Volume 64, No. 6/2005(December)
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 Clinical Nephrology
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Originals
Roles of and correlation between a-smooth muscle actin, CD44, hyaluronic acid and osteopontin in crescent formation in human glomerulonephritis
Abstract
H. Nakamura, K. Kitazawa, H. Honda and T. Sugisaki
Department of Nephrology, Showa University School of Medicine, Tokyo, Japan
Background: a-Smooth muscle actin (SMA), CD44, hyaluronic acid (HA) and osteopontin (OPN) are involved in crescent formation; however, the correlation between these molecules during the formation and progression of the crescents in human glomerulonephritis (GN) has not been fully evaluated. Methods: To investigate the expression of a-SMA, CD44, HA, OPN and CD68 renal biopsy specimens from 14 patients with crescentic GN were examined by immunohistochemistry. All crescents were separated into cellular, fibrocellular and fibrous. The extent of staining in each crescent was scored semiquantitatively. The change in the expression of each molecule and its correlation with other molecules during the formation and progression of the crescents were estimated statistically. Results: The expression of a-SMA was significantly up-regulated in the fibrocellular crescents compared with that in the cellular and fibrous crescents. The expression of CD44, OPN and CD68 was significant in the cellular crescents compared with that in the fibrocellular and fibrous crescents. The deposition of HA in the three groups of crescents was high level. However, that of HA was not significant among three groups of crescent. The expression of CD44 in the cellular crescents correlated significantly with the expression of OPN and CD68, and the deposition of HA in the cellular crescents. The expression of OPN in the cellular crescents correlated with the deposition of HA and the expression of CD68 in the cellular crescents. The expression of a-SMA in the cellular and fibrocellular crescents correlated with the deposition of HA in the cellular and fibrocellular crescents. Conclusion: The expression of CD44, HA, OPN and CD68 was up-regulated at the early stage of the crescent formation in human crescentic GN. Moreover, myofibroblasts and cell-matrix interactions mediated by the CD44-OPN and CD44HA receptor-ligand pairs may play important roles in the formation and progression of the crescents.
Correspondence to:
H. Nakamura, MD
Department of Nephrology
Showa University School of Medicine
1-5-8 Hatanodai
Shinagawa-ku, Tokyo, 142-8666
Email: Japanh-mon@east.cts.ne.jp
Originals
Risk of bleeding and restenosis among chronic kidney disease patients undergoing percutaneous coronary intervention
Abstract
N. Attallah, L. Yassine, K. Fisher and J. Yee
Department of Medicine, Henry Ford Hospital, Detroit, MI, USA
Background: Bleeding risk is increased in renal failure due to impaired platelet adhesiveness. Patients who undergo percutaneous coronary intervention (PCI) are given multiple antiplatelet agents that increase that risk. We retrospectively tested the hypothesis that chronic kidney disease (CKD) patients who undergo PCI are at higher risk of bleeding and restenosis (due to chronic inflammation) compared to patients with normal renal function. Methods: Patients who had PCI for non-ST elevation myocardial infarction or unstable angina between July 2001 and June 2003 (1,184 patients) were included in the study. All the patients were given periprocedural clopidogrel, aspirin and glycoprotein IIb/IIIa inhibitor if indicated, and then continued on clopidogrel and aspirin daily for 12 months. The patients were classified into 5 groups according to the CKD stage and followed-up for 12 months for development of major or minor bleeding, restenosis, length of hospital stay and survival. Results: The incidence of major bleeding within the first month (3.4% in normal kidney function patients (Gp1), 4.8% for CKD Stages 1 and 2 patients (Gp2), 5.2% for CKD Stage 3 patients (Gp3), 6.1% for CKD Stage 4 patients (Gp4) and 9.3% for CKD Stage 5 patients (Gp5), p = 0.001) and for minor bleeding (5.7% in Gp1, 6.5% for Gp2, 7.4% for Gp3, 9.2% for Gp4 and 11.3% for Gp5, p = 0.001) and the incidence of restenosis at one month (4.6% in Gp1, 5.3% for Gp2, 6.8% for Gp3, 7.3% for Gp4 and 9.6% for Gp5, p = 0.001) and 6 months (11.2% in Gp1, 13.5% for Gp2, 15.7% for Gp3, 16.4% for Gp4 and 19.7% for Gp5, p = 0.001) were higher with worsening CKD. Survival at one year was worse with worsening of the kidney function. Conclusion: Worsening of CKD is associated with progressively increased risk of minor and major bleeding, restenosis and death during and after PCI.Correspondence to:
N. Attallah, MD
Division of Nephrology and Hypertension
Department of Medicine, CFP-5
Henry Ford Hospital
2799 West Grand Blvd.
Detroit, MI 48202, USA
Email: Nattall1@Hfhs.Org
Originals
Relations of inflammatory markers to lipid levels and autonomic tone in patients with moderate and severe chronic kidney disease and in patients under maintenance hemodialysis
Abstract
S.N. Psychari, L. Sinos, C. Iatrou, G. Liakos and T.S. Apostolou
1Second Department of Cardiology, 2Department of Nephrology, and 3Department of Biochemistry, Nikea General Hospital, Athens, Greece
Background and aims: Chronic kidney disease is associated with enhanced inflammatory response and autonomic dysfunction. Evidence exists of a potential interaction of inflammation and nervous system. We sought to investigate determinants of heart rate variability (HRV) and relations between the inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6) and autonomic tone in patients with moderate and severe chronic kidney disease and in maintenance hemodialysis patients, and relations of CRP and IL-6 with clinical characteristics and lipid levels. Methods: This was a cross-sectional study of 51 hemodialysis and 53 moderate and severe chronic kidney disease patients. Autonomic tone was assessed using 24-hour HRV analysis in time and frequency domain. All patients underwent measurements of high sensitivity CRP, IL-6 and lipid levels. Results: CRP and IL-6 were elevated in the non-dialysis group at levels similar to hemodialysis patients. Hemodialysis patients had lower total cholesterol, LDL cholesterol and apolipoprotein B levels (p < 0.05), and in this group of patients lipids were related to CRP and IL-6 (p < 0.05). The inflammatory marker IL-6 was associated to HRV in the moderate and severe chronic kidney disease group (R = –0.4, p < 0.01 for standard deviation of RR intervals and very low frequency power, R = –0.5, p < 0.01 for standard deviation of all five-minute RR intervals, R = –0.35, p < 0.05, for total power and low frequency power). Adequacy of dialysis, but not the inflammatory markers, was associated to HRV in the hemodialysis group (R = 0.6, p < 0.01 for high frequency power). Conclusion: Enhanced inflammatory response occurs already in stages 3 and 4 chronic kidney disease. IL-6 is related to HRV in these patients, but not in the hemodialysis group, suggesting that IL-6 may interact with autonomic tone in that stage of disease. Correspondence to:
N. Stavroula Psychari, MD
2nd Cardiology Department
Nikea General Hospital
16 Picrodafnis Str., Athens 17562, Greece
Email: tglyras@ath.forthnet.gr
Originals
The effects of lanthanum carbonate and calcium carbonate on bone abnormalities in patients with end-stage renal disease
Abstract
A.J. Freemont, J.A. Hoyland and J. Denton on behalf of the Lanthanum Carbonate SPD405-303 Study Group
Osteoarticular Pathology, The Medical School, University of Manchester, Manchester, UK
Background: Renal osteodystrophy is a common complication of end-stage renal disease (ESRD) and is a major cause of morbidity in patients with ESRD. High serum levels of phosphorus, calcium and parathyroid hormone are associated with the development of this disease. The effects on bone of treatment with lanthanum carbonate, a new phosphate binder, and calcium carbonate were assessed in patients with ESRD. Methods: This was an open-label, multicenter, parallel-group study. Patients were recruited within 12 weeks of commencing dialysis. Following screening, phosphate binder administration was stopped, tetracycline labeling administered and a transiliac bone biopsy taken. After randomization to lanthanum carbonate or calcium carbonate, patients were titrated to an optimum dose for 8 weeks and maintained at this dose for 44 weeks. The bone was then labeled and a second biopsy taken. Biopsy samples were analyzed histomorphometrically. Results: Paired bone biopsies from 33 lanthanum carbonate- and 30 calcium carbonate-treated patients were suitable for analysis. None of the patients on either treatment developed osteomalacia. Assessment of activation frequency changes showed that 41% of biopsies from lanthanum carbonate-treated patients moved towards normal (observed values at the follow-up biopsy were closer to expected values than were the baseline values, so patients were considered to be improved) compared with 23% of calcium carbonate-treated patients (p = 0.15). Conclusions: This study indicates that there was no evidence of aluminum-like toxicity with lanthanum carbonate after 1 year of treatment in ESRD patients commencing dialysis, and there appeared to be a beneficial effect on bone-cell function and activity compared with calcium carbonate.Correspondence to:
Correspondence to:
Prof. A.J. Freemont
Osteoarticular Pathology
University of Manchester
Stopford Building
Oxford Road
Manchester M13 9PT, UK
Email: tony.freemont@man.ac.uk
Originals
Comparison of transplant listing strategy in two renal dialysis centers within a regional transplant alliance
Abstract
R.F. Jeffrey, H. Akbani A.J. Scally and R. Peel
1Renal Unit, St. Luke’s Hospital, Bradford, 2School of Health Studies, University of Bradford, and 3Renal Unit, Hull Royal Infirmary, Hull, Great Britain
Aims: An increasing dialysis population and insufficient supply of transplant organs necessitate that patients are carefully evaluated prior to registration on the national waiting list to ensure effective utilization of a scarce resource. We have assessed listing practice in two renal units within the North of England Transplant Alliance. Methods: Demographic, ethnic and clinical data were recorded at initiation of dialysis for patients from two northern English cities, Bradford (n = 209) and Hull (n = 202) between 1994 – 2000. Patients were stratified by two co-morbidity scoring systems. Multivariate and survival analyses were undertaken by registration status. Results: Overall, 159 patients were registered onto the waiting list. Stratification by co-morbidity predicted listing at high and low risk, but with overlap at medium scores. There was no difference in overall co-morbid burden between the two centers (p = 0.161 and 0.316, respectively, for two scoring systems). Logistic regression analysis demonstrated a center effect, Hull having an odds ratio for listing of 0.48 compared to Bradford (p = 0.041). Short- and medium-term survival in the listed group was high regardless of co-morbid score (22 vs 174 deaths in the non-listed group). In this cohort, five patients died with grafts, another three died whilst active on the waiting list. The remaining 14 patients had been removed from the list prior to death. Summary: Co-morbidity scoring schemes are unlikely to be sophisticated enough to accurately identify those who would most benefit from transplantation, and the value of clinical judgment is well-shown in this study. Standardization of registration will result in more equitable allocation of organs. However, this study has demonstrated that there are differences in listing practices even within a single alliance. Continuous assessment will allow judicious removal from the waiting list of patients who have developed an unacceptable co-morbid burden. Correspondence to:
Dr. R.F. Jeffrey
Renal Unit
St. Luke’s Hospital
Little Horton Lane
Bradford, W. Yorks, England BD5, ONA Great Britain
Email: robin.jeffrey@bradfordhospitals.nhs.uk
Case reports
Report of a case with surprising etiology of renovascular hypertension
Abstract
A. Zumrutdal, F. Tercan, L. Oguzkurt, S. Sezer and F. Nurhan Ozdemir
1Department of Nephrology, Faculty of Medicine, Baskent University, Ankara, and 2Department of Radiology, Faculty of Medicine, Baskent University, Yuregir-Adana, Turkey
Takayasu arteritis is a chronic, idiopathic, inflammatory disease that primarily affects large vessels, such as the aorta and its main branches. Epidemiologically, it is found mostly in female patients and is more prevalent in Asian and Latin American countries. Disease may be heterogeneous in presentation. In this report, we present a different clinical expression of Takayasu arteritis in a young man who had hypertension as the sole manifestation of multiple critical arterial involvement with elevated inflammation markers but no other symptoms. A 28-year-old man was admitted with hypertension. There was no evidence for systemic vasculitis by history, serologic studies or other laboratory data. The acute-phase reactants were elevated with an erythrocyte sedimentation rate of 55 mm/h, and a C-reactive protein value of 22 mg/dl. Digital subtraction angiography showed multiple severe stenoses or occlusions of the branches of the abdominal aorta and arcus aortae together with bilateral renal artery involvement. The etiology of renovascular hypertension was found to be Takayasu arteritis with the presence of at least three criteria, as outlined by the American College of Rheumatology in 1990. Patients with Takayasu arteritis may have atypical clinical expression of the disease, and a diagnosis of Takayasu arteritis should be kept in mind in the differential diagnosis of renovascular hypertension in young subjects, even if they do not have associated symptoms of multiple arterial involvement.Correspondence to:
A. Zumrutdal, MD
Baskent University Faculty of Medicine
Adana Teaching and Research Center
Dadaloglu Mah. 39/6
01250 Yuregir/Adana, Turkey
Email: azumrutdal@yahoo.com
Case reports
Laceration of gastric mucosa associated with dialysis-related amyloidosis
Abstract
M. Muraki, Y. Kanno, K. Higuchi, K. Shirotori, T. Oguchi, K. Hora and K. Kiyosawa
1Second Department of Internal Medicine, and 4Division of Blood Purification, Shinshu University School of Medicine, 2Division of Dialysis Center, and 3Pathology, Jisenkai Aizawa Hospital, Nagano, Japan
We report a 72-year-old female on long-term hemodialysis, who was admitted to the hospital because of hematemesis. On emergency laparotomy, pylorogastrectomy was performed. The resected specimen showed a giant hematoma and traversing fissure along the lesser curvature of the body of the stomach. Histologically, the specimen showed wide hematoma formation and amyloid deposits in the submucosal layer, especially in the wall of blood vessels. These deposits reacted positively to antihuman b2-microglobulin antibody. The post-operative course was favorable, and the patient was discharged on the 35th hospital day. In this case, the laceration site on the gastric mucosa was almost intact and did not demonstrate ischemic change, suggesting that the giant hematoma was caused by submucosal vessel rupture, which led to the gastric mucosa laceration. To our knowledge, this is the first case of gastric mucosa laceration associated with dialysis-related amyloidosis.Correspondence to:
K. Hora, MD
Second Department of Internal Medicine
Shinshu University School of Medicine
3-1-1 Asahi
Matsumoto, Nagano 390-8621, Japan
Email: horakazu@hsp.md.shinshu-u.ac.jp
Congress Highlights
Introduction
Abstract
K. Andrassy and G.M. Hänsch
Congress Highlights
Membrane proteinase 3 and Wegener’s granulomatosis
Abstract
S. von Vietinghoff, A. Schreiber, B. Otto, M. Choi, U. Göbel and R. Kettritz
Medical Faculty of the Charité, Franz Volhard Clinic and Max Delbrück Center for Molecular Medicine, HELIOS Klinikum-Berlin, Germany
Proteinase 3 (PR3) is found in neutrophil and monocyte lysosomal granules. Anti-neutrophil cytoplasmatic antibodies (ANCA) with specificity for PR3 are characteristic for patients with Wegener’s granulomatosis. The interaction of ANCA with neutrophilic ANCA antigens is necessary for the development of ANCA-associated diseases. ANCA bind to membrane-expressed PR3 and induce full-blown activation in primed neutrophils. We discuss two different aspects of membrane PR3 (mPR3). The first aspect is the amount of PR3 and mechanisms controlling this issue. The second aspect is the presence of two neutrophil subsets that differ in the mPR3 expression phenotype.Correspondence to:
R. Kettritz, MD
Franz Volhard Clinic
Wiltbergstrasse 50
13122 Berlin, Germany
Email: kettritz@fvk.charite-buch.de
Congress Highlights
The pathogenesis of ANCA-associated vasculitides: old hypotheses and new insights
Abstract
G.M. Hänsch1, C. Iking-Konert2 and K. Andrassy3
1Institute of Immunology, University of Heidelberg, 2Department of Endocrinology, Diabetology and Rheumatology, University Clinic of Düsseldorf, and 3Medical Clinic, University of Heidelberg, Germany
The pathomechanism of the ANCA-associated vasculitides is discussed in light of the abstracts presented at the ANCA- and Vasculitis Workshop 2005 in Heidelberg!Correspondence to:
G.M. Hänsch
Institute of Immunology
University of Heidelberg
Im Neuenheimer Feld 305
69120 Heidelberg, Germany
Email: n50@ix.urz.uni-heidelberg.de
Congress Highlights
Intravital microscopy in the study of ANCA-associated systemic vasculitis
Abstract
M.A. Little, C.D. Pusey and S. Nourshargh
1Renal Section and 2Eric Bywaters Centre for Vascular Inflammation, Imperial College London, Hammersmith Hospital, London, UK
In addition to being useful clinical markers of systemic vasculitis, anti-neutrophil cytoplasm antibodies (ANCA) may play a role in the initiation of vasculitic injury. These autoantibodies can induce neutrophil degranulation, dysregulated neutrophil apoptosis and neutrophil adhesion to endothelium in static cellular systems. This mini-review will place these sentinel findings in the context of more recent studies using the parallel plate flow chamber and novel animal models of ANCA-associated vasculitis (AASV). Rodent models lend themselves well to investigation of leukocyte endothelial interaction using intravital microscopy. In this way, one can study ANCA-induced leukocyte adhesion/transmigration, and microvascular injury in real time. These studies may then be extended to look at the impact of novel therapeutic agents on these processes.Correspondence to:
M.A. Little
Imperial College London
Renal Section
Hammersmith Hospital
London W12 0NN, UK
Email: m.little@imperial.ac.uk
Congress Highlights
The role of T lymphocytes in ANCA associated vasculitis: neglected or revisited?
Abstract
A.-I. Kälsch, F.J. van der Woude and B.A. Yard
5th Medical Department, University Hospital Mannheim, University of Heidelberg, Germany
“Antineutrophil cytoplasmic antibodies (ANCA) are pathogenic – Oh yes they are!” is the title of a recent review [Falk et al. 2002], discussing the current evidence on the pathogenic role of ANCA in vasculitis. But what about T lymphocytes? Do these cells also contribute to disease manifestation and if so to what extend? T-cells most likely play a role in delivering proper signals to autoreactive B cells for the production of ANCA, but, in the efferent arm of the immune response the involvement of T cells is less obvious and controversially discussed. Numerous studies provide evidence that peripheral T-cell phenotypes are dramatically changed in ANCA associated vasculitis (AAV) patients. How these changes relate to disease manifestation is still a matter of discussion. In an attempt to provide a better understanding of how T cells might play a role in AAV, the present paper will review recent data presented at the 12th international vasculitis and ANCA workshop.Correspondence to:
B.A. Yard
V. Medical Clinic
Clinic Mannheim
Theodor-Kutzer-Ufer 1 – 3
68167 Mannheim, Germany
Congress Highlights
Vasculitis and infection: effects of immunosuppressive therapy
Abstract
H.M. Lode and M. Schmidt-Ioanas
Department of Chest and Infectious Diseases, Helios Klinikum Emil von Behring affil. Charité Universitätsmedizin, Berlin, Germany
The immunosuppressive therapy in systemic vasculitis leads to immunological dysfunctions. The consequences of granulocytopenia and cellular immune deficits are infections of different etiologies in up to 50% of vasculitis patients. The leading severe infections are sepsis and pneumonia induced by a broad spectrum of pathogens (extra- and intra-cellular growing bacteria, fungi, parasites and viruses). The contribution of infections to the mortality of vasculitis patients is important and should induce early and careful control of these events. Correspondence to:
Prof. Dr. med. H. Lode
Department for Chest and Infectious Diseases
Helios Klinikum Emil von Behring
Zum Heckeshorn 33
14109 Berlin, Germany
Email: haloheck@zedat.fu-berlin.de
Congress Highlights
What is new in the therapy of ANCA- associated vasculitides?Take home messages from the 12th workshop on ANCA and systemic vasculitides
Abstract
K. de Groot and D. Jayne
1Medical School, Hannover, Germany, and
2Addenbrooke’s Hospital, Cambridge, UK
ANCA-associated systemic vasculitides (AASV) were previously fatal diseases, in which long-term survival is now achieved with cyclophosphamide (CYC) and prednisolone. As this standard treatment has shown considerable long-term morbidity and mortality and as more sensitive diagnostic procedures allow the earlier diagnosis of these diseases, nowadays, stage adapted treatment regimens that reduce the exposure to CYC are required. There is consensus that at present CYC remains the drug of choice in patients with generalized vasculitis for the induction of a remission period comprising 3 – 6 months. Whether pulse CYC is to be preferred over daily oral CYC is currently assessed in a RCT. There are efforts to further minimize the cumulative CYC dose for remission induction in elderly people, because the mortality is highest, and by adding monoclonal anti-B-cell antibodies. Adding Etanercept to the conventional induction regimen has not proven beneficial in a US RCT. For maintenance of remission a switch from CYC to azathioprine has proven to be safe. Methotrexate for this indication has been found to be comparable to azathioprine in one trial, but was associated with more relapses than leflunomide in another. Mycophenolate mofetil is currently studied with 48 months follow-up time. For induction of remission in patients without renal insufficiency and vital organ failure methotrexate at 0.3 mg/kg/week can replace CYC in patients with moderately extended disease and without pronounced granulomatous changes in the respiratory tract. Myfortic will be assessed for a similar indication in the future. Currently, long-term follow-up of the EUVAS patients is also sought.Correspondence to:
K. de Groot, MD
Department of Nephrology
Medical School Hannover
Carl-Neuberg-Straße 1
30625 Hannover, Germany
Email: kirsten@de-groot.de
Congress Highlights
Autologous stem cell transplantation of treatment-resistant systemic vasculitis – a single center experience and review of the literature
Abstract
I. Kötter1, T. Daikeler2, C. Amberger1, A. Tyndall2 and L. Kanz1
1University Hospital, Department of Internal Medicine II (Oncology, Hematology, Immunology, Rheumatology, Pulmology), Tübingen, Germany, and 2University Hospital and Felix-Platter Spital, Department of Rheumatology, Basel, Switzerland
Aims: Autologous peripheral blood stem cell transplantation (autoPBSCT) is increasingly and successfully applied to patients with treatment-resistant autoimmune diseases, mainly multiple sclerosis and systemic sclerosis, but also juvenile idiopathic arthritis and systemic lupus erythematosus. We intended to analyze the effects of autoPBSCT in patients with treatment-resistant systemic vasculitis by analyzing the outcome of 4 patients from our own hospital, and comparing them to cases reported in the literature. Methods: 4 patients with treatment-resistant vasculitis (Wegener granulomatosis, Churg Strauss syndrome, Takayasu arteritis and relapsing polychondritis) received an autologous PBSCT. Stem cell mobilization was performed with cyclophosphamide (CY) and G-CSF, stem cells were purged by positively selecting CD34+ stem cells over a CliniMacs device, and the conditioning was performed with high dose CY and anti-thymocyte globulin (ATG). Results: AutoPBSCT was well tolerated in all 4 patients. The patient with WG achieved complete remission although cANCA persisted, the other patients are in good partial remissions and respond to maintenance treatments which had been ineffective before PBSCT (CSA, azathioprin). Glucocorticosteroids (GC) could be reduced to a maximum of 10 mg in all patients. Shortly after the procedure, reactivation of viruses from the herpes family occurred in 3 of the patients and had to be treated. In the data base, 25 patients transplanted for severe systemic vasculitis are registered, in the literature, 6 additional vasculitis patients remitting after autoPBSCT are reported. Conclusions: Autologous PBSCT is feasible and effective in severe, treatment-resistant forms of systemic vasculitis. Data are sparse, further prospective studies are needed. These should also aim at evaluating more optimal regimens for conditioning and purging during PBSCT, as in most of the vasculitis patients reported until now, mostly good partial remissions, but less complete remissions were achieved.
Correspondence to:
PD Dr. med. I. Kötter
Department of Internal Medicine II
Otfried-Müller-Straße 10
72076 Tübingen, Germany
Email: ina.koetter@med.uni-tuebingen.de
Letters to the Editor
Coexistence of idiopathic membranous glomerulonephritis and idiopathic focal segmental glomerulosclerosis
Abstract
T. Matsuo, Y. Mori, T. Hashimoto, M. Tajima, T. Okado, Y. Tsukamoto, Y. Kobayashi and S. Sasaki
Letters to the Editor
Mycotic aneurysm in hemodialysis
Abstract
L. Mercadal, L. Chiche, C. Isnard-Bagnis, I. Tostivint and G. Deray
