Accuracy of NGAL as a Biomarker for Urinary Tract Infection in Young Febrile Children: An Individual Patient Data Meta-Analysis.

OBJECTIVE: To compare the accuracy of urine neutrophil gelatinase-associated lipocalin (NGAL) and leukocyte esterase (LE) for the diagnosis of urinary tract infection (UTI) in children. STUDY DESIGN: We performed a systematic review and individual patient data meta-analysis of studies that examined urine NGAL as a marker of UTI in children <18 years of age. We created a standardized definition of UTI and applied it to all included children. We compared sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) of NGAL with LE. RESULTS: We included individual patient data from 3 studies for a total of 845 children. Included children had a mean age of 0.9 years (SD, 0.6 years). Using a cutoff of 32.7 ng/mL, NGAL had a sensitivity of 90.3% (95% CI: 83.2%-95.0%) and specificity of 93.7% (95% CI: 91.7%-95.4%) for the diagnosis of UTI. LE, using a cutoff of ≧ trace had a sensitivity of 81.1% (95% CI: 72.5%-87.9%) and specificity of 97.0% (95% CI: 95.4%-98.1%). The AUC for NGAL was 0.95 (95% CI: 0.92-0.98). The AUC for LE was 0.90 (95% CI: 0.86-0.93). CONCLUSION: In young, febrile children, urinary NGAL is more sensitive for the diagnosis of UTI than LE but is slightly less specific.

Biomarkers for febrile urinary tract infection in children.

BACKGROUND: The sensitivity and specificity of the leukocyte esterase test for the diagnosis of urinary tract infection (UTI) are suboptimal. Recent studies have identified markers that appear to more accurately differentiate children with and without UTI. The objective of this study was to determine the accuracy of these markers, which included CCL3, IL-8, CXCL1, TNF-alpha, IL-6, IFN-gamma, IL-17, IL-9, IL-2, and NGAL, in the diagnosis of UTI. METHODS: This was a prospective cross-sectional study to compare inflammatory proteins between urine samples from febrile children with a UTI, matched febrile controls without a UTI, and asymptomatic healthy controls. RESULTS: We included 192 children (75 with febrile UTI, 69 febrile controls, and 48 asymptomatic healthy controls). Urinary proteins that best discriminated between febrile children with and without UTI were NGAL, a protein that exerts a local bacteriostatic role in the urinary tract through iron chelation; CCL3, a chemokine involved in leukocyte recruitment; and IL-8, a cytokine involved in neutrophil recruitment. Levels of these proteins were generally undetectable in asymptomatic healthy children. CONCLUSIONS: NGAL, CCL3, and IL-8 may be useful in the early diagnosis of UTI. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01391793) A higher resolution version of the Graphical abstract is available as Supplementary information.

The association between urine neutrophil gelatinase-associated lipocalin and UTI in people with neurogenic lower urinary tract dysfunction.

STUDY DESIGN: Secondary analysis of urine samples collected from a prospective within-subject clinical trial. OBJECTIVES: Describe the baseline variation in urine neutrophil gelatinase-associated lipocalin (uNGAL) levels in adults with neurogenic lower urinary tract dysfunction (NLUTD) and determine if uNGAL levels vary according to likelihood of having a UTI. SETTING: Greater Washington D.C. region. METHODS: Urine samples were collected from a cohort of adults with NLUTD from a clinical trial. Samples were divided into groups of "Not UTI", "Unlikely UTI", and "Likely UTI" based on symptoms and urine culture results. uNGAL was compared between groups using Kruskal-Wallis and post hoc Dunn's test. Mixed effects logistic model was used to assess the association of uNGAL and Likely UTI. RESULTS: Twenty-seven participants provided a total of 104 samples. uNGAL levels were lowest for the No UTI group (n = 29; 37 ng/ml interquartile range (IQR) (15, 71)), intermediate for the Unlikely UTI group (n = 67; 95 ng/ml IQR (37, 161)) and highest for the Likely UTI group (n = 8; 187 ng/ml IQR(146, 224)). uNGAL levels were higher in those with Likely UTI compared to both Unlikely UTI (p < 0.05) and No UTI (p < 0.01). uNGAL had an association with Likely UTI (OR 1.01, 95% CI (1.00-1.02), p = 0.049). CONCLUSIONS: Adults with NLUTD have notable variation in uNGAL levels in the absence of symptoms potentially due to UTI. uNGAL levels are higher in those who are likely to have UTI have higher uNGAL levels compared to those with non-specific symptoms and/or less growth on urine culture. uNGAL may have utility as a marker of UTI in people with NLUTD. SPONSORSHIP: Patient-Centered Outcomes Research Institute (PCORI) funded this work. Bioporto provided partial salary support for SLG, IL, and OKL. NGAL ELISAs were provided by Bioporto in kind.

Urine neutrophil gelatinase-associated lipocalin in girls with recurrent urinary tract infections.

BACKGROUND: Children who experience more than one urinary tract infection (UTI) are at increased risk of kidney scarring due to their UTIs. Girls are at especially high risk for developing kidney scarring as a result of recurrent UTIs. Prior work suggested that neutrophil gelatinase-associated lipocalin (NGAL) may be lower in children with recurrent UTI compared with those without. The objective of this work was to compare urine NGAL concentrations in matched urine samples in girls with single and recurrent UTIs. METHODS: Girls less than 6 years of age who presented with signs and symptoms of a UTI were eligible for enrollment. Both acute, obtained from residual urine collected as part of their clinical evaluation, and follow-up urine samples, obtained after the completion of antibiotics when the patient was in their usual state of health, were collected from patients. Acute and follow-up urine NGAL concentrations were compared between girls with single and recurrent UTIs, as well as those with negative cultures who served as controls. RESULTS: Seventy girls were included in this study, 6 controls, 43 single UTIs, and 20 girls with recurrent UTIs. Patients in the control group had lower median acute NGAL concentrations than either those with single or recurrent UTI. There were no differences in either acute or follow-up urine NGAL concentrations between those with single and recurrent UTIs. CONCLUSION: In this cohort of girls less than 6 years of age, there is no difference in urine NGAL concentrations between those with single and recurrent UTIs.

Novel catheter design enables transurethral catheterization of male mice.

The male mouse is underrepresented in research of the urinary tract due to the difficulty of transurethral catheterization. As a result, there is a lack of analysis of sex differences in urinary tract research. Here, we present a novel catheter design and technique that enables urethral catheterization of male mice for bladder inoculation. Our catheterization technique uses the resistance met at the level of the external urinary sphincter and prostate to guide the retraction, positioning, and advancement of the catheter into the urinary bladder. We have shown that this method can be used to reproducibly catheterize 12 male mice with minimal urogenital trauma but cannot be used as a cystometric technique. This method will facilitate the expansion of research into sex differences in various genitourinary conditions that require transurethral catheterization of mice.

Symptom- and urinalysis-based approach to diagnosing urinary tract infections in children with neuropathic bladders.

BACKGROUND: Accurately diagnosing urinary tract infections (UTI) in children with neuropathic bladders can be difficult given the lack of specificity of both clinical symptoms and routine screening tests. We aimed to identify a priori unknown classes/groups of children with neuropathic bladder with respect to symptoms and UA results and examine their relationships with odds of UTI. METHODS: We used latent class analysis (LCA) to identify unobserved classes/groups of children with neuropathic bladder based on symptoms and urinalysis (UA) results, respectively. Demographic and clinical data were gathered by retrospective chart review of a cohort with neuropathic bladder. Symptoms and UA results were obtained by chart review of visits where urine culture was ordered. RESULTS: Around 193 patients were included in UA results analysis and 179 in symptom-based analysis. Two latent classes of patients were identified with respect to symptoms, labeled "pyelonephritis class" and "cystitis class," and two, with respect to UA results, were labeled "positive UA class" and "negative UA class." The pyelonephritis class had significantly higher odds of UTI compared to the asymptomatic class. While odds of UTI in cystitis class were higher than the asymptomatic class, this difference was not statistically significant. Positive UA class had significantly higher odds of UTI compared to negative UA class. CONCLUSION: Two unobserved classes/groups exist in children with neuropathic bladder with respect to symptoms, corresponding to cystitis and pyelonephritis, and two classes of UA results that correspond with either a positive or negative UA. Our results suggest a differential approach to treatments may be considered.

Utility of DNA Next-Generation Sequencing and Expanded Quantitative Urine Culture in Diagnosis and Management of Chronic or Persistent Lower Urinary Tract Symptoms.

Many patients suffer from chronic, irritative lower urinary tract symptoms (LUTS). The evaluation and management of these patients have proven difficult with the use of standard diagnostic tools, including urinalysis and urine culture. The growing body of literature on the urinary microbiome has looked at the possible implications of the bladder microbiome and dysbiosis, or perturbations in the microbiome, in conditions associated with chronic LUTS. Disorders such as recurrent urinary tract infections (UTIs) and interstitial cystitis have been studied utilizing 16S rRNA rapid next-generation gene sequencing (NGS) and expanded quantitative urine culture (EQUC). In this article, we first present a brief review of the literature describing the current understanding of the urinary microbiome and the features and applications of NGS and EQUC. Next, we discuss the conditions most commonly associated with chronic, persistent LUTS and present the limitations of current diagnostic practices utilized in this patient population. We then review the limited data available surrounding treatment efficacy and clinical outcomes in patients who have been managed based on results provided by these two recently established diagnostic tools (DNA NGS and/or EQUC). Finally, we propose a variety of clinical scenarios in which the use of these two techniques may affect patients' clinical outcomes.

Predictive ability of NGAL in identifying urinary tract infection in children with neurogenic bladders.

BACKGROUND: Distinguishing between urinary tract infection (UTI) and colonization (UTC) in patients with neurogenic bladders who require clean intermittent catheterization (CIC) is difficult. Urinary neutrophil gelatinase-associated lipocalin concentrations (uNGAL) are increased in UTIs. Our objective was to determine the predictive accuracy of uNGAL for UTI in CIC-dependent children. METHODS: Cross-sectional study of CIC-dependent patients from August, 2015 to November, 2016. UTI was defined as (1) growth of ≥ 50,000 cfu/mL of a uropathogen, (2) > 10 urinary white blood cells/hpf, and (3) ≥ 2 of the following: temperature > 38 °C, abdominal pain, back pain, worsened incontinence, pain with catheterization, or malodorous/cloudy urine. Positive urine cultures that did not meet these criteria were grouped as UTC, and negative cultures were grouped as no growth. RESULTS: Two hundred one patients were included (no growth = 100, UTC = 77, UTI = 24). Median (interquartile range) uNGAL was higher in the UTI group (UTI 1361 (931, 2516) µg/g creatinine, UTC 246 (106, 548) µg/g creatinine, no growth 36 (11, 179) µg/g creatinine, p < 0.01 for all comparisons). The area under the ROC curve for uNGAL for UTI versus no UTI was 0.89, 95% CI (0.80-0.98). CONCLUSION: uNGAL is elevated in CIC-dependent children with UTI compared to those with negative cultures and those with UTC.

Does NGAL reduce costs? A cost analysis of urine NGAL (uNGAL) & serum creatinine (sCr) for acute kidney injury (AKI) diagnosis.

INTRODUCTION: Urine neutrophil gelatinase-associated lipocalin (uNGAL) is a sensitive and specific diagnostic test for acute kidney injury (AKI) in the Emergency Department (ED), but its economic impact has not been investigated. We hypothesized that uNGAL used in combination with serum creatinine (sCr) would reduce costs in the management of AKI in patients presenting to the ED in comparison to using sCr alone. MATERIALS AND METHODS: A cost simulation model was developed for clinical algorithms to diagnose AKI based on sCr alone vs. uNGAL plus sCr (uNGAL+sCr). A cost minimization analysis was performed to determine total expected costs for patients with AKI. uNGAL test characteristics were validated with eight-hundred forty-nine patients with sCr ≥1.5 from a completed study of 1635 patients recruited from EDs at two U.S. hospitals from 2007-8. Biomarker test, AKI work-up, and diagnostic imaging costs were incorporated. RESULTS: For a hypothetical cohort of 10,000 patients, the model predicted that the expected costs were $900 per patient (pp) in the sCr arm and $950 in the uNGAL+sCr arm. uNGAL+sCr resulted in 1,578 fewer patients with delayed diagnosis and treatment than sCr alone (2,013 vs. 436 pts) at center 1 and 1,973 fewer patients with delayed diagnosis and treatment than sCr alone at center 2 (2,227 vs. 254 patients). Although initial evaluation costs at each center were $50 pp higher in with uNGAL+sCr, total costs declined by $408 pp at Center 1 and by $522 pp at Center 2 due to expected reduced delays in diagnosis and treatment. Sensitivity analyses confirmed savings with uNGAL + sCr for a range of cost inputs. DISCUSSION: Using uNGAL with sCr as a clinical diagnostic test for AKI may improve patient management and reduce expected costs. Any cost savings would likely result from avoiding delays in diagnosis and treatment and from avoidance of unnecessary testing in patients given a false positive AKI diagnosis by use of sCr alone.

Urinary NGAL deficiency in recurrent urinary tract infections.

INTRODUCTION: Children with recurrent urinary tract infections (rUTI) often show no identifiable cause of their infections. Neutrophil gelatinase-associated lipocalin (NGAL) is known to be upregulated within the uroepithelium and kidney of patients with UTI and exhibits a localized bacteriostatic effect through iron chelation. We hypothesize that some patients with rUTI without an identifiable cause of their recurrent infections have locally deficient NGAL production. We therefore explored whether a lack of NGAL production may be a factor in the pathogenesis of rUTI. MATERIALS AND METHODS: Patients seen in the urology clinic for rUTI who were <21 years of age were enrolled. Patients were excluded if they had UTI at the time of enrollment, evidence of renal disease, decreased renal function, known anatomic abnormality of the genitourinary tract, or other reasons that predispose to UTI, such as neurogenic bladder, the need for intermittent catheterization, or unrepaired posterior urethral valves. Control patients were healthy children enrolled from the emergency department with no history of UTI or renal dysfunction, normal urinalysis at the time of enrollment, and presenting no diagnosis associated with increased NGAL levels, such as acute kidney injury or infection. NGAL was measured by immunoblot. RESULTS: Fifteen cases and controls were enrolled. Median urinary NGAL levels were significantly decreased in rUTI patients compared with controls [15 (14-29) ng/ml vs 30 (27-61) ng/ml; p = 0.002)] Although comparatively diminished, measurable NGAL levels were present in all patients with rUTI. CONCLUSIONS: Urinary NGAL is significantly decreased in patients with compared with patients without rUTI. These data suggest that some patients with rUTI may be predisposed to UTI because of a relative local deficiency in urinary NGAL production.

Neutrophil gelatinase-associated lipocalin: utility in urologic conditions.

Neutrophil gelatinase-associated lipocalin (NGAL) is best known as a non-invasive early marker of acute kidney injury (AKI). However, recent published reports have described additional utility of both plasma NGAL (pNGAL) and urine NGAL (uNGAL) in various pathologic conditions within the pediatric urinary tract, including urinary tract infection, vesicoureteral reflux (VUR), renal scarring, and obstructive uropathy. These two forms of NGAL have different applications related to their mechanisms of upregulation: pNGAL can serve as a marker of systemic inflammatory conditions, whereas uNGAL is specific for insults to the renal epithelium. Therefore, pNGAL has good predictive accuracy in systemic inflammation associated with pyelonephritis and renal damage, while uNGAL is an effective marker for identifying infection within the genitourinary environment as well as subclinical renal damage as a result of scarring or obstruction. Continued work should focus on the effect of trending NGAL values in patients with pyelonephritis, VUR, and hydronephrosis, to determine if longitudinal NGAL patterns have value in predicting adverse outcomes.

A Validated Method for Identifying Unplanned Pediatric Readmission.

OBJECTIVE: To validate the accuracy of pre-encounter hospital designation as a novel way to identify unplanned pediatric readmissions and describe the most common diagnoses for unplanned readmissions among children. STUDY DESIGN: We examined all hospital discharges from 2 tertiary care children's hospitals excluding deaths, normal newborn discharges, transfers to other institutions, and discharges to hospice. We performed blinded medical record review on 641 randomly selected readmissions to validate the pre-encounter planned/unplanned hospital designation. We identified the most common discharge diagnoses associated with subsequent 30-day unplanned readmissions. RESULTS: Among 166,994 discharges (hospital A: n = 55,383; hospital B: n = 111,611), the 30-day unplanned readmission rate was 10.3% (hospital A) and 8.7% (hospital B). The hospital designation of "unplanned" was correct in 98% (hospital A) and 96% (hospital B) of readmissions; the designation of "planned" was correct in 86% (hospital A) and 85% (hospital B) of readmissions. The most common discharge diagnoses for which unplanned 30-day readmissions occurred were oncologic conditions (up to 38%) and nonhypertensive congestive heart failure (about 25%), across both institutions. CONCLUSIONS: Unplanned readmission rates for pediatrics, using a validated, accurate, pre-encounter designation of "unplanned," are higher than previously estimated. For some pediatric conditions, unplanned readmission rates are as high as readmission rates reported for adult conditions. Anticipating unplanned readmissions for high-frequency diagnostic groups may help focus efforts to reduce the burden of readmission for families and facilities. Using timing of hospital registration in administrative records is an accurate, widely available, real-time way to distinguish unplanned vs planned pediatric readmissions.

α-Intercalated cells defend the urinary system from bacterial infection.

α-Intercalated cells (A-ICs) within the collecting duct of the kidney are critical for acid-base homeostasis. Here, we have shown that A-ICs also serve as both sentinels and effectors in the defense against urinary infections. In a murine urinary tract infection model, A-ICs bound uropathogenic E. coli and responded by acidifying the urine and secreting the bacteriostatic protein lipocalin 2 (LCN2; also known as NGAL). A-IC-dependent LCN2 secretion required TLR4, as mice expressing an LPS-insensitive form of TLR4 expressed reduced levels of LCN2. The presence of LCN2 in urine was both necessary and sufficient to control the urinary tract infection through iron sequestration, even in the harsh condition of urine acidification. In mice lacking A-ICs, both urinary LCN2 and urinary acidification were reduced, and consequently bacterial clearance was limited. Together these results indicate that A-ICs, which are known to regulate acid-base metabolism, are also critical for urinary defense against pathogenic bacteria. They respond to both cystitis and pyelonephritis by delivering bacteriostatic chemical agents to the lower urinary system.

NGAL (Lcn2) monomer is associated with tubulointerstitial damage in chronic kidney disease.

The type and the extent of tissue damage inform the prognosis of chronic kidney disease (CKD), but kidney biopsy is not a routine test. Urinary tests that correlate with specific histological findings might serve as surrogates for the kidney biopsy. We used immunoblots and ARCHITECT-NGAL assays to define the immunoreactivity of urinary neutrophil gelatinase-associated lipocalin (NGAL) in CKD, and we used mass spectroscopy to identify associated proteins. We analyzed kidney biopsies to determine whether specific pathological characteristics associated with the monomeric NGAL species. Advanced CKD urine contained the NGAL monomer as well as novel complexes of NGAL. When these species were separated, we found a significant correlation between the NGAL monomer and glomerular filtration rate (r=-0.53, P<0.001), interstitial fibrosis (mild vs. severe disease; mean 54 vs. 167 µg uNGAL/g Cr, P<0.01), and tubular atrophy (mild vs. severe disease; mean 54 vs. 164 µg uNGAL/g Cr, P<0.01). Monospecific assays of the NGAL monomer demonstrated a correlation with histology that typifies progressive, severe CKD.

Urinary neutrophil gelatinase-associated lipocalin predicts mortality and identifies acute kidney injury in cirrhosis.

BACKGROUND: Kidney failure predicts mortality in patients with cirrhosis. Identification of kidney failure etiology and recognition of those at the highest mortality risk remains a challenge. AIMS: We hypothesized that urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts mortality and identifies hepatorenal syndrome (HRS) in patients with cirrhosis. METHODS: Prospectively enrolled patients with cirrhosis were investigated by uNGAL immunoblot upon hospital admission. Kidney failure type was determined blinded to NGAL measurements. RESULTS: One hundred eighteen patients were enrolled. Fifty-two (44 %) patients had normal kidney function, 14 (12 %) stable chronic kidney disease, 17 (14 %) prerenal azotemia, 20 (17 %) HRS, and 15 (13 %) intrinsic acute kidney injury (iAKI). Patients with HRS had uNGAL levels intermediate between prerenal azotemia [median (IQR) 105 (27.5-387.5) vs. 20 (15-45) ng/mL, p = 0.004] and iAKI [325 (100-700), p < 0.001]. Fifteen (13 %) patients died. In unadjusted analysis, uNGAL predicted inpatient mortality (OR 2.00, 95 % CI 1.36-2.94) and mortality or liver transplantation (OR 2.01, 95 % CI 1.42-2.85). In multiple regression models, uNGAL > 110 ng/mL (OR 6.05, 95 % CI 1.35-27.2) and HRS (OR 6.71, 95 % CI 1.76-25.5) independently predicted mortality, adjusting for age and serum creatinine >1.5 mg/dL. CONCLUSIONS: uNGAL strongly predicts short-term inpatient mortality in both unadjusted and adjusted models. Patients with HRS may have uNGAL levels intermediate between those with prerenal azotemia and iAKI. Further studies are needed to determine if uNGAL can improve discrimination of HRS from other types of acute kidney injury and predict short- and long-term cirrhosis outcomes.

Diagnostic and prognostic stratification in the emergency department using urinary biomarkers of nephron damage: a multicenter prospective cohort study.

OBJECTIVES: This study aimed to determine the diagnostic and prognostic value of urinary biomarkers of intrinsic acute kidney injury (AKI) when patients were triaged in the emergency department. BACKGROUND: Intrinsic AKI is associated with nephron injury and results in poor clinical outcomes. Several urinary biomarkers have been proposed to detect and measure intrinsic AKI. METHODS: In a multicenter prospective cohort study, 5 urinary biomarkers (urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, urinary liver-type fatty acid binding protein, urinary interleukin-18, and cystatin C) were measured in 1,635 unselected emergency department patients at the time of hospital admission. We determined whether the biomarkers diagnosed intrinsic AKI and predicted adverse outcomes during hospitalization. RESULTS: All biomarkers were elevated in intrinsic AKI, but urinary neutrophil gelatinase-associated lipocalin was most useful (81% specificity, 68% sensitivity at a 104-ng/ml cutoff) and predictive of the severity and duration of AKI. Intrinsic AKI was strongly associated with adverse in-hospital outcomes. Urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule 1 predicted a composite outcome of dialysis initiation or death during hospitalization, and both improved the net risk classification compared with conventional assessments. These biomarkers also identified a substantial subpopulation with low serum creatinine at hospital admission, but who were at risk of adverse events. CONCLUSIONS: Urinary biomarkers of nephron damage enable prospective diagnostic and prognostic stratification in the emergency department.

Urine neutrophil gelatinase-associated lipocalin identifies unilateral and bilateral urinary tract obstruction.

BACKGROUND: Urinary tract obstruction (UTO) is a common problem that can lead to permanent loss of kidney function. Unilateral UTO may be difficult to diagnose. Urinary neutrophil gelatinase-associated Lipocalin (uNGAL) may identify unilateral and bilateral UTO. METHODS: Retrospective case-control study of patients undergoing hospital admission at three sites. UTO was determined by review of medical records and cases were matched to control patients. uNGAL was measured by immunoblot. RESULTS: Twenty-four unilateral UTO and 15 bilateral UTO cases were identified. Admission serum creatinine (sCr) (milligram per decilitre) was significantly higher in bilateral UTO, 2.0 (1.1-5.3), but not unilateral UTO, 1.1 (0.8-1.5), compared to controls, 0.9 (0.8-1.2). uNGAL (nanogram per millilitre) was significantly higher both in patients with bilateral UTO, 140 (40-450), and unilateral UTO, 50 (20-100), compared to controls, 20 (10-45). DISCUSSION: uNGAL identifies kidney injury in unilateral and bilateral UTO even in the absence of an elevated sCr.

The Ngal reporter mouse detects the response of the kidney to injury in real time.

Many proteins have been proposed to act as surrogate markers of organ damage, yet for many candidates the essential biomarker characteristics that link the protein to the injured organ have not yet been described. We generated an Ngal reporter mouse by inserting a double-fusion reporter gene encoding luciferase-2 and mCherry (Luc2-mC) into the Ngal (Lcn2) locus. The Ngal-Luc2-mC reporter accurately recapitulated the endogenous message and illuminated injuries in vivo in real time. In the kidney, Ngal-Luc2-mC imaging showed a sensitive, rapid, dose-dependent, reversible, and organ- and cell-specific relationship with tubular stress, which correlated with the level of urinary Ngal (uNgal). Unexpectedly, specific cells of the distal nephron were the source of uNgal. Cells isolated from Ngal-Luc2-mC mice also revealed both the onset and the resolution of the injury, and the actions of NF-κB inhibitors and antibiotics during infection. Thus, imaging of Ngal-Luc2-mC mice and cells identified injurious and reparative agents that affect kidney damage.

Urinary NGAL marks cystic disease in HIV-associated nephropathy.

Nephrosis and a rapid decline in kidney function characterize HIV-associated nephropathy (HIVAN). Histologically, HIVAN is a collapsing focal segmental glomerulosclerosis with prominent tubular damage. We explored the expression of neutrophil gelatinase-associated lipocalin (NGAL), a marker of tubular injury, to determine whether this protein has the potential to aid in the noninvasive diagnosis of HIVAN. We found that expression of urinary NGAL was much higher in patients with biopsy-proven HIVAN than in HIV-positive and HIV-negative patients with other forms of chronic kidney disease. In the HIV-transgenic mouse model of HIVAN, NGAL mRNA was abundant in dilated, microcystic segments of the nephron. In contrast, urinary NGAL did not correlate with proteinuria in human or in mouse models. These data show that marked upregulation of NGAL accompanies HIVAN and support further study of uNGAL levels in large cohorts to aid in the noninvasive diagnosis of HIVAN and screen for HIVAN-related tubular damage.

Discharge to home rates are significantly lower for octogenarians undergoing coronary artery bypass graft surgery.

BACKGROUND: The incidence of coronary artery bypass graft surgery (CABG) performed in elderly patients has been increasing over recent years. We sought to evaluate clinical outcomes of octogenarians undergoing CABG using an audited state-wide mandatory database. METHODS: New York State Department of Health's Cardiac Reporting System was analyzed from 1998 to 2002. In all, 88,154 patients undergoing isolated CABG were identified. Patients were divided into four age groups: less than 50 years (group 1, n = 6,527), 50 to 64 years (group 2, n = 30,088), 65 to 79 years (group 3, n = 43,369), and 80 years and above (group 4, n = 8,170). RESULTS: Of all patients, 9.3% were octogenarians. In addition to marginally worse coronary artery disease, octogenarians generally manifested a higher incidence of preoperative risk factors such as cerebrovascular disease, peripheral vascular disease, and congestive heart failure compared with younger patients at baseline. Both length of hospital stay and in-hospital mortality rate were significantly higher among octogenarians. The incidence of postoperative complications was higher among octogenarians. Multivariate analysis demonstrated renal failure requiring dialysis (odds ratio [OR] = 4.4), myocardial infarction within 6 hours before surgery (OR = 3.6), chronic obstructive pulmonary disease (OR = 1.7), congestive heart failure at admission (OR = 1.7), emergent operation (OR = 1.6), Canadian Cardiovascular Society functional class IV (OR = 1.5), hypertension (OR = 1.4), and low ejection fraction (OR = 0.98) to be significant independent predictors of in-hospital mortality of octogenarians. Discharge to home rates were significantly lower for octogenarians. CONCLUSIONS: Although early outcomes in octogenarians are acceptable, these factors alone are not sufficient to reflect overall success of CABG in these patients, given the strikingly lower discharge to home rates. Attention to full functional recovery in octogenarians is essential.