Volume 63, No. 3/2005(March)
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 Clinical Nephrology
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Originals
The link between circulating markers of endothelial function and proteinuria in patients with primary glomerulonephritis
Abstract
B. Mackinnon, C.J. Deighan, J. Norrie, M. Boulton-Jones, N. Sattar and J.G. Fox
1Renal Unit, Glasgow Royal Infirmary, 2Robertson Center for Biostatistics, University of Glasgow, and 3Department of Pathological Biochemistry, Glasgow Royal Infirmary, Glasgow, Scotland, UK
Introduction: It is well-established that there is an increase in the incidence of cardiovascular mortality in patients with proteinuric renal disease. The magnitude of the increase in risk is unlikely to be explained by traditional risk factors for cardiovascular disease alone. Proteinuria itself may constitute an additional risk factor, and proteinuric patients are known to have a degree of endothelial dysfunction. The nature of this relationship between proteinuria and endothelial function is the subject of intense investigation. Aim: The aim of this study was to examine the relationship between proteinuria and endothelial dysfunction, as reflected by serum von Willebrand factor (vWF), and the soluble cell adhesion molecules VCAM and ICAM, in patients with primary glomerulonephritis (GN). A secondary aim was to discern whether any relationship could be explained by renal function, lipid profile, inflammation or blood pressure. Methods: A cross-sectional study was undertaken in consecutive patients attending a general nephrology clinic with biopsy-proven primary GN. Patients with end-stage renal disease (ESRD), those on immunosuppressive drugs, or with intercurrent infective illnesses were excluded. Blood pressure and body mass index were recorded. Routine lab assays were undertaken for serum creatinine, lipid profile, and 24-hour urinary protein (UProt). Additional serum samples were stored at –80 °C for subsequent measurement of vWF, VCAM, ICAM and sensitive C reactive protein (sCRP). Results: Data were collected from 129 (86 male) patients. Mean (standard deviation) estimated creatinine clearance was 64 (32) ml/min, and median (interquartile range) 24-hour proteinuria was 1.1 (0.22 – 2.9) g. Mean vWF was 173 (68) IU/dl, median VCAM, ICAM and sCRP were 594 (410 – 708) ng/ml, 235 (208 – 286) ng/ml, and 2.33 (0.83 – 5.68) mg/l, respectively. There was a significant positive correlation between vWF and UProt (Spearman rank correlation, r = 0.41, p < 0.001). When split into tertiles, according to UProt (0 – 500 mg, 500 – 2,000 mg, and > 2,000 mg), there was a significant, stepwise increase in mean vWF (p < 0.001), log VCAM (p < 0.001), and log ICAM (p = 0.002). On multivariate analysis with vWF as the continuous dependent variable, UProt, age, total cholesterol and sCRP were the only significantly independent correlates (model-adjusted R2 = 33%). Conclusion: In patients with primary GN, there is a significant association between endothelial activation as reflected by vWF, VCAM, or ICAM and increasing proteinuria. Elevations in vWF, as well as being related to classical risk factors, are associated with increases in total proteinuria and low-grade inflammation. Thus, future prospective studies should examine the extent to which vWF and other circulating markers of endothelial activation predict coronary heart disease risk in patients with proteinuric renal disease.Correspondence to:
Dr. B. Mackinnon
Renal Unit, Glasgow Royal Infirmary
Third Floor, Walton Building
84-86 Castle Street
Glasgow, G4 OSF, Scotland, United Kingdom
Email: bmackinnon@hotmail.com
Originals
Serum potassium, cardiovascular risk, and effects of an ACE inhibitor: results of the HOPE Study
Abstract
J.F.E. Mann, Q.-L. Yi, P. Sleight, G.R. Dagenais, H.C. Gerstein, E.M. Lonn, J. Bosch and S. Yusuf on behalf of the HOPE Investigators
1Department of Nephrology, Schwabing General Hospital, Ludwig Maximilians University, Munich, and Institute for High Blood Pressure Research, Heidelberg, Germany, 2Population Health Research Institute, McMaster University, Hamilton, Canada, 4Quebec Heart
Background: Both hyper- and hypokalemia increase cardiovascular risk. Modest hyperkalemia is common with angiotensin-converting enzyme inhibition. We studied post-hoc the association of an initial, on-treatment serum potassium measurement with subsequent cardiovascular outcomes over 4.5 years in 9,297 individuals at high cardiovascular risk, randomized to an ACE inhibitor or to placebo. Methods: Post-hoc analysis of cardiovascular outcomes, as related to serum potassium levels, in the HOPE (Heart Outcomes and Prevention Evaluation) study which compared ramipril to placebo, and included 692 patients with a serum potassium level > 5.0 mM and 137 with a serum potassium level < 3.5 mM, defined as hyper- and hypokalemia, respectively. Serum potassium was measured 1 month after start of randomized treatment. Results: With hyperkalemia, the primary event rate was unchanged compared to normokalemia (15.5 vs 15.7%, p > 0.4, respectively), with hypokalemia, the primary event rate was higher (22.6% vs 15.5%, respectively, p = 0.023). The hazard ratio for the primary outcome associated with this initial hypokalemia was 1.44 (1.00 – 2.06) on multivariate analysis. The combined primary outcome (myocardial infarction, cardiovascular death, stroke) was not different throughout deciles of serum potassium but the lowest and highest deciles included many with normokalemia. Randomized treatment was withheld because of hyperkalemia in 8 and 6 people allocated to ramipril and placebo, respectively. The benefit of ramipril on cardiovascular outcomes was independent of serum potassium, but ramipril reduced hypokalemia in the entire cohort (1.15 vs 1.86% with placebo, p = 0.005), particularly in those participants on diuretics (3.8% vs 6.5%, p = 0.07). Conclusions: In patients at high cardiovascular risk, modest hypokalemia predicts a less favorable outcome while modest hyperkalemia does not. Ramipril reduces hypokalemia and decreases risk.Correspondence to:
HOPE Office
Mc Master University
Hamilton General Hospital
237 Barton Street East
Hamilton, ON, L8L 2X2 Canada
Originals
Risk factors determining active urinary stone formation in patients with urolithiasis
Abstract
J.C. Netelenbos, P.J.G. Zwijnenburg and P.M. ter Wee
1Department of Endocrinology, 2Department of Pediatrics, and
3Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands
Aims: The goal of clinical and metabolic evaluation of patients with urinary stones is to identify patients at high risk for recurrent stone formation and as such, to allow the practitioner to suggest preventive therapies. However, knowledge about risk factors for active stone formation in patients with urolithiasis is limited. This study was initiated to assess the significance of several metabolic and clinical parameters for the determination of the risk of active stone formation. Methods: Study in 320 consecutive outpatients referred to our clinic for metabolic analysis. Clinical and metabolic parameters were determined by standardized procedures of questionnaires, serum biochemical profiles and urinalysis. Results: In 21.5% of 284 patients with complete data stone formation was active. Hypercalciuria, hypocitraturia and urinary tract infections had odds ratios for active stone formation above 2.5, whereas the odds ratio of a positive family history was 0.38. Hyperuricosuria, hyperoxaluria and a low urinary volume did not influence the risk for active stone formation. Conclusion: The risk profile for active stone formation differs from the risk profile for urolithiasis in general. Metabolic evaluation and determination of those risk factors in patients with urolithiasis might improve the estimation of the risk of future stone formation.Correspondence to:
Prof. Dr. med. J.C. Netelenbos
Department of Endocrinology
VU University Medical Center
de Boelelaan 1117
1081 HV Amsterdam, The Netherlands
Email: c.netelen@vumc.nl
Originals
Compartment-specific quantitative gene expression analysis after laser microdissection from archival renal allograft biopsies
Abstract
E. Serinsöz1, O. Bock1, T. Kirsch2, H. Haller2, U. Lehmann1, H. Kreipe1 and M. Mengel1
1Institut für Pathologie und 2Abteilung Nephrologie der Medizinischen Hochschule, Hannover, Germany
Background: Various immunological and non-immunological pathomechanisms are responsible for the cellular damage in renal allografts. Since the kidney is an anatomically complex organ with functional and morphological heterogeneous compartments (interstitium, tubuli, vessels, glomeruli), the local response to injury maybe variable, therefore, the identification of local pathomechanisms is important. Aim: To elucidate any discrepancies in quantitative mRNA expression profiles between a total specimen analysis and a cell-specific evaluation after laser microdissection. Methods: Real-time RT-PCR was performed for complement component C3 and heme oxygenase-1 (HO-1) genes compared to the housekeeping gene b-actin using whole section RNA extracted from formalin-fixed and paraffin-embedded archival material of 16 explanted, rejected renal allografts. Ten non-transplant nephrectomies served as controls. For five cases from each group, five different compartments of the organs (interstitium, proximal tubuli, distal tubuli, vessels, glomeruli) were microdissected and quantitative analysis for C3 and HO-1 was performed identically. Results: Whole section mRNA expression analysis: the data showed a constant expression of the housekeeping gene b-actin, a 7-fold increased expression of C3 and a 3-fold decreased expression of HO-1 in the allograft group as compared to the control group. mRNA expression results from microdissected compartments: in the control group, C3 and HO-1 expression could only be detected in the proximal tubuli of all cases whereas all five compartments analyzed from the rejecting kidneys showed expression of the two genes. In the allografts, expression levels of the investigated genes varied considerably not only among the different compartments but between individual cases as well. Conclusion: Laser microdissection combined with real-time RT-PCR is a feasible approach for retrospective quantitative gene expression analysis in formalin-fixed and paraffin-embedded renal allograft specimens. As shown for C3 and HO-1, cell-specific expression patterns of pathogenetically relevant genes vary considerably between individual cases. A close correlation of morphology and cell-specific gene expression analysis will contribute to the elucidation of the complex pathogenesis of chronic renal allograft nephropathy.Correspondence to:
Dr. M. Mengel
Institut für Pathologie
Medizinische Hochschule Hannover
Carl-Neuberg-Straße 1
D-30625 Hannover, Germany
Email: mengel.michael@mh-hannover.de
Originals
Impact of nocturnal home hemodialysis on anemia management in patients with end-stage renal disease
Abstract
D.I. Schwartz, A. Pierratos, R.M.A. Richardson, S.S.A. Fenton and C.T. Chan
1Department of Medicine, Division of Nephrology, The Toronto General Hospital, University Health Network, 2Humber River Regional Hospital, University of Toronto, ON, Canada
Aim: Anemia is adversely associated with poor uremia control and is an established cardiovascular risk factor in patients with end-stage renal disease (ESRD). Nocturnal home hemodialysis (NHD) is a novel form of renal replacement therapy that offers superior clearance of uremic solutes and improvements in several cardiovascular outcome parameters. We conducted a retrospective cohort study to test the hypotheses that augmenting the dose and frequency of dialysis by NHD would improve hemoglobin (Hb) concentrations and decrease requirement of erythropoietin (EPO) in ESRD patients. Methods: In 63 patients (mean age: 46 ± 2 years) receiving NHD (mean duration: 2.1 ± 0.2 years), Hb, EPO dose, iron saturation, ferritin were determined before and at six monthly repeated intervals after conversion to NHD. For comparison, 32 ESRD patients (mean age: 57 ± 3 years) who remained on self-care conventional hemodialysis (CHD) were also studied. Results: There were no differences in baseline Hb concentrations, iron saturation, ferritin, or EPO dose between the two cohorts. After transfer from CHD to NHD, there were significant improvements in Hb concentrations (from 115 ± 2 to 122 ± 3 (6 months) and 124 ± 2 (12 months) g/l, p = 0.03) despite a fall in EPO requirement (from 10 400 ± 1400 to 8500 ± 1300 (6 months) and 7600 ± 1100 (12 months) U/week, p = 0.03). In contrast, CHD cohort had no change in EPO requirement (from 8300 ± 1100 to 8100 ± 1300 (6 months) and 8600 ± 1000 (12 months) U/week, p > 0.05) or Hb concentrations (from 110 ± 2 to 115 ± 3 (6 months) and 115 ± 2 (12 months), p > 0.05). There was a higher percentage of ESRD patients who did not require EPO in the NHD cohort (24% vs. 9.4%, p = 0.01). Lower Hb concentrations were noted in the CHD cohort despite higher iron saturation (0.25 ± 0.01 (NHD) vs. 0.33 ± 0.02 (CHD), p = 0.02) at the end of follow-up. Conclusions: Enhancing uremic clearance by NHD resulted in a rise in Hb and a fall in EPO requirement.Correspondence to:
Dr. C.T. Chan
200 Elizabeth Street, 12-EN 226
Toronto, ON, M5G 2C4, Canada
Email: christopher.chan@uhn.on.ca
Originals
Conversion of temporary hemodialysis catheters to tunneled hemodialysis catheters
Abstract
A. Falk and S. Parthasarathy
1Department of Radiology, Mount Sinai-NYU Medical Center, New York, and 2Amruth Foundation, New Paltz, NY, USA
Purpose: To determine the feasibility and clinical outcomes of conversion of temporary to tunneled hemodialysis catheters using the same venous insertion site. Methods: Data from 42 patients with existing temporary hemodialysis catheters referred for placement of tunneled hemodialysis catheters were retrospectively reviewed. In these patients, the temporary catheter was exchanged for a peel-away sheath, and a tunneled catheter was inserted using the existing venous access site. Technical success, procedural complications, and clinical outcomes were evaluated. Hemodialysis records were reviewed to assess catheter patency during a 30-day follow-up period. Results: The study group consisted of 20 males and 22 females (mean age: 58 years). All 42 temporary catheters were successfully converted to tunneled hemodialysis catheters without immediate procedure-related complications. Follow-up data were available for 32 patients (total: 3038; median 71 catheter days). Nine catheters were removed for infection, yielding a catheter infection rate of 0.30/100 catheter days; three catheters were removed for blood flow < 200 ml/min. 13 patients had catheters removed when catheters were no longer needed. Three patients died with working catheters. The patency rate was 72% at 30 days, with four catheters functioning at the end of the study period. Conclusion: Conversion of a temporary hemodialysis catheter to a tunneled hemodialysis catheter using the same venous insertion site is a safe procedure that avoids complications associated with venotomy and allows conservation of other central venous access sites. Patency and infection rates in these catheters are comparable to several studies of catheter exchange and de novo placement of tunneled hemodialysis catheters.Correspondence to:
A. Falk, MD
46 West 95th Street, #2B
New York, NY 10025, USA
Email: abigailfalk123@pol.net
Case reports
Resolution of primary amyloidosis by melphalan and prednisolone: a case report
Abstract
M. Nakayama, M. Kashiwagi, R. Katafuchi, K. Hori, S. Hayashi and S. Fujimi
1Department of Internal Medicine, Division of Nephrology and Clinical Research Institute, National Kyushu Medical Center Hospital, and
2The First Department of Internal Medicine, Fukuoka Red Cross Hospital, Fukuoka, Japan
We here report a case of a 50-year-old man who showed histologically evident resolution of primary amyloidosis by melphalan and prednisolone. The patient was admitted to our hospital for further evaluation of nephrotic syndrome and remarkable hepatomegaly with refractory ascites, on September 11, 1998. Laboratory tests at presentation showed nephrotic syndrome with slight renal impairment and elevation of the enzymes of the biliary system. Monoclonal light chains were not detected in the serum or urine by immunoelectrophoresis. A renal biopsy revealed global deposition of amyloid in all glomeruli, interstitium and blood vessels. Immunofluorescence staining was positive for k light chains. Liver biopsy specimens showed extensive deposition of amyloid along sinusoid walls. Bone marrow aspiration contained 7% plasma cells but no clusters or abnormal cells. Based on these findings, systemic AL- (amyloid light chain) amyloidosis was diagnosed, and the treatment with combinations of melphalan and prednisolone was started from October 1998 at intervals of 4 – 6 weeks. Renal impairment progressed, resulting in the initiation of maintenance hemodialysis in February 1999. Reinfusion of ascitic fluid into the hemodialysis circuit had been performed from March 1999 for refractory ascites, and ascites disappeared in July 1999. Furthermore, urinary output increased after 14 courses of chemotherapy. Renal function gradually ameliorated with a concomitant reduction in the enzymes of biliary system, and finally hemodialysis was discontinued in April 2001. Sixteen courses of chemotherapy were administered by April 2001. Proteinuria was negative in August 2001. A second renal biopsy was performed on November 20, 2001, which showed markedly decreased amyloid deposition and a proliferation of mesangial cells and increase in matrix in various degrees. We report a case of a patient with primary amyloidosis who was successfully treated by melphalan and prednisolone, resulting in marked resolution of renal amyloidosis.Correspondence to:
Dr. M. Nakayama
Division of Nephrology and Clinical Research Institute
Department of Internal Medicine
National Kyushu Medical Center Hospital
1-8-1 Jigyohama
Chuo-ku, Fukuoka 810-8563, Japan
Email: mnakayama@qmed.hosp.go.jp
Case reports
COX-2 inhibitor induced anuric renal failure in a previously healthy young woman
Abstract
A.S. Mühlfeld and J. Floege
Division of Nephrology and Immunology, University of Aachen, Germany
Side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) most commonly affect the gastrointestinal tract and the kidney. The recent release of selective cyclooxygenase-2 (COX-2) inhibitors has been associated with a decrease in adverse gastrointestinal effects. However, the nephrotoxic potential of these drugs still remains controversial. Here, we report the case of a previously healthy woman with reversible acute renal failure associated with eight days of anuria following the administration of valdecoxib, a newly released selective cyclooxygenase2 inhibitor, during an episode of acute febrile pyelonephritis. We suggest that selective COX-2 inhibitors should not be used in patients with volume contraction and underlying renal disease.Correspondence to:
Dr. J. Floege
Rheinisch Westfälische Technische Hochschule Aachen
Division of Nephrology and Immunology
D-52057 Aachen, Germany
Email: juergen.floege@rwth-aachen.de
Case reports
Ethylene glycol intoxication and xylitol infusion – metabolic steps of oxalate- induced acute renal failure
Abstract
M. Meier, M. Nitschke, B. Perras and J. Steinhoff
Department of Internal Medicine I, University of Lübeck, Germany
Acute renal failure is a major complication in patients with increased oxalate serum concentration. To describe the metabolic mechanisms of oxalate-induced glomerular and tubular damage, we report a case of ethylene glycol intoxication as well as a case of xylitol infusion in a patient with previously unknown primary hyperoxaluria type 1. Both patients presented with acute renal failure associated with histologically proven renal oxalate accumulation. This excessive oxalate overloading resulted from elimination and metabolization of ethylene glycol or xylitol. Thus, key enzymes in the elimination pathway of these substances represent targets for pharmacological treatment. Simultaneous hemodialysis is often necessary to reduce oxalate serum concentration. Whereas renal function of the ethylene glycol-poisoned patient recovered, the second patient who received xylitol infusion required chronic hemodialysis due to the unmasked hyperoxaluria type 1. Our cases demonstrate that patients with excessive endogenous oxalate generation are at high risk to develop acute renal failure. Therefore, to prevent end-stage renal failure in these patients, important clinical factors should be considered as indicators for the underlying cause: history of alcohol abuse and severe high anion gap acidosis for ethylene glycol intoxication or history of long-lasting parenteral nutrition for xylitol-associated acute renal failure.Correspondence to:
Dr. M. Meier
Department of Internal Medicine I
University of Lübeck
Ratzeburger Allee 160
D-23538 Lübeck, Germany
Email: meiermk@aol.com
Case reports
Severe rhabdomyolysis and renal failure triggered by a sauna visit in sickle cell trait: a case report
Abstract
Ch. Eisenbach, J. Pohl, R. Dikow, W. Stremmel and J. Encke
1Department of Gastroenterology, Infectious Diseases and Intoxications, and 2Department of Nephrology, University of Heidelberg, Germany
Sickle cell trait (SCT) is an usually asymptomatic hemoglobinopathy. Cases of sudden excertional deaths in individuals with SCT have been described. We here report an exceptional case of excessive rhabdomyolysis and acute renal failure triggered by a sauna visit in a 29 year-old African American with SCT.Correspondence to:
Dr. Ch. Eisenbach
University of Heidelberg
Department of Gastroenterology
Im Neuenheimer Feld 410
D-69120 Heidelberg, Germany
Email: Christoph_Eisenbach@med.uni-heidelberg.de
Case reports
Superiority of standard interferon-a2b compared to pegylated interferon-a2b (12 kDa) in a hemodialysis patient with chronic hepatitis C?
Abstract
A. Potthoff1, J. Wiegand1, J.B. Lüth2, H. Wedemeyer1, M.P. Manns1 and H.L Tillmann1
1Department of Gastroenterology, Hepatology and Endocrinology,
Hannover Medical School, and 2Clinic for Kidney and Hypertension Disease, Hannover, Germany
Introduction: Hepatitis C virus (HCV) infection represents an important problem for hemodialysis patients. Interferon-a (IFN-a) three times per week has been shown to clear HCV RNA in a substantial proportion of renal transplant candidates, and may thereby prevent the deleterious effect of immunosuppressive treatment on progression of liver disease in HCV-positive patients after renal transplantation. Data on the efficacy of the new pegylated interferons in hemodialysis patients are limited and general recommendations are absent. Case: A 41-year-old Caucasian man infected with hepatitis C genotype 1b was admitted with a history of renal transplantation in 1990, and reintroduced hemodialysis in 1997 because of chronic rejection. Antiviral therapy with pegylated interferon-a2b (120 mg/oiw) and ribavirin (400 mg/tiw) was initiated. A virological and biochemical response with undetectable HCV-RNA was evident already after six weeks. Two weeks later, however, HCV-RNA became detectable again with 18.000 IU/ml. The treatment regimen was changed to standard-IFN-a2b (3 MU/tiw). Shortly thereafter, ribavirin had to be withdrawn because of severe anemia. After three weeks, hemoglobin level rebounded to values higher than 10 g/dl and a lower dose of ribavirin (200 mg/tiw) could be reintroduced. Virological and biochemical response occurred after switching to standard interferon-a2b within three months with good tolerance of antiviral combination treatment until the end of 48 weeks of therapy. The patient remained HCV-RNA-negative throughout follow-up of 36 weeks. ALT levels are still within normal limits and the patient is now waiting for a kidney transplantation. Conclusion: Considering the treatment course of this patient, IFN-a2b three times per week directly after hemodialysis seems to be superior to pegylated interferon-a2b once weekly in this case. The role of pegylated IFN-a2a for dialysis patients remains to be investigated.
Correspondence to:
Prof. Dr. H.L. Tillmann
University of Leipzig
Medizinische Klinik und Poliklinik II
Philipp-Rosenthal-Straße 27
04103 Leipzig, Germany
Email: Hans.Tillmann@medizin.uni-leipzig.de
Case reports
Thrombocytopenia and anaphylaxis secondary to heparin in a hemodialysis patient
Abstract
M.A. Tejedor Alonso1, K. López Revuelta2, M.J. García Bueno3, M.L. Casas Losada3, A. Rosado Ingelmo1, E. Gruss Vergara2, C. Vila Albelda1 and M. Moro Moro1
1Allergy, 2Nephrology Units, and 3Laboratory Area, Fundación Hospital Alcorcón, Madrid, Spain
Aims: We describe a rare case of anaphylaxis and thrombocytopenia whose cause was heparin used during hemodialysis sessions. Case report: A 77-year-old woman suffered five consecutive episodes of vomiting, tachypnea, wheezing or rales, immediately after initiating hemodialysis. In the first of these episodes, arterial pressure was undetectable. In all of the episodes there was evidence of the presence of hypoxia (always below 60 mmHg) and thrombocytopenia (always below 100,000/ml), with partial platelets recovery among episodes. The episodes started immediately after hemodialysis sessions and heparin infusion; either sodium heparin or enoxaparin was used. Utilization of different filters was not able to stop the episodes. These were stopped when a switch from heparin to hirudin was tested. Tryptase levels, as a marker of mast cells activation and anaphylaxis, were not increased in two of the episodes which were assessed. IgG antibodies against heparin-PF4 complex was detected at high levels. Discussion: A diagnosis of concomitant anaphylaxis and thrombocytopenia caused by sodium heparin and a low-molecular weight heparin (enoxaparin) were assumed.Correspondence to:
Dr. M.A. Tejedor
Juan de Mariana 26,3 A
28045 Madrid, Spain
Email: nurimang@idecnet.com
Letters to the Editor
Recurrent peritonitis caused by Corynebacterium amycolatum in a patient undergoing continuous ambulatory peritoneal dialysis
Abstract
Y.-L. Chiu, V.C. Wu, K.-D. Wun and P.-R. Hsueh
Letters to the Editor
Metastatic primitive neuroectodermal tumor presenting as acute renal failure and hypercalcemia
Abstract
K.P. Kang, W. Kim, S.K. Kang, C.Y. Yim, S.K. Park and S. Lee
