Disease Severity Determines Timing of Initiating Continuous Renal Replacement Therapies: A Systematic Review and Meta-Analysis

Background: Timing of initiating continuous renal replacement therapies (CRRTs) among the patients with acute kidney injury (AKI) in intensive care units (ICU) has been discussed over decades, but the definition of early and late CRRT initiation is still unclear.Methods: The English language randomized controlled trials (RCTs) and cohort studies were searched through MEDLINE, EMBASE, and Cochrane Library on July 19, 2019, by the two researchers independently. The study characteristics; early and late definitions; outcomes, such as all-cause, in-hospital, 28- or 30-, 60-, 90-day mortality; and renal recovery were extracted from the 18 eligible studies. Pooled relative risk ratios (RRs) and 95% CIs were estimated with the fixed effects model and random effects model as appropriate. This study is registered with PROSPERO (CRD 42020158653).Results: Eighteen studies including 3,914 patients showed benefit in earlier CRRT (n = 1,882) over later CRRT (n = 2,032) in all-cause mortality (RR 0.78, 95% CI 0.66–0.92), in-hospital mortality (RR 0.81, 95% CI 0.67–0.99), and 28- or 30-day mortality (RR 0.81, 95% CI 0.74–0.88), but in 60- and 90-day mortalities, no significant benefit was observed. The subgroup analysis showed significant benefit in the disease-severity-based subgroups on early CRRT initiation in terms of in-hospital mortality and 28- or 30-day mortality rather than the time-based subgroups. Moreover, early CRRT was found to have beneficial effects on renal recovery after CRRT (RR 1.21, 95% CI 1.01–1.45).Conclusions: Overall, compared with late CRRT, early CRRT is beneficial for short-term survival and renal recovery, especially when the timing was defined based on the disease severity. CRRT initiation on Acute Kidney Injury Network (AKIN) stage 1 or Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE)-Risk or less may lead to a better prognosis.

Hourly Analysis of Mechanical Ventilation Parameters in Critically Ill Adult Covid-19 Patients: Association with Mortality

Objective: there exists controversy about the pathophysiology and lung mechanics of COVID-19 associated ARDS, because some report severe hypoxemia with preserved respiratory system mechanics, contrasting with “classic” ARDS. We performed a detailed hourly analysis of the characteristics and time course of lung mechanics and biochemical analysis of patients requiring invasive mechanical ventilation for COVID-19-associated ARDS, comparing survivors and non-survivors.Methods and measurements: retrospective analysis of the data stored in the ICU information system of patients admitted in our hospital ICU that required invasive mechanical ventilation due to confirmed SARS-CoV-2 pneumonia between March 5th and April 30th, 2020. We compare respiratory system mechanics and gas exchange during the first ten days of IMV, discriminating volume and pressure controlled modes, between ICU survivors and non-survivors.Results: 140 patients were analyzed, analyzing 11,138 respiratory mechanics recordings. Global mortality was 38.6%. Multivariate analysis showed that age (OR 1,092, 95% (CI 1,014-1,176)), previous use of ACEI/ARBs (OR 4,612, (95% CI 1,19-17,84)) and need of renal replacement therapies (OR 10,15, (95% CI 1,58-65,11)) were associated with higher mortality. Respiratory variables start to diverge significantly between survivors and non-survivors after the 96 to 120 hours from mechanical ventilation initiation, particularly respiratory system compliance. In non survivors, mechanical power at 24 and 96 hs was higher regardless ventilatory mode. Conclusions: in patients admitted for SARS-CoV-2 pneumonia and requiring mechanical ventilation, non survivors have different respiratory system mechanics than survivors in the first 10 days of ICU admission. We propose a checkpoint at 96-120 hs to assess patients` improvement or worsening in order to consider escalating to extracorporeal therapies.“TAKE HOME MESSAGE”: assessing respiratory mechanics in the first 96-120 hs from ICU admission could predict the outcome of Covid-19 patients under mechanical ventilation.

Impact of prolonged duration of different types of renal replacement therapies on serum levels of endothelin-1 and pulmonary function tests

Introduction: This study was carried out to investigate the impact of duration of different renal replacement therapies such as hemodialysis and continuous ambulatory peritoneal dialysis on potential overproduction of endothelin-1 (ET-1) and pulmonary function tests in these patients. Materials and methods: The study included 26 patients (14 males, mean age 54.9&plusmn;16.2 years) with end stage renal diseases (ESRD) receiving regular hemodialysis (HD) and 23 patients (10 males, mean age 55.8&plusmn;15.8 years) with ESRD treated with continuous ambulatory peritoneal dialysis (CAPD). The spirometry values were recorded before the onset of HD and prior to emptying the peritoneal cavity in CAPD patients and ET-1 was measured using the enzyme immunoassay (EIA) methodology. Two groups of patients (groups 1 and 2) were further divided into subgroups (group A and group B). Groups A (1-A and 2-A) included patients treated with any type of renal replacement therapy (RRT) (HD or CAPD) less than 5 years, and groups B (1-B and 2-B) included patients treated with any type of RRT (HD or CAPD) longer than 5 years. Results: Patients treated with HD or CAPD for more than five years were found to have significantly higher serum levels of ET-1 (HD = 41.49&plusmn;21.28 vs. 185.13&plusmn;73.67, p<0.01; PD = 51.24&plusmn;32.11 vs. 139.53&plusmn;42.42, p<0.01, respectively). Values of most pulmonary function parameters differed significantly between groups treated longer or shorter than 5 years: FVC (HD = 108.4&plusmn;13.34 vs. 80.82&plusmn;11.26, p<0.01; CAPD = 97.20&plusmn;18.99 vs. 73.25&plusmn;10.73, p<0.01, respectively), FEV1 (HD = 108.33&plusmn;15.8 vs. 76.73&plusmn;4.9, p<0.01; CAPD = 100.67&plusmn;18.31 vs. 66.75&plusmn;6.25, p<0.01, respectively). Conclusions: Prolonged duration of any type of renal replacement therapy is associated with higher serum levels of ET-1 and with lower pulmonary function tests in ESRD patients.

Fosfomycin single- and multiple-dose pharmacokinetics in patients undergoing prolonged intermittent renal replacement therapy

Background Fosfomycin is used increasingly in the treatment of MDR bacteria. It is eliminated by renal excretion, but data regarding dosing recommendations for patients undergoing modern means of renal replacement therapies are scarce. Objectives Evaluation of the pharmacokinetics (PK) of fosfomycin in patients undergoing prolonged intermittent renal replacement therapy (PIRRT) to guide dosing recommendations. Methods Fosfomycin was given in 11 (7 female) patients with severe infections undergoing PIRRT. Plasma levels were measured at several timepoints on the first day of fosfomycin therapy, as well as 5–6 days into therapy, before and after the dialyser, to calculate its clearance. Fosfomycin was measured in the collected spent dialysate. Results The median (IQR) plasma dialyser clearance for fosfomycin was 183.4 (156.9–214.9) mL/min, eliminating a total amount of 8834 (4556–10 440) mg of fosfomycin, i.e. 73.9% (45.3%–93.5%) of the initial dose. During PIRRT, the fosfomycin half-life was 2.5 (2.2–3.4) h. Data from multiple-dose PK showed an increase in fosfomycin Cmax from 266.8 (166.3–438.1) to 926.1 (446.8–1168.0) mg/L and AUC0–14 from 2540.5 (1815.2–3644.3) to 6714 (4060.6–10612.6) mg·h/L. Dialysis intensity during the study was 1.5 L/h. T&gt;MIC was 100% in all patients. Conclusions Patients undergoing PIRRT experience significant fosfomycin elimination, requiring a dose of 5 g/8 h to reach adequate plasma levels. However, drug accumulation may occur, depending on dialysis frequency and intensity.

GLP-1 Receptor Agonists in Diabetic Kidney Disease: From Physiology to Clinical Outcomes

Diabetic kidney disease (DKD) is one of the most common complications in type 2 diabetes mellitus (T2D) and a major cause of morbidity and mortality in diabetes. Despite the widespread use of nephroprotective treatment of T2D, the incidence of DKD is increasing, and it is expected to become the fifth cause of death worldwide within 20 years. Previous studies have demonstrated that GLP-1 receptor agonists (GLP-1 RA) have improved macrovascular and microvascular outcomes independent of glycemic differences, including DKD. GLP-1Ras’ improvement on kidney physiology is mediated by natriuresis, reduction in hyperfiltration and renin-angiotensin-aldosterone system (RAAS) activity and anti-inflammatory properties. These findings translate into improved clinical outcomes such as an enhanced urine albumin-to-creatinine ratio (UACR) and a reduction in renal impairment and the need for renal replacement therapies (RRT). In this article, we review the role of GLP-1RAs on the mechanisms and effect in DKD and their clinical efficacy.

Acute Kidney Injury in Cardiogenic Shock: An Updated Narrative Review

Acute myocardial infarction with cardiogenic shock (AMI-CS) is associated with high mortality and morbidity despite advancements in cardiovascular care. AMI-CS is associated with multiorgan failure of non-cardiac organ systems. Acute kidney injury (AKI) is frequently seen in patients with AMI-CS and is associated with worse mortality and outcomes compared to those without. The pathogenesis of AMI-CS associated with AKI may involve more factors than previously understood. Early use of renal replacement therapies, management of comorbid conditions and judicious fluid administration may help improve outcomes. In this review, we seek to address the etiology, pathophysiology, management, and outcomes of AKI complicating AMI-CS.

A vesetranszplantációval kapcsolatos betegedukációs program tapasztalatai a kelet-magyarországi régióban

Összefoglaló. Bevezetés: A tudás mint potenciálisan módosítható faktor a megfelelő döntéshozatal előfeltétele. Célkitűzés: Kutatásunk során a krónikus vesebetegek körében vizsgáltuk az egyes vesepótló kezelési módokkal kapcsolatos ismereteket, elemeztük a tudást befolyásoló tényezőket, annak érdekében, hogy feltérképezzük a betegismeretek e területen megfigyelhető hiányosságait. Egyúttal tájékoztatást és ismeretterjesztést adtunk a vesetranszplantációval kapcsolatosan. Módszer: A betegek ismereteit befolyásoló tényezőket tíz magyarázó változóra korrigált többváltozós lineáris regresszióval értékeltük, melynél a függő változó a tudáspontszám volt. Követéses vizsgálatunk első adatfelvétele során az Eurotransplant-várólistán szereplő, vesetranszplantáció irányában kivizsgálás alatt álló, valamint a veseátültetést elutasító, 18 és 75 év közötti betegeket kerestük fel. Az első körös (alaptudásszintet rögzítő) adatfelvétel összesen 254, az ismeretátadás utáni második pedig 115 vesebeteg bevonásával valósult meg. Eredmények: Eredményeink alapján elmondható, hogy a felsőfokú (β = 1,502, p<0,001) és a középfokú (β = 2,346, p<0,001) iskolai végzettséggel rendelkező betegek egyaránt magasabb tudáspontszámot értek el az alacsonyabb iskolai végzettséggel rendelkezőkhöz képest. A korábban veseátültetésen már átesett betegek 2 ponttal magasabb pontszámot értek el a veseátültetésben még nem részesültekhez viszonyítva (β = 2,024, p<0,001). Szignifikánsan magasabb pontszámot értek el azok a betegek is, akik megfelelő egészségműveltségi szinttel rendelkeztek (β = 1,344, p<0,001). Eredményeink bizonyítják programunk hatékonyságát, mert a részt vevő vesebetegek szignifikánsan magasabb pontszámot értek el a tudásszintfelmérő teszten, több hónappal a betegedukációt követően is (p<0,001). Következtetés: Az általunk azonosított hiányosságok segíthetnek az egészségügyi szakemberek számára abban, hogy melyek azok a területek, amelyekre a betegoktatási és önmegvalósító programok során hangsúlyt kell fektetni a beteg-együttműködés és az eredmények javítása érdekében. Orv Hetil. 2021; 162(26): 1012–1021. Summary. Introduction: Knowledge as a potentially modifiable factor is a prerequisite for appropriate decision making. Objective: In our study, we examined the knowledge level related to renal replacement therapies and its influencing factors among chronic kidney disease patients, in order to identify the patients’ knowledge gaps. At the same time, we provided information, education on kidney transplantation. Method: Factors influencing the patients’ knowledge were evaluated using a multivariate linear regression adjusted for ten factors, where the dependent variable was the knowledge score. During the first data collection of our follow-up study, we contacted patients on the Eurotransplant waiting list, patients undergoing medical evaluation, and patients who refuse a kidney transplant, between 18 and 75 years old. A total of 254 patients were involved in the first round of data collection (recording the basic level of knowledge), and 115 in the second one (after the education). Results: Our results show that patients with both tertiary (β = 1.502, p<0.001) and secondary (β = 2.346, p<0.001) educational attainment achieved higher knowledge scores. Patients with previous kidney transplantation scored 2 points higher than those without (β = 2.024, p<0.001). Moreover, patients with adequate health literacy level achieved significantly higher knowledge scores (β = 1.344, p<0.001). Our results prove the effectiveness of our program since the participants achieved significantly higher scores on the knowledge test, even several months after the education (p<0.001). Conclusion: The gaps we have identified can help the healthcare professionals which areas need to be focused in patient education and self-management programs in order to improve patient collaboration and outcomes. Orv Hetil. 2021; 162(26): 1012–1021.

Pharmacokinetics of Non-β-Lactam β-Lactamase Inhibitors

The growing emergence of drug-resistant bacterial strains is an issue to treat severe infections, and many efforts have identified new pharmacological agents. The inhibitors of β-lactamases (BLI) have gained a prominent role in the safeguard of beta-lactams. In the last years, new β-lactam–BLI combinations have been registered or are still under clinical evaluation, demonstrating their effectiveness to treat complicated infections. It is also noteworthy that the pharmacokinetics of BLIs partly matches that of β-lactams companions, meaning that some clinical situations, as well as renal impairment and renal replacement therapies, may alter the disposition of both drugs. Common pharmacokinetic characteristics, linear pharmacokinetics across a wide range of doses, and known pharmacokinetic/pharmacodynamic parameters may guide modifications of dosing regimens for both β-lactams and BLIs. However, comorbidities (i.e., burns, diabetes, cancer) and severe changes in individual pathological conditions (i.e., acute renal impairment, sepsis) could make dose adaptation difficult, because the impact of those factors on BLI pharmacokinetics is partly known. Therapeutic drug monitoring protocols may overcome those issues and offer strategies to personalize drug doses in the intensive care setting. Further prospective clinical trials are warranted to improve the use of BLIs and their β-lactam companions in severe and complicated infections.