post-operative 99mTc-mercaptoacetyltriglycine (MAG3) scans revealed statistically significant mild loss of renal function with p-value of0.376. Conclusion: Anatrophic nephrolithotomy can be an alternative for multi tract PCNL when there is huge stone burden as it yields excellent stone clearance, and it can be practiced fearlessly for large staghorn stones because they can become the frequent cause of infections and mortality. Although parenchymal damage after anatrophic nephrolithotomy is of concern, renal dysfunction is usually clinically insignificant. Key words: Anatrophic nephrolithotomy, Staghorn stone, Renal calculi

Residual Renal Phosphate Clearance in Patients Receiving Hemodialysis or Hemodiafiltration

Substantial levels of residual renal clearance and urine output may occur in patients treated with hemodialysis or hemodiafiltration. However, the relationships among residual renal urea, creatinine, and phosphate clearances, respectively, and between clearances and urine volume have not been well described. We performed a prospective, cross-sectional study which enrolled hemodialysis and hemodiafiltration patients with a urine volume of >100mL/day, in whom at least 2 residual renal clearances were obtained over a 6-month observation period. Urine was collected for 24hours prior to the midweek treatment session and concentrations of urea, creatinine, and phosphate were measured. Thirty-eight patients (24 men, 14 women) with a mean age of 70.4±12.4 (SD) years were included in this analysis. All patients were dialyzed 3 times per week with mean treatment duration of 243±7.89minutes. Twenty patients were undergoing hemodiafiltration and 18 patients high-flux hemodialysis. In total, 102 dialysis sessions, of which 52 were hemodiafiltration, and urine collections were analyzed. Mean urine volume was 457±254mL per 24hours. Residual renal clearance rates of urea (Kr Urea), creatinine (Kr Cr), and phosphate (Kr Phos) were 1.60±0.979, 4.69±3.79, and 1.98±1.36mL/minute, respectively. Mean ratios of Kr Cr/Kr Urea, Kr Phos/Kr Urea, and Kr Phos/Kr Cr were 2.83±1.21, 1.23±0.387, and 0.477±0.185, respectively. There was a modest correlation between Kr Phos and daily urine volume (r=0.605, P=.001). In maintenance hemodialysis and hemodiafiltration patients, residual renal phosphate clearance is approximately 23% higher than residual renal urea clearance. Urine volume is a modestly accurate surrogate for estimating residual renal phosphate clearance, but only when urine volume is <300mL/day.

Synthesis of Renal-Clearable Multicolor Fluorescent Silicon Nanodots for Tumor Imaging and In Vivo H2O2 Profiling.

Fluorescent silicon nanodots have shown great prospects for bioimaging and biosensing applications. Although various fluorescent silicon-containing nanodots (SiNDs) have been developed, there are few reports about renal-clearable multicolor SiNDs. Herein, renal-clearable multicolor fluorescent SiNDs are synthesized by using silane molecules and organic dyes through a facile one-step hydrothermal method. The fluorescence of the resulting SiNDs can be tuned to blue (bSiNDs), green (gSiNDs), and red (rSiNDs) by simply changing the categories of silane reagents or dye molecules. The as-prepared SiNDs exhibit strong fluorescence with a quantum yield up to 72%, excellent photostability, and good biocompatibility with 12 h renal clearance rate as high as 86% ID. These properties enabled the SiNDs for tumor fluorescence imaging and H2O2 imaging in living cells and tissue through in situ reduction reaction-lighted fluorescence of the nanoprobe. Our results provide an invaluable methodology for the synthesis of renal-clearable multicolor SiNDs and their potential applications for fluorescence imaging and biomarker sensing. These SiNDs are also promising for various biological and biomedical applications.

Physiologically based pharmacokinetic modeling of intravenously administered nanoformulated substances

The use of nanobiomaterials (NBMs) is becoming increasingly popular in the field of medicine. To improve the understanding on the biodistribution of NBMs, the present study aimed to implement and parametrize a physiologically based pharmacokinetic (PBPK) model. This model was used to describe the biodistribution of two NBMs after intravenous administration in rats, namely, poly(alkyl cyanoacrylate) (PACA) loaded with cabazitaxel (PACA-Cbz), and LipImage™ 815. A Bayesian parameter estimation approach was applied to parametrize the PBPK model using the biodistribution data. Parametrization was performed for two distinct dose groups of PACA-Cbz. Furthermore, parametrizations were performed three distinct dose groups of LipImage™ 815, resulting in a total of five different parametrizations. The results of this study indicate that the PBPK model can be adequately parametrized using biodistribution data. The PBPK parameters estimated for PACA-Cbz, specifically the vascular permeability, the partition coefficient, and the renal clearance rate, substantially differed from those of LipImage™ 815. This emphasizes the presence of kinetic differences between the different formulations and substances and the need of tailoring the parametrization of PBPK models to the NBMs of interest. The kinetic parameters estimated in this study may help to establish a foundation for a more comprehensive database on NBM-specific kinetic information, which is a first, necessary step towards predictive biodistribution modeling. This effort should be supported by the development of robust in vitro methods to quantify kinetic parameters.Graphical abstract

Bisphenol-diglycidyl ethers in paired urine and serum samples from children and adolescents: Partitioning, clearance and exposure assessment

Bisphenol A diglycidyl ether (BADGE), bisphenol F diglycidyl ether (BFDGE), and their derivatives are frequently used in food packaging materials. Some toxicological studies have shown that the endocrine-disrupting activities of these compounds are similar to or higher than those of bisphenol A (BPA), which may also adversely affect the growth and development of children and adolescents. Here, we investigated nine bisphenol-diglycidyl ethers (BDGEs) in 181 paired urine and serum samples from children and adolescents from Beijing to determine their partitioning, clearance and exposure levels. The results showed that nine BDGEs were detected in 181 urine and serum samples from children and adolescents from Beijing. Bisphenol A bis(2,3-dihydroxypropyl) glycidyl ether (BADGE·2H2O) was the primary pollutant. The daily intake of ∑BDGEs was 15.217 ng/kg bw/day among children and adolescents in Beijing. The ranking of BDGEs in terms of renal clearance rate (CLrenal) in this study population was BADGE > BADGE·2H2O > BFDGE > bisphenol F bis(3-chloro-2-hydroxypropyl) glycidyl ether (BFDGE·2HCl) > bisphenol A (3-chloro-2-hydroxypropyl) (2,3-dihydroxypropyl) glycidyl ether (BADGE·HCl·H2O). In addition, the serum and urine ratios (S/U ratios) of BFDGE·2HCl, BADGE·2H2O, BFDGE, BADGE, and BADGE·HCl·H2O were higher than 1, indicating that these contaminants have a higher enrichment capacity in human blood. To our knowledge, this is the first study on the partitioning and renal clearance rate of BDGEs in paired urine and serum samples from children and adolescents.