Importance of blood cultures to aid the diagnosis of Lemierre's syndrome.

This is a case report of Lemierre's syndrome, a septic thrombophlebitis of the internal jugular vein (IJV) usually preceded by pharyngitis and bacteraemia with an anaerobic organism. Fusobacterium necrophorum is ananaerobic Gram-negative bacillus and is the most common organism reported to cause Lemierre's syndrome which usually occurs one to three weeks post pharyngitis or oropharyngeal surgery. A 21-year-old patient presented with signs of sepsis and a history of sore throat, fever, and tender cervical lymph nodes. Blood cultures grew F. necrophorum and Computed Tomography (CT) showed a filling defect in the left retromandibular vein and thrombosis in the left internal jugular vein (IJV) consistent with Lemierre's syndrome. This is an uncommon condition which normally occurs in young individuals and diagnosis is often delayed.

Some biomarkers of acute kidney injury are increased in pre-renal acute injury.

Pre-renal acute kidney injury (AKI) is assumed to represent a physiological response to underperfusion. Its diagnosis is retrospective after a transient rise in plasma creatinine, usually associated with evidence of altered tubular transport, particularly that of sodium. In order to test whether pre-renal AKI is reversible because injury is less severe than that of sustained AKI, we measured urinary biomarkers of injury (cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), γ-glutamyl transpeptidase, IL-18, and kidney injury molecule-1 (KIM-1)) at 0, 12, and 24 h following ICU admission. A total of 529 patients were stratified into groups having no AKI, AKI with recovery by 24 h, recovery by 48 h, or the composite of AKI greater than 48 h or dialysis. Pre-renal AKI was identified in 61 patients as acute injury with recovery within 48 h and a fractional sodium excretion <1%. Biomarker concentrations significantly and progressively increased with the duration of AKI. After restricting the AKI recovery within the 48 h cohort to pre-renal AKI, this increase remained significant. The median concentration of KIM-1, cystatin C, and IL-18 were significantly greater in pre-renal AKI compared with no-AKI, while NGAL and γ-glutamyl transpeptidase concentrations were not significant. The median concentration of at least one biomarker was increased in all but three patients with pre-renal AKI. Thus, the reason why some but not all biomarkers were increased requires further study. The results suggest that pre-renal AKI represents a milder form of injury.

Albuminuria increases cystatin C excretion: implications for urinary biomarkers.

BACKGROUND: Low-molecular weight (LMW) proteins, including albumin and novel urinary biomarkers of acute kidney injury (AKI) such as cystatin C and neutrophil gelatinase-associated lipocalin (NGAL), are normally absorbed from the glomerular filtrate by receptor-mediated transport. We evaluated the effect of albuminuria on urinary excretion of novel biomarkers. METHODS: Sprague-Dawley rats given four injections over 2 days of 5 mg/g body wt/day bovine serum albumin (BSA) in saline were compared with controls given saline alone. Urinary cystatin C, albumin and protein excretion rates were compared prior to treatment (Day -1), after treatment (Day 2) and 4 days later (Day 6). A preliminary assessment of the clinical effect of proteinuria on the filtered urinary biomarkers cystatin C and NGAL was made by comparison with the effect on urinary interleukin-18 (IL-18) that is not absorbed from the glomerular filtrate, in a cohort of intensive care unit patients. RESULTS: BSA induced transient increases in albuminuria, proteinuria and cystatinuria (P < 0.01, P < 0.001 and P < 0.001, respectively). Beyond a threshold 6-fold increase in albuminuria, cystatin C absorption was reduced by competitive inhibition. The excretion rates of all analytes returned to preinjection levels by Day 6. Clinical proteinuria was associated with increasing cystatin C and NGAL concentrations (n = 90, P < 0.0001) but not IL-18 (P = 0.12). CONCLUSIONS: Proteinuria may increase the threshold for detection of AKI by increasing the excretion of LMW protein biomarkers.

Improved performance of urinary biomarkers of acute kidney injury in the critically ill by stratification for injury duration and baseline renal function.

To better understand the diagnostic and predictive performance of urinary biomarkers of kidney injury, we evaluated γ-glutamyltranspeptidase (GGT), alkaline phosphatase (AP), neutrophil-gelatinase-associated lipocalin (NGAL), cystatin C (CysC), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) in a prospective observational study of 529 patients in 2 general intensive care units (ICUs). Comparisons were made using the area under the receiver operator characteristic curve (AUC) for diagnosis or prediction of acute kidney injury (AKI), dialysis, or death, and reassessed after patient stratification by baseline renal function (estimated glomerular filtration rate, eGFR) and time after renal insult. On ICU entry, no biomarker had an AUC above 0.7 in the diagnosis or prediction of AKI. Several biomarkers (NGAL, CysC, and IL-18) predicted dialysis (AUC over 0.7), and all except KIM-1 predicted death at 7 days (AUC between 0.61 and 0.69). Performance was improved by stratification for eGFR or time or both. With eGFR <60 ml/min, CysC and KIM-1 had AUCs of 0.69 and 0.73, respectively, within 6 h of injury, and between 12 and 36 h, CysC (0.88), NGAL (0.85), and IL-18 (0.94) had utility. With eGFR >60 ml/min, GGT (0.73), CysC (0.68), and NGAL (0.68) had the highest AUCs within 6 h of injury, and between 6 and 12 h, all AUCs except AP were between 0.68 and 0.78. Beyond 12 h, NGAL (0.71) and KIM-1 (0.66) performed best. Thus, the duration of injury and baseline renal function should be considered in evaluating biomarker performance to diagnose AKI.

Urinary cystatin C is diagnostic of acute kidney injury and sepsis, and predicts mortality in the intensive care unit.

INTRODUCTION: To evaluate the utility of urinary cystatin C (uCysC) as a diagnostic marker of acute kidney injury (AKI) and sepsis, and predictor of mortality in critically ill patients. METHODS: This was a two-center, prospective AKI observational study and post hoc sepsis subgroup analysis of 444 general intensive care unit (ICU) patients. uCysC and plasma creatinine were measured at entry to the ICU. AKI was defined as a 50% or 0.3-mg/dL increase in plasma creatinine above baseline. Sepsis was defined clinically. Mortality data were collected up to 30 days. The diagnostic and predictive performances of uCysC were assessed from the area under the receiver operator characteristic curve (AUC) and the odds ratio (OR). Multivariate logistic regression was used to adjust for covariates. RESULTS: Eighty-one (18%) patients had sepsis, 198 (45%) had AKI, and 64 (14%) died within 30 days. AUCs for diagnosis by using uCysC were as follows: sepsis, 0.80, (95% confidence interval (CI), 0.74 to 0.87); AKI, 0.70 (CI, 0.64 to 0.75); and death within 30 days, 0.64 (CI, 0.56 to 0.72). After adjustment for covariates, uCysC remained independently associated with sepsis, AKI, and mortality with odds ratios (CI) of 3.43 (2.46 to 4.78), 1.49 (1.14 to 1.95), and 1.60 (1.16 to 2.21), respectively. Concentrations of uCysC were significantly higher in the presence of sepsis (P < 0.0001) or AKI (P < 0.0001). No interaction was found between sepsis and AKI on the uCysC concentrations (P = 0.53). CONCLUSIONS: Urinary cystatin C was independently associated with AKI, sepsis, and death within 30 days. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN012606000032550.

Rapid detection of acute kidney injury by plasma cystatin C in the intensive care unit.

BACKGROUND: Plasma cystatin C (pCysC) has been proposed as an alternative to plasma creatinine (pCr) as a measure of renal function. We compared the detection of functional change by both biomarkers in critically ill patients. METHODS: pCysC and pCr were measured on admission to one of two intensive care units (ICU) and then daily over 7 days. Patients were classified according to the analyte that first increased by either ≥25 or ≥50% above the admission value. The proportion of patients in each class was compared using McNemar's chi-square test. Sustained acute kidney injury (AKI, a ≥50% increase in pCr from baseline for ≥24 h), dialysis and death within 30 days were recorded. The ability of pCysC and pCr on admission to predict sustained AKI, dialysis or death was assessed from the area under the receiver operator characteristic curve (AUC). RESULTS: Of 442 patients, 83 had a ≥50% increase in one analyte, 17 in both and 342 in neither. Comparable numbers for a ≥25% increase were 163 in one analyte, 45 in both and 234 in neither. pCysC increased prior to pCr more frequently than vice versa in both the cohort with a ≥50% increase (P < 0.0001) and with a ≥25% increase (P < 0.0001). pCysC predicted sustained AKI with an AUC of 0.80 [95% confidence interval (CI) = 0.71-0.88]. pCysC and pCr were similarly moderately predictive of death or dialysis with AUCs of 0.61 [95% CI = 0.53-0.68] and 0.60 [95% CI = 0.51-0.67], respectively. CONCLUSION: pCysC was an effective and earlier surrogate marker of decreased renal function than pCr in a general ICU population.