Urinary Clearance Research Articles

Subcutaneous regular insulin use for the management of diabetic ketoacidosis in resource limited setting.

The standard recommendation of insulin therapy for patients with DKA is the administration of slow continuous intravenous (IV) regular insulin. Currently subcutaneous insulin is being recommended as an alternative treatment of DKA in mild and moderate cases in resource-limited settings. The purpose of this study was to assess the effectiveness and safety of six-hourly subcutaneous regular insulin use for the treatment of DKA among children with type one diabetes mellitus. A retrospective cohort study was conducted among 224 DKA episodes which occurred in 161 children who were treated at St. Paul's Hospital Millennium Medical College in Addis Ababa, Ethiopia, from November 2015 to November 2020. Majority (68.8%) of the episodes occurred in newly diagnosed cases. The median time for urinary ketones clearance was 24h. DKA severity was found to be the only significant predictor of time to DKA resolution. Only 13 (5.8%) were treated at the pediatric intensive care unit (PICU), and 27 (12.1%) developed complications during management. No death or neurological complications observed. The six-hourly subcutaneous regular insulin use was found to be safe and effective alternative to slow IV insulin infusion for the treatment of DKA in a non PICU setting. As it resulted in minimum morbidity and no mortality, we recommend its use in the treatment of DKA irrespective of its severity. It can also decrease the health care cost and patients' inconvenience.

Measured Glomerular Filtration Rate: The Query for a Workable Golden Standard Technique.

Inulin clearance has, for a long time, been considered as the reference method to determine measured glomerular filtration rates (mGFRs). However, given the known limitations of the standard marker, serum creatinine, and of inulin itself, and the frequent need for accurate GFR estimations, several other non-radioactive (iohexol and iothalamate) and radioactive (51Cr-EDTA, 99mTc-DTPA, 125I iothalamate) exogenous mGFR filtration markers are nowadays considered the most accurate options to evaluate GFR. The availability of 51Cr-EDTA is limited, and all methods using radioactive tracers necessitate specific safety precautions. Serum- or plasma-based certified reference materials for iohexol and iothalamate and evidence-based protocols to accurately and robustly measure GFR (plasma vs. urinary clearance, single-sample vs. multiple-sample strategy, effect of sampling time delay) are lacking. This leads to substantial variation in reported mGFR results across studies and questions the scientific reliability of the alternative mGFR methods as the gold standard to evaluate kidney function. On top of the scientific discussion, regulatory issues are further narrowing the clinical use of mGFR methods. Therefore, this review is a call for standardization of mGFR in terms of three aspects: the marker, the analytical method to assess concentrations of that marker, and the procedure to determine GFR in practice. Moreover, there is also a need for an endogenous filtration marker or a panel of filtration markers from a single blood draw that would allow estimation of GFR as accurately as mGFR, and without the need for application of anthropometric, clinical, and demographic characteristics.

Hypertensive Diseases in Pregnancy and Kidney Function Later in Life: The Genetic Epidemiology Network of Arteriopathy (GENOA) Study

ObjectiveTo evaluate the relationship between hypertensive diseases in pregnancy and kidney function later in life. MethodsWe evaluated measured glomerular filtration rate (mGFR) using iothalamate urinary clearance in 725 women of the Genetic Epidemiology Network of Arteriopathy (GENOA) study. Women were classified by self-report as nulliparous (n=62), a history of normotensive pregnancies (n=544), a history of hypertensive pregnancies (n=102), or a history of pre-eclampsia (n=17). We compared adjusted associations among these four groups with mGFR using generalized estimating equations to account for familial clustering. Chronic kidney disease (CKD) was defined as mGFR of less than 60 mL/min per 1.73 m2 or urinary albumin-creatinine ratio (UACR) greater than or equal to 30 mg/g. ResultsAmong women with kidney function measurements (mean age, 59±9 years, 52.9% African American), those with a history of hypertensive pregnancy had lower mGFR (–4.66 ml/min per 1.73 m2; 95% CI, -9.12 to -0.20) compared with women with a history of normotensive pregnancies. Compared with women with a history of normotensive pregnancies, women with a history of hypertensive pregnancy also had higher odds of mGFR less than 60 ml/min per 1.73 m2 (odds ratio, 2.09; 95% CI, 1.21 to 3.60). Additionally, women with a history of hypertensive pregnancy had greater odds for chronic kidney disease (odds ratio, 4.89; 95% CI, 1.55 to 15.44), after adjusting for age, race, education, smoking history, hypertension, body mass index, and diabetes. ConclusionA history of hypertension in pregnancy is an important prognostic risk factor for kidney disease. To our knowledge, this is the first and largest investigation showing the association between hypertensive diseases in pregnancy and subsequent kidney disease using mGFR in a large biracial cohort.

MP07-20 INITIAL EXPERIENCE: EX-VIVO PERFUSED PIG KIDNEY TO STUDY URINARY OXALATE EXCRETION

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology (MP07)1 Sep 2021MP07-20 INITIAL EXPERIENCE: EX-VIVO PERFUSED PIG KIDNEY TO STUDY URINARY OXALATE EXCRETION Jonathan Pavlinec, Mark Martin, William Donelan, Elizabeth Kwenda, Paul Dominguez-Gutierrez, Vincent Bird, and Benjamin Canales Jonathan PavlinecJonathan Pavlinec More articles by this author , Mark MartinMark Martin More articles by this author , William DonelanWilliam Donelan More articles by this author , Elizabeth KwendaElizabeth Kwenda More articles by this author , Paul Dominguez-GutierrezPaul Dominguez-Gutierrez More articles by this author , Vincent BirdVincent Bird More articles by this author , and Benjamin CanalesBenjamin Canales More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001980.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Existing animal models of renal oxalate excretion utilize either gut or peritoneal cavity for oxalate absorption. Ex vivo renal perfusion is an established tool for graft preservation. We sought to repurpose this concept in order to study the early pathogenesis of urinary lithiasis. METHODS: Juvenile female Yorkshire porcine kidneys were removed laparoscopically and placed on an ex vivo neonatal cardiopulmonary bypass circuit utilizing whole-blood based perfusate oxygenated with 95% carbogen. Pre-defined goals were identified for each attempt (n=5) with plans to increase physiologic model complexity. Tissue perfusion and oxygenation was monitored by serial perfusate iSTAT testing. Once steady urine production was achieved, aqueous oxalate was injected into the perfusate. Renal outcomes were assessed by histology and blood/urinary assays. RESULTS: After demonstrating proof-of-concept in early trials, normothermic (37C) ex vivo whole-blood perfusion with Steen SolutionTM was performed exceeding three hours at physiologic mean arterial pressures. Circuit parameters remained in the physiologic range for electrolytes, temperature, mean arterial pressure, lactate, and pH. Urine was produced in three experiments, with two additional attempts stopped early due to challenges related to hilar cannulation. Urinary filtrate demonstrated consistently higher urine creatinine compared to perfusate, and arterial perfusate oxalate boluses lead to urinary oxalate spikes followed by continuous oxalate clearance. Histopathologic analysis with H&E and Pizzolato’s method staining demonstrated formation of calcium oxalate crystals. CONCLUSIONS: In light of promising renal urinary oxalate and creatinine clearance, ex vivo porcine renal perfusion appears to be a feasible alternative to study oxalate excretion. Longer validation studies are necessary to establish this technique as a model for kidney stone pathogenesis. Source of Funding: No extra-instatutional funding was utilized for this project © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e147-e148 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jonathan Pavlinec More articles by this author Mark Martin More articles by this author William Donelan More articles by this author Elizabeth Kwenda More articles by this author Paul Dominguez-Gutierrez More articles by this author Vincent Bird More articles by this author Benjamin Canales More articles by this author Expand All Advertisement Loading ...

Technetium‐99m‐MAG3 and technetium‐99m‐DTPA: Renal clearance measured by the constant infusion technique – Old news?

Accurate, precise and straightforward methods for measuring glomerular filtration rate (GFR) and/or renal plasma flow (RPF) are still in demand today. The time-consuming constant infusion technique (CIT) is the gold standard and preferred for research, whereas the simple, but less precise, single injection technique (SIT) is used in clinical settings. This study investigated the use of 99m Tc-DTPA and 99m Tc-MAG3 by CIT as a measure of renal function. We developed and evaluated a model to balance the primer dose and infusion rate in an attempt to obtain plasma steady state as quickly as possible. 14healthy subjects received 99m Tc-DTPA and 6hypertensive patients received 99m Tc-MAG3 in a standardized protocol. All participants had an eGFR above 60 ml/min and none had fluid retention. An intravenous primer injection of the relevant tracer was followed by a sustained infusion over 4.5h with the same radiopharmaceutical. Blood and urine samples were collected at fixed intervals. 99m Tc-DTPA clearance reached steady state after 210min (plasma clearance 78±18ml/min, urine clearance 110±28ml/min), whereas 99m Tc-MAG3 clearance achieved steady state after 150min (plasma clearance 212±56ml/min, urine clearance 233±59ml/min). Constant infusion technique with fixed primer and infusion rate using 99m Tc-MAG3 is feasible for research purposes. The longer time for reaching plasma steady state using 99m Tc-DTPA makes CIT with this tracer less optimal. If the primer/sustained balance can be optimized, for example using a priori SIT information, 99m Tc-DTPA as tracer for CIT may also be feasible.

Expression of adipokines in children with primary nephrotic syndrome and its association with hyperlipidemia.

To study the expression of adipokines in children with primary nephrotic syndrome (PNS) before and after treatment and its correlation with blood lipids, as well as the role of adipokines in PNS children with hyperlipidemia. A total of 90 children who were diagnosed with incipient PNS or recurrence of PNS after corticosteroid withdrawal for more than 6 months were enrolled as subjects. Thirty children who underwent physical examination were enrolled as the control group. Venous blood samples were collected from the children in the control group and the children with PNS before corticosteroid therapy (active stage) and after urinary protein clearance following 4 weeks of corticosteroid therapy (remission stage). ELISA was used to measure the levels of adipokines. An automatic biochemical analyzer was used to measure blood lipid levels. Compared with the control group, the children with PNS had a significantly lower level of omentin-1 in both active and remission stages, and their level of omentin-1 in the active stage was significantly lower than that in the remission stage (P<0.001). For the children with PNS, the level of chemerin in the active stage was significantly higher than that in the remission stage, and the children with PNS in the active stage had a significantly higher level of chemerin than the control group (P<0.001). For the children with PNS, atherogenic index of plasma, atherogenic coefficient (AC), castelli risk index-1 (CRI-1), castelli risk index-2 (CRI-2), and non-high-density lipoprotein in the active stage were significantly higher than those in the remission stage (P<0.001), and these indices in the children with PNS in the active stage were significantly higher than those in the control group (P<0.001). The children with PNS in the remission stage had significantly higher atherogenic index of plasma, AC, CRI-1, and non-high-density lipoprotein than the control group (P<0.001). Compared with the control group, the children with PNS in the remission stage had significantly higher serum levels of total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, apolipoprotein B, and apolipoprotein A (P<0.01). In the children with PNS, the ratio of omentin-1 before and after corticosteroid therapy was positively correlated with that of high-density lipoprotein, 24-hour urinary protein excretion, and high-density lipoprotein/apolipoprotein A before and after treatment, and it was negatively correlated with the ratio of AC and CRI-1 before and after treatment (P<0.05). The PNS children with low omentin-1 levels in the active stage had significantly higher levels of CRI-1, CRI-2, AC, and apolipoprotein B/apolipoprotein A ratio than those with high omentin-1 levels (P<0.05). Omentin-1 may be associated with disease activity, dyslipidemia, and proteinuria in children with PNS. Blood lipid ratios may be more effective than traditional blood lipid parameters in monitoring early cardiovascular risk in children with PNS.

Impact of cumulative fluid balance on the pharmacokinetics of extended infusion meropenem in critically ill patients with sepsis

BackgroundMeropenem dosing for septic critically patients is difficult due to pathophysiological changes associated with sepsis as well as supportive symptomatic therapies. A prospective single-center study assessed whether fluid retention alters meropenem pharmacokinetics and the achievement of the pharmacokinetic/pharmacodynamic (PK/PD) targets for efficacy.MethodsTwenty-five septic ICU patients (19 m, 6f) aged 32–86 years with the mean APACHE II score of 20.2 (range 11–33), suffering mainly from perioperative intra-abdominal or respiratory infections and septic shock (n = 18), were investigated over three days after the start of extended 3-h i.v. infusions of meropenem q8h. Urinary creatinine clearance (CLcr) and cumulative fluid balance (CFB) were measured daily. Plasma meropenem was measured, and Bayesian estimates of PK parameters were calculated.ResultsEleven patients (9 with peritonitis) were classified as fluid overload (FO) based on a positive day 1 CFB of more than 10% body weight. Compared to NoFO patients (n = 14, 11 with pneumonia), the FO patients had a lower meropenem clearance (CLme 8.5 ± 3.2 vs 11.5 ± 3.5 L/h), higher volume of distribution (V1 14.9 ± 3.5 vs 13.5 ± 4.1 L) and longer half-life (t1/2 1.4 ± 0.63 vs 0.92 ± 0.54 h) (p < 0.05). Over three days, the CFB of the FO patients decreased (11.7 ± 3.3 vs 6.7 ± 4.3 L, p < 0.05) and the PK parameters reached the values comparable with NoFO patients (CLme 12.4 ± 3.8 vs 11.5 ± 2.0 L/h, V1 13.7 ± 2.0 vs 14.0 ± 5.1 L, t1/2 0.81 ± 0.23 vs 0.87 ± 0.40 h). The CLcr and Cockroft–Gault CLcr were stable in time and comparable. The correlation with CLme was weak to moderate (CLcr, day 3 CGCLcr) or absent (day 1 and 2 CGCLcr). Dosing with 2 g meropenem q8h ensured adequate concentrations to treat infections with sensitive pathogens (MIC 2 mg/L). The proportion of pre-dose concentrations exceeding the MIC 8 mg/L and the fraction time with a target-exceeding concentration were higher in the FO group (day 1–3 f Cmin > MIC: 67 vs 27%, p < 0.001; day 1%f T > MIC: 79 ± 17 vs 58 ± 17, p < 0.05).ConclusionsThese findings emphasize the importance of TDM and a cautious approach to augmented maintenance dosing of meropenem to patients with FO infected with less susceptible pathogens, if guided by population covariate relationships between CLme and creatinine clearance.

Characterization and quantification of chlordecone elimination in ewes

To reduce the exposure of the French West Indies population to the organochlorine insecticide chlordecone (Kepone; CLD), the contamination of currently consumed foodstuffs must be reduced. Depuration of contaminated animals before slaughter could be a strategy to obtain safe animal products. The aim of this study was to characterize and quantify CLD elimination in contaminated ewes during depuration process. Experiments A and B consisted in a single intravenous (i.v.) administration of CLD (n = 5) and CLDOH (chlordecol; n = 3) followed by a 84-d and 3-d depuration period respectively with collection of blood, faeces and urine samples. After CLD administration, CLD and conjugated-CLDOH (CLDOH-C) were quantified in serum and urine and CLD and CLDOH were quantified in faeces. Based on calculations of faecal, urinary and body clearances of CLD and CLDOH-C, faeces appeared as the major route of CLD excretion with 86 % of the CLD administered dose eliminated in faeces, either as CLD (51 %) or as CLDOH (35 %).

Enhanced Renal Clearance of Heme Triggers Acute Kidney Injury in Sickle Cell Disease

Circulating heme is scavenged primarily by hemopexin (Hx) for degradation in the liver, while alpha-1-microglobulin (A1M) binds heme for urinary clearance. Individuals with sickle cell disease (SCD) have acquired Hx deficiency. Hitherto, it has not been determined whether the low Hx in SCD results in a disproportionately large amount of heme exposure in the kidneys sufficient to promote acute tissue injury. Acute kidney injury (AKI) is a common downstream complication of acute chest syndrome (ACS) and vaso-occlusive pain crisis (VOC). Emerging evidence indicates acute elevations in circulating heme contributes to both ACS and VOC. Therefore, we tested the hypothesis that acute hemolytic crisis triggers AKI in SCD. We found that steady-state plasma A1M is raised significantly in SCD patients compared to controls (SS: 0.27±0.03, AA: 0.18±0.02 mg/ml p<0.05; n=12), and we determined that the molar A1M/Hx ratio is 14-fold higher in transgenic homozygous SCD (SS) mice compared to control (AA) littermates (n=6; p<0.05). Infusion of a non-lethal dose of purified heme (20 μmoles/kg) raised the concentration of heme in the liver but not in the kidneys of AA mice in 48 hours. On the contrary, the heme infusion over the same duration raised the total heme concentration in the kidneys but not in the liver of the SS mice (p<0.05). The SS mice but not the control AA mice developed severe renal tissue damage, defined by tubular atrophy and cast formation, loss of epithelial brush borders and apoptosis of the proximal tubular epithelium, within 48 hours of the heme infusion. Clinical detection of AKI is typically defined by elevation in serum creatinine and urinary albumin creatinine ratio (uACR). The acute elevation in circulating heme increased the plasma creatinine by 4-fold (p<0.001) with a 2-fold elevation in uACR (p<0.01) exclusively in the SS mice but not in control AA mice. Urinary kidney injury molecule-1 (KIM-1), which is a reliable predictor of AKI increased ~3-fold in the SS mice following the heme infusion, while no alteration of KIM-1 was evident in AA mice treated with the same challenge (n=6). To define the relationship between AKI in SCD and the hepatic and renal mechanisms of heme clearance, we measured plasma A1M and Hx, and urinary KIM-1 in a cohort of Ghanaian SCD patients aged 1-14 years (n=40). The molar ratio of A1M/Hx correlated positively with KIM-1 in this patient population (Pearson r=0.54; p=0.0003). Together, our data supports the conclusion that acute elevation of circulating heme triggers AKI in SCD. Clinically, the relative molar concentrations of plasma A1M and Hx can be developed as a biomarker to assess AKI risk in SCD patients. Finally, our data suggest acute infusions of Hx may protect SCD patients from AKI during episodes of hemolytic crisis. DisclosuresOfori-Acquah:NuvOx Pharma: Patents & Royalties.

The AGE receptor, OST48 drives podocyte foot process effacement and basement membrane expansion (alters structural composition).

AimsThe accumulation of advanced glycation end products is implicated in the development and progression of diabetic kidney disease. No study has examined whether stimulating advanced glycation clearance via receptor manipulation is reno‐protective in diabetes. Podocytes, which are early contributors to diabetic kidney disease and could be a target for reno‐protection.Materials and methodsTo examine the effects of increased podocyte oligosaccharyltransferase‐48 on kidney function, glomerular sclerosis, tubulointerstitial fibrosis and proteome (PXD011434), we generated a mouse with increased oligosaccharyltransferase‐48kDa subunit abundance in podocytes driven by the podocin promoter.ResultsDespite increased urinary clearance of advanced glycation end products, we observed a decline in renal function, significant glomerular damage including glomerulosclerosis, collagen IV deposition, glomerular basement membrane thickening and foot process effacement and tubulointerstitial fibrosis. Analysis of isolated glomeruli identified enrichment in proteins associated with collagen deposition, endoplasmic reticulum stress and oxidative stress. Ultra‐resolution microscopy of podocytes revealed denudation of foot processes where there was co‐localization of oligosaccharyltransferase‐48kDa subunit and advanced glycation end‐products.ConclusionsThese studies indicate that increased podocyte expression of oligosaccharyltransferase‐48 kDa subunit results in glomerular endoplasmic reticulum stress and a decline in kidney function.

Renoprotective effect of peanut oil on experimentally induced chronic renal failure in rats

The renoprotective effect of Peanut oil in rats suffered from chronic renal failure with adenine was evaluated. Adult male albino rats were classified as follow: normal group, Peanut oil group (0.75ml/kg), adenine fed group (0.75% w/w), the 4th group received both adenine in concomitant with peanut oil by the same dose and route as in the above groups, for 4 weeks. The antioxidant activity, total phenolic and flavonoid content of Peanut oil was estimated. Adenine administration reduced body weight, exceed the relative kidney weight as well as excessive serum creatinine, uric acid and BUN. In addition, exceed urine volume, appearance of urinary protein associated with significant increased urine NAG activity, while urinary Creatinine and creatinine clearance were decreased. It raised serum concentrations of inflammatory markers (C-RP, TNF-α, IL-6 and IL-10) relative to control group. Histopathological changes were noticed including tubulointerstitial atrophy and fibrosis. These kidney functions abnormalities were associated with increased renal oxidative stress markers (MDA and XO), decreased renal antioxidants markers (SOD, CAT, GSH and TAC). Administration of Peanut oil with adenine suppress the hazardous effect of adenine, where they keep most of the estimated parameters within normal. In conclusion, these results indicate that the use of Peanut oil has efficient protective effect against renal injury in adenine fed rats.

Iohexol Plasma Clearance: Impact of Weighing the Syringe

Measured glomerular filtration rate (mGFR) measurement is necessary in specific patients and/or specific clinical contexts.1–3 Plasma clearances are the preferred methods, as they are less costly and cumbersome than urinary clearances.4 The contrast medium iohexol is the most commonly used worldwide, partly for pragmatic reasons, as this marker is stable, not radioactive, and its measurement is easy, with the possibility of an external quality control.1,4,5 One goal of the European Kidney Function Consortium (EKFC) is to increase the standardization of GFR measurements.

MO190NORMATIVE DATA FOR GLOMERULAR FILTRATION RATE IN HEALTHY KIDNEY DONOR POPULATION

Abstract Background and Aims Glomerular filtration rate (GFR) is estimated traditionally from 24-hour urinary creatinine clearance. Creatinine is mainly filtered by glomerulus. The collection of 24-hour urinary sample is a difficult task with many patients fail to collect all the urine samples. As measuring GFR is cumbersome, expensive, and not easily available in all centers, various equations are developed for estimating GFR from creatinine like MDRD, CKD EPI creatinine. GFR obtained from serum creatinine shows wide variation as muscle mass and dietary protein intake are important determinants of serum creatinine concentration. Literature shows very few studies with GFR estimation with reference to age in Indian population. Hence, this study is planned to develop age specific nomogram for GFR in healthy kidney donor population as well as to study agreement between GFR obtained by 99m Tc DTPA three sample method and GFR estimated by 24-hour urinary creatinine. The aim of this stidy was to develop age-specific nomogram GFR in healthy kidney donor population and to study the agreement between the GFR measured by Technetium-99m diethylene triamine pentaacetic acid (99m Tc DTPA) and 24-hour urinary creatinine method. Method This study was conducted at Sir Ganga Ram hospital, New Delhi. All healthy individuals aged more than 20 years and less than 65 years, undergoing evaluation as prospective kidney donor at our hospital were the part of this study. GFR was measured by 99m Tc DTPA clearance using 3 sample method. GFR measured by DTPA method was used to develop nomogram. Creatinine Clearance was calculated from 24-hour urinary creatinine by formula U x V/P where, U is urinary creatinine level, P is plasma creatinine level and V is total volume of urine. Nomogram was developed with respect to these 3 Age groups; namely, 20 to 40 years, 40 to 50 years and 50 to 65 years Results Total 100 kidney donors were included in this study. Enrolled subjects were divided into 3 age groups; 20 to 40 years (n=28), 40 to 50 years (n=46) and 50 to 65 years (n=26). Majority of the donors were females (n=80). The agreement between GFR obtained by 99m Tc DTPA and 24-hour urinary creatinine clearance methods was 92.6 vs. 94 ml/min, 80.4 vs. 76 ml/min and 76.3 vs. 70 ml/min in respective age groups. Conclusion In the younger age group (20 to 40 years), there is better agreement in GFR measured by 99m Tc DTPA method and 24-hour urinary creatinine clearance methods.

The Performance of Equations That Estimate Glomerular Filtration Rate against Measured Urinary Creatinine Clearance in Critically Ill Patients.

The performance of glomerular filtration rate- (GFR-) estimating equations was studied against creatinine clearance measured by 24-hour urine collection (CrCl24h-urine) in critically ill patients. Methods. In this substudy of the PermiT trial (https://clinicaltrials.gov/ct2/show/ISRCTN68144998), patients from King Abdulaziz Medical City-Riyadh who had CrCl24h-urine were included. We estimated GFR using Cockroft–Gault (CG), modification of diet in renal disease study (MDRD), chronic kidney disease epidemiology collaboration (CKD-EPI), and Jelliffe equations. For the CG equation, we entered the actual weight in one calculation (CGactual-wt), and if BMI ≥30 kg/m2, we entered the ideal body weight (CGideal-wt) and the adjusted body weight (CGadjusted-wt) in two calculations. We calculated the MDRD equation based on 4 (MDRD-4) and 6 variables (MDRD-6). The performance of these equations was assessed by different ways including Spearman correlation, bias (difference between estimated GFR and CrCl24h-urine), precision (standard deviation of bias), and Bland–Altman plot analysis. Results. The cohort consisted of 237 patients (age 45 ± 20 years, males 75%, mechanically ventilated 99% with serum creatinine 101 ± 94 µmol/L and CrCl24h-urine 108 ± 69 ml/min/1.73 m2). The correlations between the different equations and CrCl24h-urine were modest (r: 0.62 to 0.79; p < 0.0001). Bias was statistically significant for CGactual-wt (21 ml/min), CGadjusted-wt (12 ml/min), and MDRD-6 (-10 ml/min) equations. Precision ranged from 46 to 54 ml/min. The sensitivity of equations to correctly classify CrCl24h-urine 30–59.9 ml/min/1.73 m2 was 17.2% for CGactual-wt, 30.0% for CGideal-wt, 31.0% for CGadjusted-wt, 31.0% for MDRD-4, 39.1% for MDRD-6, 13.8% for CKD-EPI, and 34.5% for Jelliffe equation. Conclusions. Commonly used GFR-estimating equations had limited ability to properly estimate CrCl24h-urine and to correctly classify GFR into clinically relevant ranges that usually determine dosing of medications.

Augmented renal clearance: a retrospective, cohort study of urinary creatinine clearance in critically ill patients in the United Kingdom.

ObjectiveAugmented renal clearance (ARC) is associated with sub-therapeutic antibiotic, anti-epileptic, and anticoagulant serum concentrations leading to adverse patient outcomes. We aimed to describe the prevalence and associated risk factors for ARC development in a large, single-centre cohort in the United Kingdom.MethodsWe conducted a retrospective observational study of critically unwell patients admitted to intensive care between 2014 and 2016. Urinary creatinine clearance was used to determine the ARC prevalence during the first 7 days of admission. Repeated measures logistic regression was used to determine risk factors for ARC development.ResultsThe ARC prevalence was 47.0% (95% confidence interval [95%CI]: 44.3%–49.7%). Age, sex, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and sepsis diagnosis were significantly associated with ARC. ARC was more prevalent in younger vs. older (odds ratio [OR] 0.95 [95%CI: 0.94–0.96]), male vs. female (OR 0.32 [95%CI: 0.26–0.40]) patients with lower vs. higher APACHE II scores (OR 0.94 [95%CI: 0.92–0.96]).ConclusionsThis patient group probably remains unknown to many clinicians because measuring urinary creatinine clearance is not usually indicated in this group. Clinicians should be aware of the ARC risk in this group and consider measurement of urinary creatinine clearance.

Glutathione-related genetic polymorphisms are associated with mercury retention and nephrotoxicity in gold-mining settings of a Colombian population

Mercury (Hg) vapor can produce kidney injury, where the proximal tubule region of the nephron is the main target of the Hg-induced oxidative stress. Hg is eliminated from the body as a glutathione conjugate. Thus, single nucleotide polymorphisms (SNPs) in glutathione-related genes might modulate the negative impact of this metal on the kidneys. Glutathione-related SNPs were tested for association with levels of Hg and renal function biomarkers between occupationally exposed (n = 160) and non-exposed subjects (n = 121). SNPs were genotyped by TaqMan assays in genomic DNA samples. Total mercury concentration was measured in blood, urine and hair samples. Regression analyses were performed to estimate the effects of SNPs on quantitative traits. Alleles GCLM rs41303970-T and GSTP1 rs4147581-C were significantly overrepresented in the exposed compared with the non-exposed group (P < 0.01). We found significant associations for GCLM rs41303970-T with higher urinary clearance rate of Hg (β = 0.062, P = 0.047), whereas GCLC rs1555903-C was associated with lower levels of estimated glomerular filtration rate in the non-exposed group (eGFR, β = − 3.22, P = 0.008) and beta-2-microglobulin in the exposed group (β-2MCG, β = − 19.32, P = 0.02). A SNP-SNP interaction analysis showed significant epistasis between GSTA1 rs3957356-C and GSS rs3761144-G with higher urinary levels of Hg in the exposed (β = 0.13, P = 0.04) but not in the non-exposed group. Our results suggest that SNPs in glutathione-related genes could modulate the pathogenesis of Hg nephrotoxicity in our study population by modulating glutathione concentrations in individuals occupationally exposed to this heavy metal.

Consider Urinary Creatinine Clearance for Perioperative Acute Kidney Injury Management.

Consider Urinary Creatinine Clearance for Perioperative Acute Kidney Injury Management.

Efficacy and safety of mycophenolate mofetil versus cyclophosphamide in the treatment of Henoch-Schönlein purpura nephritis with nephrotic-range proteinuria in children: a prospective randomized controlled trial

Objective To study the efficacy and safety of mycophenolate mofetil (MMF) versus cyclophosphamide (CTX) in the treatment of children with Henoch-Schonlein purpura nephritis (HSPN) and nephrotic-range proteinuria. Methods A prospective clinical trial was conducted in 68 pediatric patients who were admitted to the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics and who were diagnosed with HSPN and nephrotic-range proteinuria from August 2016 to November 2019. The patients were randomly divided into two groups:MMF treatment (n=33) and CTX treatment (n=35). The two groups were compared in terms of complete remission rate, response rate (complete remission + partial remission), urinary protein clearance time, and adverse events. Results At months 3, 6, and 12 of treatment, there was no significant difference in the complete remission rate and the response rate between the MMF treament and CTX treatment groups (P > 0.05). There was also no significant difference between the two groups in the urinary protein clearance time and the incidence rate of adverse events (P > 0.05). Conclusions MMF and CTX have similar efficacy and safety in the treatment of HSPN children with nephrotic-range proteinuria.

A case of Extensively Drug Resistant (XDR) Extended Spectrum Beta-Lactamase (ESBL) typhoid fever in the Ambulatory Emergency Care (AEC) unit

An outbreak of Extensively Drug Resistant (XDR) Salmonella Typhi (S. Typhi) has recently emerged from Pakistan. The strain is resistant to most first-line antibiotics, including cephalosporins, and has become a significant public health threat due to limited treatment options. We report one such case of S. Typhi in a 48-year-old female presenting to our West London ambulatory emergency care department. The patient, who had recently travelled to Pakistan, presented with symptoms of a dry cough, fever, maculopapular rash, and dysuria. Blood cultures initially isolated Salmonella spp, serotype Typhi and empirical ceftriaxone was commenced. Antibiotic sensitivity testing (AST) identified Salmonella spp. ESBL (Extended Spectrum Beta Lactamase-producing) subspecies I (ST1 EBG:13), with cephalosporin and fluoroquinolone resistance (ciprofloxacin MIC 2 mg/L), hence labelling it XDR. It retained susceptibility to meropenem and azithromycin (azithromycin MIC 12 mg/L). An ESBL Escherichia coli was concurrently grown in urine cultures. Once antibiotic sensitivities were available, the patient was converted from ceftriaxone to a course of azithromycin orally and ertapenem intravenously. The patient defervesced promptly, demonstrated blood and urine clearance on follow up and was successful treated. This case report highlights the limitations of ceftriaxone in our empirical management of suspected typhoid fever, especially in those returning from high-risk regions. Increased prevalence of these resistant salmonella will lead to failures of the current treatment practices and continuous surveillance and improving infection control measures are required to mitigate the spread of these XDR S. Typhi. Azithromycin and carbapenems retain in vitro activity and play an important role in treatment of XDR S. Typhi; loss of the organism’s sensitivity to these agents presents a serious public health threat. Further studies are warranted to confirm in vivo efficacy of ertapenem particularly when used as monotherapy.

Possible Protective Effect of Endothelin-1 Receptor Antagonist on Renal Impairment in Type 2 Diabetic Rats

Background: Diabetic nephropathy (DN) is characterized by persistent albuminuria and progressive decline in glomerular filtration rate (GFR). Bosentan is a non-peptide mixed antagonist of ET-1. Aim: To investigate the possible protective role of bosentan on renal impairment in T2DM rats and the mechanisms concerned. Materials: Fifty rats were randomly divided into five equal groups; Non-Diabetic (ND), Diabetic non-treated (DN), Diabetic Bosentan-treated (D-Bos.), Diabetic Metformin-treated (D-Met.), Diabetic combined Bosentan and Metformin-treated groups (D-Bos& Met.). T2DM was induced by Streptozotocin (STZ) (35mg/kg) and high fat diet (HFD) for 3 weeks. Both Bosentan and metformin were given orally for 4 weeks. At the end of the experiment, 24hrs urine samples were collected to measure urine (volume, albumin, NAG and creatinine), renal blood flow velocity (RBFV) and peripheral renal resistance (RVR) were measured using Doppler technique. Blood was collected directly from abdominal aorta to estimate fasting serum glucose, glycosylated hemoglobin (HBA1c), serum insulin, complete lipid profile, renal function tests and parameters of oxidative stress: malondialdehyde (MDA), total antioxidant capacity (TAC) and tumor necrosis factor-α (TNFα). Insulin resistance, serum LDL-cholesterol, urinary albumin creatinine ratio (UACR) and creatinine clearance (CC) were calculated. Results: Serum cysteine c, BUN, urinary albumin and UACR were significantly lowered in both D-Bos. & D-Met when compared to the corresponding values in DN while urinary volume, urinary creatinine, CC and RBFV were significantly elevated but serum creatinine, NAG & RVR were significantly lowered in D-Bos. only. Conclusion: Bosentan and metformin treatment both have a renoprotective effect. Combined treatment showed better results.