Size matters

$\bf Purpose$ Acute lung injury is a life threatening condition often requiring mechanical ventilation. Lung-protective ventilation with tidal volumes of 6 mL/kg predicted body weight (PBW, calculated on the basis of a patient’s sex and height), is part of current recommended ventilation strategy. Hence, an exact height is necessary to provide optimal mechanical ventilation. However, it is a common practice to visually estimate the body height of mechanically ventilated patients and use these estimates as a reference size for ventilator settings. We aimed to determine if the common practice of estimating visual height to define tidal volume reduces the possibility of receiving lung-protective ventilation. $\bf Methods$ In this prospective observational study, 28 mechanically ventilated patients had their heights visually estimated by 20 nurses and 20 physicians. All medical professionals calculated the PBW and a corresponding tidal volume with 6 ml/kg/PBW on the basis of their visual estimation. The patients' true heights were measured and the true PBW with a corresponding tidal volume was calculated. Finally, estimates and measurements were compared. $\bf Results$ 1033 estimations were undertaken by 153 medical professionals. The majority of the estimates were imprecise and resulting data comprised taller body heights, higher PBW and higher tidal volumes (all p$\leq$0.01). When estimates of patients' heights are used as a reference for tidal-volume definition, patients are exposed to mean tidal volumes of 6.5 $\pm$ 0.4 ml/kg/PBW. 526 estimation-based tidal volumes (51.1%) did not provide lung-protective ventilation. Shorter subjects (<175cm) were a specific risk group with an increased risk of not receiving lung protective ventilation (OR 6.6; 95%CI 1.2–35.4; p = 0.02), while taller subjects had a smaller risk of being exposed to inadequately high tidal volumes (OR 0.15; 95%CI 0.02–0.8; p = 0.02). Furthermore, we found an increased risk of overestimating if the assessor was a female (OR 1.74; 95%CI 1.14–2.65; p = 0.01). $\bf Conclusion$ The common practice of visually estimating body height and using these estimates for ventilator settings is imprecise and potentially harmful because it reduces the chance of receiving lung-protective ventilation. Avoiding this practice increases the patient safety. Instead, height should be measured as a standard procedure

Prognostic value of urinary calprotectin, NGAL and KIM-1 in chronic kidney disease

$\textbf {Background/Aims:}$ Urinary biomarkers like neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) do not only allow an early diagnosis of acute kidney injury, but also provide prognostic information in this setting. The present prospective study investigates, whether the urinary biomarkers NGAL, KIM-1 and calprotectin have prognostic information in chronic kidney disease (CKD) as well. $\textbf {Methods:}$ Urinary calprotectin, NGAL and KIM-1 concentrations were assessed in a study population of 143 patients with stable CKD comprising diabetic and hypertensive nephropathy, glomerulonephritis/vasculitis, and autosomal dominant polycystic kidney disease. An eGFR fluctuation > 5ml/min/$1.73m^{2}$ in the past 12 months was defined as an exclusion criterion in order to exclude cases with acute on chronic kidney injury. Renal function was monitored for a median follow-up of 37 months. $\textbf {Results:}$ In the overall study population, all the three biomarkers failed to predict DeGFR and DACR from baseline to follow-up in linear regression analysis adjusted for age, gender, and baseline $\Delta$eGFR. Contrarily, baseline ACR was significantly associated with $\Delta$eGFR (p< 0.001). In the subgroup of patients with vasculitis and glomerulonephritis, all the three biomarkers were significantly associated with $\Delta$eGFR, with calprotectin having the highest regression coefficient. $\textbf{Conclusion:}$ In contrast to the traditional biomarker "albuminuria", neither the inflammatory biomarker calprotectin, nor the tubular biomarkers NGAL and KIM-1, provide robust prognostic information on the loss or renal function in a heterogeneous CKD population. All of them, however, are candidate prognostic biomarkers in primarily inflammatory renal diseases

Secondary prevention of potentially life-threatening arrhythmia using implantable cardioverter defibrillators in patients with biopsy-proven viral myocarditis and preserved ejection fraction

$\bf Background:$ Arrhythmia and sudden cardiac death (SCD) are known complications of acute viral myocarditis, regardless of ejection fraction (EF) at presentation. Whether such complications confer long-term risk is unknown, especially in those who present with preserved left ventricular (LV) function. No guidelines exist to the long-term reduction of arrhythmic death in such patients. $\bf Method:$ In this retrospective study, we analyzed the long-term results of implantable cardioverter defibrillator (ICD) treatment in patients after an acute phase of myocarditis with life-threatening arrhythmia. $\bf Results:$ We identified 51 patients who had ICDs implanted following life-threatening arrhythmia presentation of confirmed acute viral myocarditis, despite preserved LVEF. Overall, 72.5% of patients had a clinical history of chest pain and viral infection with fever. Viral myocarditis was confirmed by cardiac magnetic resonance imaging (all had late enhancement) plus endomyocardial biopsies (most frequent were Epstein-Barr virus 29.4%, adenovirus 17.6%, and Coxsackie 17.6%), and 88.2% were discharged on anti-arrhythmic drugs. Overall, 12 patients (23.5%) required ICD intervention within the first 3 months, a further 7 patients (37.3% overall) between 3 and 12 months, and a further 12 patients (60.8% overall) until 58 months. During the follow-up, 3 of 51 patients (5.9%) died—deaths were due to cardiac events ($\it n$ = 1), fatal infection ($\it n$ = 1), and car accidents ($\it n$ = 1). Of the 31 patients who had ventricular tachycardias after the acute phase of myocarditis, 11 needed radiofrequency ablation due to a high number of events or electrical storm. No baseline variables were identified that would serve as a basis for risk stratification. $\bf Conclusion:$ Malignant arrhythmic events due to viral myocarditis are potential predictors of future SCD in patients not only with a reduced but also with a preserved EF

Urinary calprotectin and posttransplant renal allograft injury

$\textit {Objective:}$ Current methods do not predict the acute renal allograft injury immediately after kidney transplantation. We evaluated the diagnostic performance of urinary calprotectin for predicting immediate posttransplant allograft injury. $\textit {Methods:}$ In a multicenter, prospective-cohort study of 144 incipient renal transplant recipients, we postoperatively measured urinary calprotectin using an enzyme-linked immunosorbent assay and estimated glomerular filtration rate (eGFR) after 4 weeks, 6 months, and 12 months. $\textit {Results:}$ We observed a significant inverse association of urinary calprotectin concentrations and eGFR 4 weeks after transplantation (Spearman r = −0.33; P<0.001). Compared to the lowest quartile, patients in the highest quartile of urinary calprotectin had an increased risk for an eGFR less than 30 mL/min/1.73 $m^{2}$ four weeks after transplantation (relative risk, 4.3; P<0.001; sensitivity, 0.92; 95% CI, 0.77 to 0.98; specificity, 0.48; 95% CI, 0.31 to 0.66). Higher urinary calprotectin concentrations predicted impaired kidney function 4 weeks after transplantation, as well as 6 months and 12 months after transplantation. When data were analyzed using the urinary calprotectin/creatinine-ratio similar results were obtained. Urinary calprotectin was superior to current use of absolute change of plasma creatinine to predict allograft function 12 months after transplantation. Urinary calprotectin predicted an increased risk both in transplants from living and deceased donors. Multivariate linear regression showed that higher urinary calprotectin concentrations and older donor age predicted lower eGFR four weeks, 6 months, and 12 months after transplantation. $\textit {Conclusions:}$ Urinary calprotectin is an early, noninvasive predictor of immediate renal allograft injury after kidney transplantation

Dickkopf-3 in the prediction of contrast media induced acute kidney injury

$\bf Background$ Dickkopf-3 (DKK3) has recently been discovered as a urinary biomarker for the prediction of acute kidney injury (AKI) after cardiac surgery. This finding needs to be confirmed for AKI in other clinical settings. The present study investigates whether DKK3 can predict contrast-induced AKI (CI-AKI). $\bf Methods$ We performed a prospective study in 490 patients undergoing coronary angiography. Primary endpoint was an increase in serum creatinine concentration $\geq$ 0.3 mg/dl within 72 h after the procedure. DKK3 was assessed < 24 h before coronary angiography. Predictive accuracy was assessed by receiver operating characteristic (ROC) curves. $\bf Results$ CI-AKI was observed in 30 (6.1%) patients, of whom 27 corresponded to stage I and 3 to stage II according to the Acute Kidney Injury Network (AKIN) criteria. Subjects who developed CI-AKI had a 3.8-fold higher urinary DKK3/creatinine ratio than those without CI-AKI (7.5 pg/mg [interquartile range [IQR] 1.2–1392.0] vs. 2.0 pg/mg [IQR 0.9–174.0]; $\it p$ = 0.047). ROC analysis revealed an area under the curve (AUC) of 0.61. Among subjects without clinically overt chronic kidney disease (estimated glomerular filtration rate [eGFR] > 60 ml/min, urinary albumin creatinine ratio < 30 mg/g), the DKK3/creatinine ratio was 5.4-fold higher in those with subsequent CI-AKI (7.5 pg/mg [IQR 0.9–590.1] vs. 1.38 pg/mg [IQR 0.8–51.0]; $\it p$ = 0.007; AUC 0.62). Coronary angiography was associated with a 43 times increase in the urinary DKK3/creatinine ratio. $\bf Conclusions$ Urinary DKK3 is an independent predictor of CI-AKI even in the absence of overt chronic kidney disease (CKD). The study thereby expands the findings on DKK3 in the prediction of postoperative loss of kidney function to other entities of AKI

Biomarkers in the prediction of contrast media induced nephropathy

$\bf Background$ Subjects with chronic kidney disease are at increased risk for contrast-induced acute kidney injury (CI-AKI). Risk stratification is traditionally based on glomerular filtration rate (GFR) and proteinuria. The present trial examines, whether tubular and inflammatory biomarkers are able to identify subjects at increased risk as well. $\bf Methods$ We performed a prospective study in 490 patients undergoing coronary angiography. An increase of serum creatinine concentration $\geq$ 0.3 mg/dl from baseline to day 2–3 was defined as primary endpoint (CI-AKI). Urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and calprotectin were assessed < 24h before coronary angiography. Prognostic accuracy was assessed by receiver operating characteristics (ROC) calculations. $\bf Results$ 30 (6.1%) patients suffered from CI-AKI (27 AKIN stage I, 3 AKIN stage II, 0 AKIN stage III). Those subjects who developed CI-AKI had 3.1 fold higher baseline urinary NGAL/creatinine ratios than those without CI-AKI (60.8 [IQR 18.7–93.1] $\mu$g/mg vs. 19.9 [IQR 12.3–38.9] $\mu$g/mg, p = 0.001). In those subjects without clinically overt CKD (eGFR > 60 ml/min, urinary albumin creatinine ratio 0.05 each). ROC analyses revealed an area under the curve (AUC) of 0.68 (95% CI 0.60–0.81) for NGAL/creatinine. An NGAL/creatinine ratio < 56.4 $\mu$g/mg has a negative predictive value of 96.5%. $\bf Conclusions$ The present study is the largest investigation on the use of urinary biomarkers for CI-AKI risk stratification so far. It shows that NGAL provides prognostic information beyond the glomerular biomarkers eGFR and proteinuria

Detection of acute tubular necrosis using blood oxygenation level-dependent (BOLD) MRI

$\it Background/Aims:$ To date, there is no imaging technique to assess tubular function in vivo. Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) measures tissue oxygenation based on the transverse relaxation rate (R2*). The present study investigates whether BOLD MRI can assess tubular function using a tubule-specific pharmacological maneuver. $\it Methods:$ Cross sectional study with 28 participants including 9 subjects with ATNinduced acute kidney injury (AKI), 9 healthy controls, and 10 subjects with nephron sparing tumor resection (NSS) with clamping of the renal artery serving as a model of ischemia/reperfusion (I/R)-induced subclinical ATN (median clamping time 15 min, no significant decrease of eGFR, p=0.14). BOLD MRI was performed before and 5, 7, and 10 min after intravenous administration of 40 mg furosemide. $\it Results:$ Urinary neutrophil gelatinaseassociated lipocalin was significantly higher in ATN-induced AKI and NSS subjects than in healthy controls (p=0.03 and p=0.01, respectively). Before administration of furosemide, absolute medullary R2*, cortical R2*, and medullary/cortical R2* ratio did not significantly differ between ATN-induced AKI vs. healthy controls and between NSS-I/R vs. contralateral healthy kidneys (p>0.05 each). Furosemide led to a significant decrease in the medullary and cortical R2* of healthy subjects and NSS contralateral kidneys (p0.05 each). $\it Conclusion:$ BOLD-MRI is able to detect even mild tubular injury but necessitates a tubulespecific pharmacological maneuver, e.g. blocking the Na$^{+}$-K$^{+}$-2Cl- transporter by furosemide

Dynamics of urinary calprotectin after renal ischaemia

Background: Urinary calprotectin has been identified as a promising biomarker for acute kidney injury. To date, however, the time-dependent changes of this parameter during acute kidney injury remain elusive. The aim of the present work was to define the time-course of urinary calprotectin secretion after ischaemia/reperfusion-induced kidney injury in comparison to neutrophil gelatinase-associated lipocalin, thereby monitoring the extent of tubular damage in nephron sparing surgery for kidney tumours. Methods: The study population consisted of 42 patients. Thirty-two patients underwent either open or endoscopic nephron sparing surgery for kidney tumours. During the surgery, the renal arterial pedicle was clamped with a median ischaemic time of 13 minutes (interquartile range, 4.5–20.3 minutes) in 26 patients. Ten retro-peritoneoscopic living donor nephrectomy patients and 6 nephron sparing surgery patients in whom the renal artery was not clamped served as controls. Urinary calprotectin and neutrophil gelatinase-associated lipocalin concentrations were repeatedly measured by enzyme-linked immunosorbent assay and assessed according to renal function parameters. Results: Urinary concentrations of calprotectin and neutrophil gelatinase-associated lipocalin increased significantly after ischaemia/reperfusion injury, whereas concentrations remained unchanged after nephron sparing surgery without ischaemia/reperfusion injury and after kidney donation. Calprotectin and neutrophil gelatinase-associated lipocalin levels were significantly increased 2 and 8 hours, respectively, post-ischaemia. Both proteins reached maximal concentrations after 48 hours, followed by a subsequent persistent decrease. Maximal neutrophil gelatinase-associated lipocalin and calprotectin concentrations were 9-fold and 69-fold higher than their respective baseline values. The glomerular filtration rate was only transiently impaired at the first post-operative day after ischaemia/reperfusion injury (p = 0.049). Conclusion: Calprotectin and neutrophil gelatinase-associated lipocalin can be used to monitor clinical and sub-clinical tubular damage after nephron sparing surgery for kidney tumours. Urinary calprotectin concentrations start rising within 2 hours after ischaemia/reperfusion-induced kidney injury