adrenomedullin and Urinary-Tract-Infections

To review the recent advances in the diagnostic and therapeutic approach to adults presenting with febrile urinary tract infection (UTI) in the emergency department (ED).. Recent research suggests overdiagnosis and therefore overtreatment of UTI in the ED, especially in the elderly. Antimicrobial pretreatment, an indwelling catheter, and malignancy are independent risk factors for bacteremia with uropathogens that cannot be cultured from urine. A simple clinical prediction rule can predict clinically relevant radiologic findings in patients with invasive UTI. Procalcitonin is a marker for bacteremia; pro-adrenomedullin predicts a complicated course and 30-day mortality in complicated UTI. Several reports have identified the risk factors for resistant uropathogens in community-acquired febrile UTI. Adherence to the guidelines and early culture-guided intravenous-to-oral switch reduces the length of hospitalization.. An effective strategy is needed to improve the diagnosis of UTIs in acute care. Further research regarding biomarker-guided triage might improve the management of patients with febrile UTI. Future efforts should be directed toward the improvement of adherence to UTI treatment guidelines.

Topics: Adrenomedullin; Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Catheters, Indwelling; Clinical Protocols; Emergency Service, Hospital; Fever; Guideline Adherence; Hospitalization; Humans; Length of Stay; Practice Guidelines as Topic; Predictive Value of Tests; Protein Precursors; Risk Factors; Triage; Urinary Tract Infections

A reduction in duration of antibiotic therapy is crucial in minimizing the development of antimicrobial resistance, drug-related side effects and health care costs. The minimal effective duration of antimicrobial therapy for febrile urinary tract infections (fUTI) remains a topic of uncertainty, especially in male patients, those of older age or with comorbidities. Biomarkers have the potential to objectively identify the optimal moment for cessation of therapy.. A secondary analysis of a randomized placebo-controlled trial among 35 primary care centers and 7 emergency departments of regional hospitals in the Netherlands. Women and men aged ≥18 years with a diagnosis of fUTI were randomly assigned to receive antibiotic treatment for 7 or 14 days. Patients indicated to receive antimicrobial treatment for more than 14 days were excluded from randomization. The biomarkers procalcitonin (PCT), mid-regional proadrenomedullin (MR-proADM), and C-reactive protein (CRP) were compared in their ability to predict clinical cure or failure through the 10-18 day post-treatment visit.. Biomarker concentrations were measured in 249 patients, with a clinical cure rate of 94% in the 165 randomized and 88% in the 84 non-randomized patients. PCT, MR-proADM and CRP concentrations did not differ between patients with clinical cure and treatment failure, and did not predict treatment outcome, irrespective of 7 or 14 day treatment duration (ROC. Although the biomarkers PCT and MR-proADM were correlated to clinical parameters indicating disease severity, they did not predict treatment outcome in patients with community acquired febrile urinary tract infection who were treated for either 7 or 14 days. CRP had no added value in the management of patients with fUTI.. The study was registered at ClinicalTrials.gov [ NCT00809913 ; December 16, 2008] and trialregister.nl [ NTR1583 ; December 19, 2008].

Topics: Adrenomedullin; Aged; Anti-Bacterial Agents; Biomarkers, Pharmacological; C-Reactive Protein; Community-Acquired Infections; Female; Fever; Humans; Male; Middle Aged; Netherlands; Procalcitonin; Prognosis; Protein Precursors; Retrospective Studies; Treatment Outcome; Urinary Tract Infections

Febrile urinary tract infections (fUTI) can often be treated safely with oral antimicrobials in an outpatient setting. However, a minority of patients develop complications that may progress into septic shock. An accurate assessment of disease severity upon emergency department (ED) presentation is therefore crucial in order to guide the most appropriate triage and treatment decisions.. Consecutive patients were enrolled with presumptive fUTI across 7 EDs in the Netherlands. The biomarkers mid-regional proadrenomedullin (MR-proADM), procalcitonin (PCT), C-reactive protein (CRP), and a clinical score (PRACTICE), were compared in their ability to predict a clinically severe course of fUTI, initial hospital admission and subsequent readmission using area under the receiver operating characteristic (AUROC) curves.. Biomarker concentrations were measured in 313 patients, with 259 (83%) hospitalized upon ED presentation, and 54 (17%) treated as outpatients. Of these outpatients, 12 (22%) were later hospitalized. MR-proADM had the highest diagnostic accuracy for predicting a complicated fUTI (AUROC [95% CI]: 0.86 [0.79-0.92]), followed by PCT (AUROC [95% CI]: 0.69 [0.58-0.80]). MR-proADM concentrations were unique in being significantly elevated in patients directly admitted and in outpatients requiring subsequent hospitalization, compared to those completing treatment at home. A virtual triage algorithm with an MR-proADM cut-off of 0.80  nmol/L resulted in a hospitalization rate of 66%, with only 2% secondary admissions.. MR-proADM could accurately predict a severe course in patients with fUTI, and identify greater patient numbers who could be safely managed as outpatients. An initial assessment on ED presentation may focus resources to patients with highest disease severities.

Topics: Adrenomedullin; Adult; Aged; Algorithms; Biomarkers; C-Reactive Protein; Community-Acquired Infections; Female; Fever; Hospitalization; Humans; Male; Middle Aged; Netherlands; Outpatients; Procalcitonin; Prognosis; Protein Precursors; ROC Curve; Severity of Illness Index; Triage; Urinary Tract Infections

Urinary tract infections (UTIs) are among the most common infectious diseases and drivers of antibiotic use and in-hospital days. A reduction of antibiotic use potentially lowers the risk of antibiotic resistance. An early and adequate risk assessment combining medical, biopsychosocial and functional risk scores has the potential to optimize site-of-care decisions and thus allocation of limited health-care resources. The aim of this factorial design study is twofold: first, for Intervention A, it investigates antibiotic exposure of patients treated with a protocol based on the type of UTI, procalcitonin (PCT) and pyuria. Second, for Intervention B, it investigates the usefulness of the prognostic biomarker proadrenomedullin (ProADM) integrated into an interdisciplinary assessment bundle for site-of-care decisions.. This randomized controlled open-label trial has a factorial design (2 × 2). Randomization of patients will be based on a pre-specified computer-generated randomization list and independent for the two interventions. Adults with UTI presenting to the emergency department (ED) will be screened and enrolled after providing informed consent. For our first Intervention (A), we developed a protocol based on previous observational research to recommend initiation and duration of antibiotic use based on the clinical presentation of UTI, pyuria and PCT levels. For our second intervention (B), an algorithm was developed to support site-of care decisions based on the prognostic marker ProADM and distinct nursing factors on days 1 and 3. Both interventions will be compared with a control group conforming to the guidelines. The primary endpoints for the two interventions will be: (A) overall exposure to antibiotics and (B) length of physician-led hospitalization within a follow-up of 30 days. Endpoints are assessed at discharge from hospital, and 30 and 90 days after admission. We plan to screen 300 patients and enroll 250 for an anticipated estimated loss of follow-up of 20%. This will provide adequate power for the two interventions.. This trial investigates two strategies for improved individualized medical care in patients with UTI. The minimally effective duration of antibiotic therapy is not known for UTIs, which is important for reducing the selection pressure for antibiotic resistance, costs and drug-related side effects. Triage decisions must be improved to reflect the true medical, biopsychosocial and functional risks in order to allocate patients to the most appropriate care setting and reduce hospital-acquired disability.. ISRCTN13663741.

Topics: Adrenomedullin; Algorithms; Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Clinical Protocols; Emergency Service, Hospital; Guideline Adherence; Humans; Length of Stay; Patient Admission; Patient Discharge; Practice Guidelines as Topic; Precision Medicine; Predictive Value of Tests; Protein Precursors; Research Design; Switzerland; Time Factors; Treatment Outcome; Triage; Urinary Tract Infections

Midregional-proadrenomedullin (MR-proADM) is a useful prognostic peptide in severe infectious pathologies in the adult population. However, there are no studies that analyze its utility in febrile urinary tract infection (fUTI) in children. An accurate biomarker would provide an early detection of patients with kidney damage, avoiding other invasive tests like renal scintigraphy scans. Our objective is to study the usefulness of MR-proADM as a biomarker of acute and chronic renal parenchymal damage in fUTI within the pediatric population.. A prospective cohort study was conducted in pediatric patients with fUTI between January 2015 and December 2018. Plasma and urine MR-proADM levels were measured at admission in addition to other laboratory parameters. After confirmation of fUTI, renal scintigraphy scans were performed during the acute and follow-up stages. A descriptive study has been carried out and sensitivity, specificity and ROC curves for MR-proADM, C-reactive protein, and procalcitonin were calculated.. 62 pediatric patients (34 female) were enrolled. Scintigraphy showed acute pyelonephritis in 35 patients (56.5%). Of those patients, the median of plasmatic MR-proADM (P-MR-proADM) showed no differences compared to patients without pyelonephritis. 7 patients (11.3%) developed renal scars (RS). Their median P-MR-proADM levels were 1.07 nmol/L (IQR 0.66-1.59), while in patients without RS were 0.48 nmol/L (0.43-0.63) (p < 0.01). The AUC in this case was 0.92 (95% CI 0.77-0.99). We established an optimal cut-off point at 0.66 nmol/L with sensitivity 83.3% and specificity 81.8%.. MR-ProADM has demonstrated a poor ability to diagnose pyelonephritis in pediatric patients with fUTI. However, P-MR-proADM proved to be a very reliable biomarker for RS prediction.

Topics: Adrenomedullin; Biomarkers; Child; Female; Humans; Kidney; Male; Prognosis; Prospective Studies; Protein Precursors; Urinary Tract Infections

The aim of this paper is to investigate whether urosepsis is related to irrigation pressure of ureteroscopy (URS) and evaluate the prognostic value of adrenomedullin (ADM) and atrial and brain natriuretic peptides (ANP and BNP) in URS-induced uroseptic patients. From July 2008 to October 2013, we enrolled 332 patients with untreated unilateral ureteral obstruction (UUO). The UUO group included three subgroups of, respectively, 118, 132, and 82 patients who underwent URS under intermittent stable irrigation pressure of, respectively, 80, 120, and 160 mmHg. The plasma concentrations of ADM, ANP, and BNP were measured in all subjects. URS was performed for all UUO patients; the values of the three peptides were measured again after URS. Irrigation pressure and stone size were independent risk factors of urosepsis. After URS, the plasma concentrations of ADM, ANP, and BNP were significantly higher in uroseptic patients. Moreover, the concentrations were significantly higher depending on the disease severity. Plasma concentrations of the three peptides were correlated with plasma ET concentration in the uroseptic patients. The areas under receiver operating characteristic (ROC) curve of ADM, ANP, and BNP for predicting urosepsis were 0.811, 0.728, and 0.764, respectively. In conclusion, ADM, along with ANP and BNP, is valuable for prognosis in urosepsis secondary to URS which is associated with irrigation pressure.

Topics: Adolescent; Adrenomedullin; Adult; Aged; Atrial Natriuretic Factor; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Sepsis; Ureteroscopy; Urinary Tract Infections; Young Adult

Bacterial infections such as febrile urinary tract infection (fUTI) may run a complicated course that is difficult to foretell on clinical evaluation only. Because the conventional biomarkers erythrocyte sedimentation rate (ESR), leucocyte count, C-reactive protein (CRP) and procalcitonin (PCT) have a limited role in the prediction of a complicated course of disease, a new biomarker-plasma midregional pro-adrenomedullin (MR-proADM)-was evaluated in patients with f UTI. We conducted a prospective multicentre cohort study including consecutive patients with f UTI at 35 primary-care centres and eight emergency departments. Clinical and microbiological data were collected and plasma biomarker levels were measured at presentation to the physician. Survival was assessed after 30 days. Of 494 fUTI patients, median age was 67 (interquartile range 49-78) years, 40% were male; two-thirds of them had significant co-existing medical conditions. Median MR-proADM level was 1.42 (interquartile range 0.67-1.57) nM; significantly elevated MR-proADM levels were measured in patients with bacteraemia, those admitted to the intensive care unit, and in 30-day and 90-day non-survivors, compared with patients without these characteristics. The diagnostic accuracy for predicting 30-day mortality in fUTI, reflected by the area-under-the-curve of receiver operating characteristics were: MR-proADM 0.83 (95% CI 0.71-0.94), PCT 0.71 (95% CI 0.56-0.85); whereas CRP, ESR and leucocyte count lacked diagnostic value in this respect. This study shows that MR-proADM assessed on first contact predicts a complicated course of disease and 30-day mortality in patients with fUTI and in this respect has a higher discriminating accuracy than the currently available biomarkers ESR, CRP, PCT and leucocyte count.

Topics: Adrenomedullin; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fever; Humans; Male; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; Risk Factors; Survival Analysis; Urinary Tract Infections

Adrenomedullin (AM) is a strong vasodilator peptide with proven antimitogenic and antiproliferative effects in renal mesangial cells, as well as diuretic and natriuretic actions. Its gene expression is stimulated by endotoxins (lipopolysacharides) and cytokines. Consequently, its plasma and urinary levels are known to deviate from normal levels in many renal diseases. The purpose of this study is to determine plasma and urinary AM levels in children with renal parenchymal scar (RPS) and vesicoureteral reflux (VUR). The study was carried out on 74 children with recurrent urinary tract infections, arranged in groups: 25 patients with RPS with VUR (group I), 16 patients with RPS without VUR (group II), 12 patients with VUR without RPS (group III) and 21 healthy children as the control group. Plasma and urinary AM concentrations were both determined by high performance liquid chromotography (HPLC). Plasma AM was measured as picomoles per milliliter (pM/ml) and urinary AM as pM/mg urinary creatinine. In addition, serum creatinine, creatinine clearance and fractional sodium excretion (FE(Na)) were measured. All cases with RPS and VUR had normal blood pressure levels. The plasma AM levels were higher, although not significantly, in the control group (56.2+/-14.0 pM/ml) than in group I (50.6+/-4.2 pM/ml), group II (49.6+/-3.7 pM/ml) and group III (50.6+/-3.6 pM/ml) ( P =0.162). The urinary AM levels were higher in the control group (80.1+/-33.9 pM/mg) than in the three study groups (52+/-7.6 pM/mg, 58.6+/-7.5 pM/mg and 44.2+/-6.4 pM/mg; P =0.003, P =0.002 and P =0.002, respectively). There were no differences among the 4 groups (group I, group II, group III and the control group) in terms of FE(Na) and creatinine clearance ( P >0.05 and P >0.05, respectively). The finding that diminished urinary AM levels in patients with RPS and VUR implies that AM can be a prognostic factor in the long-term follow-up of cases with these diseases.

Topics: Adolescent; Adrenomedullin; Child; Child, Preschool; Cicatrix; Humans; Infant; Kidney; Peptides; Urinary Tract Infections; Vesico-Ureteral Reflux

Adrenomedullin (AM), a smooth-muscle relaxant peptide, is stimulated by cytokines and bacterial endotoxins. We hypothesized that urinary-tract infections may be associated with elevated urinary AM excretion.. AM in urine was quantified in eleven children with urinary-tract infection and 11 age- and sex-matched controls by radioimmunoassay. RT-PCR was used to demonstrate local AM mRNA expression in the urinary tract.. In healthy controls but not in diseased children there was a significant correlation between AM and creatinine in urine (r = 0.91, P < 0.001). AM levels in children with urinary-tract infection were significantly higher than in controls (0.6 +/- 0.41 vs 0.15 +/- 0.14 ng/micromol creatinine; P < 0.001; (means +/- SD)). There was a significant correlation between white cell count and AM in urine (r = 0.78, P < 0.001). AM mRNA was expressed in renal tissue, renal pelvis, ureter, bladder, and urethra.. The smooth-muscle relaxant peptide adrenomedullin that is synthesized in tissue of the human urinary tract is elevated in urine of patients with urinary-tract infections. A possible consequence might be the interference with the ureteral anti-reflux mechanisms.

Topics: Adrenomedullin; Base Sequence; Case-Control Studies; Child; Child, Preschool; Creatinine; Cystitis; DNA Primers; Female; Gene Expression; Humans; Infant; Infant, Newborn; Leukocytes; Male; Peptides; Polymerase Chain Reaction; Pyelonephritis; RNA, Messenger; Urinary Tract Infections; Urine