Renal Impact of Culprit-Only versus Multi-Vessel Revascularization for Cardiogenic Shock Complicating Acute Myocardial Infarction: Systematic Review and Meta-Analysis.

Background: The optimal strategy of percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) complicated with cardiogenic shock (CS) remains controversial. We aimed to elucidate the renal and cardiovascular impact of culprit-only (C) revascularization versus additional interventions on non-infarct-related arteries. Methods: PubMed, Embase, MEDLINE, and Cochrane Library were searched for relevant literature. A total of 96,812 subjects [C-PCI: 69,986; multi-vessel (MV)-PCI: 26,826] in nine studies (one randomized control trial; eight observational cohort studies) were enrolled. Results: MV-PCI was associated with a higher kidney event rate [relative risk (RR): 1.29, 95% confidence interval (CI): 1.12-1.49; p < 0.001]. However, the all-cause mortality rate was comparable both during admission (RR: 1.07, 95% CI: 0.94-1.22; p = 0.30) and at one year (RR: 0.96, 95% CI: 0.79-1.16; p = 0.65). MV-PCI was associated with a greater risk of stroke (RR: 1.19, 95% CI: 1.08-1.32; p < 0.001) and bleeding events (RR: 1.27, 95% CI: 1.07-1.51; p = 0.006), but reduced risk of recurrent MI (RR: 0.89, 95% CI: 0.82-0.97; p = 0.009) and repeat revascularization (RR: 0.34, 95% CI: 0.16-0.71; p = 0.004). No increased risk of coronary artery bypass grafting was present (RR: 1.09, 95% CI: 0.38-3.17; p = 0.87). Conclusions: C-PCI was associated with a lower rate of renal dysfunction but not all-cause mortality in patients with CS complicating acute MI.

Comparative accuracy of biomarkers for the prediction of hospital-acquired acute kidney injury: a systematic review and meta-analysis.

BACKGROUND: Several biomarkers have been proposed to predict the occurrence of acute kidney injury (AKI); however, their efficacy varies between different trials. The aim of this study was to compare the predictive performance of different candidate biomarkers for AKI. METHODS: In this systematic review, we searched PubMed, Medline, Embase, and the Cochrane Library for papers published up to August 15, 2022. We selected all studies of adults (> 18 years) that reported the predictive performance of damage biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP)), inflammatory biomarker (interleukin-18 (IL-18)), and stress biomarker (tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein-7 (TIMP-2 × IGFBP-7)) for the occurrence of AKI. We performed pairwise meta-analyses to calculate odds ratios (ORs) and 95% confidence intervals (CIs) individually. Hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the pooled test performance, and the Grading of Recommendations, Assessment, Development and Evaluations criteria were used to appraise the quality of evidence. RESULTS: We identified 242 published relevant studies from 1,803 screened abstracts, of which 110 studies with 38,725 patients were included in this meta-analysis. Urinary NGAL/creatinine (diagnostic odds ratio [DOR] 16.2, 95% CI 10.1-25.9), urinary NGAL (DOR 13.8, 95% CI 10.2-18.8), and serum NGAL (DOR 12.6, 95% CI 9.3-17.3) had the best diagnostic accuracy for the risk of AKI. In subgroup analyses, urinary NGAL, urinary NGAL/creatinine, and serum NGAL had better diagnostic accuracy for AKI than urinary IL-18 in non-critically ill patients. However, all of the biomarkers had similar diagnostic accuracy in critically ill patients. In the setting of medical and non-sepsis patients, urinary NGAL had better predictive performance than urinary IL-18, urinary L-FABP, and urinary TIMP-2 × IGFBP-7: 0.3. In the surgical patients, urinary NGAL/creatinine and urinary KIM-1 had the best diagnostic accuracy. The HSROC values of urinary NGAL/creatinine, urinary NGAL, and serum NGAL were 91.4%, 85.2%, and 84.7%, respectively. CONCLUSIONS: Biomarkers containing NGAL had the best predictive accuracy for the occurrence of AKI, regardless of whether or not the values were adjusted by urinary creatinine, and especially in medically treated patients. However, the predictive performance of urinary NGAL was limited in surgical patients, and urinary NGAL/creatinine seemed to be the most accurate biomarkers in these patients. All of the biomarkers had similar predictive performance in critically ill patients. Trial registration CRD42020207883 , October 06, 2020.

Accelerated versus standard initiation of renal replacement therapy for critically ill patients with acute kidney injury: a systematic review and meta-analysis of RCT studies.

BACKGROUND: Acute kidney injury (AKI) is a common yet possibly fatal complication among critically ill patients in intensive care units (ICU). Although renal replacement therapy (RRT) is an important supportive management for severe AKI patients, the optimal timing of RRT initiation for these patients is still unclear. METHODS: In this systematic review, we searched all relevant randomized controlled trials (RCTs) that directly compared accelerated with standard initiation of RRT from PUBMED, MEDLINE, EMBASE, and Cnki.net published prior to July, 20, 2020. We extracted study characteristics and outcomes of being free of dialysis, dialysis dependence and mortality. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. RESULTS: We identified 56 published relevant studies from 1071 screened abstracts. Ten RCTs with 4753 critically ill AKI patients in intensive care unit (ICU) were included in this meta-analysis. In our study, accelerated and standard RRT group were not associated with all-cause mortality (log odds-ratio [OR]: - 0.04, 95% confidence intervals [CI] - 0.16 to 0.07, p = 0.46) and free of dialysis (log OR: - 0.03, 95% CI - 0.14 to 0.09, p = 0.65). In the subgroup analyses, accelerated RRT group was significantly associated with lower risk of all-cause mortality in the surgical ICU and for those who received continuous renal replacement therapy (CRRT). In addition, patients in these two subgroups had higher chances of being eventually dialysis-free. However, accelerated initiation of RRT augmented the risk of dialysis dependence in the subgroups of patients treated with non-CRRT modality and whose Sequential Organ Failure Assessment (SOFA) score were more than 11. CONCLUSIONS: In this meta-analysis, critically ill patients with severe AKI would benefit from accelerated RRT initiation regarding all-cause mortality and being eventually free of dialysis only if they were surgical ICU patients or if they underwent CRRT treatment. However, the risk of dialysis dependence was increased in the accelerated RRT group when those patients used non-CRRT modality or had high SOFA scores. All the literatures reviewed in this study were highly heterogeneous and potentially subject to biases. Trial registration CRD42020201466, Sep 07, 2020. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=201466 .

Berberine inhibits colorectal tumor growth by suppressing SHH secretion.

Hedgehog plays an important role in a wide range of physiological and pathological conditions. Paracrine activation of Hedgehog pathway in stromal cells increases the expression of VEGF, which promotes neovascularization in colorectal cancer and ultimately the growth of colorectal cancer. Berberine (BBR) has anticancer activity. In this study we investigated whether BBR inhibited the growth of colon cancer through suppressing the paracrine sonic hedgehog (SHH) signaling in vitro and in vivo. We showed that BBR (1-10 µM) dose-dependently inhibited the secretion and expression of SHH protein in HT-29 and SW480 cells. BBR did not influence the transcription of SHH, but promoted the degradation of SHH mRNA, thus decreased the SHH mRNA expression in the colorectal cancer cells. In nude mice bearing HT-29 xenograft, oral administration of BBR (100 mg · kg-1 · d-1) or a positive control drug GDC-0449 (100 mg · kg-1 · d-1) for 4 weeks markedly suppressed the growth of HT-29 tumor with BBR exhibiting a better antitumor efficacy. The tumor growth inhibition caused by BBR or GDC-0449 was comparable to their respective inhibitory effect on the mouse-specific Gli mRNA expression in the tumor. However, BBR (20 µM) did not affect the expression of human transcription factor Gli1 mRNA in HT-29 and SW480 cells. In conclusion, BBR promotes the degradation of SHH mRNA in colorectal cancer cells, interrupting the paracrine Hedgehog signaling pathway activity thus suppresses the colorectal cancer growth. This study reveals a novel molecular mechanism underlying the anticancer action of BBR.

ABT-199 inhibits Hedgehog pathway by acting as a competitive inhibitor of oxysterol, rather as a BH3 mimetic.

Aberrantly activated Hedgehog (Hh) pathway is critical for driving the initiation and progression of multiple types of cancers, including medulloblastoma (MB) and basal cellular carcinoma (BCC). The majority of current Hh antagonist function by targeting the transmembrane domain of the oncoprotein Smoothened (Smo), a G-protein-coupled receptor-like receptor of Hh pathway. However, the primary and acquired resistance to current Smo inhibitors raise a critical need to develop next-generation of Smo inhibitors to improve their clinical efficacy. In this study, we identify that FDA approved drug ABT-199 significantly and selectively inhibits the Hh pathway. Mechanistically, ABT-199 acts as a competitive inhibitor of oxysterol by potentially targeting the cysteine rich domain (CRD) of Smo, rather as a BH3 mimetic. ABT-199 obviously inhibits the growth of Hh-driven tumors and possesses capacity of combating the primary and acquired resistance to Smo inhibitors caused by Smo mutations. Our data reposition ABT-199 as a Smo inhibitor for treating Hh-driven tumors, especially for those bearing Smo mutations and resistant to current Smo inhibitors. Meanwhile, our findings strengthen the argument that the CRD of Smo is a promising target for developing novel Smo inhibitors with capacity of combating the resistance to Smo inhibitors.

Renin-angiotensin-aldosterone system inhibition decreased contrast-associated acute kidney injury in chronic kidney disease patients.

BACKGROUND/PURPOSE: Chronic kidney disease (CKD) is a risk factor for contrast associated acute kidney injury (CA-AKI). The risk of renin-angiotensin-aldosterone system inhibitor (RASi) use in patients with CKD before the administration of contrast is not clear. METHODS: In this nested case-control study, 8668 patients received contrast computed tomography (CT) from 2013 to 2018 during index administration in a multicenter hospital cohort. The identification of AKI is based on the Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria within 48 h after contrast medium used. RESULTS: Finally, 986 patients (age, 63.36 ± 12.22; men, 72.92%) with CKD (estimated glomerular filtration rate (eGFR) = 35.0 ± 19.8 mL/min/1.73 m2) were eligible for analysis. After the index date, RASi users (n = 315) were less likely to develop CA-AKI (13.65% vs 30.4%, p < 0.001), and had a lower hospital mortality (8.25% vs 19.23%, p < 0.001) compared with non-users. The pre-contrast use of RASi decrease the risk of AKI (OR, 0.342, p < 0.001) and hospital mortality (OR, 0.602, p = 0.045). Even a few defined daily doses (DDDs) of RASi treatment, more than 0.02 prior to contrast CT could attenuate CA-AKI. The hospital mortality was higher in RASi non-users if their eGFR value was more than 17.9 mL/min/1.73 m2. CONCLUSION: RASi use in patients with CKD prior to contrast CT has the potential to mitigate the incidence of AKI and hospital mortality. Even a low dose of RASi will noticeably decrease the risk of AKI and will not increase the risk of hyperkalemia.

Nephrologist Follow-Up Care of Patients With Acute Kidney Disease Improves Outcomes: Taiwan Experience.

OBJECTIVES: Acute kidney injury (AKI) and acute kidney disease (AKD) are a continuum on a disease spectrum and frequently progress to chronic kidney disease. Benefits of nephrologist subspecialty care during the AKD period after AKI are uncertain. METHODS: Patients with AKI requiring dialysis who subsequently became dialysis independent and survived for at least 90 days, defined as the AKD period, were identified from the Taiwanese population's health insurance database. Cox proportional hazard models using death as the competing risk before and after propensity-score matching were applied to evaluate various endpoints. RESULTS: Among a total of 20 260 patients with AKI requiring dialysis who became dialysis independent, only 7550 (37.3%) patients were followed up with by a nephrologist (F/Unephrol group) during the AKD period. During a mean 4.04 ± 3.56 years of follow-up, the patients in the F/Unephrol group were more often administered statin, antihypertensives, angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), diuretics, antiplatelet agents, and antidiabetic agents. The patients in the F/Unephrol group had a lower mortality rate (hazard ratio [HR] = 0.87, P < .001) and were less likely to have major adverse cardiovascular events (MACE) (subdistribution HR [sHR] = 0.85, P < .001), congestive heart failure (CHF) (sHR = 0.81, P < .001), and severe sepsis (sHR = 0.88, P = .008) according to the Cox proportional model after adjusting for mortality as a competing risk. During the AKD period, an increase in the frequency of nephrology visits was associated with improved outcomes. CONCLUSIONS: In this population-based cohort, even after weaning off acute dialysis, only a minority of patients visited a nephrologist during the AKD period. We showed that nephrology follow-up is associated with a decrease in MACE, CHF exacerbations, and sepsis, as well as lower mortality; thus it may improve outcomes in patients with AKD.

Urinary biomarkers predict advanced acute kidney injury after cardiovascular surgery.

BACKGROUND: Acute kidney injury (AKI) after cardiovascular surgery is a serious complication. Little is known about the ability of novel biomarkers in combination with clinical risk scores for prediction of advanced AKI. METHODS: In this prospectively conducted multicenter study, urine samples were collected from 149 adults at 0, 3, 6, 12 and 24 h after cardiovascular surgery. We measured urinary hemojuvelin (uHJV), kidney injury molecule-1 (uKIM-1), neutrophil gelatinase-associated lipocalin (uNGAL), α-glutathione S-transferase (uα-GST) and π-glutathione S-transferase (uπ-GST). The primary outcome was advanced AKI, under the definition of Kidney Disease: Improving Global Outcomes (KDIGO) stage 2, 3 and composite outcomes were KDIGO stage 2, 3 or 90-day mortality after hospital discharge. RESULTS: Patients with advanced AKI had significantly higher levels of uHJV and uKIM-1 at 3, 6 and 12 h after surgery. When normalized by urinary creatinine level, uKIM-1 in combination with uHJV at 3 h post-surgery had a high predictive ability for advanced AKI and composite outcome (AUC = 0.898 and 0.905, respectively). The combination of this biomarker panel (normalized uKIM-1, uHJV at 3 h post-operation) and Liano's score was superior in predicting advanced AKI (AUC = 0.931, category-free net reclassification improvement of 1.149, and p <  0.001). CONCLUSIONS: When added to Liano's score, normalized uHJV and uKIM-1 levels at 3 h after cardiovascular surgery enhanced the identification of patients at higher risk of progression to advanced AKI and composite outcomes.

Optimal timing of renal replacement therapy initiation in acute kidney injury: the elephant felt by the blindmen?

Renal replacement therapy (RRT) is a key component in the management of severe acute kidney injury (AKI) in critically ill patients. Many cohort studies, meta-analyses, and two recent large randomized prospective trials which evaluated the relationship between the timing of RRT initiation and patient outcome remain inconclusive due to substantial differences in study design, patient population, AKI definition, and RRT indication. A cause-specific diagnosis of AKI based on current staging criteria plus a sensitive biomarker (panel) that allows creating a homogeneous study population is definitely needed to assess the impact of early versus late initiation of RRT on patient outcome.

Novel insights into acute kidney injury-chronic kidney disease continuum and the role of renin-angiotensin system.

Acute kidney injury (AKI) is an independent risk factor for chronic kidney disease (CKD). If injury is mild, a repair process can be adaptive and lead to complete renal recovery. However, severe injury will be accompanied by a maladaptive repair which usually leads to nephron loss, fibrosis, vascular rarefaction, and chronic inflammation. Although various mechanisms underlying AKI-CKD transition have been explored, no intervention has been proved effective to block the transition until very recently. A lack of consensus for monitoring renal function and defining renal recovery after AKI should be the reasons for the slow advance in the discovery of a timely pharmacologic treatment to block AKI-CKD transition. Recently, animal studies have shown the activation of renin-angiotensin system (RAS) after AKI. In patients with complete renal recovery after AKI defined as the decrease of serum creatinine level to within 0.3 mg/dL above the baseline, administration of RAS inhibitor can prevent the ensuing CKD. In this review, we will discuss the renal recovery after AKI and the mechanisms underlying AKI-CKD transition. We will then highlight the promising effect of RAS inhibitor on CKD prevention in patients with complete renal recovery from AKI based on the recent clinical evidence.

Nationwide epidemiology and prognosis of dialysis-requiring acute kidney injury (NEP-AKI-D) study: Design and methods.

AIM: Acute kidney injury (AKI) carries an increasing incidence rate worldwide and increases the risk of developing end-stage renal disease (ESRD) as well as the medical expenses during the post-AKI course. The Taiwan Consortium for Acute Kidney Injury and Renal Diseases (CAKs) has thus launched a nationwide epidemiology and prognosis of dialysis-requiring acute kidney injury (NEP-AKI-D) study, which prospectively enrols critically ill patients with AKI. Through thoroughly evaluating the risk and prognostic factors of AKI, we hope to lower the incidence of AKI and ESRD from the perspective of AKI-ESRD interaction. METHODS: The CAKs includes 30 hospitals which distribute widely through the four geographical regions (north, middle, south, and east) of Taiwan, and have a 1:1 ratio of medical centres to regional hospitals in each region. The NEP-AKI-D study enrols intensive care unit-based AKI patients who receive dialysis in the four seasonal sampled months (October 2014, along with January, April, and July 2015) in the included hospitals. The collected data include demographic information, pertaining laboratory results, dialysis settings and patient outcomes. The data are uploaded in a centre website and will be audited by on-site principal investigators, computer logic gates, and the CAKs staffs. The outcomes of interest are in-hospital mortality, dialysis-dependency and readmission rate within 90 days after discharge. CONCLUSION: The NEP-AKI-D study enrols a large number of representative AKI patients throughout Taiwan. The results of the current study are expected to provide more insight into the risk and prognostic factors of AKI and further attenuated further chronic kidney disease transition.

Inhaled nitric oxide therapy and risk of renal dysfunction: a systematic review and meta-analysis of randomized trials.

INTRODUCTION: Inhaled nitric oxide (iNO) is an important therapy for acute respiratory distress syndrome (ARDS), pulmonary hypertension and pediatric hypoxemic respiratory failure. Safety concerns regarding iNO and renal dysfunction have been reported; however, there are currently no systematic reviews on this issue. Our objective was to evaluate published randomized controlled trials (RCTs) to ascertain the risk of renal dysfunction associated with iNO therapy in patients with and without ARDS. METHODS: A systematic review of databases was performed to identify RCTs which compared iNO with controls up to September 2014. Effect estimates for risk ratio (RR) of acute kidney injury (AKI) were pooled using a random-effects model. RESULTS: Ten RCTs involving 1363 participants were included. Inhaled nitric oxide significantly increased the risk of AKI compared with controls (RR, 1.4, 95%CI, 1.06 to 1.83, p = 0.02). In the stratified analysis, a high cumulative-dose of iNO significantly increased the risk of AKI (RR, 1.52, 95%CI, 1.14 to 2.02, p = 0.004), whereas medium and low cumulative-doses did not (RR, 0.64, 95%CI, 0.23 to 1.81 and RR, 0.56, 95%CI, 0.11 to 2.86 respectively). In subgroup analysis by study population, an increased risk of AKI was observed in patients with ARDS (RR, 1.55, 95%CI, 1.15 to 2.09, p = 0.005) but not in those without (RR, 0.90, 95%CI, 0.49 to 1.67, p = 0.75). CONCLUSIONS: The available data show that iNO therapy may increase the risk of renal dysfunction, especially with prolonged use and in patients with ARDS. The risk in pediatric population is unknown owing to limited data. We suggest monitoring renal function during iNO therapy, and that future trials of iNO should evaluate renal safety.

Long-term remote organ consequences following acute kidney injury.

Acute kidney injury (AKI) has been a global health epidemic problem with soaring incidence, increased long-term risks for multiple comorbidities and mortality, as well as elevated medical costs. Despite the improvement of patient outcomes following the advancements in preventive and therapeutic strategies, the mortality rates among critically ill patients with AKI remain as high as 40-60 %. The distant organ injury, a direct consequence of deleterious systemic effects, following AKI is an important explanation for this phenomenon. To date, most evidence of remote organ injury in AKI is obtained from animal models. Whereas the observations in humans are from a limited number of participants in a relatively short follow-up period, or just focusing on the cytokine levels rather than clinical solid outcomes. The remote organ injury is caused with four underlying mechanisms: (1) "classical" pattern of acute uremic state; (2) inflammatory nature of the injured kidneys; (3) modulating effect of AKI of the underlying disease process; and (4) healthcare dilemma. While cytokines/chemokines, leukocyte extravasation, oxidative stress, and certain channel dysregulation are the pathways involving in the remote organ damage. In the current review, we summarized the data from experimental studies to clinical outcome studies in the field of organ crosstalk following AKI. Further, the long-term consequences of distant organ-system, including liver, heart, brain, lung, gut, bone, immune system, and malignancy following AKI with temporary dialysis were reviewed and discussed.

Long-term risk of coronary events after AKI.

The incidence rate of AKI in hospitalized patients is increasing. However, relatively little attention has been paid to the association of AKI with long-term risk of adverse coronary events. Our study investigated hospitalized patients who recovered from de novo dialysis-requiring AKI between 1999 and 2008 using patient data collected from inpatient claims from Taiwan National Health Insurance. We used Cox regression with time-varying covariates to adjust for subsequent CKD and ESRD after discharge. Results were further validated by analysis of a prospectively constructed database. Among 17,106 acute dialysis patients who were discharged, 4869 patients recovered from dialysis-requiring AKI (AKI recovery group) and were matched with 4869 patients without AKI (non-AKI group). The incidence rates of coronary events were 19.8 and 10.3 per 1000 person-years in the AKI recovery and non-AKI groups, respectively. AKI recovery associated with higher risk of coronary events (hazard ratio [HR], 1.67; 95% confidence interval [95% CI], 1.36 to 2.04) and all-cause mortality (HR, 1.67; 95% CI, 1.57 to 1.79) independent of the effects of subsequent progression to CKD and ESRD. The risk levels of de novo coronary events after hospital discharge were similar in patients with diabetes alone and patients with AKI alone (P=0.23). Our results reveal that AKI with recovery associated with higher long-term risks of coronary events and death in this cohort, suggesting that AKI may identify patients with high risk of future coronary events. Enhanced postdischarge follow-up of renal function of patients who have recovered from temporary dialysis may be warranted.

The role of brain natriuretic peptide in predicting renal outcome and fluid management in critically ill patients.

BACKGROUND/PURPOSE: Fluid overload is associated with acute kidney injury (AKI) and mortality. There is no convenient precise method to guide fluid therapy in critically ill patients. We aimed to investigate whether brain natriuretic peptide (BNP) can predict the renal outcome and mortality of critically ill patients and be used to guide fluid management. METHODS: This prospective observational study included patients who were admitted to the intensive care unit (ICU). Patients with underlying heart disease and heart dysfunction were excluded. Plasma BNP levels were obtained on admission (D0), at 24 hours (D1), and at 48 hours (D2). The primary outcome was AKI development during the ICU stay and recovery of AKI at ICU discharge. The secondary outcome was in-ICU mortality. RESULTS: One hundred and sixty-three patients were enrolled for analysis. The delta-BNP level within the initial 24 hours after ICU admission rather than fluid accumulation was significantly correlated with delta-central venous pressure levels (r = 0.219, p = 0.010). Delta-Brain natriuretic peptide levels of < 81.8% within the initial 24 hours was an independent predictor of better renal outcome (i.e., no AKI or AKI with recovery). The increment in the BNP level from D0 to D1 was also a significant risk factor of mortality. In the a priori subgroup analysis for patients with sepsis, delta-BNP levels from D0 to D1 remained a significant predictor of renal outcome and mortality. CONCLUSION: Our study showed that delta-BNP levels within 24 hours of admission to the ICU are better than fluid accumulation as a predictor of AKI, recovery, and mortality.

Effect of preoperative statin therapy on postoperative acute kidney injury in patients undergoing major surgery: systemic review and meta-analysis.

We aimed to examine the association between preoperative use of statins and postoperative acute kidney injury (AKI) in patients undergoing major surgery by performing a systemic review and meta-analysis. MEDLINE and EMBASE, from inception to April 2013, and the reference lists of related articles were searched for relevant studies. Trials comparing preoperative statin therapy with no preoperative statin in patients undergoing major surgery were included. Outcome measures of interest were the risk of cumulative postoperative AKI and postoperative AKI requiring renal replacement therapy (RRT). Fixed or random effect meta-analysis was performed to derive summary effect estimates. In five randomized controlled trials (RCTs) and 19 observational studies, comprising a total of 989 173 patients undergoing major surgery, 112 840 patients (11.41%) received preoperative statin therapy. The specific type, dosage, and duration of statin therapy were not available in most studies. Preoperative statin therapy was associated with a significant risk reduction for cumulative postoperative AKI (weighted summary odds ratio (OR) 0.87, 95% CI 0.79 to 0.95). The effect of risk reduction was also significant when considering postoperative AKI requiring RRT (OR 0.80, 95% CI 0.72 to 0.90). When restricting the analysis to the five RCTs, preoperative statin therapy did not show significant protective effect on postoperative AKI (OR 0.49, 95% CI 0.22 to 1.09). In patients undergoing major surgery, preoperative statin therapy could associate with a reduced risk for postoperative AKI. However, considerable heterogeneity existed among included studies. Future randomized trials were warranted for this critical clinical question.

Recovery Dynamics and Prognosis After Dialysis for Acute Kidney Injury.

Importance: The interplay among baseline kidney function, severity of acute kidney disease (AKD), and post-AKD kidney function has significant associations with patient outcomes. However, a comprehensive understanding of how these factors are collectively associated with mortality, major adverse cardiac events (MACEs), and end-stage kidney disease (ESKD) in patients with dialysis-requiring acute kidney injury (AKI-D) is yet to be fully explored. Objective: To investigate the associations of baseline kidney function, AKD severity, and post-AKD kidney function with mortality, MACEs, and ESKD in patients with AKI-D. Design, Setting, and Participants: This nationwide, population-based cohort study of patients with AKI-D was conducted between January 1, 2015, and December 31, 2018, using data from various health care settings included in the Taiwan nationwide population-based cohort database. Data analysis was conducted from April 28, 2022, to June 30, 2023. Exposure: Exposure to severe AKI and baseline and post-AKD kidney function. Main Outcomes and Measures: The primary outcomes were all-cause mortality and incident MACEs, and secondary outcomes were risks of permanent dialysis and readmission. Results: A total of 6703 of 22 232 patients (mean [SD] age, 68.0 [14.7] years; 3846 [57.4%] male) with AKI-D with post-AKD kidney function follow-up and AKD stage data were enrolled. During a mean (SD) 1.2 (0.9) years of follow-up, the all-cause mortality rate was 28.3% (n = 1899), while the incidence rates of MACEs and ESKD were 11.1% (n = 746) and 16.7% (n = 1119), respectively. After adjusting for known covariates, both post-AKD kidney function and baseline kidney function, but not AKD severity, were independently associated with all-cause mortality, MACEs, ESKD, and readmission. Moreover, worse post-AKD kidney function correlated with progressive and significant increases in the risk of adverse outcomes. Conclusions and Relevance: In this cohort study of patients with AKI-D, more than one-quarter of patients died after 1.2 years of follow-up. Baseline and post-AKD kidney functions serve as important factors associated with the long-term prognosis of patients with AKI-D. Therefore, concerted efforts to understand the transition from post-AKD to chronic kidney disease are crucial.

Risk of developing severe sepsis after acute kidney injury: a population-based cohort study.

INTRODUCTION: Sepsis has been a factor of acute kidney injury (AKI); however, little is known about dialysis-requiring AKI and the risk of severe sepsis after survival to discharge. METHODS: We conducted a population-based cohort study based on the Taiwan National Health Insurance Research Database from 1999 to 2009. We identified patients with AKI requiring dialysis during hospitalization and survived for at least 90 days after discharge, and matched them with those without AKI according to age, sex, and concurrent diabetes. The primary outcome was severe sepsis, defined as sepsis with a diagnosis of acute organ dysfunction. Individuals who recovered enough to survive without acute dialysis were further analyzed. RESULTS: We identified 2983 individuals (mean age, 62 years; median follow-up, 3.96 years) with dialysis-requiring AKI and 11,932 matched controls. The incidence rate of severe sepsis was 6.84 and 2.32 per 100 person-years among individuals with dialysis-requiring AKI and without AKI in the index hospitalization, respectively. Dialysis-requiring AKI patients had a higher risk of developing de novo severe sepsis than the non-AKI group. In subgroup analysis, even individuals with recovery from dialysis-requiring AKI were at high risk of developing severe sepsis. CONCLUSIONS: AKI is an independent risk factor for severe sepsis. Even patients who recovered from AKI had a high risk of long-term severe sepsis.

The Worsening Renal Perfusion Index Predicts the Prognoses of Heart Failure Patients Treated with Sacubitril/Valsartan.

INTRODUCTION: Sacubitril/valsartan (S/V) reduces all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF), but it may decline their estimated glomerular filtration rates (eGFR). In addition to eGFR, this clinical study aimed to develop a blood urea nitrogen (BUN)-based index to evaluate the status of renal perfusion and then identify predictors of all-cause death or heart transplant in patients with HFrEF receiving S/V. METHODS: From the recruited 291 patients with HFrEF who were prescribed S/V from March 2017 to March 2019, we collected demographic, drug history, laboratory, echocardiographic, and clinical data from 1 year before S/V initiation until December 2020. Regression analysis was conducted by fitting Cox's models with time-dependent covariates for the survival time and applying the modern stepwise variable selection procedure. The smoothing spline method was used to detect nonlinearity in effect and yield optimal cut-off values for continuous covariates. RESULTS: In the Cox's model, decreased hemoglobin level, decreased mean left ventricular ejection fraction, declined daily dose of S/V, decreased eGFR within 3 months, and increased BUN levels within 1 month and 9 months over time were significantly associated with an increased risk of all-cause death or heart transplant in patients with HFrEF. CONCLUSIONS: Adequate maintenance of renal perfusion is crucial for the continuous use of S/V and to avoid worsening renal function in patients with HFrEF. We defined the maximum increase in BUN levels within a specified period as the Worsening Renal Perfusion Index (WRPSV Index) to capture the prognostic effect of renal hypoperfusion in patients with HFrEF.

Advanced age affects the outcome-predictive power of RIFLE classification in geriatric patients with acute kidney injury.

The RIFLE (risk, injury, failure, loss, and end-stage) classification is widely used to gauge the severity of acute kidney injury, but its efficacy has not been formally tested in geriatric patients. To correct this we conducted a prospective observational study in a multicenter cohort of 3931 elderly patients (65 years of age or older) who developed acute kidney injury in accordance with the RIFLE creatinine criteria after major surgery. We studied the predictive power of the RIFLE classification for in-hospital mortality and investigated the potential interaction between age and RIFLE classification. In general, the survivors were significantly younger than the nonsurvivors and more likely to have hypertension. In patients 76 years of age and younger, RIFLE-R, -I, or -F classifications were significantly associated with increased hospital mortality in a stepwise manner. There was no significant difference, however, in hospital mortality in those over 76 years of age between patients with RIFLE-R and RIFLE-I, although RIFLE-F patients had significantly higher mortality than both groups. Thus, the less severe categorizations of acute kidney injury per RIFLE classification may not truly reflect the adverse impact on elderly patients.