Initiation Of Renal Replacement Therapy Research Articles

The interaction of net ultrafiltration rate with urine output and fluid balance after continuous renal replacement therapy initiation: A multi-Centre study.

PurposeDuring continuous renal replacement therapy (CRRT), a high net ultrafiltration rate (NUF) may worsen the decrease in urine output (UO) associated with starting CRRT. However, fluid balance (FB) may modulate this association. We aimed to examine the relationship between NUF, UO and FB at the start of CRRT. MethodsA retrospective cohort study of 1030 CRRT-treated patients admitted to two tertiary ICUs. ResultsMedian age was 60 years (IQR, 48–70), median APACHE III was 94 (IQR, 76–114) and median NUF rate was 0.7 mL/kg/h. In the 24 h after CRRT started, the mean hourly UO decreased from 25.5 mL to 11.9 mL (P < 0.001). Moreover, after adjusting for multiple confounders on multivariable analysis, a higher NUF was not significantly associated with a lower UO (−1.5 mL/kg for every 1 mL/kg/h increase in NUF; 95% CI -3.1 to 0.04; p = 0.064). In addition, pre-CRRT FB did not modulate the above relationship between higher NUF and lower UO. ConclusionA higher NUF rate was not significantly associated with a greater immediate and sustained reduction in UO after CRRT commencement. FB before CRRT was also not associated with a greater reduction in UO. These findings do not provide evidence for an effect of NUF on renal function.

Renal replacement therapy in critical ill patients

Acute kidney injury (AKI), especially when caused or accompanied by sepsis, is associated with prolonged hospitalization, progression of chronic kidney disease (CKD), financial burden on the health care system, and increases mortality in various entities. Extended renal replacement therapy (CRRT) is the predominant form of renal replacement therapy (RRT) in intensive care units (ICU) by providing hemodynamic stability in critically ill patients, more precise control of fluid balance, correction of acid-base imbalances, electrolyte disorders and achieving a stable level of osmolarity correction, including in multimorbid patients. This article examines the various aspects of CRRT in critically ill patients with severe AKI with high comorbidity, as well as in patients with sepsis and multiple organ failure. An analytical evaluation of the choice of CRRT over intermittent/intermittent hemodialysis (IHD) in selected clinical settings is being conducted. Filter/dialyzer life is assessed, including assessment of filtration fraction, use of anticoagulation options including regional citrate anticoagulation (RCA), dose of CRRT prescribed and delivered, vascular access management, general criteria, timing of initiation and cessation of CRRT, and initiation of renal replacement therapy for nonrenal indications. with AKI and/or sepsis.

Uremic pericarditis: a case report of favorable outcomes with early detection and management

Uremic pericarditis is a rare, potentially life-threatening complication of end-stage renal disease (ESRD) caused by the accumulation of uremic toxins. This case report describes a 32-year-old man with diabetes and ESRD on hemodialysis who developed uremic pericarditis. The patient presented with fever, chest pain, dyspnea, cough, and foot pain. Diagnostic investigations led to treatment with broad-spectrum antibiotics and surgical debridement of a necrotizing soft tissue infection of the right foot. The lack of clinical improvement in hemodynamic status prompted rapid investigation with electrocardiography and echocardiography, confirming the diagnosis of uremic pericarditis. Prompt initiation of renal replacement therapy with close monitoring led to a successful management outcome. This case report highlights the importance of early recognition, appropriate interventions, and a multidisciplinary approach in treating uremic pericarditis. Keywords: End-stage renal disease, uremic pericarditis, dialysis-associated pericarditis, pericardial friction rub

Recent developments in acute kidney injury : Definition, biomarkers, subphenotypes, and management

Acute kidney injury (AKI) is acommon problem in critically ill patients and is associated with increased morbidity and mortality. Since 2012, AKI has been defined according to the KDIGO (Kidney Disease Improving Global Outcome) guidelines. As some biomarkers are now available that can provide useful clinical information, anew definition including anew stage1S has been proposed by an expert group of the Acute Disease Quality Initiative (ADQI). At this stage, classic AKI criteria are not yet met, but biomarkers are already positive defining subclinical AKI. This stage1S is associated with aworse patient outcome, regardless of the biomarker chosen. The PrevAKI and PrevAKI-Multicenter trial also showed that risk stratification with abiomarker and implementation of the KDIGO bundle (in the high-risk group) can reduce the rate of moderate and severe AKI. In the absence of asuccessful clinical trial, conservative management remains the primary focus of treatment. This mainly involves optimization of hemodynamics and an individualized (restrictive) fluid management. The STARRT-AKI trial has shown that there is no benefit from accelerated initiation of renal replacement therapy. However, delaying too long might be associated with potential harm, as shown in the AKIKI2 study. Prospective studies are needed to determine whether artificial intelligence will play arole in AKI in the future, helping to guide treatment decisions and improve outcomes.

Assessing the role of Chemokine (C–C motif) ligand 14 in AKI: a European consensus meeting

Background Urinary Chemokine (C–C motif) ligand 14 (CCL14) is a biomarker associated with persistent severe acute kidney injury (AKI). There is limited data to support the implementation of this AKI biomarker to guide therapeutic actions. Methods Sixteen AKI experts with clinical CCL14 experience participated in a Delphi-based method to reach consensus on when and how to potentially use CCL14. Consensus was defined as ≥ 80% agreement (participants answered with ‘Yes’, or three to four points on a five-point Likert Scale). Results Key consensus areas for CCL14 test implementation were: identifying challenges and mitigations, developing a comprehensive protocol and pairing it with a treatment plan, and defining the target population. The majority agreed that CCL14 results can help to prioritize AKI management decisions. CCL14 levels above the high cutoff (> 13 ng/mL) significantly changed the level of concern for modifying the AKI treatment plan (p < 0.001). The highest level of concern to modify the treatment plan was for discussions on renal replacement therapy (RRT) initiation for CCL14 levels > 13 ng/mL. The level of concern for discussion on RRT initiation between High and Low, and between Medium and Low CCL14 levels, showed significant differences. Conclusion Real world urinary CCL14 use appears to provide improved care options to patients at risk for persistent severe AKI. Experts believe there is a role for CCL14 in AKI management and it may potentially reduce AKI-disease burden. There is, however, an urgent need for evidence on treatment decisions and adjustments based on CCL14 results.

Tissue Inhibitor Metalloproteinase-2·IGF-Binding Protein 7 for the Prediction of Acute Kidney Injury following Cardiac Surgery

Introduction: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common complication associated with increased morbidity and mortality. Tissue inhibitor metalloproteinase-2·insulin-like growth factor-binding protein 7 (TIMP-2·IGFBP7) determines tubular stress markers, which may occur prior to tubular damage. Previous studies on the use of TIMP-2·IGFBP7 for the prediction of CSA-AKI showed divergent results. Therefore, this study aimed to explore the predictive value of TIMP-2·IGFBP7 measurements for the early detection of acute kidney injury (AKI) and short-term adverse outcomes after cardiac surgery. Methods: In the prospective cohort study, blood and urine samples were collected 6–12 h after cardiac surgery. Blood samples to monitor serum creatinine levels were additionally extracted from days 1 to 7. AKI was defined based on the KDIGO consensus guidelines. AKI within 7 days following surgery was the primary outcome. The initiation of renal replacement therapy, in intensive care unit mortality, and the combination of both were secondary outcomes. Results: A total of 557 patients were enrolled; 134 (24.06%) of them developed AKI and 33 (5.9%) had moderate or severe AKI. AKI developed more frequently in elderly patients with diabetes or with higher baseline serum creatinine levels. Patients with AKI had higher EuroSCORE II, Cleveland Clinic Score, and simplified renal index (SRI) than those without AKI. Urinary TIMP-2·IGFBP7 was significantly higher in patients with AKI. The area under the curve was 0.66 in predicting all AKI and 0.70 in predicting stages 2 and 3 AKI. The resulting sensitivity and specificity were 44.0% and 83.9%, respectively, for a calculated threshold TIMP-2·IGFBP7 value of 0.265 (ng/mL)2/1,000. The TIMP-2·IGFBP7 values, SRI score, and age were significantly associated with AKI within 7 days postoperatively. A total of 33 patients reached the composite endpoint; the percentage of patients who reached the composite endpoint in the TIMP-2·IGFBP7 of >0.265 (ng/ml)2/1,000 group was significantly higher than that of ≤0.265 (ng/mL)2/1,000 group. Conclusions: Postoperative implementation of TIMP-2·IGFBP7 improved the prediction of CSA-AKI and may aid in identifying patients at risk of short-term adverse outcomes. We identified an ideal calculated cutoff value of 0.265 (ng/mL)2/1,000 for the prediction of CSA-AKI among all AKI patients.

Native T1-mapping as a predictor of progressive renal function decline in chronic kidney disease patients

BackgroundTo investigate the potential of Native T1-mapping in predicting the prognosis of patients with chronic kidney disease (CKD).MethodsWe enrolled 119 CKD patients as the study subjects and included 20 healthy volunteers as the control group, with follow-up extending until October 2022. Out of these patients, 63 underwent kidney biopsy measurements, and these patients were categorized into high (25–50%), low (< 25%), and no renal interstitial fibrosis (IF) (0%) groups. The study's endpoint event was the initiation of renal replacement therapy, kidney transplantation, or an increase of over 30% in serum creatinine levels. Cox regression analysis determined factors influencing unfavorable kidney outcomes. We employed Kaplan–Meier analysis to contrast kidney survival rates between the high and low T1 groups. Additionally, receiver-operating characteristic (ROC) curve analysis assessed the predictive accuracy of Native T1-mapping for kidney endpoint events.ResultsT1 values across varying fibrosis degree groups showed statistical significance (F = 4.772, P < 0.05). Multivariate Cox regression pinpointed 24-h urine protein, cystatin C(CysC), hemoglobin(Hb), and T1 as factors tied to the emergence of kidney endpoint events. Kaplan–Meier survival analysis revealed a markedly higher likelihood of kidney endpoint events in the high T1 group compared to the low T1 value group (P < 0.001). The ROC curves for variables (CysC, T1, Hb) tied to kidney endpoint events demonstrated area under the curves(AUCs) of 0.83 (95%CI: 0.75–0.91) for CysC, 0.77 (95%CI: 0.68–0.86) for T1, and 0.73 (95%CI: 0.63–0.83) for Hb. Combining these variables elevated the AUC to 0.88 (95%CI: 0.81–0.94).ConclusionNative T1-mapping holds promise in facilitating more precise and earlier detection of CKD patients most at risk for end-stage renal disease.

Comparison between Watchful Waiting Strategy and Early Initiation of Renal Replacement Therapy in The Critically Ill Acute Kidney Injury

Comparison between Watchful Waiting Strategy and Early Initiation of Renal Replacement Therapy in The Critically Ill Acute Kidney Injury

Deep learning algorithms for predicting renal replacement therapy initiation in CKD patients: a retrospective cohort study

BackgroundChronic kidney disease (CKD) requires accurate prediction of renal replacement therapy (RRT) initiation risk. This study developed deep learning algorithms (DLAs) to predict RRT risk in CKD patients by incorporating medical history and prescriptions in addition to biochemical investigations.MethodsA multi-centre retrospective cohort study was conducted in three major hospitals in Hong Kong. CKD patients with an eGFR < 30ml/min/1.73m2 were included. DLAs of various structures were created and trained using patient data. Using a test set, the DLAs' predictive performance was compared to Kidney Failure Risk Equation (KFRE).ResultsDLAs outperformed KFRE in predicting RRT initiation risk (CNN + LSTM + ANN layers ROC-AUC = 0.90; CNN ROC-AUC = 0.91; 4-variable KFRE: ROC-AUC = 0.84; 8-variable KFRE: ROC-AUC = 0.84). DLAs accurately predicted uncoded renal transplants and patients requiring dialysis after 5 years, demonstrating their ability to capture non-linear relationships.ConclusionsDLAs provide accurate predictions of RRT risk in CKD patients, surpassing traditional methods like KFRE. Incorporating medical history and prescriptions improves prediction performance. While our findings suggest that DLAs hold promise for improving patient care and resource allocation in CKD management, further prospective observational studies and randomized controlled trials are necessary to fully understand their impact, particularly regarding DLA interpretability, bias minimization, and overfitting reduction. Overall, our research underscores the emerging role of DLAs as potentially valuable tools in advancing the management of CKD and predicting RRT initiation risk.

Association Between Early Hyponatremia and Clinical Outcomes in Critically Ill Patients: A Retrospective Cohort Study.

Hyponatremia, frequently encountered in intensive care (ICU) settings, plays a critical role in shaping patient outcomes. Despite its prevalence, contemporary research into its newly classified severity categories and their implications on mortality, renal function, and length of stay remains limited. This study aims to fill this gap by examining the impact of hyponatremia severity on these critical outcomes. A retrospective analysis of ICU patients aged >18 years who were admitted between March 2019 and December 2022 was conducted at Hamamatsu University Hospital, Shizuoka, Japan. Patients who were readmitted or had incomplete data were excluded. Hyponatremia was categorized as mild (130-135 mmol/L), moderate (125-129 mmol/L), or severe (<125 mmol/L), following the criteria set by the European Society of Intensive Care Medicine. This classification utilized thelowest sodium concentration within 24 hours of ICU admission. The outcomes were in-hospital mortality, ICU mortality, newly implemented renal replacement therapy (RRT), and length of hospital and ICU stay. Outcomes were analyzed using multivariable logistic and linear regression models, adjusting for relevant covariates including age, sex, Acute Physiology and Chronic Health Evaluation (APACHE) III scores, and the use of mechanical ventilation. Of the 3,538 patients analyzed, 1,072 (30.3%) experienced hyponatremia: 894 (25.3%) mild, 144 (4.1%) moderate, and 34 (1.0%) severe. Multivariable analysis revealed no significant association between hyponatremia severity and in-hospital mortality rates across normonatremia (3.8%), mild (5.2%), moderate (11.8%), and severe (23.5%) groups, nor with ICU mortality. However, compared to normonatremia, moderate and severe hyponatremia were associated with increased RRT initiation (odds ratios = 3.83 and 6.36, respectively) and prolonged hospital stay (mean difference = 7.06 and 9.66 days, respectively), and ICU stays (mean difference, 1.02 and 2.70 days, respectively). Mild hyponatremia was not significantly associated with RRT or length of stay. Moderate-to-severe hyponatremia did not influence mortality but was associated with increased RRT initiation and prolonged hospital and ICU stay. By contrast, mild hyponatremia was not associated with any clinical outcome.Further research is required to determine if correcting hyponatremia directly improves ICU patient outcomes, given the observational nature of the study.

Hierarchical endpoints in critical care: A post-hoc exploratory analysis of the standard versus accelerated initiation of renal-replacement therapy in acute kidney injury and the intensity of continuous renal-replacement therapy in critically ill patients trials

PurposeTo perform a post-hoc reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) and the Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients (RENAL) trials through hierarchical composite endpoint analysis using win ratio (WR). Material and methodsAll patients with complete information from the STARRT-AKI (which compared accelerated versus standard approaches for renal replacement therapy – RRT initiation) and RENAL (which compared two different RRT doses in critically ill patients) trials were selected. WR was defined as a hierarchical composite endpoint using 90-day mortality, RRT dependency at 90-days, intensive care unit (ICU) length-of-stay (LOS), and hospital LOS (primary analysis); values above the unit represent a benefit of the intervention for the hierarchical composite endpoint. A secondary analysis replacing LOS by days alive and free of RRT was performed. Stratified analyses were performed according to illness severity score, surgical status, and the presence of sepsis. ResultsThe WR analysis produced 2,141,830 pairs for the STARRT-AKI trial and 536,446 pairs for the RENAL trial, respectively. The WR results for STARRT-AKI and RENAL were 1.04 (95% confidence interval [CI] 0.96–1.13; p = 0.33) and 1.02 (95% CI; 0.90–1.15; p = 0.75) for the primary analysis, and 0.88 (95% CI; 0.79–0.99; p = 0.03) and 1.02 (95% CI; 0.87–1.21; p = 0.77) for the secondary analysis, respectively. The stratified analysis of the primary suggested possible benefit of the accelerated-strategy in the STARRT-AKI trial for non-surgical patients with sepsis, while the secondary analysis suggested possible harm of the accelerated-strategy for surgical patients without sepsis. There was no evidence of heterogeneity in treatment effects in stratified analyses in the RENAL trial. ConclusionWR approach using a hierarchical composite endpoint is feasible for trials in critical care nephrology. The primary re-analyses of the STARRT-AKI and RENAL trials both yielded neutral results; however, there was suggestion of heterogeneity in treatment effect in stratified analyses of the STARRT-AKI trial by surgical status and sepsis. Selection of the endpoints and hierarchical ordering before trial design using the WR approach can have important implications for trial interpretation.Trial Registry: ClinicalTrials.gov number NCT02568722 (STARRT-AKI) and NCT00076219 (RENAL).

Healthcare Resource Utilization and Goals of Care Discussions in Patients with Cirrhosis and Acute Kidney Injury.

Patients with cirrhosis and acute kidney injury (AKI) are critically ill and have high health care resource utilization (HCRU). The impact and timing of goals of care discussions on HCRU are not well described. 221 patients enrolled in a prospective cohort study of patients admitted with AKI and cirrhosis were reviewed. Documentation and timing of a goals of care discussions were analyzed as predictors of HCRU, defined as a composite outcome of intubation, initiation of renal replacement therapy, and/or admission to the intensive care unit. Median MELD score was 26 [IQR 19, 33]. 29% patients were listed for liver transplant. 90-day mortality was 61%. 51% patients had at least one HCRU episode. Code status changed from admission to discharge from 91%/7%/0% to 68%/14%18% (full code/do not resuscitate/comfort measures, p < 0.001). 28% patients underwent goals of care discussions, with change in code status at a median of 16 [9, 22] days into admission. Only 18% of discussions were within 7days of admission and all were after an HCRU event. Being listed for liver transplant was not associated with whether goals of care discussions occurred (23% listed vs. 31% non-listed, p = 0.24) but was associated with higher HCRU (69% vs. 43%; p < 0.001). Goals of care discussions occurred late into the hospital course, after episodes of HCRU. Efforts should be made to engage in these discussions earlier in the hospital stay, which may decrease HCRU rates in this critically ill population and align with patients' goals of care.

Personalizing renal replacement therapy initiation in the intensive care unit: a reinforcement learning-based strategy with external validation on the AKIKI randomized controlled trials.

The timely initiation of renal replacement therapy (RRT) for acute kidney injury (AKI) requires sequential decision-making tailored to individuals' evolving characteristics. To learn and validate optimal strategies for RRT initiation, we used reinforcement learning on clinical data from routine care and randomized controlled trials. We used the MIMIC-III database for development and AKIKI trials for validation. Participants were adult ICU patients with severe AKI receiving mechanical ventilation or catecholamine infusion. We used a doubly robust estimator to learn when to start RRT after the occurrence of severe AKI for three days in a row. We developed a "crude strategy" maximizing the population-level hospital-free days at day 60 (HFD60) and a "stringent strategy" recommending RRT when there is significant evidence of benefit for an individual. For validation, we evaluated the causal effects of implementing our learned strategies versus following current best practices on HFD60. We included 3748 patients in the development set and 1068 in the validation set. Through external validation, the crude and stringent strategies yielded an average difference of 13.7 [95% CI -5.3 to 35.7] and 14.9 [95% CI -3.2 to 39.2] HFD60, respectively, compared to current best practices. The stringent strategy led to initiating RRT within 3 days in 14% of patients versus 38% under best practices. Implementing our strategies could improve the average number of days that ICU patients spend alive and outside the hospital while sparing RRT for many. We developed and validated a practical and interpretable dynamic decision support system for RRT initiation in the ICU.

Beta-blockers and chronic kidney disease: a literature review

Chronic kidney disease (CKD) and cardiovascular diseases are widespread throughout the world and are closely related to each other. Sympathetic hyperactivity, characteristic of CKD, increases cardiovascular risk and accelerates the progression of kidney disease by activating beta-adrenergic receptors. Beta-blockers play an important role in preventing the negative effects of in creased activity of the sympathetic nervous system on the cardiovascular system and kidneys, can slow the progression of renal disease, and have proven effective in reducing overall and cardiovascular mortality and treatment of coronary heart disease, heart failure, arterial hypertension, and arrhythmias in patients with CKD. Despite this, beta-blockers are still underused in patients with CKD, especially in its later stages, including ESRD. Although there are currently no clear recommendations for the choice of any specific beta blocker in CKD, factors such as the CKD stage, presence of diabetes mellitus or reduced insulin sensitivity, and pharmacodynamics (cardioselectivity, α1-blocking- and vasodilating properties) and pharmacokinetic properties (metabolism, routes of elimination from the body, degree of binding to plasma proteins and dualizability) should be considered. At present, along with ACE inhibitors, AT1-receptor antagonists, and SGLT2 inhibitors, beta-blockers remain indispensable drugs for treating cardiovascular diseases with proven positive effects on the progression of kidney failure in patients with CKD. Their broader use in this population is expected to further reduce cardiovascular mortality and delay the initiation of renal replacement therapy.

Renal replacement therapy initiation strategies in comatose patients with severe acute kidney injury: a secondary analysis of a multicenter randomized controlled trial.

The effect of renal replacement therapy (RRT) in comatose patients with acute kidney injury (AKI) remains unclear. We compared two RRT initiation strategies on the probability of awakening in comatose patients with severe AKI. We conducted a post hoc analysis of a trial comparing two delayed RRT initiation strategies in patients with severe AKI. Patients were monitored until they had oliguria for more than 72h and/or blood urea nitrogen higher than 112mg/dL and then randomized to a delayed strategy (RRT initiated after randomization) or a more-delayed one (RRT initiated if complication occurred or when blood urea nitrogen exceeded 140mg/dL). We included only comatose patients (Richmond Agitation-Sedation scale [RASS] < -3), irrespective of sedation, at randomization. A multi-state model was built, defining five mutually exclusive states: death, coma (RASS < -3), incomplete awakening (RASS [-3; -2]), awakening (RASS [-1; + 1] two consecutive days), and agitation (RASS > + 1). Primary outcome was the transition from coma to awakening during 28days after randomization. A total of 168 comatose patients (90 delayed and 78 more-delayed) underwent randomization. The transition intensity from coma to awakening was lower in the more-delayed group (hazard ratio [HR] = 0.36 [0.17-0.78]; p = 0.010). Time spent awake was 10.11 days [8.11-12.15] and 7.63 days [5.57-9.64] in the delayed and the more-delayed groups, respectively. Two sensitivity analyses were performed based on sedation status and sedation practices across centers, yielding comparable results. In comatose patients with severe AKI, a more-delayed RRT initiation strategy resulted in a lower chance of transitioning from coma to awakening.

Regional Practice Variation and Outcomes in the Standard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Trial: A Post Hoc Secondary Analysis.

Among patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant. Secondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722). One hundred-fifty-three ICUs in 13 countries. Altogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ). None. Total mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ (p < 0.001). The median time to RRT initiation among patients allocated to the standard strategy was longest in Europe compared with North America and ANZ (p < 0.001; p < 0.001). Continuous RRT was the initial RRT modality in 60.8% of patients in North America and 56.8% of patients in Europe, compared with 96.4% of patients in ANZ (p < 0.001). After adjustment for predefined baseline characteristics, compared with North American and European patients, those in ANZ were more likely to survive to ICU (p < 0.001) and hospital discharge (p < 0.001) and to 90 days (for ANZ vs. Europe: risk difference [RD], -11.3%; 95% CI, -17.7% to -4.8%; p < 0.001 and for ANZ vs. North America: RD, -10.3%; 95% CI, -17.5% to -3.1%; p = 0.007). Among STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions.

How do SGLT2 inhibitors protect the kidney? A mediation analysis of the EMPA-REG OUTCOME trial.

Mechanisms underlying kidney benefits with sodium-glucose cotransporter-2 (SGLT2) inhibition in heart failure and/or type 2 diabetes (T2D) with established cardiovascular disease are currently unclear. We evaluated post hoc the factors mediating the effect of empagliflozin on a composite kidney outcome (first sustained estimate glomerular filtration rate ≥40% reduction from baseline, initiation of renal replacement therapy, or death due to kidney disease) in EMPA-REG OUTCOME. Variables, calculated as change from baseline or updated mean, were evaluated as time-dependent covariates and using a landmark approach (at Week 12) in Cox regression analyses. In multivariable analyses, variables with the greatest mediating effect were added using a step-up procedure. In univariable time-dependent updated mean covariate analyses, the strongest mediator was hematocrit (99.5% mediation). Hemoglobin, uric acid, and urine albumin-to-creatinine ratio mediated 79.4%, 33.2%, and 31.0%, respectively. Multivariable analyses were not performed due to the very strong mediation effect of hematocrit. In univariable Week 12 landmark change from baseline analyses, the strongest mediators included hematocrit (40.7%), glycated hemoglobin (28.3%), systolic blood pressure (16.8%), and free fatty acids (16.5%), which yielded a combined mediation of 78.9% in multivariable analysis. Changes in hematocrit and hemoglobin were the strongest mediators of empagliflozin's kidney benefits in EMPA-REG OUTCOME participants with T2D and cardiovascular disease.

Time to Continuous Renal Replacement Therapy Initiation and 90-Day Major Adverse Kidney Events in Children and Young Adults

In clinical trials, the early or accelerated continuous renal replacement therapy (CRRT) initiation strategy among adults with acute kidney injury or volume overload has not demonstrated a survival benefit. Whether the timing of initiation of CRRT is associated with outcomes among children and young adults is unknown. To determine whether timing of CRRT initiation, with and without consideration of volume overload (VO; <10% vs ≥10%), is associated with major adverse kidney events at 90 days (MAKE-90). This multinational retrospective cohort study was conducted using data from the Worldwide Exploration of Renal Replacement Outcome Collaborative in Kidney Disease (WE-ROCK) registry from 2015 to 2021. Participants included children and young adults (birth to 25 years) receiving CRRT for acute kidney injury or VO at 32 centers across 7 countries. Statistical analysis was performed from February to July 2023. The primary exposure was time to CRRT initiation from intensive care unit admission. The primary outcome was MAKE-90 (death, dialysis dependence, or persistent kidney dysfunction [>25% decline in estimated glomerular filtration rate from baseline]). Data from 996 patients were entered into the registry. After exclusions (n = 27), 969 patients (440 [45.4%] female; 16 (1.9%) American Indian or Alaska Native, 40 (4.7%) Asian or Pacific Islander, 127 (14.9%) Black, 652 (76.4%) White, 18 (2.1%) more than 1 race; median [IQR] patient age, 8.8 [1.7-15.0] years) with data for the primary outcome (MAKE-90) were included. Median (IQR) time to CRRT initiation was 2 (1-6) days. MAKE-90 occurred in 630 patients (65.0%), of which 368 (58.4%) died. Among the 601 patients who survived, 262 (43.6%) had persistent kidney dysfunction. Of patients with persistent dysfunction, 91 (34.7%) were dependent on dialysis. Time to CRRT initiation was approximately 1 day longer among those with MAKE-90 (median [IQR], 3 [1-8] days vs 2 [1-4] days; P = .002). In the generalized propensity score-weighted regression, there were approximately 3% higher odds of MAKE-90 for each 1-day delay in CRRT initiation (odds ratio, 1.03 [95% CI, 1.02-1.04]). In this cohort study of children and young adults receiving CRRT, longer time to CRRT initiation was associated with greater risk of MAKE-90 outcomes, in particular, mortality. These findings suggest that prospective multicenter studies are needed to further delineate the appropriate time to initiate CRRT and the interaction between CRRT initiation timing and VO to continue to improve survival and reduce morbidity in this population.

Epidemiology and treatment outcome of ANCA-associated vasculitis in South Korea: a nationwide, population-based cohort study.

To investigate the epidemiological features of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in South Korea. We identified the index cases of GPA and MPA using the 2010-2018 Korean National Health Insurance Service database and the Rare Intractable Disease registry for the entire Korean population. Each disease's incidence and prevalence rates and trends over time were analysed. To assess the impact of disease on morbidity and mortality, a comparator group comprising the general population was established using nearest-neighbour matching by age, sex, income, and comorbidity index, at a 5:1 ratio. Morbidity outcomes included the initiation of renal replacement therapy and admission to the intensive care unit. We identified 546 and 795 patients with GPA and MPA, respectively. The incidence rates of both diseases increased with age, with peak incidence rates observed among patients aged ≥70 years. The incidence of MPA increased continuously over time, whereas that of GPA showed no significant changes. During the observation period, 132 (28.7%) and 277 (41.1%) patients in the GPA and MPA groups, respectively, died, which were significantly higher than that in the general population (standardised mortality ratio: 3.53 and 5.58, respectively) and comparator group (hazard ratio: 4.02 and 5.64, respectively). Higher mortality and morbidity rates were observed among patients with MPA than among those with GPA. In South Korea, the incidence of MPA has increased over time. Although both GPA and MPA had high rates of mortality and morbidity, MPA has a poorer prognosis than GPA.

ASSESSMENT OF CAUSES OF INTENSIVE CARE UNIT ADMISSIONS IN RENAL DISEASE PATIENTS: A CROSS-SECTIONAL STUDY

The incidence of End-Stage Renal Disease (ESRD) is on the rise, making it a significant group of patients requiring admission to critical care units. At the same time, the field of Acute Kidney Injury (AKI) has flourished, leading to an increased number of patients with kidney dysfunction in critical care units. Our objective is to assess the causes of admission of patients with kidney disease in a large tertiary care hospital, the Medical Intensive Care Unit (MICU). This is a retrospective electronic case notes study. We collected data from the electronic records of all patients admitted to the MICU with renal problems from 1/7/2022 until 1/10/2022. The data was later analyzed in Microsoft Excel. During the study period, 503 patients were admitted to the MICU, of which 160 (31.8%) had renal disease. The median age was 50 years, ranging from 17 to 92 years. Females accounted for 42.5% of patients, while males accounted for 48.5%. Of the 160 patients, 97 (60.5%) were known to have ESRD, while 63 (39.5%) had AKI due to systemic illness. Fluid overload (40/55, 76.3%), followed by uremic encephalopathy (15/55, 27.2%) and hyperkalemia (12/55, 21.8%), remained the most common causes for initiation of Renal Replacement Therapy (RRT) in 55/97 (56.7%) ESRD patients. The mortality rate was 23.7% (38/160) in renal patients in the medical ICU. Our study highlights the increasing number of patients with kidney disease requiring admission to a medical ICU and their high mortality rate. Sepsis remains the leading cause of admission for ESRD patients on Maintenance Hemodialysis (MHD). At the same time, fluid overload was found to be the primary cause of starting RRT in advanced kidney disease.