Content
User login
Enter your username and password here in order to log in on the website:
- Contact us
- About us
- Disclaimer
Dustri-Verlag
Volume 73, No. 5/2010(May)
|
The use of the online-version will be charged with an extra fee (additional to the subscription of the print-version). The service can be used until December 31st of the year of subscription. |
|
| Full Issue Price: 30.00$ |  |
Lead article
Novel immunosuppressive agents in kidney transplantation
J.E. Cooper and A.C. Wiseman
333
48$
Abstract
The last several decades have seen a substantial decrease in the prevalence of acute allograft rejection in kidney transplant recipients, while equivalent improvements in long-term graft function have not been realized. As a result, the primary focus of new immunosuppressive drug development has expanded to include ease of use, improved side effect profiles, and reduced nephrotoxicity in addition to the more traditional goal of improved short-term outcomes. A number of novel drugs are currently under investigation in Phase I, II, or III clinical trials primarily to replace the nephrotoxic but highly effective calcineurin inhibitors. ISA247 (voclosporine) is a cyclosporine (CsA) analog with reduced nephrotoxicity in Phase III study. AEB071 (sotrastaurin), a protein kinase C inhibitor, and CP-690550, a JAK3 inhibitor, are small molecules in Phase II studies. Everolimus is derived from the mTOR inhibitor sirolimus and is in Phase III study. Belatacept is a humanized antibody that inhibits T-cell costimulation and has shown encouraging results in multiple Phase II and III trials. Alefacept and Efaluzimab are humanized antibodies that inhibit T-cell adhesion and are in Phase I and II clinical trials. This article reviews the mechanisms of action as well as published and preliminary results of the Phase I – III clinical trials involving these novel immunosuppressive agents.Correspondence to:
A.C. Wiseman, MD
University of Colorado – Denver and Health Sciences Center,
Transplant Center,
1635 N Aurora Court, AOP 7089, MS F749, Aurora, CO 80045, USA
Email: Alexander.wiseman@ucdenver.edu
Clinical Nephrology, Vol. 73 – No. 5/2010 (333-343)
Novel immunosuppressive agents in kidney transplantation
J.E. Cooper and A.C. Wiseman
University of Colorado – Denver and Health Sciences Center, Transplant Center, Aurora, CO, USA The last several decades have seen a substantial decrease in the prevalence of acute allograft rejection in kidney transplant recipients, while equivalent improvements in long-term graft function have not been realized. As a result, the primary focus of new immunosuppressive drug development has expanded to include ease of use, improved side effect profiles, and reduced nephrotoxicity in addition to the more traditional goal of improved short-term outcomes. A number of novel drugs are currently under investigation in Phase I, II, or III clinical trials primarily to replace the nephrotoxic but highly effective calcineurin inhibitors. ISA247 (voclosporine) is a cyclosporine (CsA) analog with reduced nephrotoxicity in Phase III study. AEB071 (sotrastaurin), a protein kinase C inhibitor, and CP-690550, a JAK3 inhibitor, are small molecules in Phase II studies. Everolimus is derived from the mTOR inhibitor sirolimus and is in Phase III study. Belatacept is a humanized antibody that inhibits T-cell costimulation and has shown encouraging results in multiple Phase II and III trials. Alefacept and Efaluzimab are humanized antibodies that inhibit T-cell adhesion and are in Phase I and II clinical trials. This article reviews the mechanisms of action as well as published and preliminary results of the Phase I – III clinical trials involving these novel immunosuppressive agents.Correspondence to:
A.C. Wiseman, MD
University of Colorado – Denver and Health Sciences Center,
Transplant Center,
1635 N Aurora Court, AOP 7089, MS F749, Aurora, CO 80045, USA
Email: Alexander.wiseman@ucdenver.edu
Original
Addition of induction therapy offsets the hazard of marked calcineurin minimization among renal transplant recipients treated with sirolimus
B.D. Kahan, C. Benavides, L. Schoenberg, J. Podbielski and C. Green
344
44$
Abstract
Aims: We sought to examine the improvement in renal function with preserved immunosuppression consequent to reducing de novo cyclosporine (CsA) doses combined with sirolimus and induction antibody treatment. Materials and methods: 408 renal recipients treated de novo with CsA-sirolimus included 91 patients who received high (> 5); 125, medium (2.5 – 5.0); or 192, low CsA doses (< 2.5 mg/kg/day) together with induction antibody among 5, 48 and 68% of subjects, respectively. At 2 years we excluded 21 (23), 30 (24) and 49 (25%) subjects who experienced the composite end-point, yielding 70 (71), 95 (76) and 143 (74%) cases, whose mean de novo CsA C2 values were 725, 400 and 306 ng/ml; for all cohorts, sirolimus C0 = 10 – 15 de novo and 8 – 12 ng/ml during maintenance treatment. The primary end-point – mean 4-year GFR by aMDRD – ascribed “0” to patients who experienced death or graft loss after 2 years. Results: Although low-dose subjects were older (p = 0.008) and heavier (p < 0.001) with grafts exposed to longer cold ischemia times (p < 0.001), they displayed greater GFR: 64.8 versus 48.4 among the high and 54.1 ml/min/1.73 m2 in the medium dose arms (p = 0.002). Polychotomous logistic regression revealed significant GFR predictors to be CsA dose (p = 0.015) and younger donor age (p < 0.001). Between 2 and 4 years, the incidences of the composite end-point were 17, 14 and 16%; including 13, 10 and 11% rejections. Conclusion: 80% reduction in de novo CsA exposure with antibody induction improved renal function at 4 years compared with 50 or 66% reductions.Correspondence to:
B.D. Kahan, PhD, MD
Division of Immunology and Organ Transplantation
The University of Texas Medical School
6431 Fannin, Suite 6.240
Houston, TX 77030, USA
Email: Barry.D.Kahan@uth.tmc.edu
Clinical Nephrology, Vol. 73 – No. 5/2010 (344-353)
Addition of induction therapy offsets the hazard of marked calcineurin minimization among renal transplant recipients treated with sirolimus
B.D. Kahan1, C. Benavides2, L. Schoenberg1, J. Podbielski1 and C. Green3
1Division of Immunology and Organ Transplantation, The University of Texas Medical School, Houston, TX, USA, 2Hospital San Ignacio, Bogota, Columbia, and 3Center for Clinical Research, Houston, TX, USA Aims: We sought to examine the improvement in renal function with preserved immunosuppression consequent to reducing de novo cyclosporine (CsA) doses combined with sirolimus and induction antibody treatment. Materials and methods: 408 renal recipients treated de novo with CsA-sirolimus included 91 patients who received high (> 5); 125, medium (2.5 – 5.0); or 192, low CsA doses (< 2.5 mg/kg/day) together with induction antibody among 5, 48 and 68% of subjects, respectively. At 2 years we excluded 21 (23), 30 (24) and 49 (25%) subjects who experienced the composite end-point, yielding 70 (71), 95 (76) and 143 (74%) cases, whose mean de novo CsA C2 values were 725, 400 and 306 ng/ml; for all cohorts, sirolimus C0 = 10 – 15 de novo and 8 – 12 ng/ml during maintenance treatment. The primary end-point – mean 4-year GFR by aMDRD – ascribed “0” to patients who experienced death or graft loss after 2 years. Results: Although low-dose subjects were older (p = 0.008) and heavier (p < 0.001) with grafts exposed to longer cold ischemia times (p < 0.001), they displayed greater GFR: 64.8 versus 48.4 among the high and 54.1 ml/min/1.73 m2 in the medium dose arms (p = 0.002). Polychotomous logistic regression revealed significant GFR predictors to be CsA dose (p = 0.015) and younger donor age (p < 0.001). Between 2 and 4 years, the incidences of the composite end-point were 17, 14 and 16%; including 13, 10 and 11% rejections. Conclusion: 80% reduction in de novo CsA exposure with antibody induction improved renal function at 4 years compared with 50 or 66% reductions.Correspondence to:
B.D. Kahan, PhD, MD
Division of Immunology and Organ Transplantation
The University of Texas Medical School
6431 Fannin, Suite 6.240
Houston, TX 77030, USA
Email: Barry.D.Kahan@uth.tmc.edu
Original
Combination therapy with mycophenolate mofetil and prednisone in steroid-resistant idiopathic membranoproliferative glomerulonephritis
M. Yuan, J. Zou, X. Zhang, H. Liu, J. Teng, Y. Zhong and X. Ding
354
28$
Abstract
Background: To observe the efficacy of the combination therapy of mycophenolate mofetil (MMF) and glucocorticoids on steroid-resistant idiopathic membranoproliferative glomerulonephritis (IMPGN) with moderate to heavy proteinuria. Methods: 13 cases were diagnosed as IMPGN by renal biopsy after excluding secondary etiology. 9 patients had heavy proteinuria and another 4 with moderate proteinuria, 9 with hypertension and 11 with decreased renal function. Before MMF therapy, all of them were resistant to treatment of glucocorticoid (prednisone 1 mg/kg/d) for 8 weeks or more. The initial dose of MMF was 1.5 g/d. Patients were followed up every month, including blood pressure, urine protein excretion, liver and kidney function, complete blood count, and adverse events recorded. Results: At the initiation, the 24-h urine protein excretion was 4.1 ± 1.4 g, serum creatinine (Scr) 131.0 ± 44.9 mmol/l, and estimated glomerular filtration rate (eGFR) 63.3 ± 26.8 ml/min/1.73 m2. After prednisone therapy for at least 2 months, the 24-h urine protein excretion and eGFR did not change significantly (p > 0.05). After 3 months of the addition of MMF, 24-h urine protein excretion decreased slightly to 3.8 ± 1.2 g (p < 0.05),Scr decreased to 127.3 ± 43.7 µmol/l and eGFR elevated to 65.7 ± 26.8 ml/min/1.73 m2, (p < 0.05); after 6 months, 24-h urine protein excretion decreased more significantly (2.5 ± 0.9 g, p < 0.01), with improved kidney function (Scr 97.2 ± 27.3 mmol/l and eGFR 81.3 ± 24.2 ml/min/1.73 m2, p < 0.01); compared with that before MMF treatment. After 12 months, 24-h urine protein excretion decreased further (1.5 ± 0.6g, p < 0.01) with kidney function remained stable (Scr 95.9 ± 22.5 µmol/l and eGFR 81.2 ± 23.8 ml/min/1.73 m2). Conclusion: MMF combined with glucosteroids could effectively decrease proteinuria and improve renal function on steroid-resistant IMPGN. Further study with a large sample is needed to evaluate the efficacy and safety of MMF in the treatment of IMPGN.Correspondence to:
Prof. X. Ding
Director Division of Nephrology
Zhongshan Hospital
Shanghai Medical College
Fudan University
Shanghai 200032, P.R.China
Email: dxq93216@medmail.com.cn
Clinical Nephrology, Vol. 73 – No. 5/2010 (354-359)
Combination therapy with mycophenolate mofetil and prednisone in steroid-resistant idiopathic membranoproliferative glomerulonephritis
M. Yuan, J. Zou, X. Zhang, H. Liu, J. Teng, Y. Zhong and X. Ding
Division of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, P.R.China Background: To observe the efficacy of the combination therapy of mycophenolate mofetil (MMF) and glucocorticoids on steroid-resistant idiopathic membranoproliferative glomerulonephritis (IMPGN) with moderate to heavy proteinuria. Methods: 13 cases were diagnosed as IMPGN by renal biopsy after excluding secondary etiology. 9 patients had heavy proteinuria and another 4 with moderate proteinuria, 9 with hypertension and 11 with decreased renal function. Before MMF therapy, all of them were resistant to treatment of glucocorticoid (prednisone 1 mg/kg/d) for 8 weeks or more. The initial dose of MMF was 1.5 g/d. Patients were followed up every month, including blood pressure, urine protein excretion, liver and kidney function, complete blood count, and adverse events recorded. Results: At the initiation, the 24-h urine protein excretion was 4.1 ± 1.4 g, serum creatinine (Scr) 131.0 ± 44.9 mmol/l, and estimated glomerular filtration rate (eGFR) 63.3 ± 26.8 ml/min/1.73 m2. After prednisone therapy for at least 2 months, the 24-h urine protein excretion and eGFR did not change significantly (p > 0.05). After 3 months of the addition of MMF, 24-h urine protein excretion decreased slightly to 3.8 ± 1.2 g (p < 0.05),Scr decreased to 127.3 ± 43.7 µmol/l and eGFR elevated to 65.7 ± 26.8 ml/min/1.73 m2, (p < 0.05); after 6 months, 24-h urine protein excretion decreased more significantly (2.5 ± 0.9 g, p < 0.01), with improved kidney function (Scr 97.2 ± 27.3 mmol/l and eGFR 81.3 ± 24.2 ml/min/1.73 m2, p < 0.01); compared with that before MMF treatment. After 12 months, 24-h urine protein excretion decreased further (1.5 ± 0.6g, p < 0.01) with kidney function remained stable (Scr 95.9 ± 22.5 µmol/l and eGFR 81.2 ± 23.8 ml/min/1.73 m2). Conclusion: MMF combined with glucosteroids could effectively decrease proteinuria and improve renal function on steroid-resistant IMPGN. Further study with a large sample is needed to evaluate the efficacy and safety of MMF in the treatment of IMPGN.Correspondence to:
Prof. X. Ding
Director Division of Nephrology
Zhongshan Hospital
Shanghai Medical College
Fudan University
Shanghai 200032, P.R.China
Email: dxq93216@medmail.com.cn
Original
Carotid artery calcification and atherosclerosis at the initiation of hemodialysis in patients with end-stage renal disease
Y. Sumida, M. Nakayama, M. Nagata, S. Nakashita, T. Suehiro, Y. Kaizu, H. Ikeda and K. Izumaru
360
44$
Abstract
Aims: Vascular calcification and atherosclerosis frequently develop in end-stage renal disease (ESRD). Although several reports have investigated both carotid artery calcification (CAAC) and carotid atherosclerosis in ESRD patients, the relationship between the two vascular conditions has remained unclear. The aim of this study was to assess the prevalence of CAAC and carotid artery plaque (CAP) in patients with ESRD and to investigate potential factors contributing to the development of CAAC and CAP. Material and method: This cross-sectional study assessed CAAC and CAP using multidetector computed tomography and high-resolution B-mode ultrasonography, respectively, in 135 patients with ESRD at the start of hemodialysis. The prevalence of CAAC and CAP was examined. The risk factors associated with CAAC and CAP were also evaluated using a logistic regression model. Results: CAAC and CAP were found in 71% and 65%, of the patients, respectively. A logistic regression analysis adjusted for age and gender showed that CAAC was significantly associated with age, hypertension, dyslipidemia, serum albumin, calcium-phosphorus product, proteinuria and CAP. In contrast, in the same analysis, CAP was significantly correlated with age, male gender, diabetes, intact parathyroid hormone, proteinuria and CAAC. In the multivariate analysis, CAAC was independently associated with age, hypertension, and calcium-phosphorus product. Male gender was identified as an independent determinant for CAP. Furthermore, CAP remained as an independent risk factor of CAAC (odds ratio (OR): 13.89; 95% confidence interval (CI): 4.08 – 47.29), and CAAC also showed a high OR for having CAP (OR: 11.74; 95% CI: 4.12 – 33.51). Conclusion: Both CAAC and CAP were associated with traditional and/or non-traditional risk factors. The risk factors of CAAC were different from those of CAP. CAAC or CAP was identified to be an independent risk factor for each other with a high OR, thus suggesting a strong relationship between carotid calcification and atherosclerosis.Correspondence to:
M. Nakayama, MD
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: mnaka@kyumed.jp
Clinical Nephrology, Vol. 73 – No. 5/2010 (360-369)
Carotid artery calcification and atherosclerosis at the initiation of hemodialysis in patients with end-stage renal disease
Y. Sumida1, M. Nakayama1, M. Nagata2, S. Nakashita1, T. Suehiro1, Y. Kaizu1, H. Ikeda1 and K. Izumaru1
1Division of Nephrology and Clinical Research Institute, Department of Internal Medicine, National Kyushu Medical Center Hospital, Fukuoka, and 2Department of Medicine and Clinical Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan Aims: Vascular calcification and atherosclerosis frequently develop in end-stage renal disease (ESRD). Although several reports have investigated both carotid artery calcification (CAAC) and carotid atherosclerosis in ESRD patients, the relationship between the two vascular conditions has remained unclear. The aim of this study was to assess the prevalence of CAAC and carotid artery plaque (CAP) in patients with ESRD and to investigate potential factors contributing to the development of CAAC and CAP. Material and method: This cross-sectional study assessed CAAC and CAP using multidetector computed tomography and high-resolution B-mode ultrasonography, respectively, in 135 patients with ESRD at the start of hemodialysis. The prevalence of CAAC and CAP was examined. The risk factors associated with CAAC and CAP were also evaluated using a logistic regression model. Results: CAAC and CAP were found in 71% and 65%, of the patients, respectively. A logistic regression analysis adjusted for age and gender showed that CAAC was significantly associated with age, hypertension, dyslipidemia, serum albumin, calcium-phosphorus product, proteinuria and CAP. In contrast, in the same analysis, CAP was significantly correlated with age, male gender, diabetes, intact parathyroid hormone, proteinuria and CAAC. In the multivariate analysis, CAAC was independently associated with age, hypertension, and calcium-phosphorus product. Male gender was identified as an independent determinant for CAP. Furthermore, CAP remained as an independent risk factor of CAAC (odds ratio (OR): 13.89; 95% confidence interval (CI): 4.08 – 47.29), and CAAC also showed a high OR for having CAP (OR: 11.74; 95% CI: 4.12 – 33.51). Conclusion: Both CAAC and CAP were associated with traditional and/or non-traditional risk factors. The risk factors of CAAC were different from those of CAP. CAAC or CAP was identified to be an independent risk factor for each other with a high OR, thus suggesting a strong relationship between carotid calcification and atherosclerosis.Correspondence to:
M. Nakayama, MD
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: mnaka@kyumed.jp
Original
Efficacy of chewed vs. crushed lanthanum on phosphorus binding in healthy volunteers
P.P. How, D.L. Mason, J.A. Arruda and A.H. Lau
370
20$
Abstract
Background and aim: For effective dietary phosphorous (P) binding, patients are recommended to chew lanthanum tablets completely before swallowing, with or immediately after meals. However, some patients are unable to chew the tablets. It is not known if crushing the tablets prior to taking them with food is as efficacious as chewing them. This study was conducted to compare the efficacy of chewed vs. crushed lanthanum on P binding. Methods: 12 healthy subjects were randomized and crossed-over to receive: (A) a standardized meal containing 1 g (32 mmol) of elemental P; (B) a single 1 g oral dose of lanthanum, chewed and taken with the standardized meal; (C) a single 1 g oral dose of lanthanum, crushed into a fine powder using a pestle and mortar, mixed with applesauce, and taken with the standardized meal. Blood and urine samples were collected from baseline to 8 hours after meal completion. The changes in serum P, urinary P excretion and fractional excretion of P (FePi) were compared among treatment arms using ANOVA. Results: Co-administration of lanthanum with meal resulted in a smaller increase in serum P, compared with meal alone (p < 0.05). The smaller increase in serum P was similar for both chewed and crushed lanthanum. The amount of P excreted and FePi were also lower when chewed or crushed lanthanum was administered with meal, compared with meal alone (p = n.s. and p < 0.05, respectively). Conclusion: Both chewed and crushed lanthanum are effective in lowering P absorption after a dietary P load.Correspondence to:
P.P. How, PharmD
Department of Pharmacy
Faculty of Science
National University of Singapore
Block S4, Science Drive 4
117543 Singapore
Email: priscillahow@nus.edu.sg
Clinical Nephrology, Vol. 73 – No. 5/2010 (370-373)
Efficacy of chewed vs. crushed lanthanum on phosphorus binding in healthy volunteers
P.P. How1,3, D.L. Mason1, J.A. Arruda2 and A.H. Lau1
1College of Pharmacy, Department of Pharmacy Practice and 2College of Medicine, Section of Nephrology, University of Illinois at Chicago, IL, USA, and 3Department of Pharmacy, Faculty of Science, National University of Singapore Background and aim: For effective dietary phosphorous (P) binding, patients are recommended to chew lanthanum tablets completely before swallowing, with or immediately after meals. However, some patients are unable to chew the tablets. It is not known if crushing the tablets prior to taking them with food is as efficacious as chewing them. This study was conducted to compare the efficacy of chewed vs. crushed lanthanum on P binding. Methods: 12 healthy subjects were randomized and crossed-over to receive: (A) a standardized meal containing 1 g (32 mmol) of elemental P; (B) a single 1 g oral dose of lanthanum, chewed and taken with the standardized meal; (C) a single 1 g oral dose of lanthanum, crushed into a fine powder using a pestle and mortar, mixed with applesauce, and taken with the standardized meal. Blood and urine samples were collected from baseline to 8 hours after meal completion. The changes in serum P, urinary P excretion and fractional excretion of P (FePi) were compared among treatment arms using ANOVA. Results: Co-administration of lanthanum with meal resulted in a smaller increase in serum P, compared with meal alone (p < 0.05). The smaller increase in serum P was similar for both chewed and crushed lanthanum. The amount of P excreted and FePi were also lower when chewed or crushed lanthanum was administered with meal, compared with meal alone (p = n.s. and p < 0.05, respectively). Conclusion: Both chewed and crushed lanthanum are effective in lowering P absorption after a dietary P load.Correspondence to:
P.P. How, PharmD
Department of Pharmacy
Faculty of Science
National University of Singapore
Block S4, Science Drive 4
117543 Singapore
Email: priscillahow@nus.edu.sg
Original
Depression and health-related quality of life in maintenance hemodialysis patients
H.C. Park, H.-B. Yoon, M.-J. Son, E.S. Jung, K.W. Joo, H.J. Chin, K.H. Oh, C.S. Lim, Y.S. Kim, C. Ahn, J.S. Han, S. Kim, B.-J. Hahm and Y.K. Oh
374
32$
Abstract
Background: This study was designed to determine the prevalence of depression among hemodialysis (HD) patients from urban hospitals in Korea, to illustrate demographic factors and biomarkers associated with depression and health-related quality of life (HRQOL), and to demonstrate association between depression and HRQOL. Patients and methods: For this multicenter, cross-sectional study, 160 HD patients from 3 university teaching hospitals and 3 local dialysis units in Korea were enrolled. Korean Beck’s depression inventory and Korean version of Kidney Disease Quality of Life short form, version 1.3 (KDQOL-SFTM 1.3) were used to evaluate depression and quality of life, respectively. Results: Depression was found in 51 out of 160 (31.9%) patients. Old age (> 60 years old), low hemoglobin level (< 10 g/dl), and low economic status were associated with depression, and old age (OR 6.138, p = 0.001) was the most important risk factor among them. Old age, female gender, presence of diabetes mellitus, high comorbidity index score (modified Charlson comorbidity index ≥ 6), hypoalbuminemia (< 4.0 g/dl), and high CRP (> 0.5 mg/dl) were common factors associated with decreased HRQOL. Depression and HRQOL showed inverse linear relationship. Conclusions: Moderate to severe depression was common in maintenance HD patients in Korea. Among factors associated with depression and decreased HRQOL, some characteristics are potentially modifiable by social and medical intervention. Further prospective studies are warranted to see whether depression and HRQOL can be improved by modifying these factors.Correspondence to:
Y.K. Oh, MD, PhD
Department of Internal Medicine
Seoul National University College of Medicine
Seoul National University Boramae Hospital
425, Shindaebang 2-Dong, Dongjak-Gu
Seoul, 156-707, Korea
Email: yoonkyu@snu.ac.kr
Clinical Nephrology, Vol. 73 – No. 5/2010 (374-380)
Depression and health-related quality of life in maintenance hemodialysis patients
H.C. Park1, H.-B. Yoon1, M.-J. Son1, E.S. Jung1, K.W. Joo1, H.J. Chin1,2, K.H. Oh1, C.S. Lim1,3, Y.S. Kim1, C. Ahn1, J.S. Han1, S. Kim1, B.-J. Hahm4 and Y.K. Oh1,3
1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 2Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, 3Department of Internal Medicine, Seoul National University Boramae Hospital, and 4Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea Background: This study was designed to determine the prevalence of depression among hemodialysis (HD) patients from urban hospitals in Korea, to illustrate demographic factors and biomarkers associated with depression and health-related quality of life (HRQOL), and to demonstrate association between depression and HRQOL. Patients and methods: For this multicenter, cross-sectional study, 160 HD patients from 3 university teaching hospitals and 3 local dialysis units in Korea were enrolled. Korean Beck’s depression inventory and Korean version of Kidney Disease Quality of Life short form, version 1.3 (KDQOL-SFTM 1.3) were used to evaluate depression and quality of life, respectively. Results: Depression was found in 51 out of 160 (31.9%) patients. Old age (> 60 years old), low hemoglobin level (< 10 g/dl), and low economic status were associated with depression, and old age (OR 6.138, p = 0.001) was the most important risk factor among them. Old age, female gender, presence of diabetes mellitus, high comorbidity index score (modified Charlson comorbidity index ≥ 6), hypoalbuminemia (< 4.0 g/dl), and high CRP (> 0.5 mg/dl) were common factors associated with decreased HRQOL. Depression and HRQOL showed inverse linear relationship. Conclusions: Moderate to severe depression was common in maintenance HD patients in Korea. Among factors associated with depression and decreased HRQOL, some characteristics are potentially modifiable by social and medical intervention. Further prospective studies are warranted to see whether depression and HRQOL can be improved by modifying these factors.Correspondence to:
Y.K. Oh, MD, PhD
Department of Internal Medicine
Seoul National University College of Medicine
Seoul National University Boramae Hospital
425, Shindaebang 2-Dong, Dongjak-Gu
Seoul, 156-707, Korea
Email: yoonkyu@snu.ac.kr
Original
Pancreatitis following administration of iodixanol in patients on hemodialysis: a pilot study
M. Kheda, L. Brenner, D. Riggans, V. Kota and H.M. Szerlip
381
20$
Abstract
Background and objectives: We previously described the association of pancreatitis with the use of iodixanol radiocontrast in two patients on hemodialysis. This study was designed to determine whether there might be a causal link. Design: 30 consecutive hemodialysis patients without predisposition for pancreatitis who were undergoing declotting and angioplasty of their arteriovenous access were randomly assigned to either iodixanol or iohexol radiocontrast. Results: The demographics and volume of contrast used were similar between the groups. 2 of the 15 patients who received iodixanol developed elevations in serum amylase and lipase as well as signs and symptoms of pancreatitis. No patient who received iohexol developed pancreatitis. Conclusion: The use of iodixanol appears to be associated with pancreatitis in a small population of hemodialysis patients. Although the pathogenesis of iodixanol-induced pancreatitis is unclear, we speculate that it is possibly related to the hyperviscosity of this agent, which may decrease pancreatic blood flow. Larger studies are needed to verify these findings.Correspondence to:
H.M. Szerlip, MD
Deptartment of Medicine
3950 S. Country Club Road, Suite 200
Tucson, AZ 85714, USA
Email: hszerlip@deptofmed.arizona.edu
Clinical Nephrology, Vol. 73 – No. 5/2010 (381-384)
Pancreatitis following administration of iodixanol in patients on hemodialysis: a pilot study
M. Kheda1, L. Brenner1, D. Riggans2,3, V. Kota1 and H.M. Szerlip1
1Section of Nephrology, 2Department of Radiology, Medical College of Georgia, and 3Interventional and Vascular Care Center, Augusta, GA, USA Background and objectives: We previously described the association of pancreatitis with the use of iodixanol radiocontrast in two patients on hemodialysis. This study was designed to determine whether there might be a causal link. Design: 30 consecutive hemodialysis patients without predisposition for pancreatitis who were undergoing declotting and angioplasty of their arteriovenous access were randomly assigned to either iodixanol or iohexol radiocontrast. Results: The demographics and volume of contrast used were similar between the groups. 2 of the 15 patients who received iodixanol developed elevations in serum amylase and lipase as well as signs and symptoms of pancreatitis. No patient who received iohexol developed pancreatitis. Conclusion: The use of iodixanol appears to be associated with pancreatitis in a small population of hemodialysis patients. Although the pathogenesis of iodixanol-induced pancreatitis is unclear, we speculate that it is possibly related to the hyperviscosity of this agent, which may decrease pancreatic blood flow. Larger studies are needed to verify these findings.Correspondence to:
H.M. Szerlip, MD
Deptartment of Medicine
3950 S. Country Club Road, Suite 200
Tucson, AZ 85714, USA
Email: hszerlip@deptofmed.arizona.edu
Original
An amplification of IL-10 and TGF-beta in patients with IgG4-related tubulointerstitial nephritis
H. Nakashima, K. Miyake, M. Moriyama, A. Tanaka, M. Watanabe, Y. Abe, H. Sato, S. Nakamura and T. Saito
385
32$
Abstract
Background: IgG4-related tubulointerstitial nephritis (TIN) shows characteristic serum IgG4 elevation and increased IgG4-positive plasma cells in the renal interstitium, and inclusion of TIN as an IgG4-related systemic disease has been suggested. IgG4 is the rarest IgG subclass and is a Th2-dependent isotype with low affinity for target antigen. Although the pathogenesis of this disease has not been elucidated, positive serum immune complex and hypocomplementemia in some patients with this disease suggest that immune complex mechanisms are involved in the causation of this disease. Method: We selected 20 cases of histological diagnosed TIN. These cases were etiologically different and included 4 cases of IgG4-related TIN. We extracted RNA from paraffin embedded biopsied kidney and evaluated expression levels of various cytokines for each case by real time PCR. Results: Comparison of cytokine production patterns among different disease-associated TINs revealed that IgG4-related TIN exhibited a quite distinct pattern. On the one hand, there was no expression of IL-2, IFN-γ, IL-17 and IL-6, whereas production of IL-4, IL-10 and TGF-β was, on the other hand, remarkably increased in IgG4-related TIN. Conclusion: Based on these cytokine production results, Th2 and Treg appear to play a central role in IgG4-related TIN.Correspondence to:
H. Nakashima, MD, PhD
Division of Nephrology and Rheumatology
Department of Internal Medicine
Faculty of Medicine
Fukuoka University
7-45-1 Nanakuma, Jonann-ku
Fukuoka 814-0180, Japan
Email: hnakashi@fukuoka-u.ac.jp
Clinical Nephrology, Vol. 73 – No. 5/2010 (385-391)
An amplification of IL-10 and TGF-beta in patients with IgG4-related tubulointerstitial nephritis
H. Nakashima1, K. Miyake1, M. Moriyama2, A. Tanaka2, M. Watanabe1, Y. Abe1, H. Sato3, S. Nakamura2 and T. Saito1
1Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University, 2Department of Oral and Maxillofacial Surgery, Graduate School of Dental Science, Kyushu University, Fukuoka, and 3Division of Nephrology, Endocrinology and Vascular medicine, Department of Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan Background: IgG4-related tubulointerstitial nephritis (TIN) shows characteristic serum IgG4 elevation and increased IgG4-positive plasma cells in the renal interstitium, and inclusion of TIN as an IgG4-related systemic disease has been suggested. IgG4 is the rarest IgG subclass and is a Th2-dependent isotype with low affinity for target antigen. Although the pathogenesis of this disease has not been elucidated, positive serum immune complex and hypocomplementemia in some patients with this disease suggest that immune complex mechanisms are involved in the causation of this disease. Method: We selected 20 cases of histological diagnosed TIN. These cases were etiologically different and included 4 cases of IgG4-related TIN. We extracted RNA from paraffin embedded biopsied kidney and evaluated expression levels of various cytokines for each case by real time PCR. Results: Comparison of cytokine production patterns among different disease-associated TINs revealed that IgG4-related TIN exhibited a quite distinct pattern. On the one hand, there was no expression of IL-2, IFN-γ, IL-17 and IL-6, whereas production of IL-4, IL-10 and TGF-β was, on the other hand, remarkably increased in IgG4-related TIN. Conclusion: Based on these cytokine production results, Th2 and Treg appear to play a central role in IgG4-related TIN.Correspondence to:
H. Nakashima, MD, PhD
Division of Nephrology and Rheumatology
Department of Internal Medicine
Faculty of Medicine
Fukuoka University
7-45-1 Nanakuma, Jonann-ku
Fukuoka 814-0180, Japan
Email: hnakashi@fukuoka-u.ac.jp
Case report
Prolonged hyperkalemia following unilateral adrenalectomy for primary hyperaldosteronism
W.-T. Huang, T. Chau, S.-T. Wu and S.-H. Lin
392
28$
Abstract
Hypokalemia associated with aldosterone-producing adenomas (APA) are almost corrected following successful unilateral adrenalectomy. Prolonged hyperkalemia after unilateral adrenalectomy is rarely reported and may be overlooked. We describe a 62-year-old man who presented with fatigue and dizziness 2 weeks after unilateral adrenalectomy for aldosterone-producing adenomas. Physical examination showed decreased skin turgor and postural hypotension. Laboratory studies revealed hyperkalemia (6.3 mmol/l) with a low transtubular potassium gradient of 5. A relatively low plasma aldosterone concentration and high plasma renin activity in the setting of normal plasma cortisol and adrenocorticotropic hormone levels lead to a diagnosis of functional hypoaldosteronism. Fludrocortisone 0.2 mg/day for one week completely corrected his hyperkalemia which recurred after cessation of fludrocortisone. Long-term suppression of contralateral aldosterone synthesis by APA and/or chronic untreated hypokalemia may have accounted for the development of prolonged hyperkalemia after unilateral adrenalectomy. Serum potassium concentration following unilateral adrenalectomy must be meticulously monitored to avoid life-threatening hyperkalemia.Correspondence to:
S.-H. Lin, MD
Division of Nephrology
Department of Medicine
Tri-Service General Hospital
Number 325, Section 2
Cheng-Kung Road
Neihu 114, Taipei, Taiwan
Email: shihhualin@yahoo.com
Clinical Nephrology, Vol. 73 – No. 5/2010 (392-397)
Prolonged hyperkalemia following unilateral adrenalectomy for primary hyperaldosteronism
W.-T. Huang1, T. Chau2, S.-T. Wu3 and S.-H. Lin2
1Department of Internal Medicine, Zuoying Armed Forces General Hospital, Kaohsiung, 2Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, and 3Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C. Hypokalemia associated with aldosterone-producing adenomas (APA) are almost corrected following successful unilateral adrenalectomy. Prolonged hyperkalemia after unilateral adrenalectomy is rarely reported and may be overlooked. We describe a 62-year-old man who presented with fatigue and dizziness 2 weeks after unilateral adrenalectomy for aldosterone-producing adenomas. Physical examination showed decreased skin turgor and postural hypotension. Laboratory studies revealed hyperkalemia (6.3 mmol/l) with a low transtubular potassium gradient of 5. A relatively low plasma aldosterone concentration and high plasma renin activity in the setting of normal plasma cortisol and adrenocorticotropic hormone levels lead to a diagnosis of functional hypoaldosteronism. Fludrocortisone 0.2 mg/day for one week completely corrected his hyperkalemia which recurred after cessation of fludrocortisone. Long-term suppression of contralateral aldosterone synthesis by APA and/or chronic untreated hypokalemia may have accounted for the development of prolonged hyperkalemia after unilateral adrenalectomy. Serum potassium concentration following unilateral adrenalectomy must be meticulously monitored to avoid life-threatening hyperkalemia.Correspondence to:
S.-H. Lin, MD
Division of Nephrology
Department of Medicine
Tri-Service General Hospital
Number 325, Section 2
Cheng-Kung Road
Neihu 114, Taipei, Taiwan
Email: shihhualin@yahoo.com
Case report
Four cases of postrenal renal failure induced by renal stone associated with rotavirus infection
T. Morita, A. Ashida, M. Fujieda, A. Hayashi, A. Maeda, K. Ohta, M. Shimizu, T. Sekine, T. Igarashi, H. Tamai and H. Wakiguchi
398
24$
Abstract
Rotavirus (RV) is a common pathogen that causes acute gastroenteritis in childhood. Some cases with RV infection also have prerenal renal failure induced by dehydration associated with vomiting and diarrhea. Here, we report 4 patients with RV infection who developed postrenal renal failure induced by urinary tract obstruction with uroammoniac calculi or crystals. The patients did not have metabolic disorders or abnormalities of the urinary tract, and increased urinary excretion of uric acid was not recognized at discharge. In addition, no abnormalities in the uric acid transporter (URAT1) were found in any of the patients. Uric acid stone formation was considered to have originated from the low pH caused by dehydration and the increase of urinary uric acid excretion from damaged cells.Correspondence to:
M. Fujieda, MD
Department of Pediatrics
Kochi Medical School
Kochi University, Kohasu
Oko-cho, Nankoku, Kochi 783-8505, Japan
Email: fujiedam@kochi-u.ac.jp
Clinical Nephrology, Vol. 73 – No. 5/2009 (398-402)
Four cases of postrenal renal failure induced by renal stone associated with rotavirus infection
T. Morita1, A. Ashida2, M. Fujieda1, A. Hayashi1, A. Maeda1, K. Ohta3, M. Shimizu3, T. Sekine4, T. Igarashi4, H. Tamai2 and H. Wakiguchi1
1Department of Pediatrics, Kochi Medical School, Kochi University, Kochi, 2Department of Pediatrics, Osaka Medical College, Osaka, 3Department of Pediatrics, Graduate School of Medical Science, Kanazawa University, Kanazawa, and 4Department of Pediatrics, Graduate School of Medical Science, the University of Tokyo, Tokyo, Japan Rotavirus (RV) is a common pathogen that causes acute gastroenteritis in childhood. Some cases with RV infection also have prerenal renal failure induced by dehydration associated with vomiting and diarrhea. Here, we report 4 patients with RV infection who developed postrenal renal failure induced by urinary tract obstruction with uroammoniac calculi or crystals. The patients did not have metabolic disorders or abnormalities of the urinary tract, and increased urinary excretion of uric acid was not recognized at discharge. In addition, no abnormalities in the uric acid transporter (URAT1) were found in any of the patients. Uric acid stone formation was considered to have originated from the low pH caused by dehydration and the increase of urinary uric acid excretion from damaged cells.Correspondence to:
M. Fujieda, MD
Department of Pediatrics
Kochi Medical School
Kochi University, Kohasu
Oko-cho, Nankoku, Kochi 783-8505, Japan
Email: fujiedam@kochi-u.ac.jp
Case report
A case of Paget’s disease in hemodialysis
G. Cianciolo, G. La Manna, I. Capelli, G. Donati, E. Persici, V. Cuna, S. Corsini and S. Stefoni
403
24$
Abstract
Paget’s disease is the second most common bone disease after osteoporosis and causes an excessive bone turnover. Moreover, chronic kidney failure causes an impairment of bone mineral metabolism and electrolytes and PTH homeostasis. As far as we know, this is the first reported case of Paget’s disease in a hemodialysis patient: the patient was also affected by secondary hyperparathyroidism and was successfully treated with clodronate, cinacalcet and paracalcitol. The safety and efficacy of this combined therapy was periodically revised in a 12-month follow-up considering the common markers of bone turnover as well as the dosage of OPG, RANKL, IL-6 and MCSF, involved in the pathophysiology of Paget’s disease.Correspondence to:
Prof. Sergio Stefoni
Nephrology Dialysis and Renal Transplantation Unit
S. Orsola University Hospitalm
Via Massarenti 9
40138 Bologna
Email: sergio.stefoni@unibo.it
Clinical Nephrology, Vol. 73 – No. 5/2010 (403-407)
A case of Paget’s disease in hemodialysis
G. Cianciolo, G. La Manna, I. Capelli, G. Donati, E. Persici, V. Cuna, S. Corsini and S. Stefoni
Nephrology Dialysis and Renal Transplantation Unit, S. Orsola University Hospital, Bologna, Italy Paget’s disease is the second most common bone disease after osteoporosis and causes an excessive bone turnover. Moreover, chronic kidney failure causes an impairment of bone mineral metabolism and electrolytes and PTH homeostasis. As far as we know, this is the first reported case of Paget’s disease in a hemodialysis patient: the patient was also affected by secondary hyperparathyroidism and was successfully treated with clodronate, cinacalcet and paracalcitol. The safety and efficacy of this combined therapy was periodically revised in a 12-month follow-up considering the common markers of bone turnover as well as the dosage of OPG, RANKL, IL-6 and MCSF, involved in the pathophysiology of Paget’s disease.Correspondence to:
Prof. Sergio Stefoni
Nephrology Dialysis and Renal Transplantation Unit
S. Orsola University Hospitalm
Via Massarenti 9
40138 Bologna
Email: sergio.stefoni@unibo.it
Case report
Bilateral renal vein thrombosis and subsequent acute renal failure due to IVC filter migration and thrombosis
A.L. Janvier, H. Hamdan and M. Malas
408
24$
Abstract
A 53-year-old man developed a deep venous thrombus (DVT) and pulmonary embolism (PE) shortly after an open Roux-en-Y gastric bypass was performed. He later suffered a life-threatening gastrointestinal bleed while on anticoagulation for the DVT. Thus, anticoagulation was held and an inferior vena cava (IVC) filter (G2, Bard Inc., Tempe, AZ, USA) was placed for PE prophylaxis. About 10 days after filter placement, he presented with severe low back pain and syncope. He also presented with hypotension and anuria unresponsive to intravenous fluids. A STAT non-contrast CT scan of the abdomen revealed that his IVC filter had migrated from an infrarenal to a suprarenal position. Given the high clinical suspicion for renal vein thrombosis, an attempt at IVC filter retrieval was made. The filter could not be retrieved because it was embedded in a large IVC thrombus that extended from the hepatic veins down to the common iliac veins. The patient received nearly 4 days of tPA that was administered at the site of the thrombus with a long thrombolytic catheter (UNIFUSE, Angiodynamics, Queensbury, NY, USA). While his creatinine peaked at 7.6 on hospital Day 4, he eventually began to produce urine and his creatinine had declined to his baseline of 1.0 on follow-up 1 month later. About 18 months after admission, his creatinine had further declined to 0.8. We report the first published case of acute renal failure due to bilateral renal vein thrombosis in the setting of IVC filter migration and thrombosis. This report highlights an important, but rare complication of IVC filter placement as well as the non-operative management of acute bilateral renal vein thrombosis.Correspondence to:
A.L. Janvier, MD, PhD
Division of Nephrology
Johns Hopkins Bayview Medical Center
4940 Eastern Avenue
Baltimore, MD 21224, USA
Email: ajanvie1@jhmi.edu
Clinical Nephrology, Vol. 73 – No. 5/2010 (408-412)
Bilateral renal vein thrombosis and subsequent acute renal failure due to IVC filter migration and thrombosis
A.L. Janvier1, H. Hamdan2 and M. Malas3
1Division of Nephrology, Johns Hopkins Bayview Medical Center, Baltimore, MD 2Department of Medicine, Arizona Health Sciences Center, Tucson, AZ, and 3Department of Vascular Surgery, Johns Hopkins Bayview Medical Center, Baltimore, MD, USA A 53-year-old man developed a deep venous thrombus (DVT) and pulmonary embolism (PE) shortly after an open Roux-en-Y gastric bypass was performed. He later suffered a life-threatening gastrointestinal bleed while on anticoagulation for the DVT. Thus, anticoagulation was held and an inferior vena cava (IVC) filter (G2, Bard Inc., Tempe, AZ, USA) was placed for PE prophylaxis. About 10 days after filter placement, he presented with severe low back pain and syncope. He also presented with hypotension and anuria unresponsive to intravenous fluids. A STAT non-contrast CT scan of the abdomen revealed that his IVC filter had migrated from an infrarenal to a suprarenal position. Given the high clinical suspicion for renal vein thrombosis, an attempt at IVC filter retrieval was made. The filter could not be retrieved because it was embedded in a large IVC thrombus that extended from the hepatic veins down to the common iliac veins. The patient received nearly 4 days of tPA that was administered at the site of the thrombus with a long thrombolytic catheter (UNIFUSE, Angiodynamics, Queensbury, NY, USA). While his creatinine peaked at 7.6 on hospital Day 4, he eventually began to produce urine and his creatinine had declined to his baseline of 1.0 on follow-up 1 month later. About 18 months after admission, his creatinine had further declined to 0.8. We report the first published case of acute renal failure due to bilateral renal vein thrombosis in the setting of IVC filter migration and thrombosis. This report highlights an important, but rare complication of IVC filter placement as well as the non-operative management of acute bilateral renal vein thrombosis.Correspondence to:
A.L. Janvier, MD, PhD
Division of Nephrology
Johns Hopkins Bayview Medical Center
4940 Eastern Avenue
Baltimore, MD 21224, USA
Email: ajanvie1@jhmi.edu
