Renal Function Variables Research Articles

#1028 Experience with ravulizumab in atypical hemolytic uremic syndrome

Abstract Background and Aims The arrival of eculizumab revolutionized the treatment of Atypical Hemolytic Uremic Syndrome (aHUS). Ravulizumab also offers C5 inhibition, but with 3-4 times longer half- life. We describe the experience with ravulizumab in patients with aHUS in two scenarios: 1. Switching from another C5 inhibitor in stable patients; 2. Direct initiation of therapy with ravulizumab (naïve). Method We present 9 patients with an average age of 42 ± 13 years and weight of 81 ± 12.4 kg. The switch to ravulizumab was initiated 2 weeks after the last dose of eculizumab in switch patients, while in naïve patients it was initiated after excluding other causes of aHUS. The initial dose was 2700 mg, followed by a second dose of 3300 mg after 2 weeks, and subsequently every 2 months. Analytical variables of renal function, hematological parameters, and complement were collected. Results Switch : 6 patients (50% females), 4/6 were transplant recipients (3 on prophylactic treatment). Regarding renal function, 5/6 patients had a complete response with eculizumab (creatinine 1.33 ± 0.32 mg/dL, eGFR 59.5 ± 34.3 mL/min/1.73 m2, proteinuria 115 ± 91.5 mg/g), and all of them had a complete hematological response. After the switch, all patients maintained a complete hematological response, stability of renal function, and serum complement levels. Naïve : 3 cases (2 males); 2/3 required hemodialysis (HD) at presentation. The renal response was complete in two patients and partial in the third (who discontinued HD after 90 days and currently remains stable with stage G3b chronic kidney disease). All three patients had a complete hematological response. Only 3 adverse effects were documented (arthralgia, headache, and rhinitis), with no cases of infection. Conclusion The use of ravulizumab is effective both in maintaining a complete response after switching from eculizumab and as a first-line therapy. The safety profile is comparable, with the main difference being the dosing regimen, as ravulizumab requires fewer administrations and leads to a reduction in direct and indirect costs.

Impact of renal function variability on long-term prognosis in ischemic stroke patients with atrial fibrillation.

Although renal dysfunction is associated with adverse clinical outcomes in patients with atrial fibrillation (AF) following stroke, the impact of renal function variability is unclear. This study aimed to assess the association between renal function variability and various adverse clinical outcomes in patients with transient ischemic attack (TIA)/ischemic stroke and atrial fibrillation (AF). We conducted a population-based study and retrospectively identified patients hospitalized with a diagnosis of TIA/ischemic stroke and AF during 2016-2020 using the Clinical Data Analysis and Reporting System of Hong Kong. Serial serum creatinine tested upon the onset of TIA/ischemic stroke and during their subsequent follow-up was collected. Renal function variability was calculated using the coefficient of variation of the estimated glomerular filtration rate (eGFR). Clinical endpoints that occurred during the study period were captured and included ischemic stroke/systemic embolism, intracerebral hemorrhage (ICH), total bleeding, major adverse cardiovascular events (MACE), cardiovascular, non-cardiovascular, and all-cause mortality. Competing risk regression and Cox proportional hazard regression models were used to assess the associations of renal function variability with the outcomes of interest. A total of 3,809 patients (mean age 80 ± 10 years, 43% men) who satisfied the inclusion and exclusion criteria were followed up for a mean of 2.5 ± 1.5 years (9,523 patient-years). The mean eGFR was 66 ± 22 mL/min/1.73 m2 at baseline, and the median number of renal function tests per patient during the follow-up period was 20 (interquartile range 11-35). After accounting for potential confounders, a greater eGFR variability was associated with increased risks of recurrent ischemic stroke/systemic embolism [fully adjusted subdistribution hazard ratio 1.11, 95% confidence interval (CI) 1.03-1.20], ICH (1.17, 1.01-1.36), total bleeding (1.13, 1.06-1.21), MACE (1.22, 1.15-1.30), cardiovascular (1.49, 1.32-1.69), non-cardiovascular (1.43, 1.35-1.52), and all-cause mortality (fully adjusted hazard ratio 1.44, 1.39-1.50). Visit-to-visit renal function variability is independently associated with adverse clinical outcomes in TIA/ischemic stroke patients with AF. Further large-scale studies are needed to validate our results.

Multiple factors influence decision making for the surgical treatment in patients with renal cell carcinoma.

Surgical strategy in renal cell carcinoma (RCC) is considered based on the renal function. Partial nephrectomy (PN) preserves kidney function better than radical nephrectomy (RN), lowering risk of chronic kidney disease (CKD). The aim was to evaluate whether renal function and other clinical variables were important for surgical treatment selection. Patients with RCC, surgically treated between 1994 and 2018 were included. There were 663 patients in all stages, 265 women and 398 men, mean age 66 years. estimated glomerular filtration rate (eGFR), WHO performance status (WHO-PS), Charlson comorbidity index (CCI), surgery, T-stage, M-stage, RCC type, tumor size, age, and gender were extracted from the medical records. Statistical analysis included Mann-Whitney U, X2-test, and logistic regression analysis. Of 663 patients, 455 were treated with RN and 208 with PN. In all patients, preoperative eGFR was significantly higher in PN (80.8) than in RN (77.1, p = 0.015). Using logistic regression tumor size (odds ratio [OR]: 0.96; 95% confidence interval [CI]: 0.95-0.98, T-stage (OR: 0.46; 95% CI: 0.33-0.65), WHO-PS (OR: 0.39; 95% CI: 0.04-0.57), and CCI (OR: 1.23; 95% CI: 1.05-1.44), associated to treatment selection, while eGFR, M-stage, age, and gender did not. In cTa subgroup, eGFR was also higher in PN (84.6) than in RN (75.0, p = 0.007). Using logistic regression, tumor size (OR: 0.93; 95% CI: 0.83-0.98) and WHO-PS (OR: 0.36; 95% CI: 0.20-0.66) associated to treatment selection, while eGFR, CCI, age, and gender did not. Tumor size, CCI scores, T-stage, and WHO-PS, all had an impact on the surgical strategy for all RCC patients. In patients with T1a RCC, tumor size and WHO-PS associated independently with treatment decision. After adjusted analysis, renal function lost its independent association with the treatment strategy in RCC patients.

Development and Validation of a Renal Replacement after Trauma Scoring Tool.

Stress on the healthcare system requires careful allocation of resources such as renal replacement therapy (RRT). The COVID-19 pandemic generated difficulty securing access to RRT for trauma patients. We sought to develop a renal replacement after trauma (RAT) scoring tool to help identify trauma patients who may require RRT during their hospitalization. The 2017 to 2020 TQIP database was divided into a derivation (2017 to 2018 data) and validation (2019 to 2020 data) set. A 3-step methodology was used. Adult trauma patients admitted from the emergency department to the operating room or ICU were included. Patients with chronic kidney disease, transfers from another hospital, and emergency department death were excluded. Multiple logistic regression models were created to determine the risk for RRT in trauma patients. The weighted average and relative impact of each independent predictor was used to derive a RAT score, which was validated using area under receiver operating characteristic curve (AUROC). From 398,873 patients in the derivation and 409,037 patients in the validation set, 11 independent predictors of RRT were included in the RAT score derived with scores ranging from 0 to 11. The AUROC for the derivation set was 0.85. The rate of RRT increased to 1.1%, 3.3%, and 20% at scores of 6, 8, and 10, respectively. The validation set AUROC was 0.83. RAT is a novel and validated scoring tool to help predict the need for RRT in trauma patients. With future improvements including baseline renal function and other variables, the RAT tool may help prepare for the allocation of RRT machines/staff during times of limited resources.

A systematic review of statistical methodology used to evaluate progression of chronic kidney disease using electronic healthcare records.

Electronic healthcare records (EHRs) are a useful resource to study chronic kidney disease (CKD) progression prior to starting dialysis, but pose methodological challenges as kidney function tests are not done on everybody, nor are tests evenly spaced. We sought to review previous research of CKD progression using renal function tests in EHRs, investigating methodology used and investigators' recognition of data quality issues. We searched for studies investigating CKD progression using EHRs in 4 databases (Medline, Embase, Global Health and Web of Science) available as of August 2021. Of 80 articles eligible for review, 59 (74%) were published in the last 5.5 years, mostly using EHRs from the UK, USA and East Asian countries. 33 articles (41%) studied rates of change in eGFR, 23 (29%) studied changes in eGFR from baseline and 15 (19%) studied progression to binary eGFR thresholds. Sample completeness data was available in 44 studies (55%) with analysis populations including less than 75% of the target population in 26 studies (33%). Losses to follow-up went unreported in 62 studies (78%) and 11 studies (14%) defined their cohort based on complete data during follow up. Methods capable of handling data quality issues and other methodological challenges were used in a minority of studies. Studies based on renal function tests in EHRs may have overstated reliability of findings in the presence of informative missingness. Future renal research requires more explicit statements of data completeness and consideration of i) selection bias and representativeness of sample to the intended target population, ii) ascertainment bias where follow-up depends on risk, and iii) the impact of competing mortality. We recommend that renal progression studies should use statistical methods that take into account variability in renal function, informative censoring and population heterogeneity as appropriate to the study question.

Effectiveness of low-carbohydrate diets for long-term weight loss in obese individuals: A meta-analysis of randomized controlled trials.

AimTo assess whether low‐carbohydrate (LC) diets are associated with differences in weight loss and well‐being in people with obesity, and their cardiovascular and renal safety.Materials and MethodsA meta‐analysis of randomized controlled trials longer than 3 months, retrieved through an extensive search on MedLine and Embase databases, comparing weight loss with LC and control diets in people with body mass index (BMI) greater than 30 kg/m2, was conducted.ResultsWe retrieved 25 trials. Compared with controls, LC diets were associated with significant reduction of body weight at 3‐4 (MD −2.59 [−3.93, −1.25] kg) and 6‐8 months (MD −2.64 [−4.32, −0.95]), but no difference at 10‐14 and 18‐30 months, and significantly greater BMI reduction at 3‐4 months (−1.66 [−2.70, −0.61] kg/m2), but not at other time points. Because only four trials reported data on renal function and psychological variables, renal safety and impact on well‐being could not be assessed. Differences in fasting plasma glucose at any time point were not statistically significant. No significant differences in total or LDL cholesterol or blood pressure were found in the long term, whereas a long‐term reduction of triglycerides (23.26 [−45.53, −0.98] mg/dl at 18‐30 months), and increase of HDL cholesterol (MD 4.94 [0.30, 9.57] mg/dl at 18‐30 months), were observed.ConclusionLC diets are associated with greater short‐term weight loss than non‐carbohydrate–restricted diets and a longer term favourable effect on cardiovascular risk factors. Further evidence on long‐term efficacy and renal safety is needed before LC diets can be recommended as the preferred diets in obese people.

MO523: The Differential Effect of Third-Generation Intravenous Iron Preparations (Ferric Carboxymaltose, Ferric Derisomaltose) on Hematinic and Renal Function Variables in Patients With Non-Dialysis Dependent CKD and Iron Deficiency Anemia

Abstract BACKGROUND AND AIMS Iron deficiency anemia is common in patients with non-dialysis dependent chronic kidney disease (CKD). Guidelines advocate the use of oral or intravenous (IV) iron, with IV iron offering a quicker and potentially more efficacious replenishment. The advent of third-generation IV iron products [such as ferric carboxymaltose (FCM) and ferric derisomaltose (FDI)] has allowed high doses of iron to be provided in a single sitting. Despite good evidence on their efficacy in replenishing iron stores and safety in terms of renal injury and inflammation when compared against placebo, oral iron or older iron compounds (such as iron sucrose and low molecular weight iron dextran), the two compounds have never before been compared head-to-head in CKD. METHOD As part of the single-center double-blinded exploratory randomized controlled trial ‘Iron and Phosphaturia—ExplorIRON-CKD’ that took place in a tertiary center in the UK, patients with iron deficiency with/without anemia and CKD stage 3a–5 but not on dialysis were recruited to receive FCM or FDI in two divided doses—1000 mg at baseline and 500–1000 mg in a 1-month interval to achieve replenishment. Iron deficiency was defined as serum ferritin (SF) <200 µg/L or transferrin saturation (TSAT) ≤20% and SF 200–299 µg/L. Markers of treatment response such as hemoglobin and iron parameters [serum ferritin (SF), transferrin saturation (TSAT)], renal function and injury [serum creatinine, estimated glomerular filtration rate (eGFR) and protein: creatinine ratio (PCR)] and inflammation (CRP) were monitored throughout the study. Hemoglobin, renal function and inflammation were monitored at baseline, 2 weeks, 1 month and 2 months following initial infusion. Iron response was assessed at baseline, 1–2 days, 2 weeks, 1 month post-initial infusion (and time of second infusion), 1–2 days after the second infusion and 2 months after initial administration. RESULTS A total of 26 patients were recruited; 14 were randomized to receive FDI and 12 to receive FCM. All patients received at least one iron dose (1000 mg), 10 patients received two FDI doses and 11 received two FCM doses. There was an increase in hemoglobin in both groups, with no significant difference between the groups at any given time point in the study [baseline: FDI: 99.2 (12.2) g/L versus FCM: 101.6 (15.3) g/L; P = .67; 2 months: FDI: 106.0 (13.3) g/L versus FCM: 109.1 (8.3) g/L; P = .526). Both groups had a median baseline SF <100 µg/L and TSAT <20%, and by the end of follow-up, iron repletion was similarly successful in both groups as indicated by a median SF > 400 µg/L and a TSAT >20% (Figure 1). A small numerical reduction was noted in median eGFR in the FCM group from baseline to the end of the study (baseline: 18.0 (11.3) mL/min/1.73 m2 versus 2 months: 16.5 (8.5) mL/min/1.73 m2); however, there was no significant difference between the two groups at any time point in the study (Figure 2). Urinary PCR, serum creatinine and CRP remained stable throughout the study and did not differ significantly between the two groups. CONCLUSION Third-generation IV iron preparations are efficacious in replenishing iron stores. There was no adverse short-term impact on renal function, injury or inflammation. In our cohort, the two compounds were equivocal for the parameters studied, with no significant difference identified in any of the areas examined. The population was small, therefore the results should be interpreted with caution; nonetheless, newer IV iron compounds appear to be equally efficacious in the treatment of iron deficiency anemia in non-dialysis-dependent CKD.

MO668: An Increase of Free Fatty Acids on Patients Starting Peritoneal Dialysis Suggests an Increased Cardiovascular Risk Beyond Classical Dyslipidemia Biomarkers

Abstract BACKGROUND AND AIMS Chronic kidney disease (CKD) produces profound changes in lipid metabolism, and these associated lipid disorders, in turn, contribute to the progression of CKD and its cardiovascular complications. Patients on peritoneal dialysis have a more atherogenic lipid profile than non-dialysis-dependent CKD patients or on HD. In the general population, the reduction of total cholesterol and LDL levels is associated with improved clinical outcomes in terms of morbidity and mortality; however, several studies have failed to obtain these same results in patients on dialysis. The use of lipidomics to detect a broader panel of lipid species can improve the prediction of the different alterations that influence cardiovascular mortality. METHOD This is a single-center prospective observational study of a cohort of CKD patients who start renal replacement therapy with continuous ambulatory peritoneal dialysis (CAPD). Data from 39 patients were examined. All samples for routine laboratories and lipidomics studies were obtained the day before starting CAPD (T0) and 6 months after (T1). Samples were analysed on an Ultra-Performance Liquid Chromatography system. The differences in the lipid profile analytical variables between baseline and 6 months after the start of CAPD were analysed. For the lipidomic analysis, each compound was grouped with its possible adducts and compound class based on the International Lipid Classification. RESULTS Thirty-nine patients were enrolled the study. Their mean age was 57.9 ± 16.3 years. The underlying renal diseases were glomerular disease (15 patients), diabetic kidney disease (10), congenital kidney disease (4), hypertensive kidney disease (2), interstitial nephropathy (2) and others (6). Hypertension was present in 96.3% of the patients, diabetes mellitus in 30.8% and 30 of the 39 patients had dyslipidemia (76.9%). Of the group of patients with dyslipidemia, only one of them was not on statin treatment. Table 1 shows the results of the analytical variables of lipid profile, serum glucose and renal function before and 6 months after initiating CAPD. The levels of CT and LDL were lower 6 months after CAPD initiation, but these were not statistically significant. Using the plasma lipid profile, with a mass spectrometry approach, a significant increase (P < 0.05) in total free fatty acids (FFA) was observed from T0 to T1. FFA (16:1) and FFA (18:0) were the FFAs with the highest peak response (Fig. 1). CONCLUSION Our LC-QTOF/MS-based lipidomics approach to study the effect of starting renal replacement therapy with CAPD in patients with CKD shows that total FFAs increased after 6 months on this technique. Within this group of lipids, FA 16:1 (palmitoleic acid) and FA 18:0 (stearic acid) were the ones that increased the most. An earlier study demonstrated that FFA levels are increased in the plasma of CKD patients; moreover, they have reported that higher levels of saturated fatty acids in serum correlate with sudden cardiac death in patients starting HD. Likewise, monounsaturated fatty acids are the products of stearoyl-CoA desaturase (SCD) catalyzed reactions and act as substrates to synthesize phospholipids and triglycerides. The activity of SCD is very high in patients with cardiovascular disease, hypertension and diabetes.

P37 Variable adherence to and effectiveness of a vancomycin continuous infusion protocol within ICUs at a London tertiary-care hospital: a single-centre retrospective service evaluation

BackgroundAppropriate vancomycin dosing and therapeutic monitoring is important to optimize treatment for serious Gram-positive infections. In St George's Hospital ICUs, the treatment protocol is a loading dose (<65 kg, 1000 mg; ≥65 kg, 1500 mg), followed by a continuous infusion based on creatinine clearance (CLCR). Vancomycin serum concentrations are taken daily at 0600 hours (target therapeutic range 20–25 mg/L). Non-therapeutic concentrations may negatively affect clinical outcomes and prolong length of stay.1MethodsElectronic prescribing and medicine administration data (vancomycin dose, dose timings, indication, patient biochemistry and demographics) within a 66-bed ICU service were reviewed retrospectively (July 2020–July 2021). Cockcroft-Gault CLCR was calculated using total body weight (TBW), or adjusted body weight in obese1 patients.Standards(i) Proportion of patients with a therapeutic concentration within two serum samples; and (ii) time taken to achieve therapeutic concentration.ResultsNinety-four percent (51/54) of patients received a correct protocol instructed loading dose, 31% (17/54) received a correct loading and maintenance dose, and 70% (38/54) had a vancomycin serum concentration taken. Forty-one percent (7/17) of correctly protocol dosed and monitored patients were therapeutic at their first day serum concentration, which decreased to 20% (3/15) by their second day serum concentration. Consistently therapeutically dosed patient groups included obese and normal weight patients with CLCR 10–20 mL/min and 21–50 mL/min. Whereas underweight and obese patients with CLCR >50 mL/min and 21–50 mL/min became supratherapeutic by their second day serum concentration. Obese and normal weight patients with CLCR >50 mL/min were consistently subtherapeutic. The mean time taken for non-therapeutic patients who continued treatment (n = 7) to become therapeutic after dose adjustments was 4 days. Patients (n = 17) were 82% male and of a mean age of 62 ± 17 years. Mean TBW was 79 ± 23 kg and mean CLCR 65 ± 48 mL/min. Sepsis was the most common vancomycin indication (65%).ConclusionsMultiple drug recording formats, plus adherence to and dosing of different aspects of the vancomycin protocol, requires review. This is to ensure accurate vancomycin administration documentation and that therapeutic concentrations are achieved more rapidly and consistently, whilst minimizing toxicity. A quality improvement project has been instigated to focus on protocol education, accessibility and improving IT infrastructure. Increased patient volume of distribution and renal function variability within the ICU population adds complexity to vancomycin pharmacokinetics. Research into pharmacokinetic models better representing the local ICU population and AUC24 drug monitoring is being explored based on recent international guidance.1

The Effect in Renal Function and Vascular Decongestion in Type 1 Cardiorenal Syndrome Treated with Two Strategies of Diuretics, a Pilot Randomized Trial

AimThe main treatment strategy in type 1 cardiorenal syndrome (CRS1) is vascular decongestion. It is probable that sequential blockage of the renal tubule with combined diuretics (CD) will obtain similar benefits compared with stepped-dose furosemide (SF).MethodsIn a pilot double-blind randomized controlled trial of CRS1 patients were allocated in a 1:1 fashion to SF or CD. The SF group received a continuous infusion of furosemide 100 mg during the first day, with daily incremental doses to 200 mg, 300 mg and 400 mg. The CD group received a combination of diuretics, including 4 consecutive days of oral chlorthalidone 50 mg, spironolactone 50 mg and infusion of furosemide 100 mg. The objectives were to assess renal function recovery and variables associated with vascular decongestion.ResultsFrom July 2017 to February 2020, 80 patients were randomized, 40 to the SF and 40 to the CD group. Groups were similar at baseline and had several very high-risk features. Their mean age was 59 ± 14.5 years, there were 37 men (46.2%). The primary endpoint occurred in 20% of the SF group and 15.2% of the DC group (p = 0.49). All secondary and exploratory endpoints were similar between groups. Adverse events occurred frequently (85%) with no differences between groups (p = 0.53).ConclusionIn patients with CRS1 and a high risk of resistance to diuretics, the use of CD compared to SF offers the same results in renal recovery, diuresis, vascular decongestion and adverse events, and it can be considered an alternative treatment. ClinicalTrials.gov with number NCT04393493 on 19/05/2020 retrospectively registered.

Relationship between venous congestion and systemic hypoperfusion in cardiorenal syndrome

Abstract Background Renal impairment takes a relevant role in worsening clinical outcomes and increasing mortality risk in patients with heart failure (HF). In this context, the interplay between venous congestion and systemic perfusion in the pathogenesis of cardiorenal syndrome is currently a matter of extensive debate1. Purpose To investigate the relationship between renal function and hemodynamic variables, as the cardiac index and right atrial pressure, in a broad spectrum of HF patients undergoing right heart catheterization, as part of their pulmonary hypertension (PH) diagnostic work-up. Patients and methods From 1st September 2005 until 31st October 2019, hemodynamic data from 286 consecutive patients were collected, of whom 267 had available plasmatic creatinine values. The estimated glomerular filtration rate (eGFR) was calculated by using the Chronic Kidney Disease Epidemiology Collaboration formula. The overall study population was stratified in no PH group, pre-capillary PH group and post-capillary PH group, on the basis of the available hemodynamic values of mean pulmonary arterial pressure and pulmonary artery wedge pressure. Results Of the overall population, 46.1% of them were male, the mean age at the right heart catheterization was 65.5±13.7 years, and the mean eGFR value was 70.0±0.2 mL/min/1.73 m2. On the basis of hemodynamic parameters, 71 patients constituted the no PH group, 107 the pre-capillary PH group, and 63 the post-capillary PH group. Post-capillary PH patients were significantly older than both no PH and pre-capillary PH subjects (69.4±11.7 years; 61.2±16.7 years and 65.7±12.9 years respectively, p=0.003). eGFR was significantly lower in the post-capillary PH group, compared to both no PH group (63.1±22.8 mL/min/1.73 m2 vs. 73.0±23.9 mL/min/1.73 m2, p=0.029) and pre-capillary PH group (63.1±22.8 mL/min/1.73 m2 vs. 71.6±26.6 mL/min/1.73 m2, p=0.041). In post-capillary PH group, multivariate logistic regression analysis showed a significant correlation between eGFR &amp;lt;60 mL/min/1.73 m2 and both reduced cardiac index (Odds ratio [OR] 0.05, 95% confidence interval [CI] 0.00 to 0.72, p=0.027) and right atrial pressure (OR 0.75, 95% CI 0.57 to 0.99, p=0.039), compared to no PH group and pre-capillary PH group. Conclusions A significant association between renal impairment and both low systemic perfusion and venous congestion, was found in patients with post-capillary PH, rather than in other hemodynamic subsets. Further investigations are needed to disentangle the impact of the both sides of circulation on renal function, in different hemodynamic phenotypes. Funding Acknowledgement Type of funding sources: None.

Variability in estimated glomerular filtration rate and patients' outcomes in a real-world heart failure population.

AimsThe prognostic significance of renal function variability has not been fully elucidated in heart failure (HF). This multicentre, prospective cohort study aimed to evaluate the usefulness of visit‐to‐visit variability in estimated glomerular filtration rate (eGFR) for predicting patients' outcomes in a real‐world HF population.MethodsA total of 564 patients who had survived HF hospitalization were randomly assigned with a 2:1 ratio to derivation and validation cohorts, and they were then followed after discharge. Using the data for 6 months after discharge, each patient's visit‐to‐visit eGFR variability (EGV) was estimated. In the derivation cohort, Cox regression analyses were performed to assess the association of EGV with a subsequent composite event (death and HF hospitalization). In the validation cohort, the predictive performance was compared among Cox regression models with EGV, those with B‐type natriuretic peptide (BNP) and those with eGFR.ResultsIn the derivation cohort (376 patients), median age, left ventricular ejection fraction (LVEF), BNP and eGFR at discharge were 72 years, 53.3%, 134.8 pg/mL and 58.7 mL/min/1.73 m2, respectively. During a median follow‐up of 2.2 years, higher EGV was associated with an increased risk of the composite event (adjusted hazard ratio [per standard deviation increase in log‐transformed EGV], 1.5; 95% confidence interval, 1.1–2.0). A similar finding was observed in a stratified analysis by LVEF. In the validation cohort (188 patients), better model fit, discrimination, reclassification and calibration were observed for EGV than for 6‐month averaged BNP or eGFR for predicting the composite event when added to HF risk prediction models. Adding EGV to models with BNP or eGFR improved model discrimination and reclassification.ConclusionsEGV predicts HF outcomes regardless of LVEF. Risk prediction models with EGV have good performance in real‐world HF patients. The study findings highlight the clinical importance of observing visit‐to‐visit fluctuations in renal function in this population.

Population Pharmacokinetics Modeling of Vancomycin Among Chinese Infants With Normal and Augmented Renal Function.

There have been good amounts of population pharmacokinetics (PPK) models of vancomycin for Chinese pediatric patients, but none of them had a special focus on modeling infant population with different levels of renal function. Since renal function variability is prominent among infant population and the clearance (CL) of vancomycin is heavily related to renal excretion, it is important to establish precise PPK models based on individual renal function levels. We employed a PPK approach to develop three models of vancomycin in parallel for Chinese pediatric patients with normal renal function [estimated glomerular filtration rate (eGFR) between 30 and 86 ml/min/1.73 m2, Model 1], with augmented renal function (eGFR ≥ 86 ml/min/1.73 m2, Model 2), or with all levels of renal function (Model 3). Three one-compartment models with first-order elimination kinetics were established. The predictive ability of Model 1 and Model 2 among each certain population is comparable with that of Model 3 with no statistical difference. Our study revealed that among the infant population with augmented renal function, only body weight was included as a covariate, which indicated that for an infant whose eGFR ≥ 86 ml/min/1.73 m2, taking blood sample is not compulsory for predicting vancomycin blood concentration, which avoids unnecessary injury to vulnerable infants.

Maternal plasma pro-atrial and C-type natriuretic peptide levels and their associations with cardiovascular and renal function in the second half of normal pregnancy: a longitudinal study

BackgroundPhysiological adaptation in pregnancy is characterized by remodeling of endocrine, cardiovascular and renal functions leading to fluid retention, volume expansion, altered cardiac loading conditions and hyperdynamic circulation. Natriuretic peptides have been used as biomarkers of cardiovascular function, but their associations with gestational age-related changes in maternal cardiac, endothelial and renal function have not been elucidated. The aim of this study was to establish longitudinal reference values for maternal plasma atrial natriuretic peptide (proANP) and C-type natriuretic peptide (CNP) and investigate their temporal association with cardiovascular and renal function in the second half of pregnancy.MethodsThis study was a prospective longitudinal study of 53 low-risk pregnancies. Women were examined every 3–5 weeks during 22–40 weeks of gestation (252 observations). Fasting maternal blood samples were obtained to measure proANP, CNP, creatinine, cystatin C, uric acid, and fibrinogen levels. Cardiac function and systemic hemodynamics were assessed noninvasively by impedance cardiography (ICG) and vascular endothelial function by flow-mediated vasodilation of brachial artery (FMD).ResultsThe plasma proANP (R2adj = 0.79; P = 0.007), CNP (R2adj = 0.54; P = 0.005) decreased between 22 and 40 weeks. The creatinine (R2adj = 0.90; P < 0.001), cystatin C (R2adj = 0.93; P = < 0.001) and uric acid (R2adj = 0.83; P < 0.001) increased significantly, whereas the estimated glomerular filtration rate (R2adj = 0.93; P < 0.001) decreased with gestational age. The FMD did not change significantly but fibrinogen (R2adj = 0.79; P < 0.001) increased with advancing gestation. The maternal systemic vascular resistance index (R2adj = 0.50; P < 0.001) increased, stroke index (R2adj = 0.62; P < 0.001) decreased, whereas the cardiac index (R2adj = 0.62; P = 0.438) and thoracic fluid content (R2adj = 0.72; P = 0.132) did not change significantly with gestation. The proANP was associated with thoracic fluid content (R2adj = 0.74; P < 0.001) and fibrinogen (R2adj = 0.78; P = 0.034) but not with other variables of systemic hemodynamics, endothelial function, or renal function. The CNP was not associated significantly with parameters of cardiovascular or renal function.ConclusionLongitudinal reference values for maternal plasma proANP and CNP were established. These natriuretic peptides decreased slightly with advancing gestation, but they did not reflect the temporal physiological changes in maternal systemic hemodynamics, vascular endothelial function and renal function during the second half of pregnancy. The proANP correlated with the thoracic fluid content reflecting volume load in pregnancy.

Urinary C-X-C Motif Chemokine 10 Is Related to Acute Graft Lesions Secondary to T Cell- and Antibody-Mediated Damage.

BackgroundNon-invasive biomarkers of graft rejection are needed to optimize the management and outcomes of kidney transplant recipients. Urinary excretion of IFN-γ-related chemokine CXCL10 is clearly associated with clinical and subclinical T cell-mediated graft inflammation, but its relationship with antibody-mediated damage has not been fully addressed. Further, the variables influencing levels of urinary CXCL10 excretion are unknown.Material/MethodsA total of 151 kidney graft biopsies (92 surveillance and 59 indication biopsies) and 151 matched urine samples obtained before biopsy were prospectively analyzed. T cell-mediated rejection (TCMR) and antibody-mediated rejection (AbMR) were defined according to the 2017 Banff classification criteria. Urinary CXCL10 levels were measured by ELISA and corrected by urinary creatinine.ResultsBanff scores ‘t’, ‘i’, ‘g’, and ‘ptc’ were significantly related to urinary CXCL10 levels. Multivariate analysis showed that ‘t’ (β=0.107, P=0.001) and ‘ptc’ (β=0.093, P=0.002) were significantly associated with urinary CXCL10. Donor-specific antibodies (DSAs) were related to the high excretion of urinary CXCL10 at 1 year after transplantation (odds ratio [OR] 17.817, P=0.003). Urinary CXCL10 showed good discrimination ability for AbMR (AUC-ROC 0.760, P=0.001). The third tertile of urinary CXCL10 remained significantly associated with AbMR (OR 4.577, 95% confidence interval 1.799–11.646, P=0.001) after multivariate regression analysis.ConclusionsDSA was the only variable clearly related to high urinary CXCL10 levels. Urinary CXCL10 is a good non-invasive candidate biomarker of AbMR and TCMR, supplying information independent of renal function and other variables normally used to monitor kidney transplants.

Prognostic impact of renal function trajectories and temporal variability amongst anticoagulated atrial fibrillation patients: a subgroup analysis of the SPORTIF III and V trials

Abstract Background Renal function is a major determinant of major adverse outcomes in patients with atrial fibrillation (AF). Scarce data are available about the impact of renal function trajectories and creatinine clearance (CrCl) temporal variability, on prognosis. Aim To evaluate the progression and impact of renal function impairment and variability on outcomes over a long-term follow-up observation in a cohort of anticoagulated AF patients. Methods We included warfarin-treated AF patients in SPORTIF trials with available creatinine clearance (according to Cockroft-Gault) at baseline and at least 4 evaluations throughout their follow-up. Patients with a BMI ≥45 kg/m2 were excluded from the analysis. Average successive variability (ASV) was used as measure of variability. Results Among 3665 original patients, 3366 (91.8%) were included in this analysis. Median [IQR] CHA2DS2-VASc score was 3 [2–4] and HAS-BLED was 3 [2–4]. At baseline, 876 (26.0%) patients had CKD (CrCl &amp;lt;60 mL/min), with 14 (0.4%) patients having severe CKD (&amp;lt;30 mL/min), with a mean (SD) CrCl of 86.7 (47.4) mL/min. Over a mean (SD) 577.1 (122.1) days of follow-up, a total of 521 new CKD cases were found with an overall incidence of 13.1 per 100 patient-years, with 91 new severe CKD cases (1.71 per 100 patient-years). Across follow-up, prevalence of CKD and severe CKD increased progressively (both p&amp;lt;0.001) [Figure]. Mean (SD) AVS was −0.567 (±2.803) mL/min. According to AVS, patients were divided into quartiles: i) Q1: +34.012/+0.450; ii) Q2: +0.449/−0.443; iii) Q3: −0.443/−1.503; Q4: −1.505/−19.750. While no difference was found in stroke/systemic embolism, rate of major bleeding was higher in Q4 (4.5%) and Q1 (4.0%) than in other quartiles (Q2 2.5%, Q3 2.0%; p=0.009) as well as all-cause death (Q4: 6.7%; p=0.003 compared to other quartiles). A Cox multivariate adjusted model documented that AVS Q1 and Q4 were independently associated with a higher risk of major bleeding, while Q4 was associated with a higher risk of all-cause death (Table). Conclusion In a cohort of AF patients treated with warfarin, characterized by a progressive increase in the proportion with CKD and severe CKD, the largest reduction in CrCl throughout follow-up was associated to an increased risk of major bleeding and all-cause death. Renal Function Trajectories Funding Acknowledgement Type of funding source: None

Independent Predictive Ability of Procalcitonin of Acute Kidney Injury among Critically Ill Patients.

It is unclear whether serum procalcitonin (PCT) levels rise in patients with acute kidney injury (AKI), and it is also unclear whether the elevation of PCT levels in this setting is independent of the existence of infection and impaired renal clearance. We conducted a retrospective study in a regional teaching hospital in Taiwan to evaluate the AKI-predictive ability of serum PCT among critically ill patients. We enrolled 330 patients (mean age, 70.5 ± 16.4 years; 57.0% men) who were admitted to the intensive care unit (ICU) from 1 July 2016, to 31 December 2016, and who had serum PCT measurement performed within 24 h after ICU admission. We used the generalized additive model and generalized linear model to evaluate the association of serum PCT levels and renal function variables. In addition, we used the multivariate logistic regression method to demonstrate serum PCT level as an independent predictor of AKI in both the non-infected patients (odds ratio (OR) = 1.38, 95% confidence interval (CI) = 1.12–1.71, p = 0.003) and the infected patients (OR = 1.23, 95% CI = 1.03–1.46, p = 0.020). In conclusion, serum PCT level at ICU admission is an independent predictor of developing AKI irrespective of infection among critically ill patients.

Predictive Factors of Renal Function in Partial Laparoscopic Nephrectomy in Patients with a Kidney Tumor

Background: Laparoscopic partial nephrectomy has proven to be an ideal option for tumors in initial stages, preserving part of the renal parenchyma and reducing the possible risk of glomerular filtration decrease. Objectives: The main objective of this study is to determine the factors that can influence, to a greater extent, renal function deterioration after surgery. Methods: This is an observational, descriptive and longitudinal study. The renal funct ion was calculated using the Chronic Kidney Disease Epidemiology Collaboration formula, and patients were divided into 2 groups depending on whether or not their renal function had been affected after surgery. We studied the correlation between the decrease of renal function and other variables. Results: The sample comprised 48 patients. In 30 of these cases, renal function had deteriorated after surgery. We observed a statistically significant relationship between the weight of the patient (p = 0.0230), size of the tumor (p = 0.0035), ischemic time (p = 0.0287), duration of the surgery (p = 0.0297), the RENAL score (p = 0.0230) and renal function deterioration. Conclusions: Partial laparoscopic nephrectomy is associated with a deterioration in renal function, where there is a decrease in glomerular filtration after surgery. The deterioration will depend on the weight of the patient, size of the tumour, ischemic time and duration of the surgery. The RENAL score can be used to predict said deterioration.

Understanding Lactatemia in Human Sepsis. Potential Impact for Early Management.

Rationale: Hyperlactatemia in sepsis may derive from a prevalent impairment of oxygen supply/demand and/or oxygen use. Discriminating between these two mechanisms may be relevant for the early fluid resuscitation strategy.Objectives: To understand the relationship among central venous oxygen saturation (ScvO2), lactate, and base excess to better determine the origin of lactate.Methods: This was a post hoc analysis of baseline variables of 1,741 patients with sepsis enrolled in the multicenter trial ALBIOS (Albumin Italian Outcome Sepsis). Variables were analyzed as a function of sextiles of lactate concentration and sextiles of ScvO2. We defined the "alactic base excess," as the sum of lactate and standard base excess.Measurements and Main Results: Organ dysfunction severity scores, physiologic variables of hepatic, metabolic, cardiac, and renal function, and 90-day mortality were measured. ScvO2 was lower than 70% only in 35% of patients. Mortality, organ dysfunction scores, and lactate were highest in the first and sixth sextiles of ScvO2. Although lactate level related strongly to mortality, it was associated with acidemia only when kidney function was impaired (creatinine >2 mg/dl), as rapidly detected by a negative alactic base excess. In contrast, positive values of alactic base excess were associated with a relative reduction of fluid balance.Conclusions: Hyperlactatemia is powerfully correlated with severity of sepsis and, in established sepsis, is caused more frequently by impaired tissue oxygen use, rather than by impaired oxygen transport. Concomitant acidemia was only observed in the presence of renal dysfunction, as rapidly detected by alactic base excess. The current strategy of fluid resuscitation could be modified according to the origin of excess lactate.

Sequential changes in urine production, glomerular filtration rate, and electrolyte excretion after mannitol administration.

IntroductionAcute kidney injury (AKI) leading to severe uremia is associated with high morbidity and mortality. Mannitol is an osmotic diuretic, widely used in the management of AKI, both as a bolus injection and as a constant rate infusion (CRI).ObjectivesTo determine the plasma concentration of mannitol after a bolus injection and CRI at the recommended dosages, and to assess the effect of mannitol on renal function variables including urine production, glomerular filtration rate (GFR), and solute excretion.MethodsProspective cross‐over design study, using 6 healthy dogs. Each dog underwent 3 protocols with at least a 7‐day washout period between protocols. The first protocol included bolus injection of mannitol, the second protocol included bolus injection followed by CRI of mannitol and the third protocol (control) included injection of 5% dextrose in water (D5W). Urine production, GFR, and fractional excretion (FE) of solutes were measured for 10 hours.ResultsFor all protocols, urine production significantly (P < .001) increased after bolus injection, but no significant difference in urine production or GFR was observed among the treatment groups. Mannitol injection increased the FE of sodium and urea nitrogen, but these effects were short‐lived.ConclusionsMannitol has minimal effect on urine production and GFR but does increase FE of urea nitrogen and sodium, immediately after bolus injection. Constant rate infusion at a conventional dosage of 1 mg/kg/min cannot maintain these effects in dogs with normal renal function, because mannitol concentration decreases rapidly.