Abdallah Geara

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.

Immunological aspects of pancreatic islet cell transplantation.

Type 1 diabetes mellitus (T1DM) is one of the most common diseases of childhood. Insulin discovery changed the clinical course of T1DM from an acutely fatal disease to a chronic disease, but this discovery was later found to be inefficient to control its long-term complications. Whole-pancreas and islet cell transplantation seem to provide a potential solution by restoring the normal physiology of glucose–insulin homeostasis. Although islet transplantation is less invasive than whole-pancreas transplantation, the insulin-free state after islet transplantation remained low (10%) at 5 years after surgery. Here, we will present the specific immunologic challenges that are specific to islet cell transplantation, including instant blood-mediated inflammatory reaction and the recurrence of autoimmunity. We will also briefly discuss the immunosuppressive regimens used and the recent radiologic techniques in the detection of engraftment and early rejection of islet cells.

The renin-angiotensin system: an old, newly discovered player in immunoregulation

Clinical and experimental studies that discuss the different immune functions of the renin-angiotensin system (RAS) in kidney diseases were reviewed, with emphasis on studies of kidney transplantation. The RAS has been shown to affect both the innate and adaptive immune responses and has a well-established role in fibrinogenesis. Of special clinical interest is the ability of the RAS to activate the transforming growth factor beta(1) and the Smad pathways leading to fibrinogenesis. In addition to the RAS enhancing effect on the activity of T cells, several components of the RAS have also been shown to be chemotactic to macrophages, T cells, and natural killer cells. Experimental studies have found that RAS blockade decreases the histologic lesions of chronic allograft nephropathy but can enhance acute graft vasculopathy. Although the blockade of RAS has been commonly practiced to reduce posttransplantation hypertension, proteinuria, and erythrocytosis, however, its role in prolonging graft survival is not well established.

Acetazolamide therapy in meningeal involvement of nephrogenic systemic fibrosis

Campieri M et al. Recognition of bactericidal/ permeability-increasing protein by perinuclear anti-neutrophil cytoplasmic antibody-positive sera from ulcerative colitis patients: prevalence and clinical significance. Scand J Gastroenterol 1998; 33: 1284–8. 4 Zhao MH, Jayne DR, Ardiles LG, Culley F, Hodson ME, Lockwood CM. Autoantibodies against bactericidal/ permeability-increasing protein in patients with cystic fibrosis. Q J Med 1996; 89: 259–65. 5 Schultz H, Csernok E, Schuster A, Schmitz TS, Ernst M, Gross WL. Anti-neutrophil cytoplasmic antibodies directed against the bactericidal/permeability-increasing protein (BPI) in pediatric cystic fibrosis patients do not recognize N-terminal regions important for the anti-microbial and lipopolysaccharide-binding activity of BPI. Pediatr Allergy Immunol 2000; 11: 64–70.

Pseudoleukocytosis secondary to hepatitis C-associated cryoglobulinemia: a case report

IntroductionLaboratory tests play a central role in assessing a patient and orienting the diagnostic evaluation. We report a case where the discrepancy between the manual and automatic cell count gave a hint to the final diagnosis.Case presentationA 55-year-old Caucasian man, known to have hepatitis C, was admitted with acute respiratory failure secondary to acute pulmonary edema and diffuse petechial rash of the lower extremities for the previous 2 months. The initial laboratory tests showed acute renal failure (creatinine of 2.6 mg/dL). During his hospital stay, the patient had a fluctuating white blood cell count with a recorded value of 96,000 cells/mL. On a peripheral smear, the blood cell count was in the normal range. The acute renal failure was secondary to membranoproliferative glomerulonephritis secondary to essential mixed cryoglobulinemia diagnosed by biopsy. The complete blood count values, performed by Beckman/Coulter GenS, were falsely high due to precipitation of plasma cryoglobulins at room temperature. This spurious leukocytosis was previously described in several case reports, but values as high as 96,000 cells/mL were never reported.ConclusionThe presence of cryoglobulins in the blood creates a clinical challenge for the interpretation of several laboratory tests. Pseudoleukocytosis secondary to cryoglobulinemia has been observed in several reported cases with white blood cell counts up to 54,000 cells/mL at room temperature and 85,600 cells/mL at 4°C. If the cryoglobulin precipitates rapidly, aggregated cryoglobulin particles may be interpreted as blood cells. We report the first patient with pseudoleukocytosis secondary to hepatitis C cryoglobulinemia with a spurious leukocytosis of 96,000 cells/mL at room temperature. Other laboratory tests could also be affected: underestimation of true erythrocyte sedimentation rate, pseudothrombocytosis and pseudolymphocytosis. The precipitation can remove the hepatitis C virus and the antibody of cryoglobulins from serum leading to a false negative result. Any discrepancy between the automated and manual white blood cell count should lead to the suspicion of cryoglobulinemia in the clinical setting.