Urinary calprotectin and the distinction between prerenal and intrinsic acute kidney injury

Summary

Background and objectives

To date there is no reliable marker for the differentiation of prerenal and intrinsic acute kidney injury (AKI). We investigated whether urinary calprotectin, a mediator protein of the innate immune system, may serve as a diagnostic marker in AKI.

Design, setting, participants, & measurements

This was a cross-sectional study with 101 subjects including 86 patients with AKI (34 prerenal, 52 intrinsic including 23 patients with urinary tract infection) and 15 healthy controls. Assessment of urinary calprotectin concentration was by ELISA and immunohistochemistry of kidney biopsy specimens using a calprotectin antibody. Inclusion criteria were: admission to hospital for AKI stage 1 to 3 (Acute Kidney Injury Network); exclusion criteria were: prior renal transplantation and obstructive uropathy.

Results

Median urinary calprotectin was 60.7 times higher in intrinsic AKI (1692 ng/ml) than in prerenal AKI (28 ng/ml, p <0.01). Urinary calprotectin in prerenal disease was not significantly different from healthy controls (45 ng/ml, p = 0.25). Receiver operating curve curve analysis revealed a high accuracy of calprotectin (area under the curve, 0.97) in predicting intrinsic AKI. A cutoff level of 300 ng/ml provided a sensitivity of 92.3% and a specificity of 97.1%. Calculating urinary calprotectin/creatinine ratios did not lead to a further increase of accuracy. Immunostainings of kidney biopsies were positive for calprotectin in intrinsic AKI and negative in prerenal AKI.

Conclusions

Accuracy of urinary calprotectin in the differential diagnosis of AKI is high. Whereas calprotectin levels in prerenal disease are comparable with healthy controls, intrinsic AKI leads to highly increased calprotectin concentrations.     

Acute kidney injury episodes and chronic kidney disease risk in diabetes mellitus

Summary

Background and objectives

Prior studies have examined long-term outcomes of a single acute kidney injury (AKI) event in hospitalized patients. We examined the effects of AKI episodes during multiple hospitalizations on the risk of chronic kidney disease (CKD) in a cohort with diabetes mellitus (DM).

Design, setting, participants, & measurements

A total of 4082 diabetics were followed from January 1999 until December 2008. The primary outcome was reaching stage 4 CKD (GFR of <30 ml/min per 1.73 m²). AKI during hospitalization was defined as >0.3 mg/dl or a 1.5-fold increase in creatinine relative to admission. Cox survival models examined the effect of first AKI episode and up to three episodes as time-dependent covariates, on the risk of stage 4 CKD. Covariates included demographic variables, baseline creatinine, and diagnoses of comorbidities including proteinuria.

Results

Of the 3679 patients who met eligibility criteria (mean age = 61.7 years [SD, 11.2]; mean baseline creatinine = 1.10 mg/dl [SD, 0.3]), 1822 required at least one hospitalization during the time under observation (mean = 61.2 months [SD, 25]). Five hundred thirty of 1822 patients experienced one AKI episode; 157 of 530 experienced ≥2 AKI episodes. In multivariable Cox proportional hazards models, any AKI versus no AKI was a risk factor for stage 4 CKD (hazard ratio [HR], 3.56; 95% confidence interval [CI], 2.76, 4.61); each AKI episode doubled that risk (HR, 2.02; 95% CI, 1.78, 2.30).

Conclusions

AKI episodes are associated with a cumulative risk for developing advanced CKD in diabetes mellitus, independent of other major risk factors of progression.     

Relationship between acute kidney injury before thoracic endovascular aneurysm repair and in-hospital outcomes in patients with type B acute aortic dissection

Objective Acute kidney injury (AKI) frequently occurs after catheter-based interventional procedures and increases mortality. However, the implications of AKI before thoracic endovascular aneurysm repair (TEVAR) of type B acute aortic dissection (AAD) remain unclear. This study evaluated the incidence, predictors, and in-hospital outcomes of AKI before TEVAR in patients with type B AAD. Methods Between 2009 and 2013, 76 patients were retrospectively evaluated who received TEVAR for type B AAD within 36 h from symptom onset. The patients were classified into no-AKI vs. AKI groups, and the severity of AKI was further staged according to kidney disease: improving global outcomes criteria before TEVAR. Results The incidence of preoperative AKI was 36.8%. In-hospital complications was significantly higher in patients with preoperative AKI compared with no-AKI (50.0% vs. 4.2%, respectively; P < 0.001), including acute renal failure (21.4% vs. 0, respectively; P < 0.001), and they increased with severity of AKI (P < 0.001). The maximum levels of body temperature and white blood cell count were significantly related to maximum serum creatinine level before TEVAR. Multivariate analysis showed that systolic blood pressure on admission (OR: 1.023; 95% CI: 1.003–1.044; P = 0.0238) and bilateral renal artery involvement (OR: 19.076; 95% CI: 1.914–190.164; P = 0.0120) were strong predictors of preoperative AKI. Conclusions Preoperative AKI frequently occurred in patients with type B AAD, and correlated with higher in-hospital complications and enhanced inflammatory reaction. Systolic blood pressure on admission and bilateral renal artery involvement were major risk factors for AKI before TEVAR.     

Risk of poor outcomes with novel and traditional biomarkers at clinical AKI diagnosis

Summary

Background and objectives

Studies have evaluated acute kidney injury (AKI) using biomarkers in various settings, but their prognostic utility within current practice is unclear. Thus, we sought to determine the prognostic utility of newer biomarkers or traditional markers (fractional excretion of sodium [FeNa] and urea [FeUrea] and microscopy) over clinical assessment alone.

Design, setting, participants, & measurements

This is a prospective cohort study of adults on the first day of meeting AKI criteria. We measured urine concentrations of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and IL-18 and determined FeNa, FeUrea, and microscopy score for casts and tubular cells. Primary outcome was worsened AKI stage from enrollment to peak serum creatinine or in-hospital death.

Results

In 249 recipients, 57% were ≥65 years old, 48% were from intensive care, and mean baseline GFR was 69 ± 30 ml/min per 1.73 m². AKI was considered prerenal in 164 (66%), acute tubular necrosis (ATN) in 51 (20%), and “other” in 34 (14%). All mean protein biomarker concentrations, FeNa, FeUrea, and microscopy scores were statistically different between prerenal and ATN. Seventy-two patients (29%) developed the primary outcome. There was an approximate three-fold increase in adjusted risk for the outcome for upper versus lower values of NGAL, KIM-1, IL-18, and microscopy score (P values <0.05). Net reclassification improved after adding these to baseline clinical assessment. FeNa and FeUrea were not useful.

Conclusions

On the first day of AKI, urine protein biomarkers and microscopy significantly improve upon clinical determination of prognosis, indicating their potential utility in current practice.     

HMG–CoA Reductase Activation and Urinary Pellet Cholesterol Elevations in Acute Kidney Injury

Summary

Background and objectives

Experimental acute kidney injury (AKI) activates the HMG–CoA reductase (HMGCR) gene, producing proximal tubule cholesterol loading. AKI also causes sloughing of proximal tubular cell debris into tubular lumina. This study tested whether these two processes culminate in increased urinary pellet cholesterol content, and whether the latter has potential AKI biomarker utility.

Design, setting, participants, & measurements

Urine samples were collected from 29 critically ill patients with (n = 14) or without (n= 15) AKI, 15 patients with chronic kidney disease, and 15 healthy volunteers. Centrifuged urinary pellets underwent lipid extraction, and the extracts were assayed for cholesterol content (factored by membrane phospholipid phosphate content). In vivo HMGCR activation was sought by measuring levels of RNA polymerase II (Pol II), and of a gene activating histone mark (H3K4m3) at exon 1 of the HMGCR gene (chromatin immunoprecipitation assay of urine chromatin samples).

Results

AKI+ patients had an approximate doubling of urinary pellet cholesterol content compared with control urine samples (versus normal; P < 0.001). The values significantly correlated (r, 0.5; P < 0.01) with serum, but not urine, creatinine concentrations. Conversely, neither critical illness without AKI nor chronic kidney disease raised pellet cholesterol levels. Increased HMGCR activity in the AKI+ patients was supported by three- to fourfold increased levels of Pol II, and of H3K4m3, at the HMGCR gene (versus controls or AKI− patients).

Conclusions

(1) Clinical AKI, like experimental AKI, induces HMGCR gene activation; (2) increased urinary pellet cholesterol levels result; and (3) urine pellet cholesterol levels may have potential AKI biomarker utility. The latter will require future testing in a large prospective trial.     

Perioperative hyperglycemia and postoperative infection after lower limb arthroplasty

Background

One of the most serious complications after major orthopedic surgery is deep wound or periprosthetic joint infection. Various risk factors for infection after hip and knee replacement surgery have been reported, including patients'' comorbidities and surgical technique factors. We investigated whether hyperglycemia and diabetes mellitus (DM) are associated with infection that requires surgical intervention after total hip and knee arthroplasty.

Methods

We reviewed our computerized database for elective primary total hip and knee arthroplasty from 2000 to 2008. Demographic information, past medical history of patients, perioperative biochemistry, and postoperative complications were reviewed.Patients were divided into two groups: infected group (101 patients who had surgical intervention for infection at our institution within 2 years after primary surgery) and noninfected group (1847 patients with no intervention with a minimum of one year follow-up. The data were analyzed using t, chi-squared, and Fisher''s exact tests.

Results

There were significantly more diabetes patients in the infected group compared with the noninfected group (22% versus 9%, p < .001). Infected patients had significantly higher perioperative blood glucose (BG) values: preoperative BG (112 ± 36 versus 105 ± 31 mg/dl, p = .043) and postoperative day (POD) 1 BG (154 ± 37 versus 138 ± 31 mg/dl, p < .001). Postoperative morning hyperglycemia (BG >200 mg/dl) increased the risk for the infection more than two-fold. Non-DM patients were three times more likely to develop the infection if their morning BG was >140 mg/dl on POD 1, p = .001. Male gender, higher body mass index, knee arthroplasty, longer operative time and hospital stay, higher comorbidity index, history of myocardial infarction, congestive heart failure, and renal insufficiency were also associated with the infection.

Conclusions

Diabetes mellitus and morning postoperative hyperglycemia were predictors for postoperative infection following total joint arthroplasty. Even patients without a diagnosis of DM who developed postoperative hyperglycemia had a significantly increased risk for the infection.     

Circulating erythrocyte-derived microparticles are associated with coagulation activation in sickle cell disease

Background

Sickle cell disease is characterized by a hypercoagulable state as a result of multiple factors, including chronic hemolysis and circulating cell-derived microparticles. There is still no consensus on the cellular origin of such microparticles and the exact mechanism by which they may enhance coagulation activation in sickle cell disease.

Design and Methods

In the present study, we analyzed the origin of circulating microparticles and their procoagulant phenotype during painful crises and steady state in 25 consecutive patients with sickle cell disease.

Results

The majority of microparticles originated from platelets (GPIIIa,CD61) and erythrocytes (glycophorin A,CD235), and their numbers did not differ significantly between crisis and steady state. Erythrocyte-derived microparticles strongly correlated with plasma levels of markers of hemolysis, i.e. hemoglobin (r=−0.58, p<0.001) and lactate dehydrogenase (r=0.59, p<0.001), von Willebrand factor as a marker of platelet/endothelial activation (r=0.44, p<0.001), and D-dimer and prothrombin fragment F1+2 (r=0.52, p<0.001 and r=0.59, p<0.001, respectively) as markers of fibrinolysis and coagulation activation. Thrombin generation depended on the total number of microparticles (r=0.63, p<0.001). Anti-human factor XI inhibited thrombin generation by about 50% (p<0.001), whereas anti-human factor VII was ineffective (p>0.05). The extent of factor XI inhibition was associated with erythrocyte-derived microparticles (r=0.50, p=0.023).

Conclusions

We conclude that the procoagulant state in sickle cell disease is partially explained by the factor XI-dependent procoagulant properties of circulating erythrocyte-derived microparticles.     

Assessment of KDIGO Definitions in Patients with Histopathologic Evidence of Acute Renal Disease

Background and objectives

AKI is a clinical syndrome with various causes involving glomerular, interstitial, tubular, and vascular compartments of the kidney. Acute kidney disease (AKD) is a new concept that includes both AKI and the conditions associated with subacute decreases in GFR (AKD/non-AKI). This study aimed to investigate the correlation between AKI/AKD defined by clinical presentation and diffuse histologic criteria for acute abnormalities based on renal biopsy.

Design, setting, participants, & measurements

All 303 patients who were histologically diagnosed as having acute tubular necrosis (ATN), acute tubulointerstitial nephritis, cellular crescentic GN, acute thrombotic microangiopathy, or complex lesions on renal biopsy from January 2009 to December 2011 were enrolled in the study. The 2012 Kidney Disease Improving Global Outcomes AKD/AKI definitions were applied to classify patients as follows: AKI, AKD/non-AKI, non-AKD, or unclassified.

Results

A total of 273 patients (90.1%) met the AKD criteria; 198 patients (65.3%) were classified as having AKI according to serum creatinine (SCr) and urine output criteria. The urine output criteria added 4.3% to the SCr criteria and reclassified 6.7% of the AKI cases into higher stages. Of patients with ATN on pathology, 79.2% met AKI criteria; this was a higher percentage than for those who had other individual pathologic lesions (50%–64%). The major cause of not being defined as having AKI was a slower SCr increase than that required by the definition of AKI (98, 93.3%). Patients with AKI had more severe clinical conditions and worse short-term renal outcome than those in the non-AKI group.

Conclusions

Diffuse, acute abnormality defined by renal biopsy and AKI defined by clinical presentation are two different entities. Most patients who have diffuse acute histologic findings met the criteria for AKD, whereas only two thirds met the definition of AKI.     

Plasma Catalytic Iron,AKI, and Death among Critically Ill Patients

Background and objectives

Catalytic iron has been hypothesized to be a key mediator of AKI. However, the association between plasma catalytic iron levels and AKI has not been well studied in humans.

Design, settings, participants, & measurements

A single-center, prospective, nonconsecutive cohort study of 121 critically ill patients admitted to intensive care units (ICUs) between 2008 and 2012 was performed. Plasma catalytic iron, free hemoglobin, and other iron markers were measured on ICU days 1 and 4. The primary end point was in-hospital mortality or AKI requiring RRT. Secondary end points included mortality (assessed during hospitalization, at 30 days, and 1 year) and incident AKI, defined by modified Kidney Disease Improving Global Outcomes criteria.

Results

ICU day 1 plasma catalytic iron levels were higher among patients who reached the primary end point (median, 0.74 µmol/l [interquartile range, 0.31–3.65] versus 0.29 µmol/l [0.22–0.46]; P<0.01). ICU day 1 plasma catalytic iron levels were associated with number of packed red blood cell transfusions before ICU arrival (r_s=0.29; P<0.001) and plasma free hemoglobin levels on ICU day 1 (r_s=0.32; P<0.001). Plasma catalytic iron levels on ICU day 1 were significantly associated with in-hospital mortality or AKI requiring RRT, even after adjusting for age, enrollment eGFR, and number of packed red blood cell transfusions before ICU arrival (13 events; adjusted odds ratio per 1-SD higher ln[catalytic iron], 3.33; 95% confidence interval, 1.79 to 6.20). ICU day 1 plasma catalytic iron levels were also significantly associated with incident AKI, RRT, hospital mortality, and 30-day mortality.

Conclusions

Among critically ill patients, elevated plasma catalytic iron levels on arrival to the ICU are associated with a greater risk of incident AKI, RRT, and hospital mortality.     

Is cardiac resynchronisation therapy (CRT) safe, feasible and beneficial in the very elderly?

Objective To evaluate whether cardiac resynchronisation therapy (CRT) implantation was feasible and safe in octogenarians and the association with symptoms. Methods Consecutive patients undergoing CRT implantation were recruited from two UK centers. Patients grouped according to age: < 80 & ≥ 80 years. Baseline demographics, complications and outcomes were compared between those groups. Results A total of 439 patients were included in this study, of whom 26% were aged ≥ 80 years. Octogenarians more often received cardiac resynchronization therapy pacemaker in comparison to cardiac resynchronisation therapy-defibrillator. Upgrade from pacemaker was common in both groups (16% < 80 years vs. 22% ≥ 80 years, P = NS). Co-morbidities were similarly common in both groups (overall diabetes: 25%, atrial fibrillation: 23%, hypertension: 45%). More patient age ≥ 80 years had significant chronic kidney disease (CKD, estimated glomerular filtration rate < 45 mL/min per 1.73m2, 44% vs. 22%, P < 0.01). Overall complication rates (any) were similar in both groups (16% vs. 17%, P = NS). Both groups demonstrated symptomatic benefit. One-year mortality rates were almost four fold greater in octogenarians as compared with the younger cohort (13.9% vs. 3.7%, P < 0.01). Conclusions CRT appears to be safe in the very elderly despite extensive co-morbidity, and in particular frequent severe CKD. Symptomatic improvement appears to be meaningful. Strategies to increase the appropriate identification of elderly patients with CHF who are potential candidates for CRT are required.     

An initial study on left ventricular diastolic function in patients with hypertrophy cardiomyopathy using single-beat, real-time, three-dimensional echocardiography

Objectives To assess the regional diastolic function in patients with hypertrophic cardiomyopathy (HCM) by using single-beat, real-time, three-dimensional echocardiography (RT-3DE). Methods Sixty-five patients with HCM in sinus rhythm together with fifty age- and gender-matched normal controls were studied by two–dimensional echocardiography (2DE) and RT-3DE. The parameters analyzed by RT-3DE included: left ventricular (LV) volumes, left ventricular ejection fraction (LVEF), end diastolic sphericity index (EDSI), diastolic dyssynchrony index (DDI), dispersion end diastole (DISPED), and normalized 17 segmental volume-time curves. Results LVEF was slightly lower evaluated by RT-3DE compared with 2DE (63.2 ± 6.8% vs. 59.1 ± 6.4%, P < 0.0001). Normal subjects had relatively uniform volumetric curves for all LV segments. In HCM patients, the segmental volumetric curves were dyssynchronous. Increased DDI and DISPED in end diastole were observed in patients with HCM (9.95 ± 3.75, 41.76 ± 17.19, P < 0.0001), not all abnormal volumetric segments occurred in the hypertrophic regions. Conclusions Patients with HCM have presented regional diastolic dyssynchrony in the diastole phase, and this preclinical lesion can be recognized by single-beat RT-3DE.     

Acute Respiratory Distress Syndrome and Risk of AKI among Critically Ill Patients

Background and objectives

Increasing experimental evidence suggests that acute respiratory distress syndrome (ARDS) may promote AKI. The primary objective of this study was to assess ARDS as a risk factor for AKI in critically ill patients.

Design, setting, participants, & measurements

This was an observational study on a prospective database fed by 18 intensive care units (ICUs). Patients with ICU stays >24 hours were enrolled over a 14-year period. ARDS was defined using the Berlin criteria and AKI was defined using the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease criteria. Patients with AKI before ARDS onset were excluded.

Results

This study enrolled 8029 patients, including 1879 patients with ARDS. AKI occurred in 31.3% of patients and was more common in patients with ARDS (44.3% versus 27.4% in patients without ARDS; P<0.001). After adjustment for confounders, both mechanical ventilation without ARDS (odds ratio [OR], 4.34; 95% confidence interval [95% CI], 3.71 to 5.10) and ARDS (OR, 11.01; 95% CI, 6.83 to 17.73) were independently associated with AKI. Hospital mortality was 14.2% (n=1140) and was higher in patients with ARDS (27.9% versus 10.0% in patients without ARDS; P<0.001) and in patients with AKI (27.6% versus 8.1% in those without AKI; P<0.001). AKI was associated with higher mortality in patients with ARDS (42.3% versus 20.2%; P<0.001).

Conclusions

ARDS was independently associated with AKI. This study suggests that ARDS should be considered as a risk factor for AKI in critically ill patients.     

Moving Forward in GME Reform: A 4 + 1 Model of Resident Ambulatory Training

BACKGROUND

Traditional ambulatory training models have limitations in important domains, including opportunities for residents to learn, fragmentation of care delivery experience, and satisfaction with ambulatory experiences. New models of ambulatory training are needed.

AIM

To compare the impact of a traditional ambulatory training model with a templated 4 + 1 model.

SETTING

A large university-based internal medicine residency using three different training sites: a patient-centered medical home, a hospital-based ambulatory clinic, and community private practices.

PARTICIPANTS

Residents, faculty, and administrative staff.

PROGRAM DESCRIPTION

Development of a templated 4 + 1 model of residency where trainees do not attend to inpatient and outpatient responsibilities simultaneously.

PROGRAM EVALUATION

A mixed-methods analysis of survey and nominal group data measuring three primary outcomes: 1) Perception of learning opportunities and quality of faculty teaching; 2) Reported fragmentation of care delivery experience; 3) Satisfaction with ambulatory experiences. Self-reported empanelment was a secondary outcome. Residents’ learning opportunities increased (p = 0.007) but quality of faculty teaching was unchanged. Participants reported less fragmentation in the care residents provide patients in the inpatient and outpatient setting (p < 0.0001). Satisfaction with ambulatory training improved (p < 0.0001). Self-reported empanelment also increased (p < 0.0001). Results held true for residents, faculty, and staff at all three ambulatory training sites (p < 0.0001).

DISCUSSION

A 4 + 1 model increased resident time in ambulatory continuity clinic, enhanced learning opportunities, reduced fragmentation of care residents provide, and improved satisfaction with ambulatory experiences. More studies of similar models are needed to evaluate effects on additional trainee and patient outcomes.

Electronic supplementary material

The online version of this article (doi:10.1007/s11606-013-2387-3) contains supplementary material, which is available to authorized users.KEY WORDS: ambulatory training, 4 + 1 model     

Working with Patients with Alcohol Problems: A Controlled Trial of the Impact of a Rich Media Web Module on Medical Student Performance

INTRODUCTION/AIMS

We designed an interactive web module to improve medical student competence in screening and interventions for hazardous drinking. We assessed its impact on performance with a standardized patient (SP) vs. traditional lecture.

SETTING

First year medical school curriculum.

PROGRAM DESCRIPTION

The web module included pre/posttests, Flash©, and text didactics. It centered on videos of two alcohol cases, each contrasting a novice with an experienced physician interviewer. The learner free-text critiqued each clip then reviewed expert analysis.

PROGRAM EVALUATION

First year medical students conveniently assigned to voluntarily complete a web module (N = 82) or lecture (N = 81) were rated by a SP in a later alcohol case. Participation trended higher (82% vs. 72%, p < .07) among web students, with an additional 4 lecture-assigned students crossing to the web module. The web group had higher mean scores on scales of individual components of brief intervention (assessment and decisional balance) and a brief intervention composite score (1–13 pt.; 9 vs. 7.8, p < .02) and self-reported as better prepared for the SP case.

CONCLUSIONS

A web module for alcohol use interview skills reached a greater proportion of voluntary learners and was associated with equivalent overall performance scores and higher brief intervention skills scores on a standardized patient encounter.KEY WORDS: health education, alcohol use disorders/alcoholism, Internet, multimedia learning     

Validation of the Kidney Disease Improving Global Outcomes Criteria for AKI and Comparison of Three Criteria in Hospitalized Patients

Background and objectives

AKI is a major clinical problem and predictor of outcome in hospitalized patients. In 2013, the Kidney Disease: Improving Global Outcomes (KDIGO) group published the third consensus AKI definition and classification system after the Risk, Injury, Failure, Loss of Kidney Function, and End-Stage Kidney Disease (RIFLE) and the Acute Kidney Injury Network (AKIN) working group systems. It is unclear which system achieves optimal prognostication in hospital patients.

Design, setting, participants, & measurements

A retrospective observational study using hospital laboratory, admission, and discharge databases was performed that included adult patients admitted to a teaching hospital in Tokyo, Japan between April 1, 2008, and October 31, 2011. AKI occurring during each hospital stay was identified, and discriminative ability of each AKI classification system based on serum creatinine for the prediction of hospital mortality was assessed. The receiver operating characteristic curve, a graphical measure of test performance, and the area under the curve were used to evaluate how classifications preformed on the study population.

Results

In total, 49,518 admissions were studied, of which 11.0% were diagnosed with RIFLE criteria and 11.6% were diagnosed with KDIGO criteria, but only 4.8% were diagnosed with AKIN criteria. Overall hospital mortality was 3.0%. AKI staging and hospital mortality were closely correlated in all systems. Discrimination for hospital mortality was similar for RIFLE and KDIGO criteria (area under the curve=0.77 versus 0.78; P=0.02), whereas AKIN discrimination was inferior (area under the curve=0.69 versus RIFLE [P<0.001] versus KDIGO [P<0.001]).

Conclusion

Among hospital patients, KDIGO and RIFLE criteria achieved similar discrimination, but the discrimination of AKIN was inferior.     

Irreversible electroporation of the pancreas in swine: a pilot study

Background:

Irreversible electroporation (IRE) is a novel, non-thermal method of tissue ablation using short pulses of high-voltage DC current to ablate tissue.

Methods:

Irreversible electroporation of the pancreas was performed in four domestic female swine using two monopolar probes spaced 9–15 mm apart. Ninety pulses of 1500 V/cm were delivered for each ablation.

Results:

All animals survived for their designated times of 2 h (n= 1), 2 days (n= 1) and 14 days (n= 2), respectively. No procedure-related complications occurred. Three animals in which probes had been spaced at intervals of 10 ± 1 mm showed evidence of irreversible ablation, with ablation height ranging from <10 mm to 21 mm and ablation width ranging from <10 mm to 16 mm by gross appearance and triphenyltetrazolium chloride (TTC) staining. The only animal in which probes had been spaced at intervals of 15 mm did not show evidence of irreversible ablation at 2 weeks. This may be secondary to the wider probe spacing and relatively low voltage, which results in a mostly reversible form of electroporation without cell death.

Conclusions:

Irreversible electroporation appears to be a safe method for pancreas tissue ablation. Staining with TTC can predict the zone of IRE ablation within 2 h of treatment.     

AKI in Hospitalized Children: Comparing the pRIFLE,AKIN, and KDIGO Definitions

Background and objectives

Although several standardized definitions for AKI have been developed, no consensus exists regarding which to use in children. This study applied the Pediatric RIFLE (pRIFLE), AKI Network (AKIN), and Kidney Disease Improving Global Outcomes (KDIGO) criteria to an anonymized cohort of hospitalizations extracted from the electronic medical record to compare AKI incidence and outcomes in intensive care unit (ICU) and non-ICU pediatric populations.

Design, setting, participants, & measurements

Observational, electronic medical record–enabled study of 14,795 hospitalizations at the Lucile Packard Children’s Hospital between 2006 and 2010. AKI and AKI severity stage were defined by the pRIFLE, AKIN, and KDIGO definitions according to creatinine change criteria; urine output criteria were not used. The incidences of AKI and each AKI stage were calculated for each classification system. All-cause, in-hospital mortality and total hospital length of stay (LOS) were compared at each subsequent AKI stage by Fisher exact and Kolmogorov–Smirnov tests, respectively.

Results

AKI incidences across the cohort according to pRIFLE, AKIN, and KDIGO were 51.1%, 37.3%, and 40.3%. Mortality was higher among patients with AKI across all definitions (pRIFLE, 2.3%; AKIN, 2.7%; KDIGO, 2.5%; P<0.001 versus no AKI [0.8%–1.0%]). Within the ICU, pRIFLE, AKIN, and KDIGO demonstrated progressively higher mortality at each AKI severity stage; AKI was not associated with mortality outside the ICU by any definition. Both in and outside the ICU, AKI was associated with significantly higher LOS at each AKI severity stage across all three definitions (P<0.001). Definitions resulted in differences in diagnosis and staging of AKI; staging agreement ranged from 76.7% to 92.5%.

Conclusions

Application of the three definitions led to differences in AKI incidence and staging. AKI was associated with greater mortality and LOS in the ICU and greater LOS outside the ICU. All three definitions demonstrated excellent interstage discrimination. While each definition offers advantages, these results underscore the need to adopt a single, universal AKI definition.     

Average daily risk range as a measure of glycemic risk is associated with mortality in the intensive care unit: a retrospective study in a burn intensive care unit

Background

Although tight glycemic control has been associated with improved outcomes in the intensive care unit (ICU), glycemic variability may be the influential factor in mortality. The main goal of the study was to relate blood glucose (BG) variability of burn ICU patients to outcomes using a sensitive measure of glycemic variability, the average daily risk range (ADRR).

Method

Data from patients admitted to a burn ICU were used. Patients were matched by total body surface area (TBSA) and injury severity score (ISS) to test whether increased BG variability measured by ADRR was associated with higher mortality risk and whether we could identify ADRR-based classifications associated with the degree of risk.

Results

Four ADRR classifications were identified: low risk, medium-low, medium-high, and high. Mortality progressively increased from 25% in the low-risk group to over 60% in the high-risk group (p < .001). In a post hoc analysis, age also contributed to outcome. Younger (age < 43 years) survivors and nonsurvivors matched by TBSA and ISS had no significant difference in age, mean BG or standard deviation of BG; however, nonsurvivors had higher ADRR (p < .01).

Conclusions

Independent of injury severity, glycemic variability measured by the ADRR was significantly associated with mortality in the ICU. When age was considered, ADRR was the only measure of glycemia significantly associated with mortality in younger patients with burns.     

Risk factors for acute kidney injury in overweight patients with acute type A aortic dissection: a retrospective study

Background

To identify risk factors for acute kidney injury (AKI) in overweight patients who underwent surgery for acute type A aortic dissection (TAAD).

Methods

A retrospective study including 108 consecutive overweight patients [body mass index (BMI) ≥24] between December 2009 and April 2013 in Beijing Anzhen Hospital has been performed. AKI was defined by Acute Kidney Injury Network (AKIN) criteria, which is based on serum creatinine (sCr) or urine output.

Results

The mean age of the patients was 43.69±9.66 years. Seventy-two patients (66.7%) developed AKI during the postoperative period. A logistic regression analysis was performed to identify two independent risk factors for AKI: elevated preoperative sCr level and 72-h drainage volume. Renal replacement therapy (RRT) was required in 15 patients (13.9%). The overall postoperative mortality rate was 7.4%, 8.3% in AKI group and 5.6% in non-AKI group. There is no statistically significant difference between the two groups (P=0.32).

Conclusions

A higher incidence of AKI (66.7%) in overweight patients with acute TAAD was confirmed. The logistic regression model identified elevated preoperative sCr level and 72-h drainage volume as independent risk factors for AKI in overweight patients. We should pay more attention to prevent AKI in overweight patients with TAAD.     

Pancreatic polypeptide administration enhances insulin sensitivity and reduces the insulin requirement of patients on insulin pump therapy

Introduction

The effects of pancreatic polypeptide (PP) infusion were examined in patients on insulin pump therapy to determine whether PP administration can reduce insulin requirements in patients with type 1 diabetes mellitus (T1DM) or type 3c diabetes mellitus (T3cDM; pancreatogenic).

Methods

Ten subjects with long-standing T1DM (n = 7) or T3cDM (n = 3) on insulin pump treatment received a 72 h subcutaneous infusion of 2 pmol/kg/min bovine PP or saline by portable infusion pump in a single-blinded, randomized, crossover design.

Results

Pancreatic polypeptide infusion raised plasma PP levels to 450–700 pmol/liter. Daily insulin infusion requirements (I) fell from 48 ± 6.9 to 40 ± 7.5 U on day 2 (p < .05) and from 46 ± 7.7 to 37 ± 6.6 U on day 3 (p < .05) of PP infusion compared with saline. Corrected for average blood glucose concentration (G), I/G fell in 10/10 subjects during the second 24 h period and in 7/10 subjects during the third 24 h period; sensitivity to insulin, calculated as 1/(I/G), increased 45% ± 12% on day 2 (p < .01) and 34% ± 14% on day 3 (p < .05) of PP infusion. Pancreatic polypeptide responses to a test meal were compared with the change in insulin infusion requirements in 5 subjects; the reduction in insulin requirements seen during PP infusion correlated with the degree of baseline PP deficiency (p < .002).

Conclusions

A concurrent subcutaneous infusion of PP enhances insulin sensitivity and reduces insulin requirements in patients with long-standing T1DM and T3cDM on insulin pump therapy. The benefit of PP infusion correlated with the degree of PP deficiency.