OBJECTIVE: To investigate the relationship between mean perfusion pressure (MPP) and the risk of sepsis-associated acute kidney injury (SA-AKI) and its prognosis, and to determine the optimal cut-off value of MPP for predicting SA-AKI. METHODS: A retrospective cohort study was conducted. The clinical data of adult patients with sepsis were collected from the Medical Information Mart for Intensive Care-IV 2.2 (MIMIC-IV 2.2) database. The patients were divided into two groups based on the occurrence of SA-AKI. Baseline characteristics, vital signs, comorbidities, laboratory indicators within 24 hours of intensive care unit (ICU) admission, and clinical outcome indicators were collected. Mean MPP was calculated using the average values of mean arterial pressure (MAP) and central venous pressure (CVP), MPP = MAP-CVP. Cox regression models were constructed, relevant confounding factors were adjusted, and multivariate Logistic regression analysis was used to investigate the associations between MPP and the risk of SA-AKI as well as ICU death. The predictive value of MPP for SA-AKI was evaluated using receiver operator characteristic curve (ROC curve) analysis, and the optimal cut-off value was determined. RESULTS: A total of 6 009 patients were ultimately enrolled in the analysis. Among them, SA-AKI occurred in 4 755 patients (79.13%), while 1 254 patients (20.87%) did not develop SA-AKI. Compared with the non-SA-AKI group, the MPP in the SA-AKI group was significantly lowered [mmHg (1 mmHg≈0.133 kPa): 62.00 (57.00, 68.00) vs. 65.00 (60.00, 70.00), P < 0.01], and the ICU mortality was significantly increased [11.82% (562/4 755) vs. 1.59% (20/1 254), P < 0.01]. Three Cox regression models were constructed: model 1 was unadjusted; model 2 was adjusted for gender, age, height, weight and race; model 3 was adjusted for gender, age, height, weight, race, heart rate, respiratory rate, body temperature, hemoglobin, platelet count, white blood cell count, anion gap, HCO₃^-, blood urea nitrogen, serum creatinine, Cl^-, Na⁺, K⁺, fibrinogen, international normalized ratio, blood lactic acid, pH value, arterial partial pressure of oxygen, arterial partial pressure of carbon dioxide, sequential organ failure assessment score, Charlson comorbidity index score, use of vasopressors, mechanical ventilation, and urine output. Multivariate Logistic regression analysis showed that when MPP was treated as a continuous variable, there was a negative correlation between MPP and the risk of SA-AKI in model 1 and model 2 [model 1: odds ratio (OR) = 0.967, 95% confidence interval (95%CI) was 0.961-0.974, P < 0.001; model 2: OR = 0.981, 95%CI was 0.974-0.988, P < 0.001], and also a negative correlation between MPP and the risk of ICU death (model 1: OR = 0.955, 95%CI was 0.945-0.965, P < 0.001; model 2: OR = 0.956, 95%CI was 0.946-0.966, P < 0.001). However, in model 3, there was no significant correlation between MPP and either SA-AKI risk or ICU death risk. when MPP was used as a multi-categorical variable, in model 1 and model 2, referring to MPP ≤ 58 mmHg, when 59 mmHg ≤ MPP ≤ 68 mmHg, as MPP increased, the risk of SA-AKI progressively decreased (OR value was 0.411-0.638, all P < 0.001), and the risk of ICU death also gradually decreased (OR value was 0.334-0.477, all P < 0.001). ROC curve showed that MPP had a certain predictive value for SA-AKI occurrence [area under the ROC curve (AUC) = 0.598, 95%CI was 0.404-0.746], and the optimal cut-off value was 60.5 mmHg. CONCLUSION MPP was significantly associated with the risk of SA-AKI, with an optimal cut-off value of 60.5 mmHg, and also demonstrated a significant correlation with the risk of ICU death.
Humans ; Acute Kidney Injury/physiopathology* ; Retrospective Studies ; Sepsis/physiopathology* ; Middle Aged ; Prognosis ; Male ; Female ; Aged ; Risk Factors ; Intensive Care Units ; Adult ; Logistic Models ; Proportional Hazards Models

OBJECTIVE: : To screen genes involved in mitochondrial DNA (mtDNA) damage repair in rats with septic acute kidney injury (SAKI). METHODS: : Forty male C57BL/6J mice were randomly divided into SAKI group (=28) and sham operation group (=12). The SAKI mouse model was established by cecal ligation and puncture. Blood and kidney samples were collected at 8, 24, and 48 h after surgery. Serum creatinine and urea nitrogen were measured by a dry biochemical analyzer. Serum inflammatory cytokines were detected by ELISA. Histopathological changes were observed with HE staining. The mtDNA damage repair related genes were screened by RNA sequencing and bioinformatics analysis; the mRNA and protein expression levels of related genes were detected by real-time quantitative RT-PCR and immunohistochemisry, respectively. RESULTS: : Symptoms of sepsis were observed in SAKI group, and 16 out of 28 mice were died in the SAKI group; serum TNF-α, IL-6, creatinine and urea nitrogen levels were higher than those in the sham group (<0.05 or <0.01). Histopathological examination in SAKI group showed that renal tubular epithelial cells were swollen, inflammatory cells infiltrated, and a large number of cell vacuoles were seen, suggesting successful modeling. Mitochondrial DNA damage repair related genes and were screened out. The expression of these genes was detected by real-time RT-PCR, and the results were consistent with RNA sequencing trends. Immunohistochemical staining showed that Gadd45α was mainly expressed in the nucleus of renal tubular epithelial cells, and the positive rate of Gadd45α in SAKI group was higher than that in the sham operation group (<0.05). CONCLUSIONS : and genes are involved in mtDNA damage repair in rats with SAKI, indicating that these genes may be used as new targets for prevention and treatment of SAKI.
Acute Kidney Injury ; physiopathology ; Animals ; Blood Urea Nitrogen ; Creatinine ; blood ; DNA Repair ; genetics ; DNA, Mitochondrial ; Male ; Mice ; Mice, Inbred C57BL ; Random Allocation ; Rats ; Sepsis ; physiopathology

OBJECTIVEContinuous renal replacement therapy (CRRT) is a continuous process of bedside blood purification which is widely used in the treatment of acute kidney injury (AKI) and for fluid management. However, since AKI and fluid overload are often found to be associated with hemodynamic abnormalities, determining the relationship between CRRT and hemodynamics remains a challenge in the treatment of critically ill patients. The aim of this review was to summarize key points in the relationship between CRRT and hemodynamics and to understand and monitor renal hemodynamics in critically ill patients, especially those with AKI.

DATA SOURCESThis review was based on data in articles published in the PubMed databases up to January 30, 2017, with the following keywords: "continuous renal replacement therapy," "Hemodynamics," and "Acute kidney injury."

STUDY SELECTIONOriginal articles and critical reviews on CRRT were selected for this review.

RESULTSCRRT might treat AKI by hemodynamic therapy, and it was an important form of hemodynamic therapy. The targets of hemodynamic therapy should be established when using CRRT. Therefore, hemodynamic management and stability were very important during CRRT. Most studies suggested that renal hemodynamics should be clearly identified.

CONCLUSIONSCRRT is not only a replacement for organ function, but an important form of hemodynamic therapy. Improved hemodynamic management of critically ill patients can be achieved by establishing specific therapeutic hemodynamic targets and maintaining circulatory stability during CRRT. Over the long term, observation of renal hemodynamics will provide greater opportunities for the progression of CRRT hemodynamic therapy.

Acute Kidney Injury ; physiopathology ; therapy ; Animals ; Female ; Hemodynamics ; physiology ; Humans ; Male ; Renal Dialysis ; methods ; Renal Replacement Therapy ; methods

Mushroom exposures are increasing worldwide. The incidence and fatality of mushroom poisoning are reported to be increasing. Several new syndromes in mushroom poisoning have been described. Rhabdomyolytic mushroom poisoning is one of new syndromes. Russula subnigricans mushroom can cause delayed-onset rhabdomyolysis with acute kidney injury in the severely poisoned patient. There are few reports on the toxicity of R. subnigricans. This report represents the first record of R. subnigricans poisoning with rhabdomyolysis in Korea, describing a 51-year-old man who suffered from rhabdomyolysis, acute kidney injury, severe hypocalcemia, respiratory failure, ventricular tachycardia, cardiogenic shock, and death. Mushroom poisoning should be considered in the evaluation of rhabdomyolysis of unknown cause. Furthermore, R. subnigricans should be considered in the mushroom poisoning with rhabdomyolysis.
Acute Kidney Injury/*etiology ; Basidiomycota/isolation & purification/*pathogenicity ; Electrocardiography ; Heart Ventricles/physiopathology ; Humans ; Male ; Middle Aged ; Mushroom Poisoning/*diagnosis/microbiology/mortality ; Rhabdomyolysis/*etiology ; Shock, Cardiogenic/*etiology ; Tachycardia, Ventricular/etiology

OBJECTIVETo investigate the epidemiological profile of acute kidney injury (AKI) in the Chinese critical patients.

METHODSThe hospitalization data and serum creatinine data of critically ill adult patients were collected from 9 regional central hospitals across China in 2013. Kidney Disease Improving Global Outcomes (KDIGO 2012) criteria was used to define and stage AKI. The demographic characteristics of the patients, comorbidities, stage of AKI, in-hospital outcomes and risk factors were retrospectively analyzed.

RESULTSOf the total of 14 305 critically ill patients included in the study, 4298 (30.04%) were identified to have AKI, including 2240 (52.1%) in stage 1, 845 (19.7%) in stage 2, and 1213 (28.2%) in stage 3. The in-hospital mortality rate was 16.7% (716/4298) and the odds ratio for death was 7.59 (95%CI 6.54-8.79, P<0.001). The length of hospital stay, daily cost, and mortality rate were associated with the stage of AKI. Multivariate analysis identified chronic kidney disease (OR=5.45, 95%CI: 4.71-6.32, P<0.001), extra-renal organ failure (OR=12.57, 95%CI: 11.24-14.07, P<0.001), shock (OR=2.44, 95%CI: 2.01-2.96, P<0.001) and cardiac surgery (OR=5.96, 95%CI: 5.16-6.87, P<0.001) as the independent risk factors for AKI. Only 5.4% of the AKI patients whose serum creatinine change met the KDIGO criteria during hospitalization received the diagnosis of AKI upon discharge.

CONCLUSIONAKI is common in critically ill patients and associated with high mortality rates and poor outcomes. The stage of AKI is related with the in-hospital outcomes of the patients. Chronic kidney disease, extra-renal organ failure, shock and cardiac surgery are the major risk factors for AKI in these patients. Missed diagnosis occurs in most of the AKI cases, which urges more awareness of the condition in the critically ill patients during hospitalization.

Acute Kidney Injury ; epidemiology ; Adult ; Cardiac Surgical Procedures ; China ; Critical Illness ; Hospital Mortality ; Humans ; Kidney ; physiopathology ; Kidney Function Tests ; Length of Stay ; Multiple Organ Failure ; epidemiology ; Odds Ratio ; Renal Insufficiency, Chronic ; epidemiology ; Retrospective Studies ; Risk Factors ; Shock ; epidemiology

OBJECTIVETo investigate the effects of dexmedetomidine on inflammatory reaction, oxidative stress, and renal pathologies in a rat model of lipopolysaccharide (LPS)-induced sepsis.

METHODSThirty-two SD rats were randomly divided into 4 groups, including a sham-operated group, LPS group with LPS (5 mg/kg) injection via the caudal vein 30 min before the operation, dexmedetomidine (Dex) +LPS group with additional Dex (10 µg/kg) injection via the caudal vein 10 min before LPS injection, and yohimbine+DEX+LPS group with intraperitoneal yohimbine (1 mg/kg) injection 40 min before and Dex injection 10 min before LPS injection. The levels of IL-1β, SOD and MDA in the plasma and renal tissues were determined, and the renal pathologies were examined.

RESULTSCompared with the sham-operated rats, the rats in LPS group showed significantly increased IL-1β and MDA levels and lowered SOD activity in the plasma and renal tissues (P<0.05) with obvious renal pathologies. Dex pretreatment obviously lowered IL-1β and MDA levels and enhanced SOD activity in the plasma and renal tissues in LPS-challenged rats (P<0.05), and significantly lessened LPS-induced renal pathologies.

CONCLUSIONDex can protect the rats against LPS-induced renal injury by alleviating the inflammatory reactions and cytokine oxidative stress, and this effect is mediated possibly by α2 receptors.

Acute Kidney Injury ; drug therapy ; Animals ; Dexmedetomidine ; pharmacology ; Inflammation ; drug therapy ; Interleukin-1beta ; metabolism ; Kidney ; drug effects ; physiopathology ; Lipopolysaccharides ; Malondialdehyde ; metabolism ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Sepsis ; chemically induced ; drug therapy ; Superoxide Dismutase ; metabolism

BACKGROUND/AIMS: The potential physiologic roles of Klotho in acute kidney injury (AKI) have recently been demonstrated in animal models. However, to date, there have been no human studies investigating the expression of renal Klotho in AKI. METHODS: We retrospectively collected biopsy specimens and clinical data of AKI patients between January 2001 and December 2012. Klotho expression was determined by immunohistochemical staining, and the clinical-pathological correlation was examined. RESULTS: Among the 34 patients diagnosed with acute tubular necrosis or acute tubulointerstitial nephritis, 21 patients without chronic histological lesions were included. The mean age was 37.3 +/- 18.5 years and the mean peak creatinine level was 8.2 +/- 5.5 mg/dL. In total, 10 patients (47.6%) received temporary renal replacement therapy (RRT); however, 17 patients (81%) showed functional recovery with creatinine levels of < 1.3 mg/dL after 1 month. The intensity of Klotho expression was scored as a percentage of Klotho-positive area. The renal Klotho score showed a significant negative correlation with the initial or peak creatinine level. When the patients were divided into three groups according to the Klotho score (low, middle, high), the low group had a significantly higher peak creatinine level and a more frequent requirement for RRT. However, the Klotho score was not a significant predictor of renal recovery. CONCLUSIONS: The results demonstrated that renal Klotho expression in humans decreased significantly according to the severity of AKI, regardless of the etiology, and that low expression was associated with a poor short-term outcome.
Acute Kidney Injury/diagnosis/etiology/*metabolism/physiopathology/therapy ; Adolescent ; Adult ; Biomarkers/analysis ; Biopsy ; Down-Regulation ; Female ; Glucuronidase/*analysis ; Humans ; Immunohistochemistry ; Kidney/*chemistry/pathology/physiopathology ; Kidney Tubular Necrosis, Acute/diagnosis/etiology/*metabolism/physiopathology/therapy ; Male ; Middle Aged ; Necrosis ; Predictive Value of Tests ; Recovery of Function ; Renal Replacement Therapy ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Time Factors ; Treatment Outcome ; Young Adult

Some cases of Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) infection presented renal function impairment after the first MERS-CoV patient died of progressive respiratory and renal failure. Thus, MERS-CoV may include kidney tropism. However, reports about the natural courses of MERS-CoV infection in terms of renal complications are scarce. We examined 30 MERS-CoV patients admitted to National Medical Center, Korea. We conducted a retrospective analysis of the serum creatinine (SCr), estimated glomerular filtration rate (eGFR), urine dipstick tests, urinary protein quantitation (ACR or PCR), and other clinical parameters in all patients. Two consecutive results of more than trace (or 1+) of albumin and blood on dipstick test occurred in 18 (60%) (12 [40%]) and 22 (73.3%) (19 [63.3%]) patients, respectively. Fifteen (50.0%) patients showed a random urine ACR or PCR more than 100 mg/g Cr. Eight (26.7%) patients showed acute kidney injury (AKI), and the mean and median durations to the occurrence of AKI from symptom onset were 18 and 16 days, respectively. Old age was associated with a higher occurrence of AKI in the univariate analysis (HR [95% CI]: 1.069 [1.013-1.128], P = 0.016) and remained a significant predictor of the occurrence of AKI after adjustment for comorbidities and the application of a mechanical ventilator. Diabetes, AKI, and the application of a continuous renal replacement therapy (CRRT) were risk factors for mortality in the univariate analysis (HR [95% CI]: diabetes; 10.133 [1.692-60.697], AKI; 12.744 [1.418-114.565], CRRT; 10.254 [1.626-64.666], respectively). Here, we report renal complications and their prognosis in 30 Korean patients with MERS-CoV.
Acute Kidney Injury/*etiology/mortality/therapy ; Adult ; Aged ; Coronavirus Infections/*complications/physiopathology ; Creatinine/blood ; Female ; Glomerular Filtration Rate ; Hematuria/etiology ; Hospitals ; Humans ; Male ; Middle Aged ; Prognosis ; Proteinuria/etiology ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Factors

Acute kidney injury (AKI) and chronic kidney disease (CKD) are major health problems. Urinary biomarkers have both diagnostic and prognostic utility in AKI and CKD. However, how biomarker excretion rates should be reported, especially whether they should be normalised to urinary creatinine concentration (uCr), is controversial. Some studies suggest that normalisation to uCr may be inappropriate at times, as urinary creatinine excretion rate may vary greatly, depending on the situation. Notably, recent studies suggest that while normalisation of values to UCr may be valid for the evaluation of CKD and prediction of AKI sequelae and occurrences, it could be inappropriate for the diagnosis of AKI, or in the presence of certain acute kidney disease states.
Acute Kidney Injury ; urine ; Biomarkers ; urine ; Creatinine ; urine ; Glomerular Filtration Rate ; Humans ; Kidney ; physiopathology ; Nephrology ; methods ; standards ; Renal Insufficiency, Chronic ; urine ; Treatment Outcome ; Urinalysis ; standards

OBJECTIVETo investigate the risk factors for and the prognosis of acute kidney injury (AKI) in decompensated cirrhotic patients.

METHODSA total of 126 patients with decompensated cirrhosis and with (n =60) or without (n =66, control group) AKI were enrolled in this retrospective analysis. Follow-up was carried out on all patients, with durations ranging from less than 1 year to up to 4 years. Blood biochemistry, liver and renal functional parameters and prognosis of these patients were recorded. Logistic regression analysis was used to evaluate possible risk factors for decompensated cirrhotic patients developing AKI.

RESULTSThe patients with AKI had a significantly lower survival rate than the patients without AKI (55.0% vs.83.3%, x2 =13.270, p =0.001). Unconditional multivariate logistic regression analysis identified risk factors of AKI development in decompensated cirrhotic patients as increased serum creatinine (odds ratio (OR):1034), increased total bilirubin (OR:1.005), increased international normalized ratio (INR; OR:2.471), decreased plasma sodium concentration (OR:0.910), decreased serum cholinesterase (OR:0.999), and decreased glomerular filtration rate (GFR; OR:0.972) (all P less than 0.05).

CONCLUSIONThe development of acute kidney injury represents an adverse prognosis in decompensated cirrhotic patients. An increase in serum creatinine, total bilirubin or INR or a decrease in plasma sodium concentration, serum cholinesterase or GFR may be early-warning factors of development of AKI in decompensated cirrhotic patients.

Acute Kidney Injury ; diagnosis ; etiology ; Adult ; Case-Control Studies ; Female ; Humans ; Kidney Function Tests ; Liver Cirrhosis ; complications ; physiopathology ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Risk Factors