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Volume 71, No. 2/2009(February)
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Review
A new mouse model resembling human diabetic nephropathy: uncoupling of VEGF with eNOS as a novel pathogenic mechanism
T. Nakagawa
103
32$
Abstract
Diabetics develop a variety of histological abnormalities in the kidney. Early features include glomerular hypertrophy, glomerular basement membrane thickening, and mesangial expansion, whereas mesangiolysis, glomerular capillary aneurysm and nodular lesions develop in late phase. The goal of preventing diabetic nephropathy is important, but its achievement has been difficult due in part to a lack of an animal model for human diabetic nephropathy. Most animal models develop mild lesions in early phase diabetes, but not advanced lesions in late phase. Vascular endothelial growth factor (VEGF) mediates diabetic nephropathy, but its precise role remains to be determined. A complexity of VEGF function is that it is protective in nondiabetic renal diseases but is deleterious in diabetic nephropathy. Because diabetes is associated with endothelial dysfunction, we hypothesized that VEGF is deleterious in the setting of endothelial dysfunction. To test this hypothesis, we recently developed a new model of diabetic nephropathy in mice deficient in endothelial nitric oxide synthase (eNOS). Importantly, these mice developed the advanced lesions of diabetic nephropathy resembling to those in human diabetic nephropathy. In addition, these models also exhibit an uncoupling condition of VEGF with NO. In this review, we discuss our hypothesis which is that uncoupling of VEGF with NO causes advanced diabetic nephropathy.Correspondence to:
T. Nakagawa, MD, PhD; Division of Renal Disease and Hypertension, University of Colorado Denver, PO Box 6281, 12700 E. 19th Avenue, Aurora, CO 80045, USA
Email: Takahiko.Nakagawa@uchsc.edu
T. Nakagawa
Division of Renal Disease and Hypertension, University of Colorado Denver, Aurora, CO, USA Diabetics develop a variety of histological abnormalities in the kidney. Early features include glomerular hypertrophy, glomerular basement membrane thickening, and mesangial expansion, whereas mesangiolysis, glomerular capillary aneurysm and nodular lesions develop in late phase. The goal of preventing diabetic nephropathy is important, but its achievement has been difficult due in part to a lack of an animal model for human diabetic nephropathy. Most animal models develop mild lesions in early phase diabetes, but not advanced lesions in late phase. Vascular endothelial growth factor (VEGF) mediates diabetic nephropathy, but its precise role remains to be determined. A complexity of VEGF function is that it is protective in nondiabetic renal diseases but is deleterious in diabetic nephropathy. Because diabetes is associated with endothelial dysfunction, we hypothesized that VEGF is deleterious in the setting of endothelial dysfunction. To test this hypothesis, we recently developed a new model of diabetic nephropathy in mice deficient in endothelial nitric oxide synthase (eNOS). Importantly, these mice developed the advanced lesions of diabetic nephropathy resembling to those in human diabetic nephropathy. In addition, these models also exhibit an uncoupling condition of VEGF with NO. In this review, we discuss our hypothesis which is that uncoupling of VEGF with NO causes advanced diabetic nephropathy.Correspondence to:
T. Nakagawa, MD, PhD; Division of Renal Disease and Hypertension, University of Colorado Denver, PO Box 6281, 12700 E. 19th Avenue, Aurora, CO 80045, USA
Email: Takahiko.Nakagawa@uchsc.edu
Original
The role of complement activation, detected by urinary C5b-9 and urinary factor H, in the excretion of urinary albumin in cisplatin nephropathy
Y. Fuke, T. Fujita, A. Satomura, M. Endo and K. Matsumoto
110
36$
Abstract
Aims: Cis-diaminedichloroplatium II (CDDP) is an antineoplastic agent with serious renal toxicity, although the cause is not fully understood. The aim of this study was to clarify the functional roles of complement activation in cisplatin-nephropathy by examining the urinary complement components, C5b-9 and factor H. Subjects: Five patients with advanced lung cancer were included in this study as they were due to receive CDDP or 1,1-cyclobutanedicarboxylatoplatinum II (CBDA). Methods: Urine samples were collected before and after the chemotherapy for 13 days for measurements of C5b-9 (U-C5b-9), factor H (U-fH), albumin (U-Alb), beta2-microglobulin (U-beta2MG), and N-acetyl-beta-D-glucosamidase (NAG). Results: The mean level of U-Alb during the 5 – 8 day period after CDDP treatment was significantly higher than before treatment (p < 0.01). There was no significant correlation between U-Alb and NAG (r = –0.031, p = 0.994), or U-Alb and U-beta2MG (r = 0.061, p = 0.978) during the 5 – 8 day after CDDP treatment. U-Alb, U-C5b-9 and U-fH clearly increased on Days 4 – 10 after CDDP treatment. In our three patients treated with CDDP, mean estimated glomerular filtration rate (eGFR) was slightly decreased at 7 and 13 days after the treatment, compared to that of pretreatment, whereas there was no difference of eGFR between 7 and 13 days. In patients treated with CBDA, these parameters were clearly at lower levels compared to those patients treated with CDDP. Conclusion: This study demonstrates that cisplatin may activate the complement pathway in the glomerulus, with factor H regulating the activation, resulting in decreased urinary albumin excretion and renoprotection.Correspondence to:
Yoshinobu Fuke, MD; 30-1, Oyaguchi-Kamimachi, Itabashi-ku, Tokyo 173-8610, Japan
Email: fuke@med.nihon-u.ac.jp
Y. Fuke1, T. Fujita1, A. Satomura2, M. Endo3 and K. Matsumoto1
1Department of Medicine, Division of Nephrology, Hypertension and Endocrinology, 2Department of Laboratory Medicine, Nihon University School of Medicine, Tokyo, 3Faculty of Human Science, Hachinohe University, Hachinohe, Aomori, Japan Aims: Cis-diaminedichloroplatium II (CDDP) is an antineoplastic agent with serious renal toxicity, although the cause is not fully understood. The aim of this study was to clarify the functional roles of complement activation in cisplatin-nephropathy by examining the urinary complement components, C5b-9 and factor H. Subjects: Five patients with advanced lung cancer were included in this study as they were due to receive CDDP or 1,1-cyclobutanedicarboxylatoplatinum II (CBDA). Methods: Urine samples were collected before and after the chemotherapy for 13 days for measurements of C5b-9 (U-C5b-9), factor H (U-fH), albumin (U-Alb), beta2-microglobulin (U-beta2MG), and N-acetyl-beta-D-glucosamidase (NAG). Results: The mean level of U-Alb during the 5 – 8 day period after CDDP treatment was significantly higher than before treatment (p < 0.01). There was no significant correlation between U-Alb and NAG (r = –0.031, p = 0.994), or U-Alb and U-beta2MG (r = 0.061, p = 0.978) during the 5 – 8 day after CDDP treatment. U-Alb, U-C5b-9 and U-fH clearly increased on Days 4 – 10 after CDDP treatment. In our three patients treated with CDDP, mean estimated glomerular filtration rate (eGFR) was slightly decreased at 7 and 13 days after the treatment, compared to that of pretreatment, whereas there was no difference of eGFR between 7 and 13 days. In patients treated with CBDA, these parameters were clearly at lower levels compared to those patients treated with CDDP. Conclusion: This study demonstrates that cisplatin may activate the complement pathway in the glomerulus, with factor H regulating the activation, resulting in decreased urinary albumin excretion and renoprotection.Correspondence to:
Yoshinobu Fuke, MD; 30-1, Oyaguchi-Kamimachi, Itabashi-ku, Tokyo 173-8610, Japan
Email: fuke@med.nihon-u.ac.jp
Original
The MDRD equation may mask decline of glomerular filtration rate in Fabry patients with normal or nearly normal kidney function
K.M. Aakre, C. Tøndel, A. Brun, and E. Svarstad,
118
32$
Abstract
Aims: The renal prognosis in Fabry disease is better when enzyme replacement therapy (ERT) is initiated before glomerular filtration rate (GFR) deteriorates. Current studies evaluating kidney function in Fabry disease are mainly based on the MDRD equation. The aim of this cross sectional study was to compare estimated and measured GFR in adult Fabry patients with normal or near normal kidney function. Methods: Iohexol GFR (mGFR) was compared to estimated GFR (eGFR) (MDRD, Cockcroft-Gault and Counahan-Barratt equations) in 8 male and 13 female Fabry patients with minimal albuminuria and mean mGFR of 94 ml/min/1.73 m2 for both genders. Results: A significant overestimation of eGFR-MDRD by 24 ml/min/1.73 m2 was seen in male Fabry patients. The performance of the MDRD equation was similar to mGFR in female Fabry patients. GFR was significantly overestimated by the Cockcroft-Gault equation, whilst Counahan-Barratt equation gave results in agreement with mGFR for both male and female Fabry patients. Conclusions: Overestimation of eGFR-MDRD in Fabry patients with CKD stage 1 – 2 and minimal albuminuria may prevent recognition of early progressive renal failure and delayed ERT initiation may be the consequence. Exact GFR markers should be part of the routine evaluation of GFR in Fabry patients.Correspondence to:
K. Moberg Aakre, MD; Laboratory of Clinical Biochemistry, Haukeland University Hospital, 5021 Bergen, Norway
Email: kristin.moberg.aakre@gmail.com
K.M. Aakre1, C. Tøndel2,3, A. Brun1,2 and E. Svarstad2,4
1Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, 2Institute of Medicine, University of Bergen, Bergen, 3Pediatric Department and 4Medical Department, Haukeland University Hospital, Bergen, Norway Aims: The renal prognosis in Fabry disease is better when enzyme replacement therapy (ERT) is initiated before glomerular filtration rate (GFR) deteriorates. Current studies evaluating kidney function in Fabry disease are mainly based on the MDRD equation. The aim of this cross sectional study was to compare estimated and measured GFR in adult Fabry patients with normal or near normal kidney function. Methods: Iohexol GFR (mGFR) was compared to estimated GFR (eGFR) (MDRD, Cockcroft-Gault and Counahan-Barratt equations) in 8 male and 13 female Fabry patients with minimal albuminuria and mean mGFR of 94 ml/min/1.73 m2 for both genders. Results: A significant overestimation of eGFR-MDRD by 24 ml/min/1.73 m2 was seen in male Fabry patients. The performance of the MDRD equation was similar to mGFR in female Fabry patients. GFR was significantly overestimated by the Cockcroft-Gault equation, whilst Counahan-Barratt equation gave results in agreement with mGFR for both male and female Fabry patients. Conclusions: Overestimation of eGFR-MDRD in Fabry patients with CKD stage 1 – 2 and minimal albuminuria may prevent recognition of early progressive renal failure and delayed ERT initiation may be the consequence. Exact GFR markers should be part of the routine evaluation of GFR in Fabry patients.Correspondence to:
K. Moberg Aakre, MD; Laboratory of Clinical Biochemistry, Haukeland University Hospital, 5021 Bergen, Norway
Email: kristin.moberg.aakre@gmail.com
Original
Safety and tolerability of ferric carboxymaltose (FCM) for treatment of iron deficiency in patients with chronic kidney disease and in kidney transplant recipients
A.-C. Grimmelt, C.D. Cohen, T. Fehr, A.L. Serra and R.P. Wüthrich
125
24$
Abstract
Background: Iron deficiency is common in patients with chronic kidney disease and in kidney transplant recipients. Patients and methods: We analyzed the safety and tolerability of the new intravenous iron preparation ferric carboxymaltose (FCM) in these two patient groups. Adverse events after administration of the drug were assessed by using a questionnaire. Vital signs and laboratory data were collected before and after the application of FCM. A total of 46 FCM doses were applied to 44 patients (17 with chronic kidney disease and 27 kidney transplant recipients) either as single injection of 100 or 200 mg (n = 42) or as short infusion with up to 500 mg (n = 4). Results: Mild and transient adverse events (metallic taste, headache, dizziness) occurred in six patients. The estimated glomerular filtration rate remained unchanged by the FCM administration. Conclusion: We conclude that safety and tolerability of FCM were excellent. Compared with other intravenous iron preparations the considerably shorter administration time of FCM allows to save time and to reduce costs.Correspondence to:
R.P. Wüthrich, MD; Clinic for Nephrology, University Hospital, Rämistrasse 100, 8091 Zürich, Switzerland
Email: rudolf.wuethrich@usz.ch
A.-C. Grimmelt, C.D. Cohen, T. Fehr, A.L. Serra and R.P. Wüthrich
Clinic for Nephrology, University Hospital, Zürich, Switzerland Background: Iron deficiency is common in patients with chronic kidney disease and in kidney transplant recipients. Patients and methods: We analyzed the safety and tolerability of the new intravenous iron preparation ferric carboxymaltose (FCM) in these two patient groups. Adverse events after administration of the drug were assessed by using a questionnaire. Vital signs and laboratory data were collected before and after the application of FCM. A total of 46 FCM doses were applied to 44 patients (17 with chronic kidney disease and 27 kidney transplant recipients) either as single injection of 100 or 200 mg (n = 42) or as short infusion with up to 500 mg (n = 4). Results: Mild and transient adverse events (metallic taste, headache, dizziness) occurred in six patients. The estimated glomerular filtration rate remained unchanged by the FCM administration. Conclusion: We conclude that safety and tolerability of FCM were excellent. Compared with other intravenous iron preparations the considerably shorter administration time of FCM allows to save time and to reduce costs.Correspondence to:
R.P. Wüthrich, MD; Clinic for Nephrology, University Hospital, Rämistrasse 100, 8091 Zürich, Switzerland
Email: rudolf.wuethrich@usz.ch
Original
Gemcitabine nephrotoxicity and hemolytic uremic syndrome: report of 29 cases from a single institution
I. Glezerman, M.G. Kris, V. Miller, S. Seshan and C.D. Flombaum
130
44$
Abstract
Background: Gemcitabine is used in a variety of advanced malignancies. Hemolytic uremic syndrome has been reported as a side effect. Methods: we reviewed medical records of 29 patients with gemcitabine nephrotoxicity. Results: The median cumulative dose of gemcitabine was 22 g/m2 (4 – 81) given over 7.5 months (2 – 34). Prior chemotherapy with mitomycin had been given to 9 patients, and in 4 the hemolytic uremic syndrome was particularly severe and appeared shortly after gemcitabine initiation. All patients had renal insufficiency. Microhematuria and proteinuria were present in 27 patients and red blood cell casts were seen in 8. Renal biopsies in 4 patients showed thrombotic microangiopathy. Worsening or new-onset hypertension was seen in 26 patients. Edema, shortness of breath and congestive heart failure were present in 21, 15 and 7 patients, respectively. All had anemia, thrombocytopenia and elevated serum lactate dehydrogenase. Haptoglobin was low in 23 of the 26 patients who had it measured. Schistocytes were present in 21 of the 24 patients who had blood smear reviewed. Gemcitabine was discontinued once hemolytic uremic syndrome was recognized. Full or partial recovery of renal function occurred in 19 patients. 7 patients progressed to end-stage renal disease and 3 patients developed chronic renal failure. Conclusions: Gemcitabine nephrotoxicity presents as new-onset renal disease with associated hypertension, thrombocytopenia and microangiopathic hemolytic anemia. Prior chemotherapy with mitomycin, especially when given in close proximity, may be synergistic. A high index of suspicion is essential to make an early diagnosis. Stopping gemcitabine improves the outcome.Correspondence to:
C. Flombaum, MD; Memorial Sloan Kettering, Cancer Center, 1275 York Avenue, New York, NY 10065, USA
Email: flombauc@mskcc.org
I. Glezerman1, M.G. Kris2, V. Miller2, S. Seshan3 and C.D. Flombaum1
1Renal Service, 2Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, 3Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY, USA Background: Gemcitabine is used in a variety of advanced malignancies. Hemolytic uremic syndrome has been reported as a side effect. Methods: we reviewed medical records of 29 patients with gemcitabine nephrotoxicity. Results: The median cumulative dose of gemcitabine was 22 g/m2 (4 – 81) given over 7.5 months (2 – 34). Prior chemotherapy with mitomycin had been given to 9 patients, and in 4 the hemolytic uremic syndrome was particularly severe and appeared shortly after gemcitabine initiation. All patients had renal insufficiency. Microhematuria and proteinuria were present in 27 patients and red blood cell casts were seen in 8. Renal biopsies in 4 patients showed thrombotic microangiopathy. Worsening or new-onset hypertension was seen in 26 patients. Edema, shortness of breath and congestive heart failure were present in 21, 15 and 7 patients, respectively. All had anemia, thrombocytopenia and elevated serum lactate dehydrogenase. Haptoglobin was low in 23 of the 26 patients who had it measured. Schistocytes were present in 21 of the 24 patients who had blood smear reviewed. Gemcitabine was discontinued once hemolytic uremic syndrome was recognized. Full or partial recovery of renal function occurred in 19 patients. 7 patients progressed to end-stage renal disease and 3 patients developed chronic renal failure. Conclusions: Gemcitabine nephrotoxicity presents as new-onset renal disease with associated hypertension, thrombocytopenia and microangiopathic hemolytic anemia. Prior chemotherapy with mitomycin, especially when given in close proximity, may be synergistic. A high index of suspicion is essential to make an early diagnosis. Stopping gemcitabine improves the outcome.Correspondence to:
C. Flombaum, MD; Memorial Sloan Kettering, Cancer Center, 1275 York Avenue, New York, NY 10065, USA
Email: flombauc@mskcc.org
Original
Pre-transplantation glucose testing for predicting new-onset diabetes mellitus after renal transplantation
G.V. Ramesh Prasad, , M. Huang, F. Bandukwala, M.M. Nash, L. Rapi, T. Montada-Atin, G. Meliton and J.S. Zaltzman,
140
32$
Abstract
Aim: New-onset diabetes after renal transplantation (NODAT) adversely affects graft and patient survival. However, NODAT risk based on pre-transplant blood glucose (BG) levels has not been defined. Our goal was to identify the best pre-transplant testing method and cut-off values. Materials and methods: We performed a case-control analysis of non-diabetic recipients who received a live donor allograft with at least 6 months post-transplant survival. Pre-transplant glucose abnormalities were excluded through 75 g oral glucose tolerance testing (OGTT) and random BG (RBG) measurement. NODAT was defined based on 2003 Canadian Diabetes Association criteria. Multivariate logistic and Cox regression analysis was performed to determine independent predictor variables for NODAT. Receiver-operating-characteristic (ROC) curves were constructed to determine threshold BG values for diabetes risk. Results: 151 recipients met initial entry criteria. 12 had pre-transplant impaired fasting glucose and/or impaired glucose tolerance, among who 7 (58%) developed NODAT. In the remaining 139, 24 (17%) developed NODAT. NODAT risk exceeded 25% for those with pre-transplant RBG > 6.0 mmol/l and 50% if > 7.2 mmol/l. Pre-transplant RBG provided the highest AUC (0.69, p = 0.002) by ROC analysis. Increasing age (p = 0.025), acute rejection (p = 0.011), and RBG > 6.0 mmol/l (p = 0.001) were independent predictors of NODAT. Conclusion: Pre-transplant glucose testing is a specific marker for NODAT. Patients can be counseled of their incremental risk even within the normal BG range if the OGTT is normal.Correspondence to:
G. V. Ramesh Prasad, MBBS, MSc, FRCPC, FACP, Assistant Professor of Medicine, University of Toronto, Staff Nephrologist, St. Michael’s Hospital, 61 Queen Street East, 9th Floor, Toronto, ON M5C 2T2, Canada
Email: prasadr@smh.toronto.on.ca
G.V. Ramesh Prasad1, 2, M. Huang2, F. Bandukwala2, M.M. Nash2, L. Rapi2, T. Montada-Atin2, G. Meliton2 and J.S. Zaltzman1,2
1Division of Nephrology, University of Toronto, and 2Renal Transplant Program, St. Michael’s Hospital, Toronto, ON, Canada Aim: New-onset diabetes after renal transplantation (NODAT) adversely affects graft and patient survival. However, NODAT risk based on pre-transplant blood glucose (BG) levels has not been defined. Our goal was to identify the best pre-transplant testing method and cut-off values. Materials and methods: We performed a case-control analysis of non-diabetic recipients who received a live donor allograft with at least 6 months post-transplant survival. Pre-transplant glucose abnormalities were excluded through 75 g oral glucose tolerance testing (OGTT) and random BG (RBG) measurement. NODAT was defined based on 2003 Canadian Diabetes Association criteria. Multivariate logistic and Cox regression analysis was performed to determine independent predictor variables for NODAT. Receiver-operating-characteristic (ROC) curves were constructed to determine threshold BG values for diabetes risk. Results: 151 recipients met initial entry criteria. 12 had pre-transplant impaired fasting glucose and/or impaired glucose tolerance, among who 7 (58%) developed NODAT. In the remaining 139, 24 (17%) developed NODAT. NODAT risk exceeded 25% for those with pre-transplant RBG > 6.0 mmol/l and 50% if > 7.2 mmol/l. Pre-transplant RBG provided the highest AUC (0.69, p = 0.002) by ROC analysis. Increasing age (p = 0.025), acute rejection (p = 0.011), and RBG > 6.0 mmol/l (p = 0.001) were independent predictors of NODAT. Conclusion: Pre-transplant glucose testing is a specific marker for NODAT. Patients can be counseled of their incremental risk even within the normal BG range if the OGTT is normal.Correspondence to:
G. V. Ramesh Prasad, MBBS, MSc, FRCPC, FACP, Assistant Professor of Medicine, University of Toronto, Staff Nephrologist, St. Michael’s Hospital, 61 Queen Street East, 9th Floor, Toronto, ON M5C 2T2, Canada
Email: prasadr@smh.toronto.on.ca
Original
Hepatitis C virus infection in hemodialysis patients is not associated with insulin resistance, inflammation and atherosclerosis
Y. Caliskan, H. Oflaz, H. Püsüroglu, H. Boz, H. Yazici, S. Tamer, K. Karsidag and A. Yildiz
147
48$
Abstract
Background: Hepatitis C virus (HCV) infection is associated with increased levels of inflammatory markers and is also a significant risk factor for the development of Type 2 diabetes mellitus (DM) in the general population. In attempt to address this issue in chronic hemodialysis (HD) patients, we evaluated the relation of HCV infection with inflammatory markers, endothelial dysfunction, insulin resistance and atherosclerosis. Methods: In a cohort of 72 HD patients (36 (50%) had a positive HCV EIA test and 36 (50%) had a negative anti-HCV test), we examined HCV antibody status, insulin resistance (HOMA-IR) and beta-cell function (HOMA-beta), serum inflammatory parameters (high sensitive C-reactive protein (CRP), fibrinogen and procalcitonin), and performed echocardiography, high-resolution brachial artery ultrasound and B-mode carotid Doppler examination to assess the vascular functions and atherosclerosis. Results: There were no differences in age, gender, body mass index (BMI), primary disease, duration of dialysis, smoking status, laboratory parameters except glucose, total cholesterol and LDL cholesterol between anti-HCV-positive and anti-HCV-negative groups. The serum concentrations of glucose, total cholesterol and LDL cholesterol were significantly lower in the anti-HCV-positive patients than anti-HCV-negative patients (p = 0.04, p = 0.02, p = 0.01, respectively). There were no significant differences in inflammatory parameters, total insulin secretion (HOMA-beta, p = 0.76) and insulin resistance (HOMA-R, p = 0.91) between anti-HCV-positive and negative patients. The intima media thickness, carotid plaque score and brachial artery endothelium-dependent dilatation did not differ significantly between the two groups (p = 0.44, 0.45, and 0.17, respectively). Conclusion: HCV infection was not related to atherosclerosis and insulin resistance in hemodialysis patients. Since hemodialysis patients had a large number of uremia-related cardiovascular risk factors, the effect of HCV infection could disappear in this group of patients.Correspondence to:
A. Yildiz, MD; Professor in Nephrology, Istanbul School of Medicine, Department of Internal Medicine, Division of Nephrology, Capa, Topkapi, Istanbul
Email: alaattiny@hotmail.com; yildiza@edu.tr
Y. Caliskan1, H. Oflaz2, H. Püsüroglu1, H. Boz1, H. Yazici1, S. Tamer3, K. Karsidag4 and A. Yildiz1
1Department of Internal Medicine, Division of Nephrology, 2Department of Cardiology, 3Department of Physiology, School of Medicine, Istanbul University, and 4Department of Internal Medicine, Division of Endocrinology and Diabetes, Istanbul, Turkey Background: Hepatitis C virus (HCV) infection is associated with increased levels of inflammatory markers and is also a significant risk factor for the development of Type 2 diabetes mellitus (DM) in the general population. In attempt to address this issue in chronic hemodialysis (HD) patients, we evaluated the relation of HCV infection with inflammatory markers, endothelial dysfunction, insulin resistance and atherosclerosis. Methods: In a cohort of 72 HD patients (36 (50%) had a positive HCV EIA test and 36 (50%) had a negative anti-HCV test), we examined HCV antibody status, insulin resistance (HOMA-IR) and beta-cell function (HOMA-beta), serum inflammatory parameters (high sensitive C-reactive protein (CRP), fibrinogen and procalcitonin), and performed echocardiography, high-resolution brachial artery ultrasound and B-mode carotid Doppler examination to assess the vascular functions and atherosclerosis. Results: There were no differences in age, gender, body mass index (BMI), primary disease, duration of dialysis, smoking status, laboratory parameters except glucose, total cholesterol and LDL cholesterol between anti-HCV-positive and anti-HCV-negative groups. The serum concentrations of glucose, total cholesterol and LDL cholesterol were significantly lower in the anti-HCV-positive patients than anti-HCV-negative patients (p = 0.04, p = 0.02, p = 0.01, respectively). There were no significant differences in inflammatory parameters, total insulin secretion (HOMA-beta, p = 0.76) and insulin resistance (HOMA-R, p = 0.91) between anti-HCV-positive and negative patients. The intima media thickness, carotid plaque score and brachial artery endothelium-dependent dilatation did not differ significantly between the two groups (p = 0.44, 0.45, and 0.17, respectively). Conclusion: HCV infection was not related to atherosclerosis and insulin resistance in hemodialysis patients. Since hemodialysis patients had a large number of uremia-related cardiovascular risk factors, the effect of HCV infection could disappear in this group of patients.Correspondence to:
A. Yildiz, MD; Professor in Nephrology, Istanbul School of Medicine, Department of Internal Medicine, Division of Nephrology, Capa, Topkapi, Istanbul
Email: alaattiny@hotmail.com; yildiza@edu.tr
Original
Hemodialysis headache
M. Milinkovic, J. Zidverc-Trajkovic, N. Sternic, J. Trbojevic-Stankovic, I. Maric, M. Milic, B. Andric, P. Nikic, P. Jovanovic, P. Rosic and B. Stojimirovic
158
28$
Abstract
Aim: The aim of this study was to evaluate and analyze the incidence and features of headaches in patients undergoing hemodialysis. Material and methods: In this prospective study 318 patients, 119 women and 199 men, undergoing chronic HD in four hemodialysis centers in Serbia, were questioned about their problems with headaches using a questionary designed according to the diagnostic criteria of the International Headache Classification of Headache Disorders (ICHD) from 2004. Patients were distributed in two groups according to the presence of hemodialysis headaches (HDH). The groups were compared regarding sex, age, duration of HD, primary diseases that lead to ESRD, arterial systolic and diastolic blood pressure (BP) and serum levels of hemoglobin, urea nitrogen, creatinine, sodium, potassium, calcium, phosphates, albumin, glucose and calcium-phosphate product. We also analyzed features of HDH. The results were statistically compared. Results: Patients with HDH had significantly lower serum glucose, but higher serum phosphates and albumin than patients without headaches. Furthermore, HDH patients had higher calcium phosphate product and systolic blood pressure than non-HDH patients. Out of 318 patients included in the study, 21 (6.6%) patients had HDH. According to our results, HDH appeared more frequently in men, during the 3rd hour of HD in more than a half of the patients and lasted less then 4 h in the majority of HDH patients. In the majority of patients HDH was bilateral, non-pulsating, without associated symptoms and it appeared mostly during HD. Personal history was negative for primary headaches in all patients with HDH. Conclusion: We believe that the results of our investigation of more than 300 HD patients pointed to some biochemical changes, possibly implicated by pathophysiology of HDH and disclose some specific HDH features that might contribute to a better understanding of this secondary headache disorder.Correspondence to:
M. Milinkovic, MD; Institute of Nephrology, Clinical Center of Serbia, Pasterova 2, 11000 Belgrade, Serbia
Email: milinkovicmarija50@yahoo.com
M. Milinkovic1, J. Zidverc-Trajkovic2, N. Sternic2, J. Trbojevic-Stankovic3, I. Maric4, M. Milic4, B. Andric5, P. Nikic5, P. Jovanovic6, P. Rosic6 and B. Stojimirovic1
1Institute of Urology and Nephrology, 2Institute of Neurology, Clinical Center of Serbia, 3Clinical Center Dr. D. Misovic Belgrade, 4Center for Endemic Nephropathy Lazarevac, 5Hospital Center, and 6Center for Hemodialysis Obrenovac, Serbia Aim: The aim of this study was to evaluate and analyze the incidence and features of headaches in patients undergoing hemodialysis. Material and methods: In this prospective study 318 patients, 119 women and 199 men, undergoing chronic HD in four hemodialysis centers in Serbia, were questioned about their problems with headaches using a questionary designed according to the diagnostic criteria of the International Headache Classification of Headache Disorders (ICHD) from 2004. Patients were distributed in two groups according to the presence of hemodialysis headaches (HDH). The groups were compared regarding sex, age, duration of HD, primary diseases that lead to ESRD, arterial systolic and diastolic blood pressure (BP) and serum levels of hemoglobin, urea nitrogen, creatinine, sodium, potassium, calcium, phosphates, albumin, glucose and calcium-phosphate product. We also analyzed features of HDH. The results were statistically compared. Results: Patients with HDH had significantly lower serum glucose, but higher serum phosphates and albumin than patients without headaches. Furthermore, HDH patients had higher calcium phosphate product and systolic blood pressure than non-HDH patients. Out of 318 patients included in the study, 21 (6.6%) patients had HDH. According to our results, HDH appeared more frequently in men, during the 3rd hour of HD in more than a half of the patients and lasted less then 4 h in the majority of HDH patients. In the majority of patients HDH was bilateral, non-pulsating, without associated symptoms and it appeared mostly during HD. Personal history was negative for primary headaches in all patients with HDH. Conclusion: We believe that the results of our investigation of more than 300 HD patients pointed to some biochemical changes, possibly implicated by pathophysiology of HDH and disclose some specific HDH features that might contribute to a better understanding of this secondary headache disorder.Correspondence to:
M. Milinkovic, MD; Institute of Nephrology, Clinical Center of Serbia, Pasterova 2, 11000 Belgrade, Serbia
Email: milinkovicmarija50@yahoo.com
Original
Could depression be a new branch of MIA syndrome?
S. Simic Ogrizovic, D. Jovanovic, V. Dopsaj, M. Radovic, Z. Sumarac, S.N. Bogavac, M. Stosovic, M. Stanojevic and V. Nesic
164
40$
Abstract
The aims of the present study were to determine the prevalence of depression in our dialysis patients, to detect the most powerful variables associated with depression, and to determine the role of depression in prediction of mortality. The prospective follow-up study of 128 patients (77 HD and 51 CAPD, 65 male, aged 53.8 ± 13.5 years, dialysis duration 64.7 ± 64.8 months) was carried out over 36 months. Depression by the Beck Depression Inventory-BDI-II score, laboratory parameters (hemoglobin, serum albumin and creatinine concentration), immunological status (cytokines and hsCRP), comorbidity by Index of Physical Impairment (IPI) and adequacy of dialysis by Kt/V were monitored. The overall prevalence of depression in the dialysis patients (BDI score >= 14) was 45.3%, and 28.2%, respectively, for moderate and severe depression (BDI >= 20). The most powerful variable associated with depression was IL-6, but associations with albumin, hemoglobin, creatinine and IPI score were also found. During the follow-up period 36 patients died, 7 patients left the cohort and 2 patients were transplanted. If IPI score was not included in the multivariate Cox analysis, the BDI score remained one of the best predictors of mortality along with albumin. In conclusion, because of the close association of depression with inflammation, malnutrition, and cardiovascular mortality, it could be speculated that depression is one branch of the MIA (malnutrition, inflammation, atherosclerosis) syndrome.Correspondence to:
Assoc. Prof. S. Simic-Ogrizovic, MD, PhD; Clinic of Nephrology, Institute of Urology and Nephrology, Pasterova 2, 11 000 Belgrade, Serbia
Email: dst@Eunet.yu
S. Simic Ogrizovic1, D. Jovanovic1, V. Dopsaj2, M. Radovic1, Z. Sumarac2, S.N. Bogavac3, M. Stosovic1, M. Stanojevic1 and V. Nesic1
1Clinic of Nephrology, Institute of Urology and Nephrology, 2Institute of Medical Biochemistry, Clinical Center of Serbia, 3Faculty of Pharmacy, Belgrade, Serbia The aims of the present study were to determine the prevalence of depression in our dialysis patients, to detect the most powerful variables associated with depression, and to determine the role of depression in prediction of mortality. The prospective follow-up study of 128 patients (77 HD and 51 CAPD, 65 male, aged 53.8 ± 13.5 years, dialysis duration 64.7 ± 64.8 months) was carried out over 36 months. Depression by the Beck Depression Inventory-BDI-II score, laboratory parameters (hemoglobin, serum albumin and creatinine concentration), immunological status (cytokines and hsCRP), comorbidity by Index of Physical Impairment (IPI) and adequacy of dialysis by Kt/V were monitored. The overall prevalence of depression in the dialysis patients (BDI score >= 14) was 45.3%, and 28.2%, respectively, for moderate and severe depression (BDI >= 20). The most powerful variable associated with depression was IL-6, but associations with albumin, hemoglobin, creatinine and IPI score were also found. During the follow-up period 36 patients died, 7 patients left the cohort and 2 patients were transplanted. If IPI score was not included in the multivariate Cox analysis, the BDI score remained one of the best predictors of mortality along with albumin. In conclusion, because of the close association of depression with inflammation, malnutrition, and cardiovascular mortality, it could be speculated that depression is one branch of the MIA (malnutrition, inflammation, atherosclerosis) syndrome.Correspondence to:
Assoc. Prof. S. Simic-Ogrizovic, MD, PhD; Clinic of Nephrology, Institute of Urology and Nephrology, Pasterova 2, 11 000 Belgrade, Serbia
Email: dst@Eunet.yu
Case Report
Membranous nephropathy associated with IgG4-related systemic disease and without autoimmune pancreatitis
T. Saeki, N. Imai, T. Ito, H. Yamazaki and S. Nishi
173
28$
Abstract
We describe an elderly man with membranous nephropathy and lymphoplasmacytic infiltration into the renal interstitium who presented with a high serum IgG4 concentration and no organ involvement in the pancreatobiliary system. Although the patient had hypocomplementemia and was positive for antinuclear antibodies, he was negative for antibodies against Sm, SS-A, SS-B and RNP, and his anti-DNA antibody titer was not elevated. Immunohistochemistry demonstrated that the infiltrated plasma cells in the renal interstitium and glomerular capillary walls were strongly positive for IgG4. Electron microscopy showed electron-dense deposits on the glomerular basement membranes and tubular basement membranes. The present case suggests that membranous nephropathy, like tubulo-interstitial nephritis, is one of the renal features of IgG4-related systemic disease.Correspondence to:
Dr. T. Saeki, MD, PhD; Department of Internal Medicine, Nagaoka Red Cross Hospital, Senshu 2-297-1, Nagaoka, Niigata 940-2085, Japan
Email: saekit@nagaoka.jrc.or.jp
T. Saeki1, N. Imai2, T. Ito1, H. Yamazaki1 and S. Nishi2
1Department of Internal Medicine, Nagaoka Red Cross Hospital, Nagaoka, and 2Divisions of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan We describe an elderly man with membranous nephropathy and lymphoplasmacytic infiltration into the renal interstitium who presented with a high serum IgG4 concentration and no organ involvement in the pancreatobiliary system. Although the patient had hypocomplementemia and was positive for antinuclear antibodies, he was negative for antibodies against Sm, SS-A, SS-B and RNP, and his anti-DNA antibody titer was not elevated. Immunohistochemistry demonstrated that the infiltrated plasma cells in the renal interstitium and glomerular capillary walls were strongly positive for IgG4. Electron microscopy showed electron-dense deposits on the glomerular basement membranes and tubular basement membranes. The present case suggests that membranous nephropathy, like tubulo-interstitial nephritis, is one of the renal features of IgG4-related systemic disease.Correspondence to:
Dr. T. Saeki, MD, PhD; Department of Internal Medicine, Nagaoka Red Cross Hospital, Senshu 2-297-1, Nagaoka, Niigata 940-2085, Japan
Email: saekit@nagaoka.jrc.or.jp
Case Report
Remission of minimal change disease in Type 2 diabetes after streptococcus bacteremia
R. Enriquez, A.E. Sirvent, S. Padilla, E. Andrada, F. Amorós, J.A. Fernandez- Lozano and F. Gutiérrez
179
20$
Abstract
A 41-year-old man with Type 2 diabetes developed sudden onset of nephrotic syndrome. He initially refused a renal biopsy. However, 3 months later, the nephrotic syndrome persisted and percutaneous renal biopsy was performed. The study with light microscopy, immunofluorescence and electron microscopy showed minimal change disease. Three weeks after biopsy, before immunosuppressive therapy was begun, the patient presented Group A Streptococcus (GAS) bacteremia and acute renal failure which needed hemodialysis. Afterwards, the renal function recovered and complete remission of the nephrotic syndrome, maintained during a 22-month follow-up, was observed. We discuss the possible mechanisms implicated in the remission. This report extends the spectrum of infections associated with remission of minimal change disease (MCD).Correspondence to:
Dr. R. Enríquez; Sección de Nefrología, Hospital General de Elche, 03203 Elche (Alicante), Spain
Email: emma_@wanadoo.es
R. Enriquez1, A.E. Sirvent1, S. Padilla2, E. Andrada3, F. Amorós1, J.A. Fernandez- Lozano4 and F. Gutiérrez2
1Nephrology Section, 2Infectious Diseases Unit, 3Pathology Section, and 4Intensive Care Unit, Hospital General de Elche, Spain A 41-year-old man with Type 2 diabetes developed sudden onset of nephrotic syndrome. He initially refused a renal biopsy. However, 3 months later, the nephrotic syndrome persisted and percutaneous renal biopsy was performed. The study with light microscopy, immunofluorescence and electron microscopy showed minimal change disease. Three weeks after biopsy, before immunosuppressive therapy was begun, the patient presented Group A Streptococcus (GAS) bacteremia and acute renal failure which needed hemodialysis. Afterwards, the renal function recovered and complete remission of the nephrotic syndrome, maintained during a 22-month follow-up, was observed. We discuss the possible mechanisms implicated in the remission. This report extends the spectrum of infections associated with remission of minimal change disease (MCD).Correspondence to:
Dr. R. Enríquez; Sección de Nefrología, Hospital General de Elche, 03203 Elche (Alicante), Spain
Email: emma_@wanadoo.es
Case Report
An unusual case of Churg-Strauss syndrome and a shrinking renal mass
S.A. Mohiuddin and P. Pai
183
20$
Abstract
Churg-Strauss syndrome is a multisystem disorder characterized by allergic rhinitis, asthma and eosinophilia [Churg and Strauss 1951, Noth et al. 2003]. We report a case of Churg-Strauss syndrome associated with a complex renal mass, which resolved with immunosuppressive therapy.Correspondence to:
Dr. S.A. Mohiuddin, 95 Elizabeth Road, Fazakerley, Liverpool, L10 4XL, UK
Email: aatifmohiuddin@yahoo.co.uk
S.A. Mohiuddin and P. Pai
Department of Nephrology, Link 6C Royal Liverpool University Hospital, Liverpool, United Kingdom Churg-Strauss syndrome is a multisystem disorder characterized by allergic rhinitis, asthma and eosinophilia [Churg and Strauss 1951, Noth et al. 2003]. We report a case of Churg-Strauss syndrome associated with a complex renal mass, which resolved with immunosuppressive therapy.Correspondence to:
Dr. S.A. Mohiuddin, 95 Elizabeth Road, Fazakerley, Liverpool, L10 4XL, UK
Email: aatifmohiuddin@yahoo.co.uk
Case Report
Acute interstitial nephritis with prominent eosinophil infiltration
Y.-C. Wang, Y.-F. Lin, T.-K. Chao, C.-C. Wu and J.-S. Chen
187
24$
Abstract
Aims: Acute interstitial nephritis (AIN) is common, but prominent eosinophil infiltration in patients with acute interstitial nephritis is rare. The possible etiologies, predisposing factors and treatment of such patients are the subjects of this study. Methods: one patient was reported from our medical center; nine more patients with similar findings were reviewed from the literature. Suspected offending drugs, clinical presentations, predisposing factors and patient outcomes after therapy were recorded. Results: A case of clam extract-associated acute interstitial nephritis with prominent eosinophil infiltration was reported. Ten cases including ours were analyzed. A variety of drugs was thought to be causative. In all, 7 of the 10 patients had a preexisting nephrotic syndrome, and eosinophilia was found in 6. Bone marrow biopsy was not performed in most cases and only available for 2 patients including ours. 9 patients treated with steroids had good responses but 1 patient died despite treatment. Conclusions: Acute interstitial nephritis with prominent eosinophil infiltration can be caused by a great diversity of drugs, which can include clam extract tablets. A preexisting nephrotic syndrome seemed to be a predisposing factor for this condition. This disease rarely led to fatality and most patients responded well to steroid therapy.Correspondence to:
J.-S. Chen, MD, PhD; Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, 2F, No. 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan
Email: dgschen@ndmctsgh.edu.tw
Y.-C. Wang1, Y.-F. Lin1, T.-K. Chao2, C.-C. Wu1 and J.-S. Chen1
1Department of Internal Medicine, and 2Department of Pathology, Division of Nephrology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan Aims: Acute interstitial nephritis (AIN) is common, but prominent eosinophil infiltration in patients with acute interstitial nephritis is rare. The possible etiologies, predisposing factors and treatment of such patients are the subjects of this study. Methods: one patient was reported from our medical center; nine more patients with similar findings were reviewed from the literature. Suspected offending drugs, clinical presentations, predisposing factors and patient outcomes after therapy were recorded. Results: A case of clam extract-associated acute interstitial nephritis with prominent eosinophil infiltration was reported. Ten cases including ours were analyzed. A variety of drugs was thought to be causative. In all, 7 of the 10 patients had a preexisting nephrotic syndrome, and eosinophilia was found in 6. Bone marrow biopsy was not performed in most cases and only available for 2 patients including ours. 9 patients treated with steroids had good responses but 1 patient died despite treatment. Conclusions: Acute interstitial nephritis with prominent eosinophil infiltration can be caused by a great diversity of drugs, which can include clam extract tablets. A preexisting nephrotic syndrome seemed to be a predisposing factor for this condition. This disease rarely led to fatality and most patients responded well to steroid therapy.Correspondence to:
J.-S. Chen, MD, PhD; Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, 2F, No. 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan
Email: dgschen@ndmctsgh.edu.tw
Case Report
Sarcoidosis and the kidney: not only the granulomatous interstitial nephritis
M. Monge, O. Miquel, F. Dugardin, S.S. Modeliar, J.-C. Glérant, S. Hacène, C. Cordonnier, R. Makdassi and G. Choukroun,
192
20$
Abstract
Renal involvement in sarcoidosis displays a wide range of manifestations, and kidney dysfunction may involve all three mechanisms of renal failure. We report a new case of systemic sarcoidosis presenting as a severe renal failure due to hypercalcemia, sarcoidosis-related bilateral nephrolithiasis and granulomatous interstitial nephritis. A prostate adenocarcinoma was also diagnosed, but has to be regarded as an unrelated disease.Correspondence to:
M. Monge, MD; Nephrology and Internal Medicine Department, CHU Amiens, Avenue René Laënnec, 80054 Amiens Cedex 1, France
Email: mongematt@yahoo.fr
M. Monge1, O. Miquel1, F. Dugardin2, S.S. Modeliar1, J.-C. Glérant3, S. Hacène4, C. Cordonnier5, R. Makdassi1 and G. Choukroun1,6
1Nephrology and Internal Medicine, 2Urology, 3Pneumology, 4Oncology and 5Anatomo-Pathology Departments, Amiens University Hospital, and 6Jules Verne – Picardie University, Amiens, France Renal involvement in sarcoidosis displays a wide range of manifestations, and kidney dysfunction may involve all three mechanisms of renal failure. We report a new case of systemic sarcoidosis presenting as a severe renal failure due to hypercalcemia, sarcoidosis-related bilateral nephrolithiasis and granulomatous interstitial nephritis. A prostate adenocarcinoma was also diagnosed, but has to be regarded as an unrelated disease.Correspondence to:
M. Monge, MD; Nephrology and Internal Medicine Department, CHU Amiens, Avenue René Laënnec, 80054 Amiens Cedex 1, France
Email: mongematt@yahoo.fr
Case Report
Acute renal failure following intravenous immunoglobulin therapy in a HIV-infected patient
S. Metallidis, M. Papaioannou, G. Bokolas, P. Kollaras, V. Gogou and P. Nikolaidis
196
12$
Abstract
Acute renal failure is a rare complication following the administration of intravenous immunoglobulin (IVIG). Only 114 cases have been reported in the literature. The exact mechanism of IVIG-associated acute renal failure remains unclear. Hereby we describe the first case of ARF in a HIV-infected patient, who received IVIG stabilized with maltose for the treatment of HIV-related thrombocytopenic purpura.Correspondence to:
S. Metallidis, MD, PhD; 1st Internal Medicine Department, Infectious Diseases Division, AHEPA University Hospital, 1, Stilponos Kyriakidi Str, 54006, Thessaloniki, Greece
Email: metallidissimeon@yahoo.gr
S. Metallidis1, M. Papaioannou2, G. Bokolas1, P. Kollaras1, V. Gogou2 and P. Nikolaidis1
1Infectious Diseases Division and 2Hematology Division, 1st Internal Medicine Department, AHEPA University Hospital, Thessaloniki, Greece Acute renal failure is a rare complication following the administration of intravenous immunoglobulin (IVIG). Only 114 cases have been reported in the literature. The exact mechanism of IVIG-associated acute renal failure remains unclear. Hereby we describe the first case of ARF in a HIV-infected patient, who received IVIG stabilized with maltose for the treatment of HIV-related thrombocytopenic purpura.Correspondence to:
S. Metallidis, MD, PhD; 1st Internal Medicine Department, Infectious Diseases Division, AHEPA University Hospital, 1, Stilponos Kyriakidi Str, 54006, Thessaloniki, Greece
Email: metallidissimeon@yahoo.gr
Case Report
T-cell large granular lymphocyte leukemia presenting as end-stage renal disease: the diagnostic role of flow-cytometric and clonality analysis of the urine sediment T-cell large granular lymphocyte leukemia presenting as end-stage renal disease: the diag
P.D. Christopoulos, S. Katsoudas, A. Androulaki, L. Nakopoulou, T. Economopoulos and D.V. Vlahakos
198
24$
Abstract
A 65-year-old white female patient with normal baseline renal function was referred to our hospital with nonoliguric renal failure requiring hemodialysis after progressive deterioration over the previous 6 months. Her past medical history was remarkable for easy fatigability, weight loss, low-grade fever, hypogammaglobulinemia and mild hepatosplenomegaly manifested over the past 6 years. Several liver and bone marrow biopsies during that period had shown a nonspecific polyclonal T-cell infiltration, and she was administered low-dose steroids for symptomatic relief. Physical examination, laboratory workup and imaging studies at presentation showed pancytopenia, hepatosplenomegaly, large symmetric kidneys with normal cortices and no evidence of obstructive uropathy, aseptic pyuria with neutrophils and lymphocytes and mild proteinuria. On biopsy the renal interstitium was infiltrated by large, granular CD3+CD8+CD56–CD57+ lymphocytes, clonal by molecular analysis, which established the diagnosis of T-cell large granular lymphocyte leukemia. Most urinary and peripheral blood lymphocytes bore the same T-LGL surface markers and were also clonal, as shown by flow-cytometry and PCR amplification of the T-cell receptor g-chain genes. A subsequent bone marrow biopsy revealed infiltration by lymphoma cells and excluded a myelodysplastic or hemophagocytic syndrome. After exclusion of an underlying EBV, CMV, HBV, HCV or HIV infection with negative serology and blood PCR the patient received one cycle of chemotherapy with cyclophosphamide, vincristine and prednisone. No improvement of renal function was achieved, while complication with a prolonged pulmonary infection and severe sepsis precluded further treatment. Our report indicates that the T-LGL leukemia should be considered in the differential diagnosis of renal failure with large-sized kidneys, especially when hepatosplenomegaly, pancytopenia and aseptic pyuria are also present. In the latter case, flow-cytometric and clonality analysis of the urine sediment can aid in establishing a diagnosis. Since renal function may deteriorate rapidly, chemotherapy should not be delayed.Correspondence to:
P.D. Christopoulos, MD; Sundgauallee 51, 79114 Freiburg, Germany
Email: petros.christopoulos@gmail.com
P.D. Christopoulos1, S. Katsoudas2, A. Androulaki3, L. Nakopoulou4, T. Economopoulos1 and D.V. Vlahakos2
1Department of Medicine II, 2Division of Nephrology, Attikon University Hospital, 3Department of Pathology, Elpis General Hospital, and 4First Department of Pathology, Medical School of the University of Athens, Athens, Greece A 65-year-old white female patient with normal baseline renal function was referred to our hospital with nonoliguric renal failure requiring hemodialysis after progressive deterioration over the previous 6 months. Her past medical history was remarkable for easy fatigability, weight loss, low-grade fever, hypogammaglobulinemia and mild hepatosplenomegaly manifested over the past 6 years. Several liver and bone marrow biopsies during that period had shown a nonspecific polyclonal T-cell infiltration, and she was administered low-dose steroids for symptomatic relief. Physical examination, laboratory workup and imaging studies at presentation showed pancytopenia, hepatosplenomegaly, large symmetric kidneys with normal cortices and no evidence of obstructive uropathy, aseptic pyuria with neutrophils and lymphocytes and mild proteinuria. On biopsy the renal interstitium was infiltrated by large, granular CD3+CD8+CD56–CD57+ lymphocytes, clonal by molecular analysis, which established the diagnosis of T-cell large granular lymphocyte leukemia. Most urinary and peripheral blood lymphocytes bore the same T-LGL surface markers and were also clonal, as shown by flow-cytometry and PCR amplification of the T-cell receptor g-chain genes. A subsequent bone marrow biopsy revealed infiltration by lymphoma cells and excluded a myelodysplastic or hemophagocytic syndrome. After exclusion of an underlying EBV, CMV, HBV, HCV or HIV infection with negative serology and blood PCR the patient received one cycle of chemotherapy with cyclophosphamide, vincristine and prednisone. No improvement of renal function was achieved, while complication with a prolonged pulmonary infection and severe sepsis precluded further treatment. Our report indicates that the T-LGL leukemia should be considered in the differential diagnosis of renal failure with large-sized kidneys, especially when hepatosplenomegaly, pancytopenia and aseptic pyuria are also present. In the latter case, flow-cytometric and clonality analysis of the urine sediment can aid in establishing a diagnosis. Since renal function may deteriorate rapidly, chemotherapy should not be delayed.Correspondence to:
P.D. Christopoulos, MD; Sundgauallee 51, 79114 Freiburg, Germany
Email: petros.christopoulos@gmail.com
Case Report
Allopurinol-induced aplastic anemia in a patient with chronic kidney disease
Y.W. Kim, B.S. Park, C.H. Ryu, S.J. Park, S.W. Kang, Y.H. Kim, I.S. Song and J.H. Shon
203
20$
Abstract
Aplastic anemia is a rare complication of allopurinol use. We report an unusual case of aplastic anemia associated with allopurinol therapy for hyperuricemia in a patient with chronic kidney disease. A 37-year-old female patient diagnosed with Stage III chronic kidney disease was admitted with pancytopenia. She had a history of taking allopurinol for 5 months. Her bone marrow showed extremely decreased cellularity (< 20%) and there was no malignant cell infiltration. She was free of infections, including parvovirus B19, cytomegalovirus and Epstein-Barr virus. These results suggested a diagnosis of aplastic anemia. Allopurinol was discontinued immediately and treatment with blood transfusions and prednisolone was begun. After 6 months, the bone marrow cellularity improved to approximately 70%. Recently, it was suggested that decreased activity of multidrug resistance P-glycoprotein may play a role in acquired aplastic anemia. So we measured the inhibitory effect of allopurinol and oxypurinol on P-glycoprotein activity. But neither allopurinol nor oxypurinol inhibited P-glycoprotein activity.Correspondence to:
Y.W. Kim, MD; Division of Nephrology, Department of Internal Medicine, College of Medicine, Inje University, Busan Paik Hospital, Kaekeum-dong, Busanjin-gu, Busan 614-735, South Korea
Email: kyw8625@chollian.net
Y.W. Kim1, B.S. Park1, C.H. Ryu1, S.J. Park1, S.W. Kang1, Y.H. Kim1, I.S. Song2 and J.H. Shon2
Department of 1Internal Medicine and 2Pharmacology and Pharmacogenomics Research Center, School of Medicine, Inje University, Busan, South Korea Aplastic anemia is a rare complication of allopurinol use. We report an unusual case of aplastic anemia associated with allopurinol therapy for hyperuricemia in a patient with chronic kidney disease. A 37-year-old female patient diagnosed with Stage III chronic kidney disease was admitted with pancytopenia. She had a history of taking allopurinol for 5 months. Her bone marrow showed extremely decreased cellularity (< 20%) and there was no malignant cell infiltration. She was free of infections, including parvovirus B19, cytomegalovirus and Epstein-Barr virus. These results suggested a diagnosis of aplastic anemia. Allopurinol was discontinued immediately and treatment with blood transfusions and prednisolone was begun. After 6 months, the bone marrow cellularity improved to approximately 70%. Recently, it was suggested that decreased activity of multidrug resistance P-glycoprotein may play a role in acquired aplastic anemia. So we measured the inhibitory effect of allopurinol and oxypurinol on P-glycoprotein activity. But neither allopurinol nor oxypurinol inhibited P-glycoprotein activity.Correspondence to:
Y.W. Kim, MD; Division of Nephrology, Department of Internal Medicine, College of Medicine, Inje University, Busan Paik Hospital, Kaekeum-dong, Busanjin-gu, Busan 614-735, South Korea
Email: kyw8625@chollian.net
Case Report
Cinacalcet reduces vascular and soft tissue calcification in secondary hyperparathyroidism (SHPT) in hemodialysis patients
M.J. Aladrén Regidor
207
32$
Abstract
Management of secondary hyperparathyroidism (SHPT) in chronic kidney disease patients on hemodialysis (HD) can be challenging. Conventional treatments can lead to hypercalcemia and hyperphosphatemia, both of which are associated with vascular and soft tissue calcification and increased risk of cardiovascular disease. We report the effect of treatment with the Type II calcimimetic cinacalcet on vascular calcification in a HD patient with SHPT. A 40-year-old male with a 24-year history of kidney failure secondary to mesangial proliferative glomerulonephritis, commenced HD in October 2004 following chronic graft dysfunction. The patient was admitted to hospital with renal insufficiency and metabolic abnormalities. An anatomopathological study showed calcium (Ca) deposits in the alveolar septa, bronchial wall and pulmonary arterioles. Parathyroid methoxy isobutyl isonitrile (MIBI) scintigraphy revealed multiglandular parathyroid disease and an ectopic gland behind the sternal notch. Serum intact parathyroid hormone (iPTH) was repeatedly found to be >= 2,500 pg/ml, and was accompanied by significant abnormalities in phosphorus (P) and Ca metabolism which were difficult to control. The patient was initially treated with sevelamer, low dose calcium carbonate, a low P and reduced protein diet and high doses of intravenous erythropoietin. In addition, he received HD with a high efficiency membrane for 4.5 hours, 4-times weekly. Treatment with cinacalcet was initiated at 30 mg/day and adjusted to achieve National Kidney Foundation Kidney Disease Outcomes Quality Initiative targets for iPTH, P, Ca and Ca-P product. One year following cinacalcet treatment, a chest x-ray showed a moderate reduction in Ca deposits, a bone X-ray showed a significant reduction in vascular calcifications, and parathyroid MIBI scintigraphy showed a disappearance of ectopic focus and minimal remains of glands. Significant reductions in calcemia were controlled by concomitant modifications to oral Ca supplementation, Ca concentration in the dialysis liquid, and administration of paricalcitriol. In the second year of treatment, iPTH was maintained within the target range, with moderate rises in P and stabilization of serum Ca. An echocardiogram showed an improvement in left ventricular hypertrophy. Chest and hand X-rays showed a progressive reduction in calcifications. Radiology showed an improvement in bone morphology, with reduced trabeculation and better cortical definition in the phalanx bones. In conclusion, the changes in iPTH, P and Ca associated with cinacalcet treatment were accompanied by reduced vascular and soft tissue calcification in this patient. There were no cardiovascular events and the patient experienced a marked improvement in quality of life.Correspondence to:
M.J. Aladrén Regidor, MD; Pº de los Tilos, 7, 1º, Zaragoza 50012, Spain
Email: maladren@senefro.org
M.J. Aladrén Regidor
Hospital Ernest Lluch, Calatayud, SpainManagement of secondary hyperparathyroidism (SHPT) in chronic kidney disease patients on hemodialysis (HD) can be challenging. Conventional treatments can lead to hypercalcemia and hyperphosphatemia, both of which are associated with vascular and soft tissue calcification and increased risk of cardiovascular disease. We report the effect of treatment with the Type II calcimimetic cinacalcet on vascular calcification in a HD patient with SHPT. A 40-year-old male with a 24-year history of kidney failure secondary to mesangial proliferative glomerulonephritis, commenced HD in October 2004 following chronic graft dysfunction. The patient was admitted to hospital with renal insufficiency and metabolic abnormalities. An anatomopathological study showed calcium (Ca) deposits in the alveolar septa, bronchial wall and pulmonary arterioles. Parathyroid methoxy isobutyl isonitrile (MIBI) scintigraphy revealed multiglandular parathyroid disease and an ectopic gland behind the sternal notch. Serum intact parathyroid hormone (iPTH) was repeatedly found to be >= 2,500 pg/ml, and was accompanied by significant abnormalities in phosphorus (P) and Ca metabolism which were difficult to control. The patient was initially treated with sevelamer, low dose calcium carbonate, a low P and reduced protein diet and high doses of intravenous erythropoietin. In addition, he received HD with a high efficiency membrane for 4.5 hours, 4-times weekly. Treatment with cinacalcet was initiated at 30 mg/day and adjusted to achieve National Kidney Foundation Kidney Disease Outcomes Quality Initiative targets for iPTH, P, Ca and Ca-P product. One year following cinacalcet treatment, a chest x-ray showed a moderate reduction in Ca deposits, a bone X-ray showed a significant reduction in vascular calcifications, and parathyroid MIBI scintigraphy showed a disappearance of ectopic focus and minimal remains of glands. Significant reductions in calcemia were controlled by concomitant modifications to oral Ca supplementation, Ca concentration in the dialysis liquid, and administration of paricalcitriol. In the second year of treatment, iPTH was maintained within the target range, with moderate rises in P and stabilization of serum Ca. An echocardiogram showed an improvement in left ventricular hypertrophy. Chest and hand X-rays showed a progressive reduction in calcifications. Radiology showed an improvement in bone morphology, with reduced trabeculation and better cortical definition in the phalanx bones. In conclusion, the changes in iPTH, P and Ca associated with cinacalcet treatment were accompanied by reduced vascular and soft tissue calcification in this patient. There were no cardiovascular events and the patient experienced a marked improvement in quality of life.Correspondence to:
M.J. Aladrén Regidor, MD; Pº de los Tilos, 7, 1º, Zaragoza 50012, Spain
Email: maladren@senefro.org
Case Report
Kaposi’s sarcoma in renal transplantation: Report of three cases
E. Razeghi, A. Hadadi, P. Khashayar and G. Pourmand
214
16$
Abstract
Kaposi’s sarcoma (KS) is one of the most common post transplant malignancies. A variety of factors appears to contribute to the development of KS including genetic factors, sex hormones, immunosuppression and oncogene viruses. We present 3 cases with concurrent KS and cytomegalovirus (CMV) infection in the first year after kidney transplantation. The suspicion on KS due to the skin lesions was confirmed by biopsy. The diagnosis of CMV infection was made by detecting pp65 antigen in blood. The KS lesions were limited to the skin in 2 patients, while skin and gastrointestinal tract were involved in 1 patient. Many factors are reported to be involved in KS development, but the simultaneous occurrence of KS and CMV infection in our three cases suggested CMV as an inducing factor for KS.Correspondence to:
E. Razeghi, MD; Associate Professor of Nephrology, Urology Research Center, Sina Hospital, Imam Khomeini St. 11367-46911, Tehran, Iran
Email: Effatl62@yahoo.com
E. Razeghi1, A. Hadadi2, P. Khashayar3 and G. Pourmand4
1Nephrology, 2Infectious Diseases, 3Research and Development Center and 4Urology, Urology Research Center, Sina Hospital, Medical Sciences, University of Tehran, Iran Kaposi’s sarcoma (KS) is one of the most common post transplant malignancies. A variety of factors appears to contribute to the development of KS including genetic factors, sex hormones, immunosuppression and oncogene viruses. We present 3 cases with concurrent KS and cytomegalovirus (CMV) infection in the first year after kidney transplantation. The suspicion on KS due to the skin lesions was confirmed by biopsy. The diagnosis of CMV infection was made by detecting pp65 antigen in blood. The KS lesions were limited to the skin in 2 patients, while skin and gastrointestinal tract were involved in 1 patient. Many factors are reported to be involved in KS development, but the simultaneous occurrence of KS and CMV infection in our three cases suggested CMV as an inducing factor for KS.Correspondence to:
E. Razeghi, MD; Associate Professor of Nephrology, Urology Research Center, Sina Hospital, Imam Khomeini St. 11367-46911, Tehran, Iran
Email: Effatl62@yahoo.com
Case Report
Nephrogenic systemic fibrosis in a patient on long-term hemodialysis
K. Nakai, K. Takeda, H. Kimura, S. Miura and A. Maeda
217
20$
Abstract
Patients with renal failure sometimes develop nephrogenic systemic fibrosis (NSF) following administration of gadolinium, and a few cases have been reported in Japan. There is no definitive cure; the disease is progressive and can be fulminant. We report a case of a 54-year-old woman with multiple pathologies, including lupus nephritis at 23 years, peritoneal dialysis at 34 years, hepatocellular carcinoma at 47 years, a switch to hemodialysis, partial hepatectomy and axillo-femoral bypass grafting for severe aortic stenosis at 52 years, as well as multiple MRI exposures. One month after the last MRI including an intravenous gadolinium contrast agent (Magnevist®), she developed thickening of the skin with brownish hyperpigmentation on the lower legs spreading later to all extremities, which limited joint movement and resulted in contractures. She was treated with low-dose prednisolone and cyclosporine, however, she remains at present unable to walk or extend the joints of the upper and lower extremities and needs analgesia for sharp pain in the thickened skin. Various factors including multiple exposures to gadolinium-containing MRI contrast agents, inflammatory burden, and hepatic disease might have played a role in the development of NSF. This is the case of a Japanese patient with gadopenate-dimeglumine (Magnevist®) related NSF. Regardless of ethnicity and the type of contrast agent, we should be aware of the potential development of NSF in patients with renal failure.Correspondence to:
K. Nakai, MD; Department of Nephrology and Kidney Center, Aso-Iizuka Hospital, 3-83 Yoshio-machi, Iizuka City, Fukuoka 820-8505, Japan
Email: kentaro-kyu@umin.net
K. Nakai, K. Takeda, H. Kimura, S. Miura and A. Maeda
Department of Nephrology and Kidney Center, Aso-Iizuka Hospital, Iizuka City, Fukuoka, Japan Patients with renal failure sometimes develop nephrogenic systemic fibrosis (NSF) following administration of gadolinium, and a few cases have been reported in Japan. There is no definitive cure; the disease is progressive and can be fulminant. We report a case of a 54-year-old woman with multiple pathologies, including lupus nephritis at 23 years, peritoneal dialysis at 34 years, hepatocellular carcinoma at 47 years, a switch to hemodialysis, partial hepatectomy and axillo-femoral bypass grafting for severe aortic stenosis at 52 years, as well as multiple MRI exposures. One month after the last MRI including an intravenous gadolinium contrast agent (Magnevist®), she developed thickening of the skin with brownish hyperpigmentation on the lower legs spreading later to all extremities, which limited joint movement and resulted in contractures. She was treated with low-dose prednisolone and cyclosporine, however, she remains at present unable to walk or extend the joints of the upper and lower extremities and needs analgesia for sharp pain in the thickened skin. Various factors including multiple exposures to gadolinium-containing MRI contrast agents, inflammatory burden, and hepatic disease might have played a role in the development of NSF. This is the case of a Japanese patient with gadopenate-dimeglumine (Magnevist®) related NSF. Regardless of ethnicity and the type of contrast agent, we should be aware of the potential development of NSF in patients with renal failure.Correspondence to:
K. Nakai, MD; Department of Nephrology and Kidney Center, Aso-Iizuka Hospital, 3-83 Yoshio-machi, Iizuka City, Fukuoka 820-8505, Japan
Email: kentaro-kyu@umin.net
Case Report
Pericatheter herniation complicated by bowel incarceration in a patient on continuous ambulatory peritoneal dialysis (CAPD)
K.P. Ng, M. Ferring, D. Luke and S. Smith
221
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Abstract
We report a rare case of pericatheter herniation with small bowel incarceration in a patient on continuous ambulatory peritoneal dialysis (CAPD). However, the predominant clinical features were signs of a severe catheter tunnel infection rather than ileus. We propose that pericatheter herniation should be considered as part of the differential diagnosis of CAPD tunnel infection, even when there are no clinical signs of bowel obstruction.Correspondence to:
Dr. K.P. Ng, STI CMT (MBChB); Birmingham Heartlands Hospital, Heart of England NHS Trust, Bordersley Green East, Birmingham B9 5SS, UK
Email: khaiping@doctors.org.uk
K.P. Ng, M. Ferring, D. Luke and S. Smith
Birmingham Heartlands Hospital, Heart of England NHS Trust, Bordersley Green East, Birmingham, UK We report a rare case of pericatheter herniation with small bowel incarceration in a patient on continuous ambulatory peritoneal dialysis (CAPD). However, the predominant clinical features were signs of a severe catheter tunnel infection rather than ileus. We propose that pericatheter herniation should be considered as part of the differential diagnosis of CAPD tunnel infection, even when there are no clinical signs of bowel obstruction.Correspondence to:
Dr. K.P. Ng, STI CMT (MBChB); Birmingham Heartlands Hospital, Heart of England NHS Trust, Bordersley Green East, Birmingham B9 5SS, UK
Email: khaiping@doctors.org.uk
Case Report
Mesenteric panniculitis: an unusual cause of dyspepsia in a hemodialysis patient
Y.K. Wen and M.L. Chen
224
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Abstract
Many patients with chronic renal failure have dyspeptic symptoms. However, mesenteric panniculitis as a cause of dyspepsia has not been described in this patient group. We report a 78-year-old hemodialysis patient who was admitted because of intractable dyspepsia. Investigations with ultrasonography, endoscopy and barium studies were all inconclusive. Computed tomography of the abdomen demonstrated a large encapsuled soft-tissue mass in the root of mesentery. Percutaneous biopsy confirmed the diagnosis of mesenteric panniculitis. Percutaneous drainage was performed when liquefaction of the mesenteric mass lesion was noted on follow-up computed tomography 1 month later. Improvement of gastrointestinal symptoms occurred soon after drainage of the fluid component of the mesenteric mass. Microbiologic and cytologic studies of the drainage specimens were negative. Follow-up computed tomography 3 months later showed reduction in the size of the mesenteric mass.Correspondence to:
Dr. Y.K. Wen; Division of Nephrology, Department of Medicine, Changhua Christian Hospital, 135 Nanhsiao Street, Changhua, 500, Taiwan
Email: 45440@cch.org.tw
Y.K. Wen1 and M.L. Chen2
1Division of Nephrology, Department of Medicine and 2Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan Many patients with chronic renal failure have dyspeptic symptoms. However, mesenteric panniculitis as a cause of dyspepsia has not been described in this patient group. We report a 78-year-old hemodialysis patient who was admitted because of intractable dyspepsia. Investigations with ultrasonography, endoscopy and barium studies were all inconclusive. Computed tomography of the abdomen demonstrated a large encapsuled soft-tissue mass in the root of mesentery. Percutaneous biopsy confirmed the diagnosis of mesenteric panniculitis. Percutaneous drainage was performed when liquefaction of the mesenteric mass lesion was noted on follow-up computed tomography 1 month later. Improvement of gastrointestinal symptoms occurred soon after drainage of the fluid component of the mesenteric mass. Microbiologic and cytologic studies of the drainage specimens were negative. Follow-up computed tomography 3 months later showed reduction in the size of the mesenteric mass.Correspondence to:
Dr. Y.K. Wen; Division of Nephrology, Department of Medicine, Changhua Christian Hospital, 135 Nanhsiao Street, Changhua, 500, Taiwan
Email: 45440@cch.org.tw
Case Report
Superior mesenteric artery syndrome with vascular calcification in a maintenance hemodialysis patient
K. Kitaura and K. Harima
228
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Abstract
Introduction: Superior mesenteric artery (SMA) syndrome is defined as trapping of the third portion of the duodenum between the SMA and the aorta. In this case, vascular calcification associated with dialysis might have contributed to the onset of SMA syndrome. Case: The patient was a 74-year-old woman who had been receiving maintenance hemodialysis. She developed sudden onset of severe recurrent vomiting during admission for pseudo-gout. CT of the abdomen revealed duodenal obstruction with an abrupt cutoff in the third portion of the duodenum, and dilatation of the first and second portions of the duodenum. The aortomesenteric angle was significantly sharp. In addition, severe vascular calcification was revealed in the SMA and aorta. The initial treatment was decompression of the obstruction by a nasogastric tube and parenteral nutrition for the management of fluid and electrolyte imbalance. She recovered with only conservative treatment. Conclusion: Vascular calcification of the SMA and aorta might have contributed to compression of the third portion of the duodenum. Vascular calcification associated with dialysis could be a factor in SMA syndrome.Correspondence to:
K. Kitaura, MD; Department of Internal Medicine, Suzuran Hospital, 2-21-5, Suzurandai-Nishimachi, Kita-ku, Kobe-city, Hyogo, 651-1114, Japan
Email: keisukekitaura@yahoo.co.jp
K. Kitaura1 and K. Harima2
1Department of Internal Medicine, and 2Department of Radiology, Suzuran Hospital, Suzurandai-Nishimachi, Kita-ku, Kobe-city, Hyogo, Japan Introduction: Superior mesenteric artery (SMA) syndrome is defined as trapping of the third portion of the duodenum between the SMA and the aorta. In this case, vascular calcification associated with dialysis might have contributed to the onset of SMA syndrome. Case: The patient was a 74-year-old woman who had been receiving maintenance hemodialysis. She developed sudden onset of severe recurrent vomiting during admission for pseudo-gout. CT of the abdomen revealed duodenal obstruction with an abrupt cutoff in the third portion of the duodenum, and dilatation of the first and second portions of the duodenum. The aortomesenteric angle was significantly sharp. In addition, severe vascular calcification was revealed in the SMA and aorta. The initial treatment was decompression of the obstruction by a nasogastric tube and parenteral nutrition for the management of fluid and electrolyte imbalance. She recovered with only conservative treatment. Conclusion: Vascular calcification of the SMA and aorta might have contributed to compression of the third portion of the duodenum. Vascular calcification associated with dialysis could be a factor in SMA syndrome.Correspondence to:
K. Kitaura, MD; Department of Internal Medicine, Suzuran Hospital, 2-21-5, Suzurandai-Nishimachi, Kita-ku, Kobe-city, Hyogo, 651-1114, Japan
Email: keisukekitaura@yahoo.co.jp
Letter to the Editor
An unusual presentation of emphysematous pyelonephritis
Y.P. Hsieh and Y.K. Wen
231
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Abstract
Y.P. Hsieh and Y.K. Wen
Letter to the Editor
Effect of hemodialysis procedure in prohepcidin serum levels in regular hemodialysis patients
E. Costa, S. Rocha, P. Rocha-Pereira, F. Reis, E. Castro, F. Teixeira, V. Miranda, M. do Sameiro Faria, A. Loureiro, A. Quintanilha, L. Belo and A. Santos-Silva
233
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Abstract
E. Costa, S. Rocha, P. Rocha-Pereira, F. Reis, E. Castro, F. Teixeira, V. Miranda, M. do Sameiro Faria, A. Loureiro, A. Quintanilha, L. Belo and A. Santos-Silva
Letter to the Editor
Low BMI is a prognostic predictor in pre-dialysis patients with Type 2 diabetes
G. Biesenbach, G. Bodlaj and H. Pieringer
235
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Abstract
G. Biesenbach, G. Bodlaj and H. Pieringer
Book Review
Nephrology in a Nutshell
238
Abstract
