The Nasal Microbiome in ANCA-Associated Vasculitis: Picking the Nose for Clues on Disease Pathogenesis.

PURPOSE OF REVIEW: The onset and progression of small vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies has been linked to microbial infections. Here, we provide a brief overview of the association of nasal colonization of Staphylococcus aureus with ANCA-associated vasculitis (AAV) and discuss several recent studies mapping the nasal microbiome in AAV patients in particular. RECENT FINDINGS: Nasal microbiome studies revealed dysbiosis as a common trait in active AAV which tends to normalize upon immunosuppressive treatment and quiescent disease. However, due to differences in study design, patient selection, and methodology, the reported microbiome profiles differ considerably precluding conclusions on causal relationships. The microbiome is an emerging area of research in AAV warranting further investigation. Ideally, such studies should be combined with mechanistic studies to unravel key elements related to host-microbe interactions and their relevance for AAV pathogenesis.

Routine tests and automated urinalysis in patients with suspected urinary tract infection at the ED.

BACKGROUND: Urinary tract infections (UTIs) are frequently encountered. Diagnostics of UTI (urine dipstick, Gram stain, urine culture) lack proven accuracy and precision in the emergency department. Utility of automated urinalysis shows promise for UTI diagnosis but has not been validated. METHODS: A total of 381 cases presenting with fever and/or clinically suspected UTI were analyzed. Diagnosis was based on clinical presentation, urine culture and/ or blood culture, and successful treatment. Performance of standard diagnostics and automated urinalysis (Sysmex UF-1000i) was analyzed at various cutoff values, and diagnostic algorithms were tested. RESULTS: One hundred forty-three (37.5%) cases were diagnosed with UTI. Sensitivity of urine dipstick nitrite was 32.9% and specificity was 93.7%. Sensitivity of urine dipstick leukocyte esterase (3+) was 80.4% and specificity was 82.8%. Receiver operating characteristic curves of automated bacterial and leukocyte count showed area under the curve of 0.851 and 0.872, respectively. Cutoff values of 133 bacteria/µL and 48 leukocytes/µL resulted in >90% sensitivity. Diagnostic values for complicated cases (antibiotics, catheters) were inferior to uncomplicated cases. Algorithms combining dipstick and automated counts did not improve accuracy with the exception of a 5.2% increase in uncomplicated cases (n=247). CONCLUSIONS: Automated leukocyte and bacterial count can be used in the emergency department setting with comparable accuracy compared with standard dipstick analysis with minor improvement when combined.

Are urinary levels of high mobility group box 1 markers of active nephritis in anti-neutrophil cytoplasmic antibody-associated vasculitis?

The objective of this study is to evaluate urinary high mobility group box 1 (HMGB1) levels as markers for active nephritis in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in comparison with urinary CD4(+) effector memory T cells and urinary monocyte chemoattractant protein-1 (MCP-1). Twenty-four AAV patients with active nephritis and 12 healthy controls (HC) were evaluated. In nine patients, samples were also obtained during remission. Urinary levels of HMGB1 were measured by Western blot. CD4(+) T cells and CD4(+) effector memory T cells (CD4(+) CD45RO(+) CCR7(-) ) were determined in urine and whole blood by flow cytometry. Measurement of urinary levels of MCP-1 and serum HMGB1 levels were performed by enzyme-linked immunosorbent assay (ELISA). AAV patients with active nephritis had higher median intensity of HMGB1 in urine than HC [10·3 (7·05-18·50) versus 5·8 (4·48-7·01); P = 0·004]. Both urinary HMGB1 and MCP-1 levels decreased significantly from active nephritis to remission. The urinary MCP-1/creatinine ratio correlated with Birmingham Vasculitis Activity Score (BVAS) (P = 0·042). No correlation was found between the HMGB1/creatinine ratio and 24-h proteinuria, estimated glomerular filtration rate (eGFR), MCP-1/creatinine ratio, BVAS and serum HMGB1. A positive correlation was found between urinary HMGB1/creatinine ratio and CD4(+) T cells/creatinine ratio (P = 0·028) and effector memory T cells/creatinine ratio (P = 0·039) in urine. Urinary HMGB1 levels are increased in AAV patients with active nephritis when compared with HC and patients in remission, and urinary HMGB1 levels are associated with CD4(+) T cells and CD4(+) effector memory T cells in urine. Measurement of urinary HMGB1 may be of additional value in identifying active glomerulonephritis in AAV patients.

Characterization of urinary CD4⁺ and CD8⁺ T cells in kidney transplantation patients with polyomavirus BK infection and allograft rejection.

BACKGROUND AND OBJECTIVES: The objective of this study was to characterize CD4(+) and CD8(+) T-cell populations in blood and urine of renal transplant patients with BK virus (BKV) infection or allograft rejection. MATERIALS AND METHODS: Percentages and absolute numbers of CD4(+) and CD8(+) effector memory T-cell subtype (TEM ) and terminal differentiated T cells (TTD ) in renal transplant patients with BKV infection (n = 14), with an episode of allograft rejection (n = 9), and in uncomplicated renal transplant patients with a stable kidney function (n = 12) were measured and compared using 4-color fluorescence-activated cell sorting. Results were correlated with the number of CD4(+) and CD8(+) T cells in renal biopsies. RESULTS: In patients with allograft rejection, the number of urinary CD4(+) TEM and CD8(+) TEM cells was significantly increased compared to patients with BKV infection or patients without complications. Positive correlation was found between the number of CD4(+) and CD8(+) cells in the renal biopsies and the number of CD4(+) and CD8(+) cells in urine. In patients with rejection, after 2 months of immunosuppressive therapy, a reduction in urinary CD8(+) TEM cells was found. CONCLUSIONS: CD4(+) TEM and CD8(+) TEM cells in urine could be a marker to distinguish allograft rejection from BKV-associated nephropathy and to monitor therapy effectiveness in renal transplant patients with allograft rejection.

Pathogenesis of antineutrophil cytoplasmic autoantibody-associated vasculitis and potential targets for biologic treatment.

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) are autoimmune diseases in which the small vessels are inflamed. Clinical observations suggest a pathogenic role for ANCA. Such a role is supported by in vitro experimental data and animal models, particularly for myeloperoxidase-ANCA. An in vivo pathogenic role of ANCA directed to proteinase 3 has, however, not been fully substantiated. Additionally, the pathogenic role of B cells, T cells, and the alternative pathway of complement in AAV have been elucidated. Insight into these pathogenic pathways involved in AAV has opened and will further open new ways for targeted biologic treatment. In this review the pathogenesis of AAV and potential targets for biologic treatment are discussed.

Influence of gender on the performance of urine dipstick and automated urinalysis in the diagnosis of urinary tract infections at the emergency department.

BACKGROUND: Urinary tract infections (UTIs) are frequently encountered at the Emergency Department (ED). Given the anatomical differences between men and women, we aimed to clarify differences in the diagnostic performance of urinary parameters at the ED. METHODS: A cohort study of adults presenting at the ED with fever and/or clinical suspected UTI. Performance of urine dipstick (UD) and automated urinalysis (UF-1000i) were analysed for the total study population and men and women separately. We focused on 1) UTI diagnosis and 2) positive urine culture (UC, ≥105 CFU/ml) as outcome. RESULTS: In 360 of 917 cases (39.3%) UTI was established (men/women 35.1%/43.6%). Diagnostic accuracy of UD was around 10% lower in women compared to men. Median automated leucocyte and bacterial count were higher in women compared to men. Diagnostic performance by receiver operating analysis was 0.851 for leucocytes (men/women 0.879/0.817) and 0.850 for bacteria (men/women 0.898/0.791). At 90% sensitivity, cut-off values of leucocyte count (men 60/µL, women 43/µL), and bacterial count (men 75/µL, women 139/µL) showed performance differences in favour of men. In both men and women, diagnostic performance using specified cut-off values was not different between normal and non-normal bladder evacuation. UC was positive in 327 cases (men/women 149/178), as with UTI diagnosis, diagnostic values in men outperformed women. CONCLUSIONS: Overall diagnostic accuracy of urinary parameters for diagnosing UTI is higher in men. The described differences in cut-off values for leukocyte and bacterial counts for diagnosing UTI necessitates gender-specific cut-off values, probably reflecting the influence of anatomical and urogenital differences.

ADAM17 upregulation in human renal disease: a role in modulating TGF-alpha availability?

A disintegrin and metalloproteinase (ADAM)17 sheds growth factors from the cell membrane, including epidermal growth factor receptor (EGFR) ligand transforming growth factor (TGF)-alpha. In mice, angiotensin II infusion induces renal fibrosis via ADAM17-mediated TGF-alpha shedding and subsequent EGFR activation. Pharmacological ADAM17 inhibition reduced renal fibrotic lesions and improved renal function, positioning ADAM17 as a promising target of intervention in renal disease. We studied ADAM17 expression in the human kidney. ADAM17 mRNA was constitutively expressed in normal adult kidneys, with highest expression in distal tubules. In human renal disease, ADAM17 was de novo expressed in proximal tubules, peritubular capillaries, and glomerular mesangium and upregulated in podocytes. Glomerular mesangial and endothelial ADAM17 were associated with mesangial matrix expansion, focal glomerulosclerosis, and glomerular macrophage infiltration (P < 0.01). Peritubular capillary and proximal tubular ADAM17 were associated with interstitial fibrosis and interstitial macrophage infiltration (P < 0.05). Both glomerular and interstitial ADAM17 were associated with decreased renal function (P < 0.05). In renal fibrosis, ADAM17 colocalized with TGF-alpha. Moreover, in cultured human podocytes and proximal tubular cells, pharmacological ADAM17 inhibition reduced constitutive TGF-alpha shedding by 78% (P < 0.005) and 100% (P < 0.05), respectively, and phorbol ester-induced TGF-alpha shedding by 84% (P < 0.005) and 92% (P = 0.005), respectively. Finally, ADAM17 inhibition reduced cellular proliferation. In conclusion, the ADAM17 expression pattern and its role in shedding TGF-alpha from cultured human kidney cells suggest a role in the development of fibrosis. Since EGFR signaling is implicated in renal fibrosis, targeting ADAM17 to reduce availability of EGFR ligand TGF-alpha may represent a promising way of intervention in human renal disease.

Wegener's granulomatosis patients show an adequate antibody response to influenza vaccination.

OBJECTIVES: Wegener's granulomatosis (WG) is a systemic vasculitis characterised by relapsing and remitting disease activity. Immunosuppressive drugs are used to control disease, but increase susceptibility to infection. Therefore, influenza vaccination should be considered in WG patients. This study was performed to assess the immunogenicity of influenza vaccination in WG patients. METHODS: A randomised, controlled trial was performed in WG patients with quiescent disease, defined as a Birmingham vasculitis activity score (BVAS) less than 2. Patients were randomly assigned to receive influenza vaccination (n = 49) or to participate as controls (n = 23). In addition, healthy controls (n = 49) were vaccinated. At entry and at 1 and 3-4 months after entry, antibody responses to vaccination were determined. Furthermore, disease activity was measured (BVAS), adverse effects were recorded and antineutrophil cytoplasmic autoantibody (ANCA) titres were determined. RESULTS: WG patients achieved high seroprotection rates to all three influenza strains, comparable with healthy controls. Only the A/H1N1 strain patients had a lower seroconversion rate (p = 0.002) and geometric mean titre (p = 0.037) than controls. After 1 month, one control and one vaccinated WG patient had developed active disease. At 3-4 months, two additional control patients had developed active disease compared with none of the vaccinated patients (p = 0.099). Vaccination did not influence ANCA titres. Adverse effects did not differ between patients and healthy controls. CONCLUSIONS: Influenza vaccination in WG patients with quiescent disease induced a sufficient antibody response. TRIAL REGISTRATION NUMBER: NTR1130.

A novel enzyme-linked immunosorbent assay using a mixture of human native and recombinant proteinase-3 significantly improves the diagnostic potential for antineutrophil cytoplasmic antibody-associated vasculitis.

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA) with a C-ANCA or P-ANCA pattern are detected in ANCA-associated vasculitis (AAV). While in most patients with AAV a C-ANCA pattern is due to reactivity with proteinase-3 (PR3)-ANCA, some C-ANCA-positive sera do not react with PR3. OBJECTIVE: The development and evaluation of a direct enzyme-linked immunosorbent assay (ELISA) for PR3-ANCA with increased sensitivity. METHODS: A mixture of human native (hn) and human recombinant (hr) PR3 was used as antigen coating. The resulting ELISA (anti-PR3-hn-hr) was compared with ELISAs using directly coated hn-PR3 or hr-PR3, as well as with a hn-PR3 capture ELISA. Assay characteristics were determined in patients with AAV (n = 248), with special attention for those patients with C-ANCA (n = 132), as well as disease controls (n = 585) and healthy controls (n = 429). Additionally, for prediction of relapses serial samples of 46 patients with PR3-AAV were analysed. RESULTS: At a predefined specificity of 99% both ELISAs containing hr-PR3 revealed a substantial increase in sensitivity. For the prediction of relapses by rises in PR3-ANCA titres the capture ELISA was most optimal (odds ratio 12.5). With an odds ratio of 8.9 the novel anti-PR3-hn-hr ELISA was second best. CONCLUSIONS: Owing to the very high sensitivity of the novel anti-PR3-hn-hr ELISA for the detection of PR3-ANCA in C-ANCA-positive samples of patients with AAV this assay has an excellent diagnostic performance. This feature is combined with a good predictability of clinical relapses in patients with PR3-AAV. These characteristics challenge the dogma that, for detection of PR3-ANCA, capture ELISAs are superior for diagnosis and follow-up.

Patients' representations of their end-stage renal disease: relation with mortality.

BACKGROUND: Self-regulation theory explains how patients' illness perceptions influence self-management behaviour (e.g. via adherence to treatment). Following these assumptions, we explored whether illness perceptions of ESRD-patients are related to mortality rates. METHODS: Illness perceptions of 182 patients participating in the NECOSAD-2 study in the period between December 2004 and June 2005 were assessed. Cox proportional hazard models were used to estimate whether subsequent all-cause mortality could be attributed to illness perception dimensions. RESULTS: One-third of the participants had died at the end of the follow-up. Mortality rates were higher among patients who believed that their treatment was less effective in controlling their disease (perceived treatment control; RR = 0.71, P = 0.028). This effect remained stable after adjusting for sociodemographic and clinical variables (RR = 0.65, P = 0.015). CONCLUSIONS: If we consider risk factors for mortality, we tend to rely on clinical parameters rather than on patients' representations of their illness. Nevertheless, results from the current exploration may suggest that addressing patients' personal beliefs regarding the effectiveness of treatment can provide a powerful tool for predicting and perhaps even enhancing survival.

Postoperative renal dysfunction and preoperative left ventricular dysfunction predispose patients to increased long-term mortality after coronary artery bypass graft surgery.

BACKGROUND: Both preoperative left ventricular dysfunction and postoperative renal function deterioration are associated with increased long-term mortality after cardiac surgery. The influence of preoperative left ventricular dysfunction on postoperative renal dysfunction and long-term mortality is not defined. METHODS: We collected data from 641 consecutive patients undergoing coronary bypass surgery with cardiopulmonary bypass in 1991 at our institution. Prospective follow-up was through to July 2004. RESULTS: In-hospital mortality was 2.7% (17 of 641). During follow-up, 248 (40%) patients discharged alive died (5 and 10 yr survival 90% and 70%, respectively). On univariate analysis, preoperative left ventricular dysfunction (ejection fraction <50%) and an increase in serum creatinine > or =25% in the first postoperative week were associated with long-term mortality. The associated mortality risk was additive in predominantly non-overlapping patients groups: the hazard ratio (HR) for renal function deterioration only was 1.41 [95% confidence interval (CI) 0.95-2.32, P=0.083; n=64] and for left ventricular dysfunction only 1.71 (95% CI 1.26-2.95, P=0.0026; n=73). In patients in whom both were present, HR was 3.23 (95% CI 2.52-20.28, P<0.0001; n=20). Although postoperative renal dysfunction was associated with left ventricular dysfunction (P=0.008), both left ventricular dysfunction and postoperative renal function deterioration were independently associated with long-term mortality on multivariate analysis, as were age and the use of venous conduits. CONCLUSIONS: Both postoperative renal function deterioration and preoperative left ventricular dysfunction independently identify largely non-overlapping groups of patients with increased long-term mortality after coronary bypass surgery. In the group of patients with both factors present, the mortality risks appear additive.

Venous thromboembolism in ANCA-associated vasculitis--incidence and risk factors.

OBJECTIVES: In patients with ANCA-associated vasculitis (AAV), an increased incidence of venous thromboembolism (VTE), mainly during active disease, has been described. In a large cohort of AAV patients, we assessed the incidence of VTE and its relation with disease activity and classic risk factors for VTE. METHODS: Patients newly diagnosed with AAV between 1990 and 2005 and treated with cyclophosphamide and corticosteroids were included. Data were retrospectively retrieved from charts and by questionnaire. The incidence of VTE associated with and following a diagnosis of AAV was calculated (VTE/100 person-years) and related to periods with active disease. RESULTS: One hundred and ninety-eight patients with AAV were followed for 6.1 (0.2-17.6) yrs. In 23 patients (12%), 25 VTEs (17 deep venous thromboses, 3 pulmonary emboli, 5 both) occurred in association with AAV, of which 52% occurred during active disease, defined as 3 months before and after diagnosis or relapse of AAV. Overall, VTE incidence was 1.8/100 person-years, increasing to 6.7/100 during active disease. VTEs occurred significantly less frequently in patients with WG than in patients with microscopic polyangiitis and renal limited vasculitis. Classic risk factors were present in most patients at some moment during follow-up. There were no significant differences in classic risk factors between patients with and without AAV-associated VTE. CONCLUSIONS: Patients with AAV have an increased risk of developing VTEs, especially when AAV is active. This finding could not be explained by classic risk factors, but is probably related to endothelial changes and hypercoagulability induced by AAV and its therapy.

Evaluation of the FIDIS vasculitis multiplex immunoassay for diagnosis and follow-up of ANCA-associated vasculitis and Goodpasture's disease.

We have evaluated a new-multiplex immunoassay (FIDIS Vasculitis) for simultaneous detection and quantification of anti-MPO, -PR3, and -glomerular basement membrane (GBM) antibodies in diagnosis and follow-up of ANCA-associated vasculitides (AAV) and Goodpasture's disease. ANCA were determined in sera of (a) 87 consecutive patients with biopsy-proven pauci-immune NCGN and 72 controls; (b) 9 patients with Goodpasture's disease; and (c) 60 WG patients and 60 controls, previously used in a multicenter comparison of direct and capture ELISA for PR3-ANCA. Finally, for prediction of relapses, PR3-ANCA was measured in samples preceding relapse in 23 PR3-AAV patients and in 23 matched PR3-AAV patients without relapse. The relative sensitivity of the FIDIS Vasculitis assay was 97.4% for MPO-ANCA and 92.3% for PR3-ANCA; specificity was 100% and 97.2%, respectively. Evaluation of the anti-GBM antibody detection revealed a sensitivity of 100% and a specificity of 99.6%. The sensitivity for WG of the PR3-ANCA detection (71.6%) approached the performance of capture ELISA (74%), although at the cost of specificity (96.7% versus 100%). For prediction of relapses a rise of 50% in ANCA level by FIDIS Vasculitis appeared optimal (ROC curve) for prediction of relapses. However, as compared to capture ELISA, both positive (63% versus 76%) and negative (68% versus 72%) predictive values were reduced. In conclusion, simultaneous detection of anti-MPO, -PR3, and -GBM antibodies in the multiplex FIDIS Vasculitis assay has excellent performance in terms of diagnosis of patients with AAV or Goodpasture's disease. However, detection of rises in PR3-ANCA for prediction of relapses gives less optimal results when compared to capture ELISA.

Stridor and Horner's syndrome, weeks after attempted right subclavian vein cannulation.

A 23-year-old woman presented with renal failure resulting from polycystic kidney disease (PKD) aggravated by tubulo-interstitial nephritis. Emergency haemodialysis was planned, and cannulation of the right subclavian vein was attempted, but failed. During this procedure, inadvertent arterial puncture occurred. Transient mild ischaemia of the right arm, and a transient Horner's syndrome were noted. Seven weeks later she presented with severe stridor with impending respiratory failure necessitating emergency intubation; the right-sided Horner's syndrome had recurred. CT imaging showed a large pseudo-aneurysm of the brachiocephalic artery resulting in severe compression of the trachea. Using a prosthetic graft, the operation for the pseudo-aneurysm was successful; there were mild neurological sequelae. Although her family history was negative, autosomal dominant PKD should be considered, and we discuss the possible role of a pre-existing PKD-associated aneurysm.

[Prevention of contrast nephropathy; guidelines from the Department Nephrology of the University Medical Centre Groningen]. / Preventie van contrastnefropathie; richtlijnen vanuit de afdeling Nefrologie van het Universitair Medisch Centrum Groningen.

Contrast nephropathy' is commonly defined as an increase in serum creatinine concentration of more than 44 micromol/l or 25% of the reference value within 48 hours after administration of radiological contrast media. Risk factors are pre-existing renal dysfunction, diabetes mellitus, heart failure, paraproteinaemia, advanced age, use of nephrotoxic medication, intra-arterial use of contrast media and use of large volumes of contrast media. The only form of therapy possible is supportive care, such as renal function replacement therapy. Prevention of contrast nephropathy is of great importance. For patients with risk factors, the treatment of first choice is hydration with intravenous sodium chloride 0.9% combined with oral acetylcysteine given before and after the administration of contrast media.

Native and recombinant proteins to analyze auto-antibodies to myeloperoxidase in pauci-immune crescentic glomerulonephritis.

The prevalence of Anti-Neutrophil Cytoplasmic Antibodies (ANCA) directed against myeloperoxidase (MPO) in pauci-immune necrotizing crescentic glomerulonephritis (NCGN) is dependent on the assay(s) used. We investigated the frequency of MPO-ANCA as detected by different assays for MPO-ANCA in a large cohort of patients with biopsy-proven pauci-immune NCGN. Sera from 121 consecutive untreated patients presenting with pauci-immune NCGN were tested for ANCA directed to proteinase-3 (PR3) at diagnosis. PR3-ANCA negative sera were tested by direct ELISA using recombinant or native MPO and by capture ELISA using two different specific monoclonal antibodies directed to MPO and three different antigenic sources. Sera from 80 relevant disease controls were tested to explore the specificity of the different assays. Thirty-eight out of 121 patients (31%) with pauci-immune NCGN did not have PR3-ANCA. Sufficient amounts of serum from 30 of these 38 PR3-ANCA negative patients were available for further testing. Recombinant and native MPO were recognized by similar numbers of sera in a direct ELISA (recombinant MPO: 93%, native MPO: 93%) and a capture ELISA (recombinant MPO: 77-87%, native MPO: 93%). Sera of patients with PR3-ANCA positive pauci-immune NCGN and disease controls were less frequently positive for MPO-ANCA in a capture ELISA (recombinant MPO: 3-7%, native MPO: 6-7%) than in a direct ELISA (recombinant MPO: 25%, native MPO: 13%). Both direct and capture ELISA assays using either native or recombinant MPO are sensitive techniques to detect MPO-ANCA in patients with pauci-immune NCGN. A capture ELISA performs better than a direct ELISA because it combines a higher specificity with a comparable sensitivity. Recombinant MPO is a good alternative for native MPO when used as antigen in a capture ELISA, but not when used in a direct ELISA because of lower specificity in this latter assay.

Nitric oxide production and nitric oxide synthase expression in acute human renal allograft rejection.

BACKGROUND: Nitric oxide (NO) is produced by nitric oxide synthases (NOS), which are either constitutively expressed in the kidney or inducible, in resident and infiltrating cells during inflammation and allograft rejection. NO is rapidly degraded to the stable end products nitrite and nitrate, which can be measured in serum and urine, and may serve as noninvasive markers of kidney allograft rejection. METHODS: Total nitrite and nitrate levels (NOx) were measured in serum and urine thrice weekly after an overnight fast in 18 consecutive patients following renal cadaveric transplantation. Inducible NOS (iNOS) and endothelial NOS (eNOS) expression was immunochemically determined in renal biopsy specimens with or without acute rejection (AR). RESULTS: Serum NOx levels increased days before AR and were significantly higher at the moment of AR (27+/-12.4 micromol/L) compared with recipients with an uncomplicated course (13+/-7.6 micromol/L), but not compared with recipients with cyclosporine (CsA) toxicity (20+/-13.0 micromol/L). Urinary NOx levels were significantly lower during AR (20+/-13.6 micromol/mmol creatinine) compared with an uncomplicated course (64+/-25.2 micromol/mmol creatinine) or CsA toxicity (53.8+/-28.3 micromol/mmol creatinine). Interstitial and glomerular iNOS expression was significantly increased in biopsy specimens showing AR. Unexpectedly, glomerular eNOS expression was significantly decreased in patients with AR. CONCLUSIONS: This study reports differences in NOx levels in serum and urine, which may help discriminate AR episodes from an uncomplicated course or CsA toxicity. As expected, renal iNOS expression is increased in acute allograft rejection. The decrease in glomerular eNOS expression suggests an intriguing link between acute and chronic rejection.

Long-term renal outcome after lung transplantation is predicted by the 1-month postoperative renal function loss.

BACKGROUND: Progressive renal function loss is common after lung transplantation. To facilitate the design of renoprotective strategies, identification of early predictors for long-term renal function loss would be useful. METHODS: We prospectively analyzed renal function [glomerular filtration rate (GFR); 125I-iothalamate clearance] in a closely monitored cohort (minimum 24-month follow-up) of 57 patients who received lung transplants between November 1990 and September 1996 in our center. The analyzed end points were the slope of the GFR from 6 months posttransplant onward and the GFR at 24 months after transplantation. RESULTS: Before transplantation, the GFR was 100 ml/min (median, range 59-163). It decreased to 67 ml/min (29-123) at 6 months, 53 ml/min (17-116) at 24 months, and 51 ml/min (20-87) at 36 months after transplantation. The magnitude of the loss of GFR 1 month post-transplantation was the only factor significantly correlated with absolute GFR at 24 months after transplantation. Pulmonary diagnosis was significantly associated with long-term rate of renal function loss. Median loss of GFR was greatest in patients with cystic fibrosis (-10 ml/min/year, range -14 to -6 ml/min/year), preserved in pulmonary hypertension (-1 ml/min/year, range -6 to +7 ml/min/year), and in between in emphysema (-6 ml/min/year, range -27 to +12 ml/min/year). No other factors could be identified. CONCLUSIONS: In lung transplant recipients, the 1-month postoperative loss of GFR is an early marker for long-term renal prognosis. Pulmonary diagnosis appears to be a relevant predictor as well. These factors may guide further research and the development of preventive strategies.

Hemolytic uremic syndrome due to Capnocytophaga canimorsus bacteremia after a dog bite.

The hemolytic uremic syndrome (HUS) is known to have several causes, including infectious diseases, drugs, pregnancy, and malignant disease. We report a patient who developed acute renal failure attributable to HUS in the course of Capnocytophaga canimorsus bacteremia. Acute tubular necrosis as well as HUS should be considered as a cause of acute renal failure in the setting of Capnocytophaga canimorsus bacteremia.