Real-World Experience With Avacopan in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis.

Introduction: Postmarketing data on outcomes of avacopan use in antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) are lacking. Methods: We performed a multicenter retrospective analysis of 92 patients with newly diagnosed or relapsing AAV who received therapy with avacopan. The coprimary outcome measures were clinical remission at 26 and 52 weeks. We use descriptive statistics and univariate logistic regression to assess outcomes and predictors of remission, respectively. Results: Of the 92 patients, 23% (n = 21) had a baseline estimated glomerular filtration rate (eGFR) < 15 ml/min per 1.73 m2 and 10% on kidney replacement therapy at baseline. Among those with kidney involvement, mean (SD) enrollment eGFR was 33 (27) ml/min per 1.73 m2 with a mean (SD) change of +12 (25) and +20 (23) ml/min per 1.73 m2 at weeks 26 and 52, respectively. In addition to avacopan, 47% of patients received combination therapy of rituximab and low-dose cyclophosphamide, and 14% of patients received plasma exchange (PLEX). After induction, the median (interquartile range [IQR]) time to start avacopan was 3.6 (2.1-7.7) weeks, and the median time to discontinue prednisone after starting avacopan was 5.6 (3.3-9.5) weeks. Clinical remission was achieved in 90% of patients at week 26 and 84% of patients at week 52. Of the patients, 20% stopped avacopan due to adverse events, with the most common being elevated serum aminotransferases (4.3%). Conclusion: A high rate of remission and an acceptable safety profile were observed with the use of avacopan in the treatment of AAV in this postmarketing analysis, including the populations excluded from the ADVOCATE trial.

Long-term outcome of COVID-19 patients with acute kidney injury requiring kidney replacement therapy.

BACKGROUND: Limited data existed on the burden of coronavirus disease 2019 (COVID-19) renal complications and the outcomes of the most critical patients who required kidney replacement therapy (KRT) during intensive care unit (ICU) stay. We aimed to describe mortality and renal function at 90 days in patients admitted for COVID-19 and KRT. METHODS: A retrospective cohort study of critically ill patients admitted for COVID-19 and requiring KRT from March 2020 to January 2022 was conducted in an Italian ICU from a tertiary care hospital. Primary outcome was mortality at 90 days and secondary outcome was kidney function at 90 days. RESULTS: A cohort of 45 patients was analyzed. Mortality was 60% during ICU stay and increased from 64% at the time of hospital discharge to 71% at 90 days. Among 90-day survivors, 31% required dialysis, 38% recovered incompletely, and 31% completely recovered renal function. The probability of being alive and dialysis-free at 3 months was 22%. CONCLUSIONS: Critically ill patients with COVID-19 disease requiring KRT during ICU stay had elevated mortality rate at 90 days, with low probability of being alive and dialysis-free at 3 months. However, a non-negligible number of patients completely recovered renal function.

Impact of Acute Kidney Injury After Transcatheter Aortic Valve Replacement: A Nationwide Study.

BACKGROUND: In patients undergoing transcatheter aortic valve replacement (TAVR), the impact of acute kidney injury (AKI) on the prognosis and especially on future kidney function has been sparsely examined, and data from large cohorts are warranted. METHODS AND RESULTS: With Danish nationwide registries, we identified all patients undergoing TAVR from 2014 to 2021 with no previous dialysis treatment. According to 2 plasma creatinine samples, we identified those suffering a postprocedural AKI within 21 days after TAVR. With 1 year of follow-up, we compared the associated rates of dialysis treatment and death between patients with and without an AKI using multivariable Cox analysis. Finally, according to the lowest recorded creatinine sample, we assessed the kidney function among AKI survivors between 90 and 180 days after the index date. We identified 4091 TAVRs: 193 (4.7%) with AKI (55.4% men; median age, 82 years) and 3898 (95.3%) without AKI (57.0% men; median age, 81 years). Compared with those without AKI, patients with AKI showed increased associated 1-year rates of dialysis treatment (hazard ratio [HR], 7.20 [95% CI, 4.10-12.66]) and death (HR, 2.39 [95% CI, 1.59-3.58]). After 6 months, 74% of AKI survivors had complete kidney recovery, 14.7% had incomplete kidney recovery, 6.3% failed to recover, and 5.1% were on dialysis treatment. CONCLUSIONS: We identified that AKI after TAVR was associated with an increased rate of future dialysis treatment and all-cause death. Among survivors, 74% had complete kidney recovery within 6 months.

The effect of cytosorb® application on kidney recovery in critically ill patients with severe rhabdomyolysis: a propensity score matching analysis.

Severe rhabdomyolysis frequently results in acute kidney injury (AKI) due to myoglobin accumulation with the need of kidney replacement therapy (KRT). The present study investigated whether the application of Cytosorb® (CS) led to an increased rate of kidney recovery in patients with KRT due to severe rhabdomyolysis. Adult patients with a myoglobin-concentration >10,000 ng/ml and KRT were included from 2014 to 2021. Exclusion criteria were chronic kidney disease and CS-treatment before study inclusion. Groups 1 and 2 were defined as KRT with and without CS, respectively. The primary outcome parameter was independence from KRT after 30 days. Propensity score (PS) matching was performed (predictors: myoglobin, SAPS-II, and age), and the chi2-test was used. 35 pairings could be matched (mean age: 57 vs. 56 years; mean myoglobin: 27,218 vs. 26,872 ng/ml; mean SAPS-II: 77 vs. 76). The probability of kidney recovery was significantly (p = .04) higher in group 1 (31.4 vs. 11.4%, mean difference: 20.0%, odds ratio (OR): 3.6). Considering patients who survived 30 days, kidney recovery was also significantly (p = .03) higher in patients treated with CS (61.1 vs. 23.5%, mean difference: 37.6%, OR: 5.1). In conclusion, the use of CS might positively affect renal recovery in patients with severe rhabdomyolysis. A prospective randomized controlled trial is needed to confirm this hypothesis.

The Spectrum of Biopsy-Proven Kidney Diseases, Causes, and Renal Outcomes in Acute Kidney Injury Patients.

INTRODUCTION: Acute kidney injury (AKI) is a group of highly heterogeneous, complicated clinical syndromes. Although kidney biopsy plays an irreplaceable role in evaluating complex AKI, a few studies have focused on the clinicopathology of AKI biopsies. This study analyzed the pathological disease spectrum, causes, and renal outcomes of biopsied AKI patients. METHODS: We retrospectively included 2,027 AKI patients who underwent kidney biopsies at a national clinical research center of kidney diseases from 2013 through 2018. To compare the biopsied AKI cases without and with coexisting glomerulopathy, patients were classified into acute tubular/tubulointerstitial nephropathy-associated AKI (ATIN-AKI) and glomerular disease-associated AKI (GD-AKI) groups. RESULTS: Of 2,027 biopsied AKI patients, 65.1% were male, with a median age of 43 years. A total of 1,590 (78.4%) patients had coexisting GD, while only 437 (21.6%) patients had ATIN alone. The AKI patients with GD mainly (53.5%) manifested as stage 1 AKI, while most ATIN-AKI patients (74.8%) had stage 3 AKI. In the ATIN-AKI group, 256 (58.6%) patients had acute interstitial nephritis (AIN), and 77 (17.6%) had acute tubular injury (ATI). ATIN-AKI was mainly caused by drugs in 85.5% of AIN and 63.6% of ATI cases, respectively. In AKI patients with coexisting GD, the leading pathological diagnoses in over 80% of patients were IgA nephropathy (IgAN, 22.5%), minimal change disease (MCD, 17.5%), focal segmental glomerulosclerosis (FSGS, 15.3%), lupus nephritis (LN, 11.9%), membranous nephropathy (MN, 10.2%), and ANCA-associated vasculitis (AAV, 4.7%). A total of 775 patients were followed up within 3 months after renal biopsy; ATIN-AKI patients achieved statistically higher complete renal recovery than the GD-AKI patients (83.5% vs. 70.5%, p < 0.001). CONCLUSIONS: Most biopsied AKI patients have coexisting GD, while ATIN alone is seen less frequently. ATIN-AKI is mainly caused by drugs. In GD-AKI patients, IgAN, MCD, FSGS, LN, MN, and AAV are the leading diagnoses. Compared to AKI patients without GD, patients with GD suffer from worse renal function recovery.

The Optimization of Outpatient Hemodialysis Management for Acute Kidney Injury Requiring Dialysis Patients: A Quality Improvement Study.

INTRODUCTION: In 2017, the Centers for Medicare and Medicaid Services allowed survivors of hospitalized acute kidney injury requiring dialysis (AKI-D) who were ambulatory and still dependent on hemodialysis (HD) to receive treatment in outpatient dialysis facilities. This policy change generated the ongoing need to improve AKI-D care in the outpatient setting. METHODS: Quality improvement study in adult patients admitted to an outpatient HD unit with the diagnosis of AKI-D. We developed a protocol to manage these patients that included: (a) multidisciplinary evaluations; (b) personalized 3-tier HD prescription for dose/ultrafiltration rate and frequency; (c) weekly assessment of kidney recovery; and (d) patient empowerment. Patient- and protocol-specific characteristics were described. We analyzed hourly HD data and protocol adherence, and relevant hemodynamic data were compared according to HD-free survival at 90 days. RESULTS: A total of 457.3 h of HD from 9 patients under the AKI-D protocol were interrogated. Three out of 9 patients were alive and liberated from HD within the first 90 days of outpatient HD. Overall protocol adherence was 53.8% and did not differ by HD-free survival (54.5% vs. 53.7% in those that recovered vs. not). Protocol adherence was associated with fewer intradialytic hypotension events (peak to nadir blood pressure, p < 0.01), while intradialytic hypotension (pre- to post-blood pressure) occurred more frequently in patients who did not recover kidney function (p = 0.009). CONCLUSION: We demonstrated the feasibility of implementing a management protocol for AKI-D patients in an outpatient dialysis facility. We found that fewer episodes of intradialytic hypotension occurred when the outpatient HD management was adherent to the protocol. The feasibility of this protocol should be confirmed in other facilities, and importantly, efficacy testing to evaluate its impact on AKI-D outpatient care is necessary.

Perioperative renal function change after transcatheter aortic valve replacement: A single-center retrospective study in China.

BACKGROUND: In recent years, the kidney function after Transcatheter Aortic Valve Replacement (TAVR) has gradually become a hot spot that arouse extensive attention.Our study is aimed to evaluate the incidence and predictors of acute kidney recovery (AKR) after TAVR. METHODS: A total of 102 patients undergoing TAVR in Beijing Anzhen Hospital from June 2021 to March 2022 were enrolled in our study. Patients were divided into AKR group (n = 54), unchanged group (n = 40) and acute kidney injury (AKI) group (n = 8) based on the percent change of estimated glomerular filtration rate (eGFR). Univariate analysis was used to compare the differences in general clinical characteristics and other related indicators between the three groups to analyze the risk factors of AKR. RESULTS: The incidence of AKR was 53% (54/102) after TAVR. Multivariate analysis showed that the incidence of age and proportion of severe NYHA class (III or IV) was significantly higher in the AKR group while renal dysfunction (eGFR <60 mL/min/1.73 m2) was lower. Besides, fluid management/volume therapy was significantly different among the three groups. CONCLUSIONS: AKR is a generalizable phenomenon occurring frequently after TAVR. The age, proportion of severe NYHA class and the baseline renal function are independent predictors of AKR events in patients with severe aortic stenosis undergoing TAVR.

Acute Kidney Injury: Clinical Characteristics and Short-Term Outcomes in 1,519 Patients.

Introduction: Complex integrated information on disease mechanisms and in-hospital outcomes in mild to moderate acute kidney injury (AKI) is scarce. Methods: The Stockholm Prospective AKI Cohort Study (SAKIS) included all patients (≥18 years, n = 1,519) with community-acquired AKI (KDIGO criteria) admitted to the nephrology ward at Danderyd University Hospital, Stockholm, Sweden, between 2009 and 2018. Detailed laboratory measures were registered. Odds ratio for hypo- and hyperkalemia, recovery of kidney function by 30% and 50%, and in-hospital mortality were assessed by logistic regression analysis. Results: Factors independently associated with the presence of hyperkalemia at admission were high age, high serum creatinine (sCr), and low C-reactive protein (CRP). Signs of malnutrition, inflammation, and acidosis were seen in 31% of patients. Kidney recovery, defined as a reduction of sCr by 30% in-hospital (63% of all patients), was associated with higher age, female sex, lower body mass index (BMI), higher hemoglobin, and higher CRP. Factors independently associated with mortality (4.4% of patients) were high age, high BMI, and low albumin. Conclusion: This study provides a detailed description of community-acquired AKI and comprehensive analyses of integrated clinical and laboratory data associated with kidney recovery. Features related to anemia, albuminuria, malnutrition, inflammation, and acidosis associate with partial or moderate short-term recovery of kidney function, with disturbances in potassium homeostasis, and with in-hospital mortality. Future studies are warranted to analyze the long-term consequences of AKI in terms of risk of kidney failure, cardiovascular morbidity, and mortality.

The Nutritional Risk Index as a Predictor of 90-Day Dialysis Dependence After Acute Renal Failure: A Pilot Study.

OBJECTIVE: Return of sufficient renal function to discontinue dialysis following acute renal failure is an important clinical and patient-oriented outcome. Our study sought to develop a model using the Nutritional Risk Index (NRI) to predict 90-day dialysis dependence. METHODS: We retrospectively analyzed 77 patients with acute renal failure admitted to a single university medical center's intensive care units between January 2015 and January 2019 with the need for continuous renal replacement therapy. We assessed the predictive ability of the NRI for 90-day dialysis dependence using age, serum total protein, number of vasopressor days, baseline predialysis estimated glomerular filtration rate (eGFR), and Sequential Organ Failure Assessment (SOFA) score as covariates. RESULTS: Of the analytic group, 20 (25.9%) had severe nutritional risk, and 16 (20.8%) recovered from acute renal failure at 90 days. The mean age was 57.1 years. The clinical model comprising the NRI, age, serum total protein, number of vasopressor days, SOFA score, and baseline predialysis eGFR had an area under the curve (AUC) of 0.89 (95% confidence interval [CI], 0.81-0.97), sensitivity 56.3%, and specificity 95%. Exclusion of baseline predialysis eGFR and SOFA score did not significantly decrease model discrimination, AUC 0.87 (95% CI, 0.78-0.97). The AUC was least when serum total protein was dropped from the final model, 0.79 (95% CI, 0.66-0.92). CONCLUSIONS: The NRI when used together with other clinical parameters, including serum total protein, may improve the accuracy of predicting renal recovery and independence from dialysis at 90 days.

Prediction of Mortality and Major Adverse Kidney Events in Critically Ill Patients With Acute Kidney Injury.

RATIONALE & OBJECTIVE: Risk prediction tools for assisting acute kidney injury (AKI) management have focused on AKI onset but have infrequently addressed kidney recovery. We developed clinical models for risk stratification of mortality and major adverse kidney events (MAKE) in critically ill patients with incident AKI. STUDY DESIGN: Multicenter cohort study. SETTING & PARTICIPANTS: 9,587 adult patients admitted to heterogeneous intensive care units (ICUs; March 2009 to February 2017) who experienced AKI within the first 3 days of their ICU stays. PREDICTORS: Multimodal clinical data consisting of 71 features collected in the first 3 days of ICU stay. OUTCOMES: (1) Hospital mortality and (2) MAKE, defined as the composite of death during hospitalization or within 120 days of discharge, receipt of kidney replacement therapy in the last 48 hours of hospital stay, initiation of maintenance kidney replacement therapy within 120 days, or a ≥50% decrease in estimated glomerular filtration rate from baseline to 120 days from hospital discharge. ANALYTICAL APPROACH: Four machine-learning algorithms (logistic regression, random forest, support vector machine, and extreme gradient boosting) and the SHAP (Shapley Additive Explanations) framework were used for feature selection and interpretation. Model performance was evaluated by 10-fold cross-validation and external validation. RESULTS: One developed model including 15 features outperformed the SOFA (Sequential Organ Failure Assessment) score for the prediction of hospital mortality, with areas under the curve of 0.79 (95% CI, 0.79-0.80) and 0.71 (95% CI, 0.71-0.71) in the development cohort and 0.74 (95% CI, 0.73-0.74) and 0.71 (95% CI, 0.71-0.71) in the validation cohort (P < 0.001 for both). A second developed model including 14 features outperformed KDIGO (Kidney Disease: Improving Global Outcomes) AKI severity staging for the prediction of MAKE: 0.78 (95% CI, 0.78-0.78) versus 0.66 (95% CI, 0.66-0.66) in the development cohort and 0.73 (95% CI, 0.72-0.74) versus 0.67 (95% CI, 0.67-0.67) in the validation cohort (P < 0.001 for both). LIMITATIONS: The models are applicable only to critically ill adult patients with incident AKI within the first 3 days of an ICU stay. CONCLUSIONS: The reported clinical models exhibited better performance for mortality and kidney recovery prediction than standard scoring tools commonly used in critically ill patients with AKI in the ICU. Additional validation is needed to support the utility and implementation of these models. PLAIN-LANGUAGE SUMMARY: Acute kidney injury (AKI) occurs commonly in critically ill patients admitted to the intensive care unit (ICU) and is associated with high morbidity and mortality rates. Prediction of mortality and recovery after an episode of AKI may assist bedside decision making. In this report, we describe the development and validation of a clinical model using data from the first 3 days of an ICU stay to predict hospital mortality and major adverse kidney events occurring as long as 120 days after hospital discharge among critically ill adult patients who experienced AKI within the first 3 days of an ICU stay. The proposed clinical models exhibited good performance for outcome prediction and, if further validated, could enable risk stratification for timely interventions that promote kidney recovery.

Recovery From Dialysis-Treated Acute Kidney Injury in Patients With Cirrhosis: A Population-Based Study.

RATIONALE & OBJECTIVE: The decision to initiate kidney replacement therapy (KRT) for acute kidney injury (AKI) in cirrhosis remains controversial because it is unclear which patients will benefit. We sought to characterize factors associated with recovery from KRT-treated AKI in patients with cirrhosis to inform shared clinical decision-making. STUDY DESIGN: Population-based retrospective cohort study. SETTING & PARTICIPANTS: Adult patients from Ontario, Canada, identified using administrative data to have cirrhosis at the time of hospital admission with AKI (based on serum creatinine level) who were treated with KRT (January 1, 2009, to December 31, 2016) and followed up until the end of 2017. EXPOSURES: Demographic characteristics and comorbidities before admission. OUTCOMES: Kidney recovery defined as the absence of KRT for at least 30 days. ANALYTICAL APPROACH: The cumulative incidences of kidney recovery, death, and liver transplant were calculated at 1, 3, 6, and 12 months, and independent predictors of kidney recovery were evaluated using Fine and Gray competing risk regression models that generated subdistribution hazards ratios (sHRs). RESULTS: Overall, 722 patients were included (median age, 61 [interquartile range, 54-68] years; Model for End-Stage Liver Disease (MELD)-Na score, 26 [interquartile range, 22-34]; 66% were male; 52% had viral hepatitis, 25% nonalcoholic fatty liver disease, 18% alcohol-associated liver disease). The cumulative incidences of kidney recovery at 1, 3, 6, and 12 months were 3%, 22%, 25%, and 26%, respectively. Higher MELD-Na score (sHR per 5 units greater, 0.72 [95% CI, 0.65-0.80]), acute-on-chronic liver failure (sHR, 0.61 [95% CI, 0.43-0.86]), and sepsis (sHR, 0.57 [95% CI, 0.41-0.81]) were associated with a lower hazard of kidney recovery, whereas those on a liver transplant waitlist (sHR, 3.10 [95% CI, 1.96-4.88]) and who were admitted to a teaching hospital (sHR, 1.48 [95% CI, 1.05-2.08]) were more likely to experience kidney recovery. LIMITATIONS: Observational design, AKI etiology not identified. CONCLUSIONS: Kidney recovery from KRT occurred in only one quarter of patients and was very unlikely after 3 months. These findings provide information regarding prognosis that may guide decisions regarding KRT initiation and continuation.

Recovery after acute kidney injury requiring kidney replacement therapy in patients with left ventricular assist device: A meta-analysis.

BACKGROUND: Acute kidney injury (AKI) is a common and severe complication after left ventricular assist device (LVAD) implantation with an incidence of 37%; 13% of which require kidney replacement therapy (KRT). Severe AKI requiring KRT (AKI-KRT) in LVAD patients is associated with high short and long-term mortality compared with AKI without KRT. While kidney function recovery is associated with better outcomes, its incidence is unclear among LVAD patients with severe AKI requiring KRT. AIM: To identify studies evaluating the recovery rates from severe AKI-KRT after LVAD placement, which is defined by regained kidney function resulting in the discontinuation of KRT. Random-effects and generic inverse variance method of DerSimonian-Laird were used to combine the effect estimates obtained from individual studies. METHODS: A total of 268 patients from 14 cohort studies that reported severe AKI-KRT after LVAD were included. Follow-up time ranged anywhere from two weeks of LVAD implantation to 12 mo. Kidney recovery occurred in 78% of enrollees at the time of hospital discharge or within 30 d. Overall, the pooled estimated AKI recovery rate among patients with severe AKI-KRT was 50.5% (95%CI: 34.0%-67.0%) at 12 mo follow up. Majority (85%) of patients used continuous-flow LVAD. While the data on pulsatile-flow LVAD was limited, subgroup analysis of continuous-flow LVAD demonstrated that pooled estimated AKI recovery rate among patients with severe AKI-KRT was 52.1% (95%CI: 36.8%-67.0%). Meta-regression analysis did not show a significant association between study year and AKI recovery rate (P = 0.08). There was no publication bias as assessed by the funnel plot and Egger's regression asymmetry test in all analyses. RESULTS: A total of 268 patients from 14 cohort studies that reported severe AKI-KRT after LVAD were included. Follow-up time ranged anywhere from two weeks of LVAD implantation to 12 mo. Kidney recovery occurred in 78% of enrollees at the time of hospital discharge or within 30 d. Overall, the pooled estimated AKI recovery rate among patients with severe AKI-KRT was 50.5% (95%CI: 34.0%-67.0%) at 12 mo follow up. Majority (85%) of patients used continuous-flow LVAD. While the data on pulsatile-flow LVAD was limited, subgroup analysis of continuous-flow LVAD demonstrated that pooled estimated AKI recovery rate among patients with severe AKI-KRT was 52.1% (95%CI: 36.8%-67.0%). Meta-regression analysis did not show a significant association between study year and AKI recovery rate (P = 0.08). There was no publication bias as assessed by the funnel plot and Egger's regression asymmetry test in all analyses. CONCLUSION: Recovery from severe AKI-KRT after LVAD occurs approximately 50.5%, and it has not significantly changed over the years despite advances in medicine.

Kidney Recovery in Patients With Acute Kidney Injury Treated in Outpatient Hemodialysis or Rehabilitation Facilities.

RATIONALE & OBJECTIVE: Since January 2017, patients with acute kidney injury requiring dialysis (AKI-D) can be discharged to outpatient dialysis centers for continued hemodialysis (HD) support. We aimed to examine the rate of kidney recovery, time to recovery, and hospitalization-related clinical parameters associated with kidney recovery in patients with AKI-D. STUDY DESIGN: Single-center prospective cohort study. SETTING & PARTICIPANTS: 111 adult patients who were admitted to the University of Kentucky Hospital, experienced AKI-D, and were discharged with need of outpatient HD. EXPOSURE: Hospitalization-related clinical parameters were evaluated. OUTCOME: Kidney recovery as a composite of being alive and no longer requiring HD or other form of kidney replacement therapy. ANALYTICAL APPROACH: Discrete-time survival analysis and logistic regression were used to determine adjusted probabilities of kidney recovery at prespecified time points and to evaluate clinical parameters associated with recovery. RESULTS: 45 (41%) patients recovered kidney function, 25 (55.5%) within the first 30 days following discharge, 16 (35.5%) within 30 to 60 days, and 4 (9%) within 60 to 90 days. Adjusted probabilities of recovery were 36.7%, 27.4%, and 6.3%, respectively. Of the remaining patients, 49 (44%) developed kidney failure requiring chronic kidney replacement therapy and 17 (15%) died or went to hospice. Patients who did not recover kidney function were older, had more comorbid conditions, had lower estimated glomerular filtration rates at baseline, and received more blood transfusions during hospitalization when compared with those who recovered kidney function. LIMITATIONS: Selection bias given that patients included in the study were all eligible for AKI management with outpatient HD as part of Medicare/Medicaid services. CONCLUSIONS: At least one-third of AKI-D survivors discharged from an acute care hospital dependent on HD recovered kidney function within the first 90 days of discharge, more commonly in the first 30 days postdischarge. Future studies should elucidate clinical parameters that can inform risk classification and interventions to promote kidney recovery in this vulnerable and growing population.

Serum metabolite profiles predict outcomes in critically ill patients receiving renal replacement therapy.

Acute kidney injury (AKI) requiring renal replacement therapy (RRT) is associated with increased incidence of dialysis dependence and portends high mortality in critically ill patients. At the early stage of RRT, serum metabolic biomarkers might differntiate patients with a high risk of mortality or permanent kidney injury from those who can recover. Serum samples from participants enrolled in the Veteran's Affairs/National Institutes of Health Acute Renal Failure Trial Network study were collected on day 1 (n = 97) and day 8 (n = 105) of randomized RRT. The samples were further evaluated using LC/MS-based metabolic profiling. A model predicting mortality by day 8 was built from samples collected on day 1 and based on four metabolites with an area under the curve (AUC) of 0.641. A model most predictive of mortality by day 28 was built from the levels of 11 serum metabolites from day 8 with an AUC of 0.789. Both day 1 and day 8 samples had lower serum levels of 1-arachidonoyl-lysoPC and 1-eicosatetraenoyl-lysoPC (involved in anti-inflammatory processes) in the critically ill patients who died by day 8 or day 28. Higher levels of amino acids and amino acid metabolites in the day 8 model predicting < day 28 mortality may be indicative of muscle wasting. A kidney recovery biomarker panel based on the serum levels of three metabolites from day 8 samples with an AUC of 0.70 was devised. Serum metabolic profiling of AKI critically ill patients requiring RRT revealed predictive models of mortality based on observed differences in four serum metabolites at day 1 and 11 metabolites at day 8 which were predictive of mortality. Significant changes in the levels of these metabolites suggest links to inflammatory processes and/or muscle wasting.

Assessment of Kidney Function After Transcatheter Aortic Valve Replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR), although associated with an increased risk for acute kidney injury (AKI), may also result in improvement in renal function. OBJECTIVE: The aim of this study is to evaluate the magnitude of kidney function improvement (KFI) after TAVR and to assess its significance on long-term mortality. DESIGN: This is a prospective single center study. SETTING: The study was conducted in cardiology department, interventional unit, in a tertiary hospital. PATIENTS: The cohort included 1321 patients who underwent TAVR. MEASUREMENTS: Serum creatinine level was measured at baseline, before the procedure, and over the next 7 days or until discharge. METHODS: Kidney function improvement was defined as the mirror image of AKI, a reduction in pre-procedural to post-procedural minimal creatinine of more than 0.3 mg/dL, or a ratio of post-procedural minimal creatinine to pre-procedural creatinine of less than 0.66, up to 7 days after the procedure. Patients were categorized and compared for clinical endpoints according to post-procedural renal function change into 3 groups: KFI, AKI, or preserved kidney function (PKF). The primary endpoint was long-term all-cause mortality. RESULTS: The incidence of KFI was 5%. In 55 out of 66 patients patients, the improvement in kidney function was minor and of unclear clinical significance. Acute kidney injury occurred in 19.1%. Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 was a predictor of KFI after multivariable analysis (odds ratio = 0.93 to develop KFI; confidence interval [95% CI]: 0.91-0.95, P < .001). Patients in the KFI group had a higher Society of Thoracic Surgery (STS) score than other groups. Mortality rate did not differ between KFI group and PKF group (43.9% in KFI group and 33.8% in PKF group) but was significantly higher in the AKI group (60.7%, P < .001). LIMITATIONS: The following are the limitations: heterozygous definitions of KFI within different studies and a single center study. Although data were collected prospectively, analysis plan was defined after data collection. CONCLUSIONS: Improvement in kidney function following TAVR was not a common phenomenon in our cohort and did not reduce overall mortality rate.

CONTEXTE: L'implantation transcathéter de valvule aortique (ITVA), bien qu'elle soit associée à un risque accru d'insuffisance rénale aiguë (IRA), est susceptible d'améliorer la fonction rénale. OBJECTIFS: Évaluer l'ampleur de l'amélioration de la fonction rénale (AFR) après une ITVA et évaluer son incidence sur le taux de mortalité à long terme. TYPE D'ÉTUDE: Étude prospective menée dans un seul centre hospitalier. CADRE: Le service de cardiologie, unité interventionnelle, d'un centre de soins tertiaires. SUJETS: La cohorte était constituée de 1 321 patients ayant subi une ITVA. MESURES: Le taux de créatinine sérique a été mesuré à l'inclusion, avant l'intervention et pour les 7 jours suivants, ou jusqu'au congé du patient. MÉTHODOLOGIE: L'AFR a été définie comme l'image miroir de l'IRA, soit une réduction de plus de 0,3 mg/dl du taux de créatinine après l'intervention par rapport au taux minimum de créatinine mesuré pré-ITVA, ou un rapport entre la créatinine minimale post-ITVA et la créatinine pré-ITVA inférieur à 0,66 jusqu'à 7 jours après l'intervention. Les patients ont été classés en trois groupes et comparés selon des critères cliniques en fonction de la modification de la fonction rénale après l'intervention : un groupe AFR, un groupe IRA et un groupe « fonction rénale préservée ¼ (FRP). Le critère principal était la mortalité toutes causes confondues. RÉSULTATS: L'incidence d'une AFR était de 5 % et elle s'est avérée mineure et d'importance clinique incertaine pour 55 des 66 patients concernés. La proportion de patients atteints d'IRA était de 19,1 %. Après l'analyse multivariée, un débit de filtration glomérulaire estimé (DFGe) inférieur à 60 ml/min/1,73 m2 s'est avéré un facteur prédictif de l'AFR [rapport de cotes pour une AFR : 0,93 (IC : 0,91-0,95; p < 0,001)]. Les patients du groupe AFR présentaient un score de la Society of Thoracic Surgery (STS) plus élevé que ceux des autres groupes. Le taux de mortalité était similaire pour les groupes AFR et FRP (respectivement 43,9 % et 33,8 %), mais s'est avéré significativement plus élevé dans le groupe IRA (60,7 %; p < 0,001). LIMITES: Manque de consensus autour de la définition d'une amélioration de la fonction rénale dans les différentes études.Étude menée dans un seul centre.Bien que les données aient été recueillies de façon prospective, le plan d'analyse n'a été défini qu'après la collecte des données. CONCLUSION: L'amélioration de la fonction rénale après l'ITVA n'était pas un phénomène courant dans notre cohorte et n'a pas permis de réduire le taux de mortalité global.

Predictors of kidney function recovery among incident ESRD patients.

BACKGROUND: ESRD is considered an irreversible loss of renal function, yet some patients will recover kidney function sufficiently to come off dialysis. Potentially modifiable predictors of kidney recovery, such as dialysis prescription, have not been fully examined. METHODS: Retrospective cohort study using United States Renal Data System (USRDS) data to identify incident hemodialysis (HD) patients between 2012 and 2016, the first 4 years for which dialysis treatment data is available. The primary outcome was kidney recovery within 1 year of ESRD and HD initiation, defined by a specific recovery code and survival off dialysis for at least 30 days. Patient and treatment characteristics were compared between those that recovered versus those that remained dialysis-dependent. A time-dependent survival model was used to identify independent predictors of kidney recovery. RESULTS: During the study period, there were 372,387 incident HD patients with available data, among whom 16,930 (4.5%) recovered to dialysis-independence. Compared to non-recovery, a higher proportion of patients with kidney recovery were of white race, and non-Hispanic ethnicity. Both groups had a similar age distribution. Patients with an acute kidney injury diagnosis as primary cause of ESRD were most likely to recover, but the most common ESRD diagnosis among recovering patients was type 2 diabetes (29.8% of recovery cases). Higher eGFR and lower albumin at ESRD initiation were associated with increased likelihood of recovery. When examining HD ultrafiltration rate (UFR), each quintile above the first quintile was associated with a progressively lower likelihood of recovery (HR 0.45, 95% CI 0.43-0.48 for highest versus lowest quintile, p < 0.001). CONCLUSIONS: We identified non-modifiable and potentially modifiable factors associated with kidney recovery which may assist clinicians in counseling and monitoring incident ESRD patients with a greater chance to gain dialysis-independence. Clinical trials are warranted to examine the impact of dialysis prescription on subsequent kidney function recovery.

Role of Damage-Associated Molecular Patterns in Septic Acute Kidney Injury, From Injury to Recovery.

Damage-associated molecular patterns (DAMPs) are a group of immunostimulatory molecules, which take part in inflammatory response after tissue injury. Kidney-specific DAMPs include Tamm-Horsfall glycoprotein, crystals, and uromodulin, released by tubular damage for example. Non-kidney-specific DAMPs include intracellular particles such as nucleus [histones, high-mobility group box 1 protein (HMGB1)] and cytosol parts. DAMPs trigger innate immunity by activating the NRLP3 inflammasome, G-protein coupled class receptors or the Toll-like receptor. Tubular necrosis leads to acute kidney injury (AKI) in either septic, ischemic or toxic conditions. Tubular necrosis releases DAMPs such as histones and HMGB1 and increases vascular permeability, which perpetuates shock and hypoperfusion via Toll Like Receptors. In acute tubular necrosis, intracellular abundance of NADPH may explain a chain reaction where necrosis spreads from cell to cell. The nature AKI in intensive care units does not have preclinical models that meet a variation of blood perfusion or a variation of glomerular filtration within hours before catecholamine infusion. However, the dampening of several DAMPs in AKI could provide organ protection. Research should be focused on the numerous pathophysiological pathways to identify the relative contribution to renal dysfunction. The therapeutic perspectives could be strategies to suppress side effect of DAMPs and to promote renal function regeneration.

Acute Kidney Disease to Chronic Kidney Disease.

Acute kidney injury (AKI) and chronic kidney disease are common interconnected syndromes that represent a public health problem. Acute kidney disease (AKD) is defined as the post-AKI status of acute or subacute kidney damage/dysfunction manifested by persistence of AKI beyond 7 to 90 days after the initial AKI diagnosis. Limited clinical data exist regarding AKD epidemiology but its incidence is observed in ∼25% of AKI survivors. Useful risk-stratification tools to predict risk of AKD and its prognosis are needed. Interventions on fluid management, nephrotoxic exposure, and follow-up care hold promise to ameliorate the burden of AKD and its complications.

Renal Functional Recovery Confounding the Assessment of Contrast Nephropathy: Propensity Score Analysis.

BACKGROUND: Large data analyses confirm the relative safety of contrast-enhanced computed tomography (CT), except for those with advanced renal failure. However, the prevalence of post-contrast acute kidney injury may be masked by acute kidney functional recovery (AKR) in unstable inpatients, irrespective of contrast-enhanced imaging. METHODS: In this work we aimed to assess AKI and AKR along with need for dialysis and mortality, among inpatients undergoing contrast-enhanced or non-enhanced CT. We performed a large-scale retrospective data analysis using propensity score matching (PSM) that compared patients undergoing contrast-enhanced and non-enhanced imaging. We also performed a subgroup analysis of subjects stratified by baseline renal function. RESULTS: A total of 41,456 patients were analyzed. PSM resulted in well-balanced groups. AKR occurred substantially more often than AKI among hospitalized patients following CT imaging, especially among those with low baseline renal function. Yet, in this population, whereas the rate of AKI significantly increased, the rate of AKR significantly decreased following contrast-enhanced studies as compared to patients that underwent non-enhanced CT. A significantly higher proportion of patients with baseline advanced renal failure that underwent contrast-enhanced imaging required dialysis. CONCLUSIONS: The increased incidence of AKI and AKR as seen in patients with lower pre-imaging kidney function possibly suggests that both entities reflect impaired renal functional reserve. Unstable kidney function in inpatients, as demonstrated by rates of AKR and AKI, is an important confounder which requires attention in similar observational studies on the renal effects of contrast media and of various other renal injurious events.