Volume 57, No. 5/2002(May)
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 Clinical Nephrology
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Original
Cardiovascular disease risk factors in chronic renal insufficiency
M.J. Sarnak, B.E. Coronado, T. Greene, S.-R. Wang, J.W. Kusek, G.J. Beck and A.S. Levey
Abstract
M.J. Sarnak1, B.E. Coronado1, T. Greene2, S.-R. Wang2, J.W. Kusek3, G.J. Beck2 and A.S. Levey1
1New England Medical Center and Tufts University School of Medicine, Boston, MA, 2The Cleveland Clinic Foundation, Cleveland, OH, and 3National Institutes of Health, Bethesda, MD, USA
Background: Coronary heart disease (CHD) is an important cause of morbidity and mortality in end-stage renal disease (ESRD). Prevention of CHD in ESRD requires identification and treatment of coronary risk factors in chronic renal insufficiency (CRI). Methods: We evaluated the prevalence of “traditional coronary risk factors” in CRI in 1,795 patients enrolled in the baseline period of Modification of Diet in Renal Disease (MDRD) Study. Using a cross-sectional design, we determined the relationship of these risk factors to the level of glomerular filtration rate (GFR) and proteinuria. We also predicted the CHD risk in the MDRD Study baseline cohort using the coronary point score. Results: 64.0% had blood pressure > 130/85 mmHg despite antihypertensive therapy. 64.2% had LDL cholesterol > 130 mg/dl, while 38.3% had HDL cholesterol < 35 mg/dl. After adjustment for age, gender and the presence of diabetes, GFR was inversely associated with systolic blood pressure and positively associated with HDL cholesterol, but not associated with total or LDL cholesterol. After adjustment for age, gender and the presence of diabetes, proteinuria was positively associated with systolic and diastolic blood pressure, total serum cholesterol and LDL cholesterol, and inversely associated with HDL cholesterol. Nonetheless, the predicted CHD risk, even at a very low GFR, was similar to the risk in the general population and lower than the observed rate of de novo CHD in incident dialysis patients. Conclusions: “Traditional coronary risk factors” are highly prevalent in CRI and vary with the level of renal function. However, the coronary point score does not appear to explain the extent of increased CHD risk in ESRD. Non-traditional risk factors may also contribute to CHD in ESRD.Correspondence to:
M.J. Sarnak, MD; New England Medical Center, Box 391, 750 Washington Street, Boston, MA 02111, USA
Email: msarnak@lifespan.org
Original
Protease inhibitors are associated with a slowed progression of HIV-related renal diseases
L.A. Szczech, L.J. Edwards, L.L. Sanders, C. van der Horst, J.A. Bartlett, A.E. Heald and L.P. Svetkey
Abstract
L.A. Szczech1,2, L.J. Edwards3, L.L. Sanders4, C. van der Horst5, J.A. Bartlett6, A.E. Heald6 and L.P. Svetkey1
1Department of Medicine, Division of Nephrology, Duke University Medical Center, 2Duke Clinical Research Institute, Institute for Renal Outcomes Research and Health Policy, Duke University Medical Center, Durham, NC, 3 Department of Biostatistics, University of North Carolina, Chapel Hill, NC, 4Department of Medicine, Duke University Medical Center, Durham, NC, 5Department of Medicine, Division of Infectious Diseases, University of North Carolina Hospitals, Chapel Hill, NC, and 6Department of Medicine, Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA
Aims: While angiotensin-converting enzyme inhibitors and zidovudine may improve the course of the most common HIV-related renal disease, HIV-associated nephropathy (HIVAN), the effect of antiretroviral combination therapy on this and other HIV-related renal diseases has not been assessed. This study describes the clinical course of HIV-related renal diseases and the effect of protease inhibitors on their progression. Methods: This retrospective cohort study reviews the clinical course of 19 patients with a clinical or biopsy-proven diagnosis of HIVAN or other HIV-related renal diseases. Groups progressing and not progressing to ESRD were compared using longitudinal analyses to assess the association between creatinine clearance and clinical and therapeutic factors. Results: The cohort consisted of 16 African-Americans, 2 Caucasians and 1 Native American. Their modes of HIV infection were intravenous drug use (7), a history of men having sex with men (3) and heterosexual behavior (5). Patients were followed for a median of 16.6 months. Seven patients reached ESRD. Loss of creatinine clearance over time did not differ among genders, races, or patients with different modes of HIV infection. Longitudinal analyses demonstrated an association between protease inhibitors and prednisone and a slower decline in creatinine clearance in multivariable models (p = 0.04 and 0.003, respectively). Conclusions: The epidemiology and clinical course of HIV-related renal diseases is more heterogeneous than previously described. This study suggests a benefit to the use of protease inhibitors and prednisone on the progression of these nephropathies.Correspondence to:
Dr. L.A. Szczech; Duke University Medical Center, Box 3646, Durham, NC 27710, USA
Email: szcze001@mc.duke.ed
Original
Analysis of the genes SLC7A9 and SLC3A1 in unclassified cystinurics: mutation detection rates and association between variants in SLC7A9 and the disease
C. Schmidt, A. Albers, J. Tomiuk, K. Eggermann, C. Wagner, G. Capasso, S. Lahme, A. Hesse, F. Lang, K. Zerres and T. Eggermann
Abstract
C. Schmidt1, A. Albers2, J. Tomiuk3, K. Eggermann1, C. Wagner2, G. Capasso4, S. Lahme5, A. Hesse6, F. Lang2, K. Zerres1 and T. Eggermann1
1Institute of Human Genetics, Technical University of Aachen, 2Institute of Physiology I, 3Institute of Anthropology and Human Genetics, University of Tübingen, 4Department of Pediatric Nephrology, University of Naples, Italy, 5Department of Urology, University of Tübingen, and 6Department of Experimental Urology, University of Bonn, Germany
Cystinuria is a common inherited disorder of defective renal reabsorption of cystine and dibasic amino acids. Recently, 2 responsible genes have been identified: mutations in the SLC3A1 gene encoding the glycoprotein rBAT cause cystinuria type I, while variants in the SLC7A9 gene have been demonstrated in non-type I cystinuria; its gene product b0,+AT is the light chain of the renal cystine transport system rBAT/b0,+AT. To estimate the role of both genes in the etiology of cystinuria, we searched for sequence alterations in SLC7A9 and SLC3A1: 30 unclassified cystinurics were investigated. In 50% of patients (15/30), point mutations in SLC3A1 were detected. Screening of the SLC7A9 gene revealed 10 mutations in 8 patients corresponding to a frequency of 27%. In addition to previously published mutations in the SLC7A9 gene, we detected 2 new mutations (F140S, c747delG). An overall detection rate of 73% (22/30) in unclassified patients is delineated for mutations in both genes. In 33% (10/30), 2 mutations were detected, in 40% (12/30) 1 mutation. Furthermore, 5 new polymorphic sites were identified in SLC7A9. While the base pair variation in intron 9 is homogeneously distributed in patients and control individuals, the allelic and genotypic distributions of the polymorphisms in 3 exons of SLC7A9 – exons 2, 5 and 6 – and intron 3 differ significantly between both groups. Our results suggest that some haplotypes defined through the exons 2, 5 and 6 and intron 3 might be markers of a functional variant in the SLC7A9 gene. Evidently, since the mutation detection rates in the 2 so far known cystinuria genes never reach 100%, further genes and modulating factors should influence the phenotype in a subset of patients. However, the presented data show that testing for mutations in the 2 currently known cystinuria genes is already a meaningful approach to the molecular diagnostics of the disease.Correspondence to:
Dr. T. Eggermann;I nstitute of Human Genetics, Pauwelsstraße 30, D-52074 Aachen, Germany
Email: teggermann@post.klinikum.rwth-aachen.de
Original
Negligible urinary cysteamine loss in cystinosis patients with Fanconi syndrome
E.N. Levtchenko, A. de Graaf-Hess, H.J. Blom and L.A.H. Monnens
Abstract
E.N. Levtchenko, A. de Graaf-Hess, H.J. Blom and L.A.H. Monnens
Department of Paediatrics, Laboratory of Paediatrics and Neurology, UMC St. Radboud, Nijmegen, The Netherlands
Cystinosis is an inborn error of lysosomal cystine transporter, resulting in cystine accumulation in lysosomes of all cells. Renal Fanconi syndrome is an early sign of kidney involvement in cystinosis patients. Cysteamine, a small amino-thiol, depletes intralysosomal cystine content and reduces organ damage. However, it does not reverse renal Fanconi syndrome and only postpones the progression to renal failure. We examined whether cysteamine could be lost in the urine of cystinosis patients with Fanconi syndrome, which may explain the inefficiency of treatment. Urinary cysteamine loss was studied in 6 cystinosis patients with and without Fanconi syndrome and was less than 1% of ingested dose in all patients.Correspondence to:
Dr. E.N. Levtchenko; Department of Paediatrics, Laboratory of Paediatrics and Neurology, P.O. Box 9101, NL-6500 HB Nijmegen, The Netherlands
Email: E.Levtchenko@ ckskg.azn.nl
Original
Carvedilol does not modulate moderate exercise-induced hyperkalemia in hemodialysis patients
M. Nowicki, G. Szewczyk-Seifert, D. Klimek and F. Kokot
Abstract
M. Nowicki1,2, G. Szewczyk-Seifert1, D. Klimek1 and F. Kokot1
1Department of Nephrology, Endocrinology and Metabolic Diseases, Silesian University School of Medicine, Katowice, and 2Department of Nephrology “Polish Mother’s Memorial Hospital” Research Institute, Lódz, Poland
Background and aim: Non-selective b-adrenergic blockers may cause hyperkalemia in patients with end-stage renal failure. In contrast, a-adrenergic blockade has been found to decrease the hyperkalemic effect of physical exercise in healthy subjects, although we were unable to confirm this effect in hemodialysis patients. In a crossover design, we studied the effect of carvedilol, a non-selective b-adrenergic blocker with an additional a1-blocking activity, on exercise-induced hyperkalemia in 17 anuric hemodialysis patients. Methods: All subjects were given either carvedilol (25 mg/day) or placebo for 2 weeks in a random order with a 2-week wash-out period. At the end of each treatment period they underwent a 30-minute exercise test on a bicycle ergometer with a fixed load of 20 W. Results: The treatment with carvedilol caused a significant decrease in blood pressure. Serum potassium before exercise tests was similar (5.37 ± 0.2 and 5.24 ± 0.2 mmol/l on carvedilol and placebo, respectively; mean ± SE). During the exercise, serum potassium increased significantly (p < 0.001 in both tests) and subsequently decreased during 30 minutes of recovery (p < 0.05). The mean rate of potassium increment during the exercise was similar (23.3 ± 3.3 mmol/l/min on carvedilol and 20.0 ± 3.6 mmol/l/min on placebo). During recovery, the mean rate of potassium decrement was 5.0 ± 3.0 mmol/l/min and 6.7 ± 2.7 mmol/l/min, respectively. Serum sodium, ionized calcium, insulin and plasma renin activity were similar before the exercise tests and did not change during the exercise. Conclusion: Carvedilol does not enhance the hyperkalemic effect of moderate physical exercise in anuric hemodialysis patients.Correspondence to:
Dr. M. Nowicki; Department of Nephrology, “Polish Mother’s Memorial Hospital” Research Institute, Rzgowska 281/289, PL-93-338 Lódz
Email: Poland nefro@wp.pl
Original
Isolated ultrafiltration affects dynamic vectorcardiographic ischemia monitoring parameters
S. Ojanen, A.-M. Koivisto, T. Kööbi, P. Korhonen, J. Mustonen, P. Laippala and A. Pasternack
Abstract
S. Ojanen1, A.-M. Koivisto2, T. Kööbi3, P. Korhonen1, J. Mustonen1,4, P. Laippala2 and A. Pasternack1,4
1Department of Medicine, 2Tampere School of Public Health, 3Department of Clinical Physiology, Tampere University Hospital, and 4Medical School, University of Tampere, Finland
Aims: The present study was undertaken to assess the role of isolated ultrafiltration (UF phase) and hemodialysis with minimal ultrafiltration (HD phase) in changes in parameters reflecting myocardial ischemia: QRS vector difference (QRS-VD), ST change vector magnitude (STC-VM) and ST vector magnitude (ST-VM6) registered by MIDA (myocardial infarction dynamic analysis). Patients and methods: Twelve patients on maintenance hemodialysis were first ultrafiltrated for 2.5 h without dialysis (UF) followed by a 2.5-hour session of hemodialysis with minimal ultrafiltration (HD). Computerized vectorcardiography (VCG) was used for on-line dynamic analysis of ST segment and QRS complex changes. Blood volume (BV) changes were monitored non-invasively and continuously with the CRIT-LINE instrument. Whole-body bioelectric impedance analysis (BIA) was used for extracellular water (ECW) estimation. Results: During the UF phase QRS-VD and STC-VM showed a statistically significant increasing linear trend (time effect for both QRS-VD and STC-VM p < 0.0001, while no changes were noted in ST-VM6; time effect p = 0.986). During the HD phase none of these parameters changed (time effect for QRS-VD p = 0.855, for STC-VM p = 0.275 and for ST-VM6 p = 0.976). During the UF, phase changes in QRS-VD were in close relation to those in ECW. Conclusion: Isolated ultrafiltration leads to an increase in the VCG ischemia monitoring parameters QRS-VD and STC-VM. The increase of QRS-VD is related to changes in ECW. Hemodialysis with minimal ultrafiltration has no effect on VCG ischemia monitoring parameters.Correspondence to:
Dr. S. Ojanen; Department of Medicine, Tampere University Hospital, Box 2000, Teiskontie 35, FIN-33521 Tampere, Finland
Email: seppo.ojanen@fimnet.fi
Original
An (CA)n dinucleotide repeat polymorphism of the interleukin-6 (IL-6) gene is associated with metacarpal bone mineral density in hemodialysis patients
T. Gohda, T. Shike, K. Funabiki, I. Shirato and Y. Tomino
Abstract
T. Gohda, T. Shike, K. Funabiki, I. Shirato and Y. Tomino
Division of Nephrology, Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan
Genetic factors may play an important role in the pathogenesis of reduced bone mineral density (BMD). IL-6 is a multifunctional cytokine and a candidate gene for regulation of bone mineral density (BMD). The relationship between a microsatellite polymorphism of the IL-6 gene and metacarpal BMD in Japanese hemodialysis patients was examined. We selected 165 patients (96 males and 69 females) with a mean age of 62.0 ± 13.7 years (mean ± standard deviation (SD) in this study. They were dialyzed for an average of 75.8 ± 60.8 months (mean ± SD). The microsatellite polymorphism in the IL-6 gene was examined. According to the number of cytosine-adenine repeats, varying from 13 to 18, 6 alleles could be distinguished. Patients were categorized based on the presence or absence of the allele with 126 bp (i.e. 14 CA repeats) (allele A, all others allele O). The frequencies of IL-6 gene genotypes in hemodialysis patients were 16.4% for OO, 52.1% for AO and 31.5% for AA. The BMD score adjusted for age and body weight (Z score) in the AA genotype group (–0.93 ± 1.17) was significantly lower than that in the OO (–0.09 ± 1.42, mean ± SD, p < 0.005) or AO group (–0.48 ± 1.15, mean ± SD, p < 0.01). Serum intact PTH in the OO genotype group (79.3 ± 84.6) was lower than that in the AA (120.8 ± 113.6, mean ± SD, p = 0.10) or AO group (132.1 ± 106.5, mean ± SD, p < 0.05). These results suggest that polymorphism of the IL-6 gene may be a useful marker for reduced BMD.Correspondence to:
Dr. Y. Tomino; Division of Nephrology, Department of Medicine, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan
Email: yasu@ med.juntendo.ac.jp
Original
Decline of high hepatitis C virus prevalence in a hemodialysis unit with no isolation measures during a 6-year follow-up
R. Valtuille, H. Moretto, L. Lef, P. Rendo and J.L. Fernández
Abstract
R. Valtuille1, H. Moretto1, L. Lef1, P. Rendo2 and J.L. Fernández2
1RTC, Monte Grande, and 2Bio Sidus, Department of Clinical Research, Buenos Aires, Argentina
Aims: It has been recently suggested that isolation measures may be necessary to avoid hepatitis C virus (HCV) spread in hemodialysis units with a high HCV prevalence. To assess the variation in prevalence and long-term incidence of HCV infection, we studied our hemodialysis patients during a 6-year follow-up period. Material and methods: We compared anti-HCV prevalence in 1994, 1996, 1998 and 2000 according to the anti-HCV status, and we analyzed the seroconversion of anti-HCV. Strict adherence to universal precautions has been fulfilled since 1993 and systematic anti-HCV testing in blood donors has been performed since 1994. No isolation measures were adopted. Results: In 1994, 22 of 53 (41.5%) patients tested positive for anti-HCV; in 1996, 18 of 67 (26.9%); in 1998, 9 of 75 (12.0%); and in 2000, 7 of 82 (8.5%) (p < 0.001). In 2000, 7 of 14 (50.0%) patients who had been attending the unit since 1994 and 0 of 68 (0%) who had entered after 1994 were anti-HCV-positive (p = 0.000). Eight of 171 (4.7%) patients who entered the unit and 24 of 142 (16.9%) who left it were anti-HCV-positive (p < 0.001). Two patients became anti-HCV-negative. Seroconversion of anti-HCV was observed in 3 patients. The yearly seroconversion rate was 0.5% during the period 1994 – 1996 (1 of 98 patients at risk), 0.5% during the period 1996 – 1998 (1 of 91 patients at risk), and 0.4% during the period 1998 – 2000 (1 of 120 patients at risk). Conclusions: It was possible to reduce a high HCV prevalence in a hemodialysis unit when a low incidence was achieved without taking isolation measures. All anti-HCV-positive patients in 2000 had been undergoing hemodialysis since 1994.Correspondence to:
Dr. J.L. Fernández; Constitución 4234 (1254), Buenos Aires, Argentina
Email: j.fernandez@ biosidus.com.ar
Original
Arteriovenous fistula using transposed basilic vein in chronic hypotensive hemodialysis patients
Y.-T. Tsai, S.-H. Lin, G.-C. Lee, G.-G. Huen, Y.-F. Lin and C.-S. Tsai
Abstract
Y.-T. Tsai1, S.-H. Lin2, G.-C. Lee1, G.-G. Huen1, Y.-F. Lin2 and C.-S. Tsai1
1Department of Surgery, Division of Cardiovascular Surgery, and 2Department of Medicine, Division of Nephrology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Aim: Chronic hypotension is not uncommon in uremic patients on regular hemodialysis. This subset of patients often requires multiple operations to maintain their vascular access due to frequent thrombosis and occlusion of the arteriovenous fistula. Our aims was to assess whether surgical intervention with the brachial artery-transposed basilic vein fistula is effective in chronic hypotensive hemodialysis patients. Materials and methods: Fifty-four hemodialysis patients with chronic hypotension were enrolled in this study. Most of them were referred from local hospitals. They were 23 men and 31 women. The brachial artery-transposed basilic vein arteriovenous fistula was performed in a period of 46 months at the teaching hospital. Primary patency was defined as the length of time from the fistula creation until the development of thrombosis or a complication that required operative revision of the fistula. Secondary patency was defined by whether the fistula could be salvaged by revision such that blood flow was maintained. Results: There was no technical failure and none of these patients died due to the surgical operation. The primary patency rate was 89.80% at 1 year, 73.08% at 2 years, and 64.71% at 3 years. The secondary patency rate was 95.92% at 1 year, 84.62% at 2 years, and 76.47% at 3 years. Conclusions: Brachial artery-transposed basilic vein arteriovenous fistula may present good primary alternative vascular access in chronic hypotensive hemodialysis patients.Correspondence to:
Dr. C.-S. Tsai; Division of Cardiovascular Surgery, Department of Surgery, Tri-Service General Hospital, NO. 325, Cheng Kung Rd, Sec. 2, Neihu 114, Taipei, Taiwan
Email: Sung1500@ms42.hinet.net
Case Report
Diabetic nephropathy with interstitial nephritis presenting with a false-positive anti-GBM antibody
A.J. DeAngelo, K.J. Lancaster-Weiss, S. Eliason, D. Troyer and W.G. Wortham
Abstract
A.J. DeAngelo1, K.J. Lancaster-Weiss2, S. Eliason2, D. Troyer3 and W.G. Wortham4
1Department of Medicine, Brooke Army Medical Center, Fort Sam Houston, 2Department of Pathology, Wilford Hall Medical Center, Lackland AFB, 3Department of Pathology, The University of Texas Health Science Center at San Antonio, and 4Division of Nephrology, Department of Medicine, Brooke Army Medical Center, Fort Sam Houston, Texas, USA
A 56-year-old male with DM and HTN presented with flank pain and nausea. Review of systems was negative, physical examination was notable for mild hypovolemia and laboratory revealed BUN 51 mg/dl, creatinine (Cr) 5.1 mg/dl (baseline 1.5), Westergren ESR 122 mm/h, fractional excretion of sodium 0.2% and UA positive for blood and protein. Despite volume resuscitation the Cr continued to rise. Urine sediment analysis revealed granular casts, renal tubular epithelial cells and a negative Hansel’s stain. Hemodialysis was initiated with Cr 13.7 mg/ dl for dyspnea and dysgeusia. Subsequent laboratory data revealed 2 separate positive anti-GBM antibody titers and prednisone therapy was initiated. Renal biopsy was performed for further diagnostic, therapeutic and prognostic information and demonstrated interstitial nephritis with linear IgG and albumin deposition consistent with diabetic nephropathy. Follow-up antibody titers were negative, prednisone was discontinued and Cr stabilized with conservative therapy. Anti-GBM antibody disease is characterized by circulating IgG antibodies directed against the glomerular basement membrane, specifically the a-3 (IV) collagen chain. Anti-GBM nephritis is a rapidly progressive, isolated glomerulonephritis in association with circulating anti-GBM antibodies. A positive immunofluorescence (IF) test is considered diagnostic in the appropriate clinical setting. Therapies include immunosuppressive agents to suppress new antibody production and plasmapheresis to eliminate circulating antibodies. Anti-GBM antibody is not rapidly cleared by steroid therapy and the recovery of renal function is rare if initiation Cr is greater than 7 mg/dl. This case demonstrates that the current ELISA for a-3 (IV) collagen is not pathognomonic for anti-GBM nephritis and that renal biopsy with IF for IgG and albumin may be indicated to prevent administration of potentially toxic treatment.Correspondence to:
Dr. A.J. DeAngelo; Brooke Army Medical Center, ATTN: MCHE-MD, 3851 Roger Brooke Drive, Fort Sam Houston, TX 78234-6200, USA
Email: adeangelo@pol.net
