Necessity Of Renal Replacement Therapy Research Articles

#1348 Acute kidney injury: evaluation of factors to predict the need of dialysis therapy

Abstract Background and Aims Acute kidney injury (AKI) is a clinical syndrome with heterogeneous pathophysiological mechanisms, associated with higher morbidity and mortality risk. The existing evidence shows that an episode of AKI increases the risk of chronic kidney disease and end-stage kidney disease, with considerable effects on long term outcomes. Current risk prediction scores were mostly calculated in the setting of contrast induced nephropathy and cardiac surgery reporting the patient's risk of AKI immediately before and after the invasive procedure. To date, no scoring models are available to assess the risk of progression and necessity of renal replacement therapy (RRT) for patients in the course of AKI. Method A prospective observational cohort study was conducted enrolling patients with AKI treated within the Nephrology, Dialysis and Kidney Transplant Unit of IRCCS Azienda Ospedaliero-Universitaria di Bologna from January 2022 to July 2023. The inclusion criteria were: 1) age >18 years, 2) stage 3 AKI according to the current KDIGO guidelines or presence of urgent RRT indication (severe hyperkalemia, metabolic acidosis or fluid overload refractory to medical treatment). The indication for RRT was given based on clinical judgement. Type of RRT, dialyzer and ultrafiltration rate were applied according to the clinical features of the patient. The primary endpoint was the association between AKI features and RRT. Secondary endpoints were evaluation of patients treated with RRT for factors associated with renal recovery. Results We studied 56 patients. The mean age ± SD was 69.8 ± 15.3 years (range, 18-94) and 37 (66.1%) were males. 18 patients (32.1%) were treated with conservative therapy and 38 (67.9%) with RRT. The factors correlated with the necessity of RRT were previous cardiovascular disease (p = 0.002), diabetes mellitus (p = 0.017), Charlson score >5 (p = 0.035), volume overload (p = 0.002), urine output level (p = 0.033) and C reactive protein (CRP; p = 0.020). Multivariate analysis found significant association of cardiovascular disease (OR, 5.94; 95% CI, 1.45 to 24.34; p = 0.013) and elevated CRP (OR, 1.08; 95% CI, 1.00 to 1.16; p = 0.049) during AKI episode with the RRT need in the study cohort. Higher ultrafiltration rate during RRT was correlated with non recovery of kidney function (OR, 1.86; 95% CI, 1.09 to 3.14; p = 0.021). Conclusion Cardiovascular disease and higher CRP were associated with necessity of RRT. More intensive fluid removal during RRT resulted as negative predictor of kidney function recovery. Further studies with larger study samples and randomized design are necessary to confirm these findings.

Acute kidney injury and necessity of renal replacement therapy in acutely intoxicated patients with rhabdomyolysis

Introduction/Objective. This study aimed to analyse the characteristics of the selective parameters related to the development of acute kidney injury and the necessity of renal replacement therapy in patients with rhabdomyolysis due to acute intoxication with psychotropic and chemical substances in the first 24 hours. Methods. In a clinically controlled prospective study, 140 patients with rhabdomyolysis were divided into two groups depending on the intoxicating substance, i.e., psychotropic or chemical. Patients were selected according to predetermined inclusion and exclusion criteria. Results. Acute kidney injury occurred in 15% of 140 patients with rhabdomyolysis of whom 14 (66.7%) had psychotropic intoxication and seven (33.3%) had chemical intoxication. Statistical analysis showed significantly increased prevalence in the psychotropic group compared to those with chemical intoxication (p 0.0002). Creatine kinase values for median interquartile range in patients without/with renal replacement therapy were in psychotropic ? 753 (446?753) vs. 42,670 (22,357?42,670) U/L; and chemical ? 478.3 (321.5?1111.9) vs. 648.6 (495.6?2065) U/L. In psychotropic intoxications this difference was significant (p = 0.00002), while in the chemical ones it was insignificant (p =0.2885). The renal replacement therapy was applied in 13 (9.3%) patients with rhabdomyolysis, nine of which (69.2%) were with psychotropic intoxication and four (30.8%) were with chemical intoxication. Conclusion. The prevalence of acute kidney injury and necessity for necessity for renal replacement therapy was significantly higher in psychotropic intoxication compared to chemical intoxication. The level of creatine kinase and myoglobin on the first day in the group with psychotropic substances, and high-sensitivity troponin I in both groups ?psychotropic and chemical substances ? are significantly higher in patients who need renal replacement therapy compared to those who do not need this therapy.

Association between Serum Lactate and Morbidity and Mortality in Neonates: A Systematic Review and Meta-Analysis.

Lactate is a marker of hypoperfusion in critically ill patients. Whether lactate is useful for identifying and stratifying neonates with a higher risk of adverse outcomes remains unknown. This study aimed to investigate the association between lactate and morbidity and mortality in neonates. A meta-analysis was performed to determine the association between blood lactate levels and outcomes in neonates. Ovid MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched from inception to 1 May 2021. A total of 49 observational studies and 14 data accuracy test studies were included. The risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies and the QUADAS-2 tool for data accuracy test studies. The primary outcome was mortality, while the secondary outcomes included acute kidney injury, necessity for renal replacement therapy, neurological outcomes, respiratory morbidities, hemodynamic instability, and retinopathy of prematurity. Of the 3184 articles screened, 63 studies fulfilled all eligibility criteria, comprising 46,069 neonates. Higher lactate levels are associated with mortality (standard mean difference, -1.09 [95% CI, -1.46 to -0.73]). Using the estimated sensitivity (0.769) and specificity (0.791) and assuming a prevalence of 15% for adverse outcomes (median of prevalence among studies) in a hypothetical cohort of 10,000 neonates, assessing the lactate level alone would miss 346 (3.46%) cases (false negative) and wrongly diagnose 1776 (17.76%) cases (false positive). Higher lactate levels are associated with a greater risk of mortality and morbidities in neonates. However, our results do not support the use of lactate as a screening test to identify adverse outcomes in newborns. Research efforts should focus on analyzing serial lactate measurements, rather than a single measurement.

Conversion to tacrolimus alone compared to full immunosuppression following cardiac transplantation (TACTFUL).

Cardiac transplantation requires lifelong immunosuppressant medications to prevent rejection. However, some patients may not tolerate multiple immunosuppressants due to adverse effects. At our institution, patients may be converted to monotherapy with tacrolimus if unable to tolerate a combination regimen. This study evaluated the outcomes among patients converted to tacrolimus monotherapy compared with those maintained on combination immunosuppression. This single-center, retrospective cohort study included patients who received heart transplants at Sentara Norfolk General Hospital between January 2015 and July 2021. Patients were classified as receiving tacrolimus monotherapy (Mono) or combination immunosuppression (Combo). The primary outcome was all-cause mortality with key secondary outcomes including incidence of 2R/3R rejection, necessity for renal replacement therapy, and infection. 112 patients were included (Mono=25, Combo=87). Median age at transplant was 53.8 years (Mono) and 52.1 years (Combo). The most common reasons for conversion to monotherapy were leukopenia, infection, and gastrointestinal (GI) distress. There was no difference in mortality (0 in Mono, 11 in Combo; p=.09) or percentage of patients with 2R/3R rejection (24% in Mono, 32.2% in Combo; p=.43). No Mono group patients experienced rejection after converting from combination therapy. 24% of Mono group patients resumed at least one additional immunosuppressive medication during the study period. Median time to monotherapy was 9.0 months, with a total median duration on monotherapy of 16.0 months. A median of 3.3 years of follow-up was observed for patients in Mono and 3.4 years in Combo (p=.29). Selected patients who do not tolerate combination immunosuppression can be safely transitioned to tacrolimus monotherapy as a means of controlling adverse events without an increased risk of mortality or rejection.

Use of angiotensin converting enzyme inhibitors in chronic kidney disease - a review of the literature

Introduction: Chronic Kidney Disease (CKD) has become one of the most common chronic diseases of the XXI century and affects around 16% of the world's population. Despite the advancements of contemporary science and a range of therapeutic methods it considered a progressive and irreversible process. Nevertheless, use of ACEI halts the progression of the disease and postpones the necessity of renal replacement therapy and is the method of choice for this group of patients. 
 Purpose of the work: The article reviews current literature and writing regarding Chronic Kidney Disease (CKD) and the impact of ACEI on the progression of this condition. 
 Materials and methods: The sources available in the PubMed database have been analyzed using the keywords: “ACEI”, “angiotensin-converting-enzyme inhibitors”, ”chronic kidney disease”, “CKD”. Related publications to the topic of the work have been selected and utilized. 
 Description of the state of knowledge: Pharmacological therapy using ACEI is the main method of treatment for patients with CKD and should primarily serve to reduce proteinuria and control blood pressure. It inhibits the progression of the disease and delays the development of end-stage renal failure. However, the treatment of CKD using ACEI is controversial in cases of advanced stages of the disease. 
 Summary: ACEI inhibitors are one of the major advances in the treatment of patients dealing with CKD. Due to the increasing number of cases of the disease being observed, further research will be needed regarding the use of these drugs. Particularly ambiguous is the therapy for patients with advanced, just before end-stage renal failure, which will require a more in-depth analysis of these cases.

Neutrophil Gelatinase-Associated Lipocalin Acts as a Robust Early Diagnostic Marker for Renal Replacement Therapy in Patients with Russell's Viper Bite-Induced Acute Kidney Injuries.

Snakebite-induced acute kidney injury (AKI) is frequently observed in patients following bites from vipers such as Russell’s viper (Daboia russelii) in India. Currently, the levels of serum creatinine are mainly used as a marker to determine the necessity for renal replacement therapy (RRT) (haemodialysis) in severe cases of AKI. However, it takes up to 48 h to ascertain a distinct change in creatinine levels compared to its baseline level upon admission. The time lost between admission and the 48 h timepoint significantly affects the clinical management of snakebite victims. Moreover, early diagnosis of AKI and decision on the necessity for RRT in snakebite victims is critical in saving lives, reducing long-term complications, and minimising treatment costs arising from expensive haemodialysis. Neutrophil gelatinase–associated lipocalin (NGAL) has been recently studied as a robust early marker for AKI in non-snakebite patients. However, its suitability for clinical use in snakebite victims has not been rigorously established. Here, we demonstrate the clinical significance of plasma NGAL as a robust marker for RRT following AKI using a large cohort (309) of Russell’s viper victims without any pre-existing health conditions. NGAL levels upon admission are positively correlated with creatinine levels at 48 h in different stages of AKI. Overall, NGAL acts as a robust early marker to ascertain the need for RRT following Russell’s viper bites. The quantification of NGAL can be recommended as a routine test in hospitals that treat snakebites to decide on RRT at early time points instead of waiting for 48 h to confirm the increase in creatinine levels. The diagnostic use of NGAL in Russell’s viper victims with pre-existing comorbidities and for other vipers should be evaluated in future studies.

Early Laboratory Predictors for Necessity of Renal Replacement Therapy in Patients With Spontaneous Deep-Seated Intracerebral Hemorrhage

Objective: The need for continuous renal replacement therapy (CRRT) in patients with deep-seated intracerebral hemorrhage (ICH) requires sustained intensive care and often postpones further rehabilitation therapy. Therefore, an early identification of patients at risk is essential.Methods: From 2014 to 2019, all patients with deep-seated ICH who were admitted to intensive care for >3 days were included in the further analysis and retrospectively reviewed for the need for CRRT. All patients underwent CRRT with regional citrate anticoagulation for continuous veno-venous hemodialysis (CVVHD). Outcome was evaluated after 3 months using the modified Rankin scale. A multivariate analysis was performed to identify potential predictors for CRRT in patients with deep-seated ICH.Results: After applying the inclusion criteria, a total of 87 patients with deep-seated spontaneous ICH were identified and further analyzed. During the first 48 h after admission, 21 of these patients developed early acute kidney injury (AKI; 24%). During treatment course, CRRT became necessary in nine patients suffering from deep-seated ICH (10%). The multivariate analysis revealed “development of AKI during the first 48 h” [p = 0.025, odds ratio (OR) 6.1, 95% confidence interval (CI) 1.3–29.8] and “admission procalcitonin (PCT) value >0.5 μg/l” (p = 0.02, OR 7.7, 95% CI 1.4–43.3) as independent and significant predictors for CRRT in patients with deep-seated ICH.Conclusions: Elevated serum levels of procalcitonin on admission as well as early development of acute renal injury are independent predictors of the need for renal replacement therapy in patients with deep-seated intracerebral bleeding. Therefore, further research is warranted to identify these vulnerable patients as early as possible to enable adequate treatment.

Mortality among Critically Ill Acute Kidney Injury Patients Stratified with RIFLE Classification

Acute kidney injury, also referred to as AKI, is a common complication seen in critically ill patients . There has been a significant increase in the number of AKI cases over the past few decades. In order to standardize the classification of AKI, the RIFLE (Risk, Injury, Failure, Loss, End-Stage) and AKIN (AKI Network) criteria were developed.This is a prospective, observational, and longitudinal cohort study where data from all patients admitted to the hospital intensive care unit (ICU) were collected. The study duration ranged from March 2019 to September 2020. During the study period, 198 patients were admitted to the ICU. Of these, 69 were excluded while the remaining 104 patients were included in the study.About 66–67% of the total critically ill patient population admitted in the ICU suffer from some etiology related to AKI. Our study highlights the aspect in which the cases of AKI are underreported. RIFLE class R or class I is still associated with excess mortality compared with patients who maintained normal function. RIFLE is a reliable system of classification, which is well classified and indicates the immediate necessity of renal replacement therapy (RRT); the prognosis of early RRT is fairly good in critically ill patients with AKI.

COVID-19 em Pediatria: Relato de um caso com múltiplas complicações e bom desfecho clínico

Coronavirus disease 2019 (COVID-19) is an acute infectious disease that caused the emergence of the new serious global pandemic. The infection in children is much less prevalent than in adults and most cases are asymptomatic or have mild symptoms. Severe cases represent less than 1% of the total, therefore information about the disease in this age group is scarce compared to data in older individuals. We exposed a case of a 16-year-old male adolescent with a previous diagnosis of myelomeningocele, hydrocephalus with peritoneal ventricle bypass (PVB), recurrent urinary tract infection, epilepsy, and obesity. The patient presented cough and convulsive crises, which worsened during hospitalization with severe acute respiratory syndrome due to SARS-CoV-2, septic shock, and cardiorespiratory arrest and invasive mechanical ventilation (IMV) for 9 days was required. Also presented several other complications and factors of critical prognosis, such as elevated inflammatory markers (C-reactive protein, D-dimer), elevated cardiac troponin, and the necessity of renal replacement therapy. Nevertheless, the clinical outcome was satisfactory and he was discharged after a 40-day stay in the Pediatric Intensive Care Unit.

N-acety-b-D-glucosaminidase: A potential biomarker for early detection of acute kidney injury in acute chest pain.

Acute kidney injury (AKI) is often underdiagnosed due to several limitations of the renal marker creatinine. Tubular urinary biomarkers may substantially contribute to diagnose AKI early. For early detection of AKI, we evaluated for the first time N-acetyl-β-d-glucosaminidase (NAG), Kidney-injury-molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in acute chest pain. We included 402 chest pain patients aged 18 to 95 years seen in the emergency department. From 311 subjects, blood and urine samples were collected. Thirty-three patients developed an AKI and showed a significant increase in all three tubular markers compared to patients without AKI (each P < .001). According to receiver operating characteristic (ROC) analysis, combining NAG and creatinine showed a significantly increased area under the curve (AUC) compared to creatinine alone (AUC: 0.75 vs 0.87; P < .001). KIM-1, NGAL and cystatin C showed no significant differences in AUC compared to creatinine. In 120 individuals with blood and urine sampling before contrast media exposure, ROC analysis showed a significantly improved diagnostic performance for the combination of both (AUC: 0.83 vs creatinine AUC: 0.66; P = .004). AKI occurrence showed no dependency from CM volume. NAG presented as an independent AKI predictor beside creatinine, age, the diagnosis of myocardial infarction and mean arterial pressure. Regarding the prognostic value for renal replacement therapy, the combination of NAG and creatinine showed a significantly lager AUC than creatinine (AUC: 0.95 vs AUC: 0.85; P < .001). NAG presented as a promising marker of impending AKI and the necessity of renal replacement therapy.

Successful peritoneal dialysis for the end-stage kidney disease associated with Prader\u2013Willi syndrome: a case report

Prader–Willi Syndrome (PWS) is characterized by hyperphagia, severe obesity, and mental retardation from early childhood and occurs 1/10,000 to 1/15,000 live births in Japan. There is high prevalence of diabetes mellitus because of hyperphagia. The patient may sometimes face the necessity of renal replacement therapy (RRT) because of end-stage kidney disease (ESKD) caused by diabetes-associated kidney disease (DKD). Since mental retardation and extreme obesity usually prevent to introduce peritoneal dialysis (PD), hemodialysis (HD) has been the first choice of RRT. In this report, we experienced one case of patient with PWS suffering from ESKD due to DKD who started PD as an initial RRT and succeeded to continue for total of 40 months. The patient was 37-year-old man at the time of initiation of dialysis. PD was chosen for RRT because we suspected that he might have more technical difficulties for continuing HD. After several episodes of peritonitis, he successfully continues PD without peritonitis for next 27 months until the present time with good support by his family member. To our best knowledge, this is the first reported case of ESKD associated with PWS who was successfully treated with PD for long period.

Controlled arterial hypertension and adverse event free survival rate in heart recipients

Aim.To evaluate the prevalence of arterial hypertension (AH) in heart transplant recipients, and its influence on the risk of adverse events, as the efficacy and safety of antihypertension medications (AHM).Material and methods.To the study, were consequently included all heart transplant recipients operated in the Shumakov Centre during the years 2013 to 2016 and survived 90 days after orthotopic heart transplantation.Results.Totally, 353 recipients included, with AH or AHM intake in anamnesis in 62 (17,6%). Within 90 days post-surgery, AH that demanded for medication therapy was found in 151 (42,8%) patients. In posttransplant AH patients there were the following specific parameters in preoperational period: higher body mass index — 25,7±4,1 vs 24,9±4,4 (р=0,026), blood creatinine concentration — 100,6±62,6 vs 68,8±4,8 (р&lt;0,001), donor heart posterior wall thickness — 11,9±0,8 vs 11,3±0,7 (р=0,034), creatinine concentration in 3 month after operation — 131,7±101,6 vs 94,1±46,5 (p&lt;0,001). There was relation revealed, of AH development risk with anamnesis of AH and renal failure, as a necessity for renal replacement therapy within 30 days post surgery and episodes of acute antibody-mediated reaction on transplant. In the recipients taking angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ACEi/ARB) before operation, the survival rate free from adverse events was better than in those taking calcium channel blockers (CCB) (plog-rank=0,042).Conclusion.The results of the study point on high prevalence of AH in heart recipients. Presence of AH in anamnesis, renal failure, episodes of humoral, but not cellular, reaction to the transplant, and donor heart hypertrophy do significantly increase the probability of AH development after transplantation. Comparison revealed significant benefit of ACEi/ ARB versus CCB as antihypertension medications in either monotherapy or in combination with diuretics.

RISK FACTORS AND OUTCOMES OF ACUTE KIDNEY INJURY IN EARLY PERIOD POST CARDIOSURGERY

Aim. To assess the rate of acute kidney injury (AKI) development, incl. the necessity of renal replacement therapy (RRT), to evaluate the risk factors and outcomes of AKI. Material and methods. In the study, 2958 patients included, after a variety of cardiosurgical operations. The stage of AKI and indications for RRT were set based on the criteria of Kidney Disease: Improving Global Outcomes. Results. The rate of AKI development in general was 14%. AKI 1 stage was diagnosed in 10,2% (n=303), stage 2 in 3% (n=88) and stage 3 in 0,8% (n=23). RRT was implemented in 1,3% (n=38) of patients. The rate of AKI development post single coronary bypass (CBG) was 9,5% (n=35), single valve replacement (VR) and/or valve plastics (VP) — 19,8% (n=35), CBG+VR+VP — 33% (n=84), combination operations — 19,5% (n=107). Necessity of RRT post CBG — 0,3% (n=6), post VP/ VR — 0,56% (n=1), post CBG+VR/VP — 5,5% (n=14), post combination surgeries — 3% (n=17). Conclusion. The risk factors for AKI: age, body mass index, left atrium volume index, surgery type, the syndrome of low cardiac output, atrial fibrillation in early post operation period, inotropic and vasopressory support, lactat-acidosis. Development of AKI does prolong hospitalization time and increase mortality.

Proteinuria and the Clinical Course of Dobrava-Belgrade Hantavirus Infection

Purpose: Human infection with Dobrava-Belgrade virus (DOBV) in Northern Germany causes a mild form of hantavirus disease predominantly characterized by acute kidney injury due to interstitial nephritis. We evaluated the largest number of DOBV-infected patients so far regarding clinical course, proteinuria, and prognostic markers. Patients and Methods: Patients with DOBV-associated hantavirus disease admitted to the Renal Division of the University of Lübeck (Germany) between 1997 and 2012 were included in this study. Symptoms, clinical course, laboratory parameters, and urinary protein analysis were investigated at admission (baseline, t₀), 3–5 days (t_3–5), 10–17 days (t_10–17), and after 1 year of follow-up (t₃₆₅). Results: Of the 34 patients (male/female ratio: 23/11; age: 41 ± 14 years) included in the study, 4 underwent hemodialysis (HD). Glomerular filtration rate was 17 ± 14 mL/min at t₀ and increased to 27 ± 26 mL/min (t_3–5), 57 ± 20 mL/min (t_10–17), and 84 ± 16 mL/min (t₃₆₅). Albuminuria and tubular proteinuria (α₁- and β₂-microglobulin) decreased during follow-up; the urinary α₁-microglobulin concentration in patients who required HD was significantly higher than that in patients not requiring HD (t₀: 186 ± 51 vs. 45 ± 26 mg/g creatinine; t_3–5: 87 ± 14 vs. 32 ± 16 mg/g creatinine; t_10–17: 63 ± 18 vs. 28 ± 12 mg/g creatinine; p < 0.001). Conclusions: DOBV infection of inpatients in Northern Germany is associated with severe kidney injury that recovers within a few weeks and normalizes within 1 year. Tubular proteinuria is associated with the severity of kidney injury and the necessity of renal replacement therapy in these DOBV-infected patients.

Outcome and features of acute kidney injury complicating hypoxic hepatitis at the medical intensive care unit

BackgroundHypoxic hepatitis (HH) is a frequent and potentially life-threatening event typically occurring in critically ill patients as a consequence of hemodynamic impairment. While acute kidney injury (AKI) has been well described in patients with acute liver failure, incidence and outcome of AKI accompanying HH are unclear. The aim of this study was to assess incidence, clinical implications and outcome of AKI and renal replacement therapy (RRT) in critically ill patients with HH.MethodsA total of 1948 consecutive critically ill admissions were studied at the Medical University of Vienna. Laboratory and clinical parameters as well as the presence of HH and AKI were assessed on a daily basis. Outcome, renal recovery and length of stay were assessed and documented, and patients were followed for 1 year.ResultsA total of 295 admissions (15 %) developed HH. Main precipitators were cardiogenic (44 %) and septic shock (36 %). Occurrence of HH was significantly associated with AKI [OR 4.50 (95 % CI 3.30–6.12)] and necessity of renal replacement therapy [RRT; OR 3.36 (95 % CI 2.58–4.37)], p < 0.001 for both. Two hundred forty admissions with HH (81 %) developed AKI, 159 of whom (66 %) had AKI stage 3. Both HH and AKI were significantly linked to mortality. AKI stage 3, international normalized ratio (INR, during HH) and the presence of septic shock were identified as independent predictors of 28-day mortality in admissions with HH, whereas RRT was identified as an independent protective factor. There was a synergistic effect of HH and AKI on length of stay at the ICU. Of all HH survivors treated with RRT, 71 % showed renal recovery during follow-up.ConclusionHH is frequently complicated by occurrence of AKI. Severity of HH, AKI stage and the presence of septic shock seem to contribute to poor outcome in these patients. Initiation of RRT in HH with AKI may enable renal recovery and should not be withheld in medical ICU patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13613-016-0162-4) contains supplementary material, which is available to authorized users.

Impact of Acute Kidney Injury on Outcome in Patients With Severe Acute Respiratory Failure Receiving Extracorporeal Membrane Oxygenation*

Extracorporeal lung support is currently used in the treatment of patients with severe respiratory failure until organ recovery and as a bridge to further therapeutic modalities. The aim of our study was to evaluate the impact of acute kidney injury on outcome in patients with acute respiratory distress syndrome under venovenous extracorporeal membrane oxygenation support and to analyze the association between prognosis and the time of occurrence of acute kidney injury and renal replacement therapy initiation. Retrospective observational study. A large European extracorporeal membrane oxygenation center, University Medical Center Regensburg, Germany. A total of 262 consecutive adult patients with acute respiratory distress syndrome have been treated with extracorporeal membrane oxygenation between January 2007 and May 2012. None. Patient median age was 49 years (range, 18-78 yr); 183 (69.8%) were male. The leading cause of lung failure was pneumonia. The median Sequential Organ Failure Assessment score was 12.0 (8.8-15.0), and the median lung injury score was 3.3 (3.3-3.7). The median extracorporeal membrane oxygenation support duration was 9 days (6-15 d). One hundred eighty-three patients (69.8%) were successfully weaned and 156 patients (59.9%) survived to hospital discharge. One hundred thirty-one patients (50.0%) were treated with renal replacement therapy during extracorporeal membrane oxygenation support. The survival rate was significantly lower in patients requiring renal replacement therapy compared with those without renal replacement therapy (47.3% vs 71.8%; p < 0.001) overall. The Kaplan-Meier survival curves differed significantly for patients without renal replacement therapy versus patients with renal replacement therapy prior to extracorporeal membrane oxygenation support (p = 0.003). Furthermore, the multivariate logistic regression analysis suggests that the necessity of renal replacement therapy prior to extracorporeal membrane oxygenation insertion was an independent risk factor for mortality (95% CI, 0.77-0.88; p < 0.001). However, the necessity of renal replacement therapy during extracorporeal membrane oxygenation support was not an independent risk factor for mortality in these patients (p = 0.37). Acute kidney injury is a major complication in acute respiratory distress syndrome probably mirroring severe systemic disease. In our cohort, development of acute kidney injury requiring renal replacement therapy prior to extracorporeal membrane oxygenation insertion was negatively associated with survival, whereas acute kidney injury that developed during extracorporeal membrane oxygenation support was not.

Novel targets of antifibrotic and anti-inflammatory treatment in CKD.

Chronic kidney disease (CKD) is becoming a worldwide epidemic, driven largely by the dramatic rise in the prevalence of diabetes and obesity. Novel targets and treatments for CKD are, therefore, desperately needed-to both mitigate the burden of this disease in the general population and reduce the necessity for renal replacement therapy in individual patients. This Review highlights new insights into the mechanisms that contribute to CKD, and approaches that might facilitate the development of disease-arresting therapies for CKD. Particular focus is given to therapeutic approaches using antifibrotic agents that target the transforming growth factor β superfamily. In addition, we discuss new insights regarding the roles of vascular calcification, the NADPH oxidase family, and inflammation in the pathogenesis of CKD. We also highlight a new understanding regarding kidney energy sensing pathways (AMPK, sirtuins, and mTOR) in a variety of kidney diseases and how they are linked to inflammation and fibrosis. Finally, exciting new insights have been made into the role of mitochondrial function and mitochondrial biogenesis in relation to progressive kidney disease. Prospective therapeutics based on these findings will hopefully renew hope for clinicians and patients in the near future.

Pulsatile Cardiopulmonary Bypass With Intra-Aortic Balloon Pump Improves Organ Function and Reduces Endothelial Activation

We aimed to evaluate if the use of an intra-aortic balloon pump (IABP) during cardioplegic arrest improves organ function and reduces endothelial activation in patients undergoing coronary artery bypass graft (CABG). Five-hundred and one CABG patients were randomized into 2 groups: (Group A n=270) linear cardiopulmonary bypass (CPB); and (Group B n=231) automatic 80 beats/min IABP-induced pulsatile CPB. We evaluated hemodynamic response, coagulation and fibrinolysis, transaminase, bilirubin, amylase, lactate, renal function (estimated glomerular filtration rate [eGFR], creatinine and any possibility of renal insufficiency or failure), respiratory function and endothelial markers (vascular endothelial growth factor [VEGF] and monocyte chemotactic protein-1 [MCP-1]). IABP, which induced surplus hemodynamic energy, was 21,387 ± 4,262 ergs/cm(3). Group B showed lower chest drainage, transfusions, international normalized ratio, and antithrombin III, together with higher platelets, activated partial thromboplastin time, fibrinogen and D-dimer. Transaminases, bilirubin, amylase, lactate were lower in Group B; there were better results for eGFR in Group B from ICU-arrival to 48 h, resulting in lower creatinine from ICU-arrival to 48 h. The necessity for renal replacement therapy was lower in Group B Stage-3. Group B P(a)O(2)/F(i)O(2) and lung compliance improved with aortic de-clamping on the first day with shorter intubation time. Group B showed lower VEGF and MCP-1. Pulsatile flow by IABP improves whole-body perfusion and reduces endothelial activation during CPB.

Obesity and acute kidney injury: reply to Dr. Robert and coworkers

Dear Editor, We thank Dr. Robert and colleagues [1] for their comments on our study on the impact of BMI on the evolution and prognosis of acute kidney injury (AKI) [2]. We remind the readers that in this study the impact of BMI on the evolution AKI was corrected for by several potential confounders, such as age, severity of disease, diabetes status, or comorbidities. Dr. Robert raises another possibility for a bias, i.e., the criteria for AKI diagnosis used in the Risk, Injury, Failure, Loss, and End-Stage Kidney (RIFLE) classification. They discuss whether urinary output should—as required in both RIFLE and Acute Kidney Injury Network (AKIN) classifications—be corrected for by body weight which might introduce a bias in obese patients. Our diagnosis of AKI, however (as in most studies), was not based on urine criterion but on the creatinine criterion and the necessity of renal replacement therapy. Dr. Robert also questions the validity of the creatinine criterion because obese persons also have a higher muscle mass and thus a higher creatinine formation. This fact—they argue—may result in an erroneous allocation of several subjects into the F category and also in an earlier initiation of renal replacement therapy in obese patients. This is certainly a point well taken; it is a problem which is inherent to currently used AKI classifications which all are based on serum creatinine. However, we only included patients in a really ‘‘failure’’ situation and the necessity of renal replacement therapy, a decision which rarely is based on creatinine concentration alone. A substantial impact of this potential bias on our results can largely be ruled out. References

Fractional excretion of urea in the follow-up of acute renal failure due to prerenal azotemia

Fractional excretion of urea (FEU) is a major issue to discriminate between prerenal azotemia and acute tubular necrosis in acute renal failure (ARF). Its role in the course of ARF remains unclear. The aim of this study was to evaluate FEU in the follow-up of ARF due to prerenal azotemia in order to predict the necessity of renal replacement therapy (RRT). The prospective study took place at the ICU of Stadtspital Waid, Zurich. All patients admitted starting from 19 February 2006 were evaluated for ARF according to the RIFLE classification. ARF due to prerenal azotemia was defined as ARF combined with FEU of less than or equal to 35%. FEU was calculated as [(urine urea/blood urea)/(urine creatinine/plasma creatinine)] × 100. Urine specimens were taken and FEU was calculated daily until complete or partial renal recovery was reached or the criteria for RRT were met. The goal of therapy was reconstitution of renal function by treatment of the underlying condition. RRT was initiated according to the usual criteria. Statistics were determined using Fisher's exact test. By 7 December 2006, 15 patients met the inclusion criteria for ARF due to prerenal azotemia (nine males, six females). The mean age was 71 ± 11 (SD) years for male patients and 58 ± 31 years for female patients. Twelve out of the 15 patients responded to conservative management and had complete or partial renal recovery. Three patients needed RRT. Two of them refused RRT and died during the course of the disease. During the first 48 hours after initiation of conservative therapy, FEU remains less than or equal to 35% in all three patients who needed RRT. By contrast, nine out of 12 patients in whom renal function recovered without RRT showed a FEU of more than 35% within the first 48 hours (P < 0.05) (Figure ​(Figure11). Figure 1 Fractional excretion of urea (FEU) in the follow-up of acute renal failure (ARF) due to prerenal azotemia. Data presented as mean ± SD. n = number of patients. In patients presenting with ARF due to prerenal azotemia, an increase of FEU above 35% within the first 48 hours after initiation of conservative therapy for ARF is a valuable parameter to predict renal recovery. After initiation of conservative therapy, measurement of FEU is of no value concerning discrimination of prerenal azotemia and acute tubular necrosis in ARF.