Volume 61, No. 5/2004(May)
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 Clinical Nephrology
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Originals
Undertreatment of hyperlipidemia in a cohort of United States kidney dialysis patients
Abstract
C.S. Fox, J.C. Longenecker, N.R. Powe, M.J. Klag, N.E. Fink, R. Parekh and J. Coresh for the CHOICE Study
1Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD, 2National Heart, Lung and Blood Institute’s Framingham Heart Study, Bethesda, MD, 3Brigham and Women’s Hospital Department of Medicine, 4Department of Epidemiology, 5Department of Medicine, 6Department of Health Policy and Management, 7Department of Biostatistics, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD, and 8Kuwait University Faculty of Medicine, Kuwait, Saudi Arabia
Background: Application of national guidelines regarding cardiovascular disease risk reduction to kidney dialysis patients is complicated by the conflicting observations that dialysis patients have a high risk of atherosclerotic cardiovascular disease (ASCVD), but dialysis patients with higher serum cholesterol have lower mortality rates. Actual treatment patterns of hyperlipidemia are not well studied. Methods: We assessed the prevalence, treatment and control of hyperlipidemia in this high-risk patient population from 1995 – 1998. We measured low-density lipoprotein cholesterol, treatment with a lipid-lowering agent, and prevalence of hyperlipidemia as defined by the National Cholesterol Education Program (NCEP), Adult Treatment Panel (ATP) II guidelines in 812 incident hemodialysis (HD), and peritoneal dialysis (PD) patients from dialysis clinics in 19 states throughout the United States. Results: Hyperlipidemia was present in 40% of HD and 62% of PD patients. Among subjects with hyperlipidemia, 67% of HD and 63% of PD patients were untreated and only 22% of HD and 14% of PD patients were treated and controlled. Those who entered the study in 1997 or 1998, those with diabetes, males and Caucasians were more likely to be treated and controlled, whereas subjects on PD and those with ASCVD were less likely to be treated and controlled. Conclusion: These data suggest that high rates of undertreatment exist in the United States ESRD dialysis population. Whether improved rates of treatment will result in decreased cardiovascular disease events needs to be tested in randomized clinical trials.
Originals
Early detection of prostate cancer in the ESRD population
Abstract
Q.T. Khairullah, S.D. Pamatmat, M. Chatha, R. Provenzano, D. Telang and M. Temple
1Department of Internal Medicine, Division of Nephrology, and 2Department of Surgery, Division of Urology, St. John Hospital and Medical Center, Detroit, MI, USA
Background: There are currently no prostate cancer screening guidelines specific to the end-stage renal disease (ESRD) population. With this in mind, we evaluated the clinical usefulness of digital rectal examination (DRE), serum total prostate-specific antigen (PSA), prostate-specific antigen density (PSAD) and transrectal ultrasound (TRUS) in predicting prostate cancer in men with ESRD. Methods: Fifty male ESRD patients age 40 years and older with no prior history of prostate cancer were enrolled in the study. All patients underwent PSA measurement and a DRE followed by a TRUS. PSAD was calculated as the total PSA divided by the prostate volume. Ultrasound-guided prostate biopsies were performed on any patient with 1 or more of the following abnormal findings: a nodule detected on DRE; an abnormal TRUS; PSA > 4.0 ng/ml, or a PSAD > 0.15 ng/ml/cm3. Results: Abnormal findings were detected in 19 patients. Two (4%) had an abnormal DRE, 3 (6%) had PSA > 4.0 ng/ml, 3 (6%) had PSAD > 0.15 ng/ml/cm3 and 16 (32%) had abnormal findings on TRUS. Three patients had 2 abnormal findings and 1 had 3. Of the 15 prostate biopsies performed, 4 (27%) revealed prostate cancer and 3 (20%) high-grade prostatic intraepithelial neoplasm (HGPIN) comprising 8% and 6%, respectively, of the studied population. Of the 4 patients diagnosed with prostate cancer, none had abnormal DRE, 2 (50%) had PSA > 4.0 ng/ml (sensitivity = 66.7% and PPV = 50% (p = 0.236)), 3 (75%) had PSAD > 0.15 ng/ ml/cm3 (sensitivity = 100% and PPV = 75% (p < 0.018)), and 3 (75%) had abnormal findings on TRUS (sensitivity = 30% and PPV = 75% (p = 1.000)). Conclusion: Routine screening with PSA and DRE does not seem sensitive enough to predict the presence of the disease. Although TRUS detected abnormalities in 16 patients (32%), sensitivity was very low (30%). In our patients, PSAD increased the sensitivity and positive predictive value (PPV) of detecting prostate cancers compared to PSA alone.
Originals
Effect of propranolol on heart rate variability in patients with end-stage renal disease: a double-blind, placebo-controlled, randomized crossover pilot trial
Abstract
K. Tory1, E. Horváth1, Z. Süveges1, A. Fekete1, P. Sallay1, K. Berta2, T. Szabó1, A.J. Szabó1, T. Tulassay3 and G.S. Reusz1
1First Department of Pediatrics, 2First Department of Medicine,
Semmelweis University of Budapest, and 3Joint Research Program of the Hungarian Academy of Sciences and the First Department of Pediatrics, Semmelweis University of Budapest, Hungary
Background: Low heart rate variability (HRV) is an independent risk factor of cardiac mortality in patients with end-stage renal disease (ESRD). It has been explained by uremic parasympathetic neuropathy. Sympathetic overactivity can also reduce HRV. Our aim was to determine whether there is vagal activity in ESRD patients that is masked by sympathetic activity. Methods: The effect of propranolol on HRV was examined in 13 patients with ESRD, aged 20.1 ± 7.6 years without diabetes. All patients were given intravenous propranolol (0.05 mg/kg) once and placebo once in a randomized, double-blind way, with an interval of 6.6 days (mean, range: 2 – 9). Propranolol was administered before hemodialysis treatment, after 40 minutes supine resting period. HRV was registered for 10 minutes, during supine, before and after the injection. Patients’ HRV data were compared to that of 29 age-matched healthy controls. Results: Initially, both high- (HFV) and low-frequency (LFV) bands of heart rate variability were lower in ESRD patients compared to controls (p < 0.001 for both). Propranolol resulted in a significant increase of HFV (propranolol: DlgHFV = 0.182 (0.027 – 0.337), placebo: DlgHFV = –0.029 (–0.128 – +0.070); p = 0.032). Elevation of LFV was not significant. Six patients had an elevated plasma norepinephrine and/or epinephrine level. Plasma dopamine level was elevated in all but 1 patient (mean: 432 pmol/l, 95% CI: 320 – 543) and showed an inverse relationship with the increase of lgHFV secondary to propranolol (r = –0.66, p = 0.014). Conclusions: Low HFV of ESRD patients can be improved by b-adrenergic blockade. It demonstrates that there is some vagal activity in ESRD that is masked by sympathetic activity. Therefore, altered sympathovagal balance of ESRD patients should be taken into consideration in the assessment of vagal uremic neuropathy.
Originals
Effect of advanced glycation end products on endotoxin-induced TNF-a, IL-1b and IL-8 in human peripheral blood mononuclear cells
Abstract
L.L. Reznikov, J. Waksman, T. Azam, S.-H. Kim, P. Bufler, T. Niwa, A. Werman, X. Zhang, M. Pischetsrieder, S. Shaldon and C.A. Dinarello
1Department of Medicine, Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, CO, USA, 3Institute for Pharmaceutics and Nutritional Chemistry, Universität Erlangen-Nürnberg, Erlangen, Germany, 2Nagoya University, Daiko Medical Center, Nagoya, Japan, and 4Monte Carlo, Monaco
Background/aims: Advanced glycated end products (AGE) are endogenous proteins that have formed covalent complexes with sugars by a nonenzymatic process. Being proinflammatory molecules, AGE are thought to contribute to chronic systemic and local inflammatory processes associated with pathological changes in various diseases. In patients with end-stage renal disease, AGE are believed to play a role in the progression of atherosclerosis and worsening of renal failure. In patients receiving hemodialysis, AGE are thought to contribute to the inflammatory components of the therapy, particularly in diabetic patients. Methods: In the present study, AGE were produced using 5% human serum albumin (HSA) and 50% glucose, both used for intravenous infusion into humans and both released after strict control for endotoxin content. The presence of AGE formed by HSA and glucose was confirmed using 2 independent assays. The inflammatory properties of these AGE were assessed using synthesis and release of the proinflammatory cytokines interleukin-1 (IL-1), tumor necrosis factor (TNF) and IL-8, a chemokine. Results: Alone, AGE did not induce these cytokines from peripheral blood mononuclear cells (PBMC) obtained from 14 healthy human donors. However, in the presence of 1 or 10 ng/ml of endotoxin, AGE augmented the production of IL-1 and TNF above that induced by endotoxin alone. Although the amount of augmentation of LPS-induced cytokines by AGE varied between the blood donors, the response was consistently observed and reached statistical significance. The augmentation of cytokine production was confirmed using AGE prepared with different lots of HSA and glucose. Conclusion: These results demonstrate that in the strict absence of endotoxins, AGE are formed that do not stimulate cytokine production from PBMC of healthy donors, however, AGE significantly augment the synthesis and release of proinflammatory cytokine in the presence of low concentrations of endotoxins. The data suggest that renal replacement therapies should consider the role of microbial products in potentiating the biological consequences of naturally formed AGE and their potential to contribute to systemic and local inflammation in renal replacement therapies. Therefore, although the formation of AGE is unavoidable, excluding microbial products during renal replacement therapy should reduce the pathological consequences of AGE.
Originals
Variable parathyroid hormone(1-84)/carboxyl- terminal PTH ratios detected by 4 novel parathyroid hormone assays
Abstract
H. Koller, E. Zitt, G. Staudacher, U. Neyer, G. Mayer and A.R. Rosenkranz
1Klinische Abteilung für Nephrologie, Universitätsklinik für Innere Medizin, Leopold-Franzens-Universität, Innsbruck, 2Landeskrankenhaus Feldkirch, Abteilung für Nephrologie und Dialyse und VIVIT, Feldkirch, und 3Klinische Abteilung fur Allgemeine Innere Medizin, Universitätsklinik für Innere Medizin, Leopold-Franzens-Universität, Innsbruck, Austria
Aim: Parathyroid hormone (PTH) measurement is important in the evaluation of bone disease in patients with chronic renal failure. Large carboxyl-terminal PTH fragments (C-PTH) cross-react with second-generation PTH assays, lead to an overestimation of biologically active PTH, and are evaluated by a combination of second- and third-generation PTH assays. The aim of our study was to examine whether the use of 4 different PTH assays of putatively same specificity leads to comparable results detecting C-PTH fragments. Subjects and methods: In 70 chronic dialysis patients, total PTH and PTH(1-84) were measured in parallel by 4 novel PTH assays (Nichols Advantage Intact PTH and Bio-Intact PTH Chemiluminescence Assay, Nichols Institute Diagnostics, USA, DUO Total and CAP PTH IRMA, Scantibodies Laboratory, USA). The C-PTH concentration was quantitated by subtracting PTH(1-84) from total PTH. Consecutively, the PTH(1-84)/ C-PTH ratio was calculated. Results: Nichols Intact PTH and DUO Total PTH assays were highly correlated (r = 0.985), as well as Nichols Bio-Intact and DUO CAP assays (r = 0.984). However, total PTH values measured by the Nichols assay were 30% higher (median (range): 185 (9.9 – 2,332) versus 130 (2.3 – 1,271.1) pg/ml, p < 0.01). PTH(1-84) values, measured by the Nichols Bio-Intact PTH assay were 8% higher compared to the Scantibodies CAP assay (median (range): 79.6 (7.5 – 1,060.9) versus 73.7 (4.4 – 918.9) pg/ml, p = NS). Thirty-six patients had a ratio < 1 measured by the Nichols assays, whereas only 8 patients showed the same ratio when measured by the Scantibodies assays. In 28 patients (40%), contradictory PTH(1-84)/C-PTH ratios were found, showing a ratio < 1 when measured by the Nichols assays, but > 1 when the Scantibodies assays were used. Conclusion: In conclusion, our results suggest that the PTH(1-84)/C-PTH ratio cannot be equally used as a predictor of bone turnover when different PTH assays are used. Depending on those assays, differences in total PTH values mathematically lead to varying amounts of C-PTH fragments resulting in variable, even contradictory PTH(1-84)/C-PTH ratios.
Originals
Vascular abnormalities in patients with autosomal dominant polycystic kidney disease – the influence on arteriovenous fistula creation
Abstract
W. Weyde, M. Krajewska, J. Penar, H. Bartosik and M. Klinger
Department of Nephrology and Transplantation Medicine, University of Medicine, Wroclaw, Poland
Aim: Patients with autosomal dominant polycystic kidney (ADPKD) present a number of vascular abnormalities, including cerebral aneurysms, heart valve lesions, coarctations of aorta and abdominal aortic aneurysms. The aim of our study was to investigate whether vascular abnormalities that occur in wrist vessels, make native arteriovenous fistula creation difficult in this group of patients. Patients and methods: The problem was analyzed retrospectively in 783 patients with chronic kidney failure who had had arteriovenous fistula created in our centre in the period between 1991 and 2001. ADPKD was the cause of terminal renal failure in 57 patients (7.3%). These were 31 men and 26 women aged 28 – 69 years (52 ± 16 years on average). Results: A difference between left and right radial artery diameters and a narrow radial artery (below 2 mm), unsuitable for fistula creation, occurred in 12% of patients with ADPKD and in 0.38% of other patients. Instead of a cephalic vein in the typical place, a few small vessels were present in 14% of patients with ADPKD and in 2.17% of patients with other causes of renal failure. Conclusion: Our experience shows a higher incidence of wrist vascular abnormalities in patients with ADPKD. This decreases the possibility of wrist native arteriovenous fistula creation in this group of patients.
Originals
Lower erythropoietin and iron supplementation are required in hemodialysis patients with hepatitis C virus infection
Abstract
L. Altintepe1, E. Kurtoglu2, Z. Tonbul1, M. Yeksan1, A. Yildiz3 and S. Türk1
Department of Internal Medicine, 1Division of Nephrology, and 2Division of Hematology, Selcuk University Medical School, Konya, 3Department of Internal Medcine, Division of Nephrology, Istanbul University, Istanbul School of Medicine, Istanbul, Turkey
Background: Chronic hepatitis C virus (HCV) infection is a common infectious agent in chronic hemodialysis (HD) patients. In this prospective case-control study, we aimed to investigate the influence of chronic HCV infection on erythropoietin (EPO) and iron requirement in HD patients. Patients and methods: 49 HD patients (24 male, 25 female, mean age 47 ± 15 years) were included. The mean time spent on dialysis was 39 ± 38 months, and follow-up time was 1 year for this study. Biochemical analyses and complete blood counts together with iron status of the patients (transferrin saturation and serum ferritin levels) were measured monthly. Highly sensitive C-reactive protein (hs-CRP) levels were measured within 3-month intervals. Endogenous EPO levels were measured by enzyme-linked immunoassay 2 weeks after cessation of EPO treatment. Results: Eleven of the HD patients (22%) were anti-HCV(+). There was no difference in age, sex, time on dialysis, distribution of primary renal diseases, predialytic BUN, Kt/V, albumin and i-PTH levels between HCV(+) and (–) patients. Anti-HCV-positive patients required significantly lower weekly doses of EPO (87 ± 25 IU/kg vs 129 ± 11 IU/kg, p = 0.042) and iron (16.8 ± 12.2 mg vs 32.6 ± 16.1 mg, p = 0.02) replacement than anti-HCV(–) group; hs-CRP levels were similar between study groups. Serum endogenous EPO levels were significantly higher in HCV(+) patients than HCV(–) HD patients (9.43 ± 6.47 mU/ml vs 3.59 ± 2.08 mU/ml, p = 0.008). Conclusion: Anti-HCV(+) HD patients had higher serum EPO levels and required less EPO and iron replacement as compared to anti-HCV(–) patients. Because of the changes in iron metabolism, iron treatment should be carefully administered in HD patients with HCV.
Case reports
Remission of nephrotic syndrome after thalidomide therapy in a patient with Castleman’s disease
Abstract
M. Adorati Menegato, M. Fanni Canelles, E. Tonutti and S. Pizzolitto
1Nephrology and Dialysis Unit, ASS 4 “Medio Friuli”, 2Pathology Department, SMM Hospital, and 3Biochemistry Department, SMM Hospital, Udine, Italy
Castleman’s is an uncommon lymphoproliferative disorder secondary to lymphoid follicle hyperplasia and marked capillary proliferation with endothelial hyperplasia. This illness can be associated with glomerulonephritis (GN). Here, we report a case with steroid-dependent nephrotic syndrome secondary to proliferative mesangial glomerulonephritis in a patient with Castleman’s disease, that was diagnosed several years before. Considering the involvement of IL-6 in Castleman’s disease we treated the patient with thalidomide obtaining the remission of the nephrotic syndrome. Our experience suggests a possible role of thalidomide in the treatment of glomerular pathology when a role of IL-6 is hypothesized.
Case reports
Renal transplantation in a C-ANCA(+) patient with Behcet disease and rapidly progressive glomerulonephritis
Abstract
J. Moisés, J.V. Torregrosa, J. Ybarra and F. Oppenheimer
Renal Transplant Unit, Hospital Clinic i Provincial, Barcelona, Spain
Behcet’s disease (BD) is a chronic, relapsing, inflammatory disorder, and the underlying histophatological lesion is vasculitis of unknown cause. Some case reports of BD with positive C-ANCA titers have been reported, but only 2 case reports have documented the association of ANCA-associated glomerulonephritis (GN) and BD, and no renal transplantation cases have been described. We report such a case. A 27-year-old male was referred for consultation due to acute renal failure. Seven years before, BD was diagnosed. At the time of consultation he suffered from uveitis and generalized arthralgias. The serum creatinine was 14 mg/dl and urinalysis showed 4+ protein and microscopic hematuria. Results of serological tests were normal. The ANCA PR 3 titer was 1 : 100 of cytoplasmic pattern. A renal biopsy showed a rapidly progressive type III glomerulonephritis. In spite of immunosuppressive therapy with cyclophosphamide and high steroid doses, renal function did not recover and hemodialysis therapy was initiated. One year later, the patient underwent a renal transplantation. Follow-up was absolutely normal, and 5 years after transplantation, renal function persisted to be normal, without urinary abnormalities and signs of reactivation of original disease, except for occasional arthralgias. C-ANCA titer was decreased and remained stable (< 1 : 30). He is now receiving maintenance immunosupression with cyclosporin and prednisone. This report shows the long-term successful renal transplantation in a patient with ANCA-associated glomerulonephritis and BD. The success of renal transplant in BD with renal involvement is encouraging and should be pursued.
Case reports
Maxillary brown tumor and uremic leontiasis ossea in a patient with chronic renal insufficiency
Abstract
H. Taskapan, C. Taskapan, T. Baysal, I. Sahin, R. Ulu, N. Karadag and V. Kirimlioglu
1Nephrology, 2Endocrinology, 3Radiology, 4Pathology and General Surgery, 5Departments of Inonu University, Faculty of Medicine, Turgut Ozal Medical Center, and 6Biochemistry Department of State Hospital, Malatya, Turkey
Findings of renal osteodystrophy in cranial bones are not uncommon and include osteomalacia, osteosclerosis, erosion of the cortical bone, brown tumors and resorption of the lamina dura. However, massive thickening of the cranial vault and facial bones, called uremic leontiasis ossea, have been reported very rare. In the present article, we describe the case of an uncooperative female patient with a brown tumor, involving the left maxillary sinus and massive thickening of the cranial vault and facial bones, secondary to severe secondary hyperparathyroidism during 8 years of regular hemodialysis treatment.
Letters to the Editor
Acute non-cardiogenic pulmonary edema in a 2003 French Puumala virus case: cautions and corrections
Abstract
J. Clement, G. van der Groen, N. Lameire, P. Colson and M. Van Ranst
Letters to the Editor
Reply to Clement et al.
Abstract
D. Launay and P. Vanhille
Letters to the Editor
Change in the Circadian rhythm of blood pressure in pseudo-hypoaldosteronism type 2 in response to thiazide diuretics
Abstract
T. Uzu, K. Takahara and A. Yamauchi
