Abstract P247: Elastin Insufficiency Impairs Renal Hemodynamics And Accelerates Aging-associated Structural And Functional Remodeling Of Preglomerular Arterioles

Elastin degradation and fragmentation are hallmarks of arterial stiffness and renal dysfunction associated with aging. However, it is unclear whether elastin insufficiency contributes to the changes in the structure and function of the resistance vasculature of the kidney during aging. Here we determined how increased vascular stiffness due to elastin insufficiency alters renal hemodynamics and mechanical properties of preglomerular arterioles. We assessed renal hemodynamics under anesthesia in 14-16-month-old female wild type (WT) and elastin heterozygous ( Eln +/- ) mice. Renal autoregulation was assessed by a stepwise increase in renal perfusion pressure (RPP) by simultaneously occluding the superior mesenteric and celiac arteries. Myogenic constriction and arterial stiffness were assessed by pressure myography of isolated renal interlobar arteries. Baseline renal vascular resistance (RVR) was elevated in Eln +/- mice (13.8 ± 2.9 vs 11.2 ± 1.4 mmHg/μL/min/g left kidney weight), while systolic blood pressure (SBP; 75.1 ± 7.4 vs 91 ± 4.2mmHg), renal blood flow (RBF; 6.3 ± 1.2 vs 7.4 ± 1.7 μL/min/g left kidney weight), renal plasma flow (RPF; 3.4 ± 0.8 vs 5 ± 1.2 mL/min/g/ left kidney weight) and urine flow rate, all trended lower in Eln +/- mice compared to WT mice. Glomerular filtration rate (GFR) and filtration fraction (FF) were similar between the two groups. A stepwise increase in RPP caused a slower decline and rise in RBF and RVR, respectively, in Eln +/- relative to WT mice. The maximal changes in RBF (5 ± 1.1 vs 4.7 ± 0.8 μL/min/g left kidney weight), RVR (17.6 ± 7.3 vs 22.5 ± 2.1 mmHg/μL/min/g left kidney weight), urine flow rate,GFR, and FF were less robust in Eln +/- mice. RPF decreased in WT mice in response to raising RPP, whereas it remained unchanged in Eln +/- mice. Myogenic response and increases in elastic modulus and wall tension following stepwise changes in intraluminal pressure were all augmented in interlobar arteries from Eln +/- relative to WT mice. However, there was no difference in kidney weight/tibia length ratio between the two genotypes. We conclude that elastin insufficiency impairs renal hemodynamics by exacerbating age associated increase in vascular stiffness.

Urine Quantification Following Furosemide for Severe Acute Kidney Injury Prediction in Critically Ill Children

A standardized, quantified assessment of furosemide responsiveness predicts acute kidney injury (AKI) in children after cardiac surgery and AKI progression in critically ill adults. The purpose of this study was to determine if response to furosemide is predictive of severe AKI in critically ill children outside of cardiac surgery. We performed a multicenter retrospective study of critically ill children. Quantification of furosemide response was based on urine flow rate (normalized for weight) measurement 0 to 6 hours after the dose. The primary outcome was presence of creatinine defined severe AKI (Kidney Disease Improving Global Outcomes stage 2 or greater) within 7 days of furosemide administration. Secondary outcomes included mortality, duration of mechanical ventilation and length of stay. A total of 110 patients were analyzed. Severe AKI occurred in 20% (n = 22). Both 2- and 6-hour urine flow rate were significantly lower in those with severe AKI compared with no AKI (p = 0.002 and p < 0.001). Cutoffs for 2- and 6-hour urine flow rate for prediction of severe AKI were <4 and <3 mL/kg/hour, respectively. The adjusted odds of developing severe AKI for 2-hour urine flow rate of <4 mL/kg/hour was 4.3 (95% confidence interval [CI]: 1.33–14.15; p = 0.02). The adjusted odds of developing severe AKI for 6-hour urine flow rate of <3 mL/kg/hour was 6.19 (95% CI: 1.85–20.70; p = 0.003). Urine flow rate in response to furosemide is predictive of severe AKI in critically ill children. A prospective assessment of urine flow rate in response to furosemide for predicting subsequent severe AKI is warranted.

Tailored Versus Standard Hydration to Prevent Acute Kidney Injury After Percutaneous Coronary Intervention: Network Meta‐Analysis

Background Contrast‐induced acute kidney injury (CI‐AKI) is a serious complication after percutaneous coronary intervention. The mainstay of CI‐AKI prevention is represented by intravenous hydration. Tailoring infusion rate to patient volume status has emerged as advantageous over fixed infusion‐rate hydration strategies. Methods and Results A systematic review and network meta‐analysis with a frequentist approach were conducted. A total of 8 randomized controlled trials comprising 2312 patients comparing fixed versus tailored hydration strategies to prevent CI‐AKI after percutaneous coronary intervention were included in the final analysis. Tailored hydration strategies included urine flow rate–guided, central venous pressure–guided, left ventricular end‐diastolic pressure–guided, and bioimpedance vector analysis–guided hydration. Primary endpoint was CI‐AKI incidence. Safety endpoint was incidence of pulmonary edema. Urine flow rate–guided and central venous pressure–guided hydration were associated with a lower incidence of CI‐AKI compared with fixed‐rate hydration (odds ratio [OR], 0.32 [95% CI, 0.19–0.54] and OR, 0.45 [95% CI, 0.21–0.97]). No significant difference in pulmonary edema incidence was observed between the different hydration strategies. P score analysis showed that urine flow rate–guided hydration is advantageous in terms of both CI‐AKI prevention and pulmonary edema incidence when compared with other approaches. Conclusions Currently available hydration strategies tailored on patients' volume status appear to offer an advantage over guideline‐supported fixed‐rate hydration for CI‐AKI prevention after percutaneous coronary intervention. Current evidence suggests that urine flow rate–guided hydration as the most convenient strategy in terms of effectiveness and safety.

Clinical Relevance of Urine Flow Rate and Exposure to Polycyclic Aromatic Hydrocarbons

Background: Polycyclic aromatic hydrocarbon (PAH) metabolites have received increasing attention because several of these organic substances are highly carcinogenic or mutagenic. Exposure to PAHs is associated with many harmful health effects; however, we are not aware of any study that has explored the exposure to PAHs and urinary conditions in the general population. The present work aimed to investigate the correlation among PAH and urine flow rate (UFR). Method: Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2009–2012 were used in our study. A total of 4172 participants and a total of nine PAH metabolites were examined. The UFR was measured as the amount of urine excreted in a period of time (mL/h). Several covariates were adjusted in linear regression models. Result: After adjusting for variables, the PAH metabolites in urine showed a significant correlation with UFR. Dose-dependent associations between PAH metabolites in the urine and UFR were also found. Higher quartiles of PAH metabolites in urine exhibited higher regression coefficients. Conclusion: Our study highlighted that PAH metabolites in urine had a strong association with decreased UFR in the US adult population. These findings support the possibility that PAH exposure is related to bladder dysfunction. Further prospective studies are warranted.

Correlation of prostate volume with severity of lower urinary tract symptoms as measured by international prostate symptoms score and maximum urine flow rate among patients with benign prostatic hyperplasia

Background The aim of the study is to find the correlation between the prostate volume and severity of lower urinary tract symptoms (LUTS) as measured by international prostate symptoms score and maximum urine flow rate among patients with benign prostatic hyperplasia (BPH). Methods The study was a prospective correlational study conducted between June 2016 and November 2017. A total of 290 patients who presented with LUTS suggestive of BPH and satisfied the inclusion criteria were consecutively recruited. Clinical evaluation including digital rectal examination of the prostate was done. Symptoms severity was assessed using the self-administered international prostate symptoms score (IPSS) questionnaire. Prostate volume was determined by transrectal ultrasound scan, and the urine flow rate was measured using uroflowmeter. Data were analyzed using SPSS version 20.0, and p value < 0.05 was taken to be statistically significant. Results The mean age of the patients was 64.22 ± 9.04 years with a range of 40 to 95 years. Most of the patients had moderate symptoms (55%) on IPSS with the mean IPSS value of 16.41 ± 7.43. The mean Qmax value was 16.55 ± 7.41 ml/s, and the median prostate volume (IQR) was 45.05 (35, 59). There was a positive significant correlation between prostate volume and IPSS (r = 0.179, p = 0.002) and a negative significant correlation between prostate volume and Qmax (r = − 0.176, p = 0.003). Conclusion This study showed a significant correlation between the prostate volume and IPSS, and also between prostate volume and maximum flow rate (Qmax).

Outcome of Anastomotic Urethroplasty in Posterior Urethral Distraction Defect With or Without Mucosal Fixation- a Randomized Clinical Trial

Introduction: Anastomotic urethroplasty is the treatment of choice for posterior urethral distraction defect. To notice the high failure rate of anastomotic urethroplasty, several peri-operative factors are identified. Among the per-operative factors, mucosal fixation of the both urethral ends is one of the outcome influencing factor that is recently identified. So, this randomized clinical trial has been designed to compare the outcome of anastomotic urethroplasty in posterior urethral distraction defects with or without mucosal fixation. Objective: To compare the outcome of anastomotic urethroplasty of PUDD patient groups with or without mucosal fixation in terms of post-operative IPSS, maximum urine flow rate and post void residual urine. Patients and Methods: The present study was conducted in the department of Urology, BSMMU between January’16 - November’17. Posterior urethral distraction defects with length of gap between two urethral segments upto 3 cm. were included in the study. The patients in whom anastomotic urethroplasty were done with mucosal fixation were enrolled as study group(n=21) and patients in whom anastomotic urethroplasty were done without mucosal fixation were included as control group(n=21). All the patients were followed upto 6 months of anstomotic urethroplasty and failure of anastomotic urethroplasty (by RGU and MCU), PVR and maximum urine flow rate (Qmax) in between two groups were compared. Result: The failure rate was found significantly higher in control group than in the study group (p=0.043). The control group showed highly significant (0.001) increase in postoperative PVR than the study group and the study group showed significant (0.007) increase in post operative maximum urine flow rate than the control group as was assumed in the hypothesis. Conclusion: In conclusion, it can be said that anastomotic urethroplasty with mucosal fixation is a better option than anstomotic urethroplasty without mucosal fixation. But multicentric trial is needed to further comment. Bangladesh Journal of Urology, Vol. 21, No. 1, January 2018 p.31-34

Exploring the Association between Urine Caffeine Metabolites and Urine Flow Rate: A Cross-Sectional Study

Examination of urine excretion of caffeine metabolites has been a simple but common way to determine the metabolism and effect of caffeine, but the relationship between urinary metabolites and urine flow rate is less discussed. To explore the association between urinary caffeine metabolite levels and urine flow rate, 1571 participants from the National Health and Nutrition Examination Survey (NHANES) 2011–2012 were enrolled in this study. We examined the association between urinary caffeine metabolites and urine flow rate with linear regression models. Separate models were constructed for males and females and for participants aged <60 and ≥60 years old. A positive association was found between concentrations of several urinary caffeine metabolites and urine flow rate. Three main metabolites, namely, paraxanthine, theobromine, and caffeine, showed significance across all subgroups. The number of caffeine metabolites that revealed flow-dependency was greater in males than in females and was also greater in the young than in the elderly. Nevertheless, the general weakness of NHANES data, a cross-sectional study, is that the collection is made at one single time point rather than a long-term study. In summary, urinary concentrations of several caffeine metabolites showed a positive relationship with the urine flow rate. The trend is more noticeable in males and in young subgroups.