Volume 66, No. 5/2006(November)
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 Clinical Nephrology
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Originals
Increased serum levels of S100A12 in patients with MPO-ANCA-associated glomerulonephritis
Abstract
A. Komatsuda, H. Ohtani, H. Wakui, K.A. Chyzh, T. Hatakeyama, K. Iwamoto, N. Maki, T. Kimura, J. Hitomi and K. Sawada
A. Komatsuda, H. Ohtani, H. Wakui, K.A. Chyzh, T. Hatakeyama, K. Iwamoto, N. Maki, T. Kimura, J. Hitomi and K. Sawada
Background: Increased serum levels of S100A12, a proinflammatory protein secreted by activated neutrophils, have recently been shown in patients with active inflammatory diseases, such as rheumatoid arthritis and Kawasaki disease. In this study, we investigated serum levels of S100A12 in patients with small-vessel vasculitis, myeloperoxidase anti-neutrophil cytoplasmic antibodies- (MPO-ANCA) associated pauci-immune glomerulonephritis. Methods: Serum S100A12 concentrations were measured by a sandwich enzyme-linked immunosorbent assay (ELISA) in 46 patients with MPO-ANCA-associated glomerulonephritis and 29 healthy controls. We analyzed correlations between serum S100A12 levels and a clinical index of vasculitis activity, the Birmingham Vasculitis Activity Score (BVAS), various laboratory parameters, and pathological activity scores in the patients. We also analyzed changes of serum S100A12 levels in 10 patients after treatment. Results: ELISA showed about 4-fold higher levels of serum S100A12 in patients with MPO-ANCA-associated glomerulonephritis than healthy controls. Serum S100A12 levels correlated with the BVAS scores, the peripheral white blood cell count, levels of serum C-reactive protein and creatinine, and pathological activity scores in the patients, but did not correlate with serum MPO-ANCA titers. Serum S100A12 levels after treatment decreased in all the 10 patients examined. Conclusion: We demonstrated that increased serum S100A12 levels correlate with clinical, laboratory and pathological parameters of disease activity in patients with MPO-ANCA-associated glomerulonephritis. Serum S100A12 level may be one of the useful markers of disease activity in MPO-ANCA-associated glomerulonephritis.Correspondence to:
A. Komatsuda, MD
Third Department of Internal Medicine
Akita University School of Medicine
1-1-1 Hondo, Akita City, Akita 010-8543, Japan
Email: komatsud@med.akita-u.ac.jp
Originals
Nephrotoxicity of iso-osmolar versus low-osmolar contrast media is equal in low risk patients
Abstract
T. Feldkamp, D. Baumgart, M. Elsner, S. Herget-Rosenthal, F. Pietruck, R. Erbel, T. Philipp and A. Kribben
1Department of Nephrology and Hypertension, 2Department of Cardiology, University Hospital Essen, Germany
Background: Contrast media-induced nephropathy (CIN) is an increasing cause of hospital-acquired acute kidney injury and leads to a significant increase in mortality. There is uncertainty whether the use of iso-osmolar contrast media as opposed to the use of low-osmolar contrast media would be associated with a lower incidence of CIN. Therefore, we compared the nephrotoxicity of isoosmotic contrast media iodixanol with the low-osmotic contrast media iopromid in patients receiving contrast media during coronary angiography. Methods: In this prospective double-blind study we examined 221 patients with normal renal function who received up to 1,000 ml of contrast media during coronary angiography, and compared the effect of iodixanol and iopromid on inducing contrast media nephropathy. Patients received 800 ml fluid orally before contrast media administration and 1,000 ml saline i.v. thereafter. Creatinine clearance, serum creatinine and urine-N-acetyl-b-D-glucosaminidase (NAG) concentration was obtained 24 h before and 48 h after contrast media administration. Decrease of 20% of the creatinine clearance, increase of 25% of serum creatinine and increase of 20% of the urine concentration of NAG was defined as CIN. Results: Incidence of CIN assessed by decreased creatinine clearance was 22.2% in the iopromid group and 19.7% in the iodixanol group. CIN defined by increased serum creatinine was 6.9% in the iopromid group and 8.6% in the iodixanol group. The difference between these two groups was not significant. Subgroup analysis of the diabetic patients or the patients that received high dose of contrast media revealed no significant difference in the incidence of CIN between the two contrast media. Conclusion: The iso-osmolar and the low-osmolar contrast media exhibited the same incidence of CIN in our study population. If fluid administration is sufficient, the selection of either iopromid or iodixanol has no impact on the risk of developing CIN in patients with normal renal function, even when they are diabetic or receive a high dose of more than 500 ml contrast media.Correspondence to:
Dr. T. Feldkamp
Department of Nephrology and Hypertension,
University Hospital Essen
Hufelandstraße 55, 45122 Essen, Germany
Email: thorsten.feldkamp@uni-duisburg-essen.de
Originals
Rapid detection of urinary tract infection – evaluation of flow cytometry
Abstract
N. Gässler1, H. Paul1 and M. Runge2
1Center of Laboratory Diagnostics, St. Bernward-Hospital, Hildesheim, 2Lower Saxony Federal State Office for Consumer Protection and Food Safety, Veterinary Institute, Hannover, Germany
Aims: Urogenital tract infection (UTI) due to bacteria is not only a common infection but also a complication during hospitalization. Therefore, the identification and quantification of bacteria in urine samples are routinely performed methods in microbiological laboratories. To differentiate between infection and contamination it is also important to quantify the leukocyte count. In this study, we suggest a screening procedure using the flow cytometer analyzer BACSYS-40i as tool for the diagnosis of UTI. Material and methods: Each urine sample was inoculated onto agar plates (MacConkey agar, sheep blood agar and enterococcosel agar (Bio Merieux, Nürtingen, Germany)) within 4 hours after collection. After 24 up to 48 hours incubation at 37°C, bacteria were quantified by evaluation of colony-forming units (CFU) according to the criteria given by the German recommendation [MIQ 1997]. Additionally, each sample was submitted to the BACSYS-40i analyzer. The technological principle is a fluorescence flow cytometer with a laser and a fluorescent dye to identify bacteria and leukocytes with high analytical sensitivity. Results: Coefficients of variation (CV) for examination of within-run reproducibility ranged from 1.7 – 9.0% for leukocytes and from 6.2 – 24.6% for bacteria. Linearity was found to be very good, with coefficients of determination of r = 0.9998 for leukocytes, and r = 0.9994 for bacteria. Carry-over was calculated and found to be extremely low, ranging up to 0.03% for leukocytes and up to 0.002% for bacteria. The correlation coefficient for leukocyte counting is 0.979, regression y = 1.0x + 1.0. The number of bacteria determined with the BACSYS-40i (total cell count) is higher than the number determined by culture (viable cell count). If the cut-offs of the analyzer were fixed at ³ 106 and < 105 bacteria/ml for positive, respectively negative results, 39 out of 42 patients (93%) showing unambiguous predominant clinical signs of UTI and in addition growth of bacteria involved in UTI were recognized. Six samples were questionable. Conclusions: Results obtained by the BACSYS-40i can be reported after a few minutes. Urine samples from all 57 patients with predominant clinical signs and in addition growth of bacteria isolated from urine and known as pathogens of UTI had positive results with the analyzer (100%) for elevated bacteria and leukocyte counts. Furthermore, all patients without symptoms for UTI were negative after analysis with the BACSYS-40i (44/44; 100%).
Correspondence to:
Prof. Dr. N. Gässler
Center of Laboratory Diagnostic
St. Bernward Hospital
31132 Hildesheim, Germany
Email: n.gaessler@bernward-khs.de
Originals
The utility of non-HDL in managing dyslipidemia of Stage 5 chronic kidney disease
Abstract
P. Pennell, B. Leclercq, M.I. Delahunty and B.A.J. Walters
1Division of Nephrology and Hypertension, Miller School of Medicine, University of Miami, Miami, FL, USA
2Gambro Healthcare, Lund, Sweden
Background: The Kidney Disease Outcomes Quality Initiative (K/DOQI) treatment guidelines for managing dyslipidemia in patients with chronic kidney disease (CKD) designate CKD as a high-risk category for coronary heart disease and, in Stage 5 CKD patients, recommend maintaining low-density lipoprotein (LDL) < 100 mg/dl and, for patients with hypertriglyceridemia (³ 200 mg/ dl), non-high-density lipoprotein (non-HDL) < 130 mg/dl, the latter to achieve very low-density lipoprotein (VLDL) < 30 mg/dl. More recently, the National Cholesterol Education Program has recommended an LDL target of < 70 mg/dl for high-risk patients. Aims: The purposes of this study were: to document the point prevalence of dyslipidemia in CKD patients at hemodialysis inception, prior to potential impact of dialysis treatments; to assess the hypothesis that non-HDL serves as a reliable surrogate marker for elevated VLDL; to examine the performance of K/DOQI guidelines in treating dyslipidemia; and to evaluate the utility of non-HDL as an alternative primary trigger/target of lipid-lowering therapy in Stage 5 CKD patients. Methods: Consistent with K/DOQI guidelines, lipid levels drawn immediately prior to hemodialysis sessions, thus possibly non-fasting, were analyzed in 21,893 incident dialysis patients by laboratory measurements of triglycerides, total cholesterol, and HDL and from calculated values of non-HDL, LDL, VLDL and intermediate-density lipoprotein. Results: Prevalence of dyslipidemia, by guideline definitions, was 82%, predominantly manifested by elevated triglycerides (52%) and VLDL (52%) and decreased HDL (51%), with less frequent elevations of LDL (40%) and total cholesterol (24%). Non-HDL ³ 130 mg/dl was neither a sensitive (61%) nor specific (75%) marker for elevated VLDL. There was a striking disparity between the high prevalence of dyslipidemia and the percentage of dyslipidemic patients qualified by K/DOQI guidelines for therapy. Non-HDL ³ 130 mg/dl was as effective in qualifying dyslipidemic patients for lipid-lowering therapy (54%) as the entire K/DOQI treatment algorithm (57%). Lowering the trigger of non-HDL to ³ 100 mg/dl would qualify 81% of dyslipidemic patients for treatment while offering the important advantage of being uninfluenced by the non-fasting state. Conclusions: In Stage 5 CKD patients at hemodialysis inception, dyslipidemia is highly prevalent with predominance of the atherogenic triad (hypertriglyceridemia, elevated VLDL and reduced HDL). Non-HDL is a poor surrogate marker for VLDL. As a valid non-fasting lipid parameter, non-HDL alone at the level of ³ 130 mg/dl qualifies dyslipidemic Stage 5 CKD patients for therapy as effectively as the K/DOQI guidelines. Setting the non-HDL trigger/target cut-off at 100 mg/dl overcomes the insensitivity of non-HDL as a marker for atherogenic lipoproteins represented by the VLDL designation while ensuring more aggressive lipid-lowering therapy for Stage 5 CKD patients at high risk for cardiovascular events. Accordingly, non-HDL of 100 mg/dl is proposed as the all-encompassing primary trigger/target of lipid-lowering therapy in high-risk Stage 5 CKD patients, particularly those patients on dialysis in whom lipid samples obtained before dialysis cannot be guaranteed to be fasting.Correspondence to:
P. Pennell, MD
Division of Nephrology and Hypertension (R-126)
Miller School of Medicine
University of Miami
P.O. Box 016960, Miami 33101, FL, USA
Email: ppennell@med.miami.edu
Originals
Association of different intravenous iron preparations with risk of bacteremia in maintenance hemodialysis patients
Abstract
G. Sirken, R. Raja and A.R. Rizkala
1Langhorne Nephrology, Langhorne, 2Albert Einstein Medical Center, Philadelphia, PA and 3Watson Laboratories Inc., Morristown, NJ, USA
Aim: In vitro evidence suggests that different intravenous iron (i.v. Fe) preparations may be associated with different infection rates. This observational study was to determine if different bacteremia rates are associated with different types or amounts of i.v. Fe preparations. Materials and Methods: This retrospective, single-center study was carried out from April 2001 – November 2002, a period in which a global switch from ferric gluconate (FG) to iron sucrose (IS) occurred. During Period I (April 2001 – January 2002) FG was the only i.v. Fe administered in our hemodialysis unit. During Period II (February 2002 – November 2002) IS was the only i.v. Fe administered in our unit. Group A (n = 63) received hemodialysis during both Period I and Period II. Group B (n = 41) received hemodialysis either during Period I or Period II. Results: More bacteremic episodes occurred while IS than while FG was being administered. The adjusted bacteremia incidence rate ratios (IRRs) associated with use of IS vs. FG were 2.92 (95% CI, 1.01 – 8.5) and 2.84 (95% CI 1.32 – 6.09) in Groups A and B, respectively. The adjusted bacteremia IRRs associated with receiving > 2,000 mg of i.v. Fe were 2.42 (95% CI 1.03 – 5.6) and 1.54 (95% CI 0.43 – 5.69) in Groups A and B, respectively. Use of catheters as hemodialysis access increased bacteremia risk in both groups. Conclusions: Use of iron sucrose is associated with higher bacteremia rates than ferric gluconate. The potential association between the cumulative amount of i.v. Fe administered and bacteremia risk is unclear. Randomized clinical trials are needed to verify our findings. Correspondence to:
G. Sirken, DO
Langhorne Nephrology
183B Bristol Oxford Valley Road
Langhorne, PA 19147, USA
Email: sirkumczn@aol.com
Originals
Comparative evaluation of oxidative and antioxidative capacity during high-flux hemodialysis using two different membranes
Abstract
U. Schönermarck1, C. Dengler1, F. Ebeling2, M. Heydenreich2, G.F. Hillebrand1,2 and W. Samtleben1,2
1Department I of Internal Medicine, Nephrology Division, University Hospital Munich Großhadern, Ludwig Maximilians University, Munich and 2Kuratorium Kidney Centre, Neuried, Munich, Germany
Aim: In patients with end-stage renal disease (ESRD) cardiovascular morbidity and mortality are increased. Apart from traditional and uremia-specific factors oxidative stress has been implicated as a main risk factor. This study investigated the influence of two different high-flux hemodialysis membranes on parameters of oxidative stress during a dialysis session. Patients and methods: 14 stable ESRD patients were enrolled in the study and randomly assigned to high-flux hemodialysis using either a polyamide membrane (Polyflux 14; PA group) or a new polysulfone membrane (Diacap Polysulfone HI PS 15; PS group). All patients received 6 treatments with the same membrane. During the 5th treatment parameters of dialysis efficiency, biocompatibility (cell counts, complement C3a, thrombin-antithrombin complex) and oxidative stress (lipid peroxides, total antioxidative capacity) were measured. Results: Parameters of dialysis efficiency and biocompatibility were similar in both treatment groups. At the beginning of the dialysis session both groups showed a low to moderate level of oxidative stress and a reduced total antioxidative capacity as compared to healthy controls. Both parameters deteriorated significantly during the extracorporeal procedure with a similar magnitude in both membrane groups. No correlation between oxidative or antioxidative capacity and parameters of biocompatibility or dialysis efficiency could be found. Conclusions: Dialysis with synthetic high-flux membranes induces a temporary deterioration of oxidative stress parameters in ESRD patients despite good dialysis efficiency and biocompatibility.Correspondence to:
U. Schönermarck, MD
Nephrology Division
Department I of Internal Medicine
University Hospital Munich Großhadern
81366 Munich, Germany
Email: Ulf.Schoenermarck@med.uni-muenchen.de
Originals
Withdrawal from dialysis: a palliative care perspective
Abstract
S. Chater, S.N. Davison, M.J. Germain and L.M. Cohen
1Edinburgh Cancer Center, Western General Hospital, Edinburgh, Scotland, UK (formerly Institute of Palliative Care, University of Ottawa, Ontario, Canada 1990-2004), 2Department of Medicine, Division of Nephrology, University of Alberta, Edmonton, Canada, 3Department of Medicine, 4Department of Psychiatry, Baystate Medical Center, Springfield, MA, USA
A retrospective chart review was conducted in this pilot study of 35 patients who withdrew from dialysis and were followed by a palliative care team. Data included etiology of end-stage renal disease, comorbid illnesses, mode of dialysis and duration, survival time after withdrawal, reason for withdrawal, mental competency, symptom management, and the nature of death. Mean survival time was 10 days. The most frequent symptoms following withdrawal were confusion, agitation, pain and dyspnea. 1/3 of the sample were cognitively impaired at the time of the withdrawal decision. 17% experienced suffering during the withdrawal period, 24% had unrelieved symptoms, 19% psychological distress, while just over 1/3 of patients died alone. With the provision of palliative care, symptom prevalence in the last 24 hours dropped from 53 to 20% for pain, 68 to 33% for agitation and 46 to 26% for dyspnea. Opioids and benzodiazepines were used in the treatment of over 90% of patients. Palliative medicine has the potential to improve the care of patients who discontinue dialysis.
Correspondence to:
S. Chater, MD
Edinburgh Cancer Center
Western General Hospital
Crewe Road, Edinburgh, EH4 2XU, Scotland, UK
Email: schater@doctors.org.uk
Originals
Folate supplementation fails to affect vascular function and carotid artery intima media thickness in cyclosporin A-treated renal transplant recipients
Abstract
S.K. Austen, R.G. Fassett, D.P. Geraghty and J.S. Coombes
1School of Human Movement Studies, University of Queensland, St. Lucia, Qld, 2Center for Aging Rehabilitation and Exercise Science, Victoria University, Melbourne, 3Renal Research Tasmania, Launceston General Hospital, 4School of Human Life Sciences, University of Tasmania, Launceston, Tas, Australia
Background: Cyclosporin A (CsA)-treated renal transplant recipients (RTR) exhibit relative hyperhomocystinemia and vascular dysfunction. Folate supplementation lowers homocysteine and has been shown to improve vascular function in healthy subjects and patients with coronary artery disease. The aim of this study was to assess the effects of 3 months of folate supplementation (5 mg/day) on vascular function and structure in RTR. Methods: A double-blind, placebo-controlled crossover study was conducted in 10 CsA-treated RTR. Vascular structure was measured as carotid artery intima media thickness (IMT) and function was assessed as changes in brachial artery diameter during reactive hyperemia (RH) and in response to glyceryl trinitrate (GTN). Function data were analyzed as absolute and percent change from baseline and area under the diameter/time curve. Blood samples were collected before and after supplementation and analyzed for total plasma homocysteine, folate, vitamin B12 and asymmetric dimethyl arginine (ADMA) in addition to regular measures of hemoglobin, hematocrit, mean corpuscular volume (MCV) and serum creatinine. Results: Folate supplementation significantly increased plasma folate by 687% (p < 0.005) and decreased homocysteine by 37% (p < 0.05) with no changes (p > 0.05) in vitamin B12 or ADMA. There were no significant (p > 0.05) changes in vascular structure or function during the placebo or the folate supplementation phases; IMT; placebo pre mean ± SD, 0.52 ± 0.12, post 0.50 ± 0.11; folate pre 0.55 ± 0.17, post 0.49 ± 0.20 mm, 5% change in brachial artery diameter (RH, placebo pre 10 ± 8, post 6 ± 5; folate pre 9 ± 7, post 7 ± 5; GTN, placebo pre 18 ± 10, post 17 ± 9, folate pre 16 ± 9, post-supplementation 18 ± 8). Conclusion: Three months of folate supplementation decreases plasma homocysteine but has no effect on endothelial function or carotid artery IMT in RTR.Correspondence to:
J.S. Coombes, PhD
School of Human Movement
Room 520, Connell Building
University of Queensland
St. Lucia, Qld 4072, Australia
Email: jcoombes@hms.uq.edu.au
Case Reports
Metformin and antihypertensive therapy with drugs blocking the renin angiotensin system, a cause of concern?
Abstract
H. Gudmundsdottir, H. Aksnes, K. Heldal, A. Krogh, S. Froyshov, N. Rudberg and I. Os
1Department of Nephrology, Ulleval University Hospital, Oslo, 2Department of Medicine, Helse-Innlandet HF, Lillehammer, 3Department of Medicine, Telemark Hospital, Skien, 4Medical Intensive Care Unit, Akershus University Hospital, Lorenskog, 5Medical Intensive Care Unit,Ulleval University Hospital, Oslo, 6Department of Clinical Chemistry, Ulleval University Hospital, Oslo, 7Faculty of Medicine, Medical School, University of Oslo, Oslo, Norway
Background: The burden of diabetes mellitus type 2 (DM2) is increasing worldwide. The combination of DM2 and hypertension (HT) is frequently encountered. Concurrent use of drugs blocking the renin angiotensin system (angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB)) and metformin have become frequent in this group of patients. That combination can become life-threatening under certain circumstances. Method: We present 5 patients with DM2 and HT who developed severe metformin-associated lactic acidosis in a setting with acute renal failure, precipitated by dehydration and aggravated by the use of ACEI or ARB. Results: None of the patients had reduced renal function before the acute illness. They were admitted to the hospital in critical condition with severe metabolic acidosis (pH 6.60 – 6.94), high S-lactate (14 – 23 mmol/l) and S-creatinine 796 – 1,621 mmol/l. They were all hypothermic and 3 were hypoglycemic. All developed circulatory and respiratory collapse. They were treated with either intermittent bicarbonate hemodialysis (HD) or with continuous venovenous hemodiafiltration (CVVHDF) and bicarbonate buffering. All patients recovered without renal sequela. Conclusion: We believe that the incidence of metformin-associated lactic acidosis in Norway may become more frequent due to increased use of metformin and drugs blocking the renin angiotensin system. The awareness of lactic acidosis as a complication to the use of metformin in predisposed individuals is important. General advice should be given to patients regarding reduction of dosage or withdrawal of the drugs during acute intercurrent illness with dehydration. Early diagnosis and treatment of metformin-associated lactic acidosis are crucial for the patient outcome. Hemodialysis can be life-saving and should be started without delay. Correspondence to:
H. Gudmundsdottir, MD
Department of Nephrology
Ulleval University Hospital
0407 Oslo, Norway
Email: helga.gudmundsdottir@ulleval.no
Case Reports
Cholesterol atheroembolic disease in kidney allografts – case report and review of the literature
Abstract
U. Schönermarck1, M. Guba2, M. Weiss3, W.D. Illner2, H. Arbogast2 and T. Bosch1
1Department I of Internal Medicine, Nephrology Division, 2Department of Surgery, Transplant Center, 3Institute of Pathology, University Hospital Großhadern, Ludwig Maximilians University, Munich, Germany
Cholesterol atheroembolic renal disease is a rare cause of renal allograft dysfunction. Two recipients of cadaveric kidney transplantats from the same donor are discussed with presumed graft failure due to cholesterol emboli of donor origin. A review of the literature summarizes the reported cases in renal transplant recipients. While cholesterol embolization of presumed donor origin seems to have a poor renal outcome, cholesterol emboli originating in the recipient have a more favorable prognosis. As donors and recipients of increasing age or prominent atherosclerosis are accepted for transplantation, cholesterol atheroembolic renal disease may become more prevalent and should be considered in patients with renal allograft dysfunction.Correspondence to:
Dr. U. Schönermarck
Nephrology Division, Department I of Internal Medicine
University Hospital Munich Großhadern
81366 Munich, Germany
Email: Ulf.Schoenermarck@med.uni-muenchen.de
Case Reports
Metabolic alkalosis in a hemodialysis patient – successful treatment with a proton pump inhibitor
Abstract
B.M. Kirsch, G. Sunder-Plassmann and C. Schwarz
Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Austria
Hemodialysis patients develop metabolic acidosis due to their impaired excretion of daily produced protons (H+). The following report will show a rare case of severe metabolic alkalosis (predialysis pH 7.52, base excess (BE) +17) in a hemodialysis woman caused by self-provoked upper gastrointestinal H+ losses based on an eating disorder. Treatment with a proton pump inhibitor resulted in the normalization of acid/base homeostasis (predialysis pH 7.40, BE +1.6). Correspondence to:
B.M. Kirsch, MD
Division of Nephrology and Dialysis
Department of Medicine III
Medical University of Vienna
Währingergürtel 18-20
1090 Vienna, Austria
Email: bernhard.kirsch@meduniwien.ac.at
Letter to the Editor
Life-threatening infections following rituximab therapy in renal transplant patients with mixed cryoglobulinemia
Abstract
G. Basse, D. Ribes, N. Kamar, L. Esposito and L. Rostaing
