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Volume 71, No. 6/2009(June)
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Review
Paricalcitol and outcome: A manual on how a vitamin D receptor activator (VDRA) can help us to get down the “U”
M. Cozzolino and V. Brandenburg
593
40$
Abstract
Modern strategies to prevent secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients give great relevance to vitamin D replacement therapy. However, a sound approach to treatment requires taking into account many factors, including stage of CKD, underlying renal disorder, levels of circulating PTH, bone status, vitamin D deposits, and serum calcium (Ca) and phosphate (P) levels. The aim of vitamin D replacement therapy should be to prevent SHPT from the early stages of CKD, because once parathyroid hyperplasia and osteodystrophy develop, they cannot be completely reverted. The therapeutic strategies for SHPT are now changing. The availability of VDRAs allows inhibition of parathyroid glands with less effect on calcium and phosphate levels, and perhaps reduces the mortality of dialysis patients. Actual objectives for treating CKD patients with new generation VDRAs are to retain or amplify the effects of calcitriol on PTH suppression, with no effects on serum Ca and P levels. Paricalcitol is such a new VDRA with minimal impact on serum Ca and P levels. Since cardiovascular disease is the leading cause of morbidity and mortality in dialysis patients, these data suggest that the beneficial effect associated with paricalcitol injection on patient survival is at least partially related to its effect on the cardiovascular system.Correspondence to:
M. Cozzolino, MD, PhD
Renal Division, S. Paolo Hospital
University of Milan
Via A. di Rudinì 8
20142 Milan, Italy
Email: mariocozzolino@hotmail.com
M. Cozzolino1 and V. Brandenburg2
1Division of Nephrology, University of Milan, S Paolo Hospital, Milan, Italy, and 2Division of Nephrology, University Hospital Aachen, RWTH Aachen, Germany Modern strategies to prevent secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients give great relevance to vitamin D replacement therapy. However, a sound approach to treatment requires taking into account many factors, including stage of CKD, underlying renal disorder, levels of circulating PTH, bone status, vitamin D deposits, and serum calcium (Ca) and phosphate (P) levels. The aim of vitamin D replacement therapy should be to prevent SHPT from the early stages of CKD, because once parathyroid hyperplasia and osteodystrophy develop, they cannot be completely reverted. The therapeutic strategies for SHPT are now changing. The availability of VDRAs allows inhibition of parathyroid glands with less effect on calcium and phosphate levels, and perhaps reduces the mortality of dialysis patients. Actual objectives for treating CKD patients with new generation VDRAs are to retain or amplify the effects of calcitriol on PTH suppression, with no effects on serum Ca and P levels. Paricalcitol is such a new VDRA with minimal impact on serum Ca and P levels. Since cardiovascular disease is the leading cause of morbidity and mortality in dialysis patients, these data suggest that the beneficial effect associated with paricalcitol injection on patient survival is at least partially related to its effect on the cardiovascular system.Correspondence to:
M. Cozzolino, MD, PhD
Renal Division, S. Paolo Hospital
University of Milan
Via A. di Rudinì 8
20142 Milan, Italy
Email: mariocozzolino@hotmail.com
Hypothesis
Evolving practices in the management of acute kidney injury in the ICU (Intensive Care Unit)
S. Yohannes and L.S. Chawla
602
28$
Abstract
2Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University Medical Center, Washington, D.C., USA
Acute kidney injury (AKI) is a life-threatening illness whose mortality has remained high since the introduction of hemodialysis three decades ago. Current therapeutic options have been limited to dialytic support because there are no approved pharmacologics for the treatment of AKI. Previous clinical trials have focused on drugs and interventions that increase renal perfusion. These approaches have not been fruitful to date. However, early goal-directed therapy (EGDT) appears to improve renal and overall outcomes. The mechanism whereby EGDT improves outcomes appears to be related to decreased levels of proinflammatory cytokines and apoptosis. Inflammation and AKI are intimately related in preclinical studies. This relationship has been recently confirmed in clinical studies as well. Elevated concentrations of plasma IL-6 predict AKI in patients with sepsis, acute respiratory distress syndrome (ARDS), and hospital-acquired pneumonia. We postulate that inflammation causes AKI. This hypothesis could explain why clinical interventions focused on improving renal perfusion alone have not been effective. If inflammation causes AKI, than therapeutic interventions that decrease inflammation should improve renal outcome. Lung-protective strategies in patients with ARDS increase survival and decrease levels of proinflammatory cytokines. As expected, these decreased levels of proinflammatory cytokines as a result of implementing a lung-protective strategy are associated with improved renal outcome. Mounting evidence supports the hypothesis that inflammation is an important causal component of AKI. Interventions that safely decrease inflammation should be integrated in good clinical practice in order to maximize benefit. In the future, interventions and drugs targeted at inflammation may prove to be robust agents for the treatment of AKI.Correspondence to:
L.S. Chawla, MD
Department of Anesthesiology and Critical Care Medicine
The George Washington University Medical Center
900 23rd Street, NW, Room G-105
Washington, D.C. 20037, USA
Email: lchawla@mfa.gwu.edu
S. Yohannes1 and L.S. Chawla1,2
1Department of Critical Care Medicine and Anesthesiology, and2Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University Medical Center, Washington, D.C., USA
Acute kidney injury (AKI) is a life-threatening illness whose mortality has remained high since the introduction of hemodialysis three decades ago. Current therapeutic options have been limited to dialytic support because there are no approved pharmacologics for the treatment of AKI. Previous clinical trials have focused on drugs and interventions that increase renal perfusion. These approaches have not been fruitful to date. However, early goal-directed therapy (EGDT) appears to improve renal and overall outcomes. The mechanism whereby EGDT improves outcomes appears to be related to decreased levels of proinflammatory cytokines and apoptosis. Inflammation and AKI are intimately related in preclinical studies. This relationship has been recently confirmed in clinical studies as well. Elevated concentrations of plasma IL-6 predict AKI in patients with sepsis, acute respiratory distress syndrome (ARDS), and hospital-acquired pneumonia. We postulate that inflammation causes AKI. This hypothesis could explain why clinical interventions focused on improving renal perfusion alone have not been effective. If inflammation causes AKI, than therapeutic interventions that decrease inflammation should improve renal outcome. Lung-protective strategies in patients with ARDS increase survival and decrease levels of proinflammatory cytokines. As expected, these decreased levels of proinflammatory cytokines as a result of implementing a lung-protective strategy are associated with improved renal outcome. Mounting evidence supports the hypothesis that inflammation is an important causal component of AKI. Interventions that safely decrease inflammation should be integrated in good clinical practice in order to maximize benefit. In the future, interventions and drugs targeted at inflammation may prove to be robust agents for the treatment of AKI.Correspondence to:
L.S. Chawla, MD
Department of Anesthesiology and Critical Care Medicine
The George Washington University Medical Center
900 23rd Street, NW, Room G-105
Washington, D.C. 20037, USA
Email: lchawla@mfa.gwu.edu
Original
GATA-3 is upregulated in peripheral blood mononuclear cells from patients with minimal change nephrotic syndrome
A. Komatsuda, H. Wakui, K. Iwamoto, M. Togashi, R. Masai, N. Maki and K. Sawada
608
40$
Abstract
Background: An imbalance of Th1 and Th2 cytokines has been reported in MCNS. Interleukin-13 (IL-13: Th2 cytokine) has been implicated in the pathogenesis of MCNS, but Th1/Th2 regulators such as T-bet (Th1-specific transcription factor) and GATA-3 (Th2-specific transcription factor) have not been examined. Methods: We isolated PBMC from 25 patients with MCNS during nephrosis and remission phases, from 17 nephrotic patients with membranous nephropathy (MN), and from 25 healthy subjects. We measured mRNA expression levels of T-bet, GATA-3, Stat5A (regulator of Th2 priming), IFN-gamma (Th1 cytokine), IL-2 (Th1 cytokine and activator of Stat5), IL-4 (Th2 cytokine), and IL-13 in PBMC, using real-time RT-PCR. Results: GATA-3, Stat5A, and IL-13 mRNA expression levels were higher in the nephrotic MCNS group compared to the others. IL-2 mRNA expression levels were higher in nephrotic patients with MCNS and MN than in MCNS patients in remission and healthy controls. There were no differences in mRNA expression levels of T-bet, IFN-gamma, and IL-4 between MCNS and MN patients and healthy controls. Conclusions: This study is the first to reveal increased mRNA expression levels of GATA-3 and Stat5A in PBMC from MCNS patients in nephrosis. This study also supports recent findings suggesting the role of IL-13 in the development of MCNS. A predominant Th2 type of T cell activation may be involved in the pathogenesis of MCNS.Correspondence to:
A. Komatsuda MD
Third Department of Internal Medicine
Akita University School of Medicine
1-1-1 Hondo, Akita City
Akita 010-8543, Japan
Email: komatsud@med.akita-u.ac.jp
A. Komatsuda, H. Wakui, K. Iwamoto, M. Togashi, R. Masai, N. Maki and K. Sawada
Third Department of Internal Medicine, Akita University School of Medicine, Akita, Japan Background: An imbalance of Th1 and Th2 cytokines has been reported in MCNS. Interleukin-13 (IL-13: Th2 cytokine) has been implicated in the pathogenesis of MCNS, but Th1/Th2 regulators such as T-bet (Th1-specific transcription factor) and GATA-3 (Th2-specific transcription factor) have not been examined. Methods: We isolated PBMC from 25 patients with MCNS during nephrosis and remission phases, from 17 nephrotic patients with membranous nephropathy (MN), and from 25 healthy subjects. We measured mRNA expression levels of T-bet, GATA-3, Stat5A (regulator of Th2 priming), IFN-gamma (Th1 cytokine), IL-2 (Th1 cytokine and activator of Stat5), IL-4 (Th2 cytokine), and IL-13 in PBMC, using real-time RT-PCR. Results: GATA-3, Stat5A, and IL-13 mRNA expression levels were higher in the nephrotic MCNS group compared to the others. IL-2 mRNA expression levels were higher in nephrotic patients with MCNS and MN than in MCNS patients in remission and healthy controls. There were no differences in mRNA expression levels of T-bet, IFN-gamma, and IL-4 between MCNS and MN patients and healthy controls. Conclusions: This study is the first to reveal increased mRNA expression levels of GATA-3 and Stat5A in PBMC from MCNS patients in nephrosis. This study also supports recent findings suggesting the role of IL-13 in the development of MCNS. A predominant Th2 type of T cell activation may be involved in the pathogenesis of MCNS.Correspondence to:
A. Komatsuda MD
Third Department of Internal Medicine
Akita University School of Medicine
1-1-1 Hondo, Akita City
Akita 010-8543, Japan
Email: komatsud@med.akita-u.ac.jp
Original
Beneficial effects of high-dose losartan in IgA nephritis
K.-T. Woo, C.-M. Chan, H.-K. Tan, H.-L. Choong, M. Foo, A. Vathsala, E.J.C. Lee, C.-C. Tan, G.S.L. Lee, S.H. Tan, C.-H. Lim, G.S.C. Chiang, S. Fook-Chong, and S.K.S. Wong
617
36$
Abstract
Aim: Several short-term studies have reported the efficacy of high-dose ARB in reducing proteinuria in patients with diabetic nephropathy. The benefits of long-term high-dose ARB losartan in IgA nephritis have not been explored. Method: This was a 6-year randomized trial in 207 patients with IgA nephritis comparing high-dose ARB (losartan 200 mg/day) with normal dose ARB (losartan 100 mg/day), normal dose ACEI (20 mg/day) and low-dose ACEI (10 mg/day). Multivariate ANOVA was used to test the effect of drug treatment on both eGFR and total urinary protein (TUP). Results: Comparing patients on high-dose ARB (n = 63) with those on normal dose ARB (n = 43), normal dose ACEI (n = 61) and low-dose ACEI (n = 40), patients on high Dose ARB had significantly higher eGFR (p < 0.0005) and lower proteinuria (p < 0.005) at the end of the study. The loss in eGFR was 0.7 ml/min/year for high-dose ARB compared to 3.2 – 3.5 ml/ min/year for the other 3 groups (p = 0.0005). There were more patients on high-dose ARB with improvement in eGFR compared to other 3 groups (p < 0.001). Conclusion: Data from this study suggest that high-dose ARB therapy is more efficacious in reducing proteinuria and preserving renal function when compared with normal dose ARB and ACEI. In Year 5, patients on high-dose ARB had a gain in eGFR suggesting that there is possibility of recovery of renal function in these patients on long-term high-dose therapy.Correspondence to:
K.T. Woo, FRACP
Department of Renal Medicine
Singapore General Hospital
Outram Road
169608 Singapore
Email: woo.keng.thye@sgh.com.sg
K.-T. Woo1, C.-M. Chan1, H.-K. Tan1, H.-L. Choong1, M. Foo1, A. Vathsala1, E.J.C. Lee2, C.-C. Tan3, G.S.L. Lee4, S.H. Tan5, C.-H. Lim1, G.S.C. Chiang1, S. Fook-Chong1,2 and S.K.S. Wong1
1Department of Renal Medicine, Singapore General Hospital, 2Division of Nephrology, National University Hospital, 3Gleneagles Medical Centre, 4Department of Renal Medicine, Tan Tock Seng Hospital, and 5Department of Clinical Research, Singapore General Hospital, Singapore Aim: Several short-term studies have reported the efficacy of high-dose ARB in reducing proteinuria in patients with diabetic nephropathy. The benefits of long-term high-dose ARB losartan in IgA nephritis have not been explored. Method: This was a 6-year randomized trial in 207 patients with IgA nephritis comparing high-dose ARB (losartan 200 mg/day) with normal dose ARB (losartan 100 mg/day), normal dose ACEI (20 mg/day) and low-dose ACEI (10 mg/day). Multivariate ANOVA was used to test the effect of drug treatment on both eGFR and total urinary protein (TUP). Results: Comparing patients on high-dose ARB (n = 63) with those on normal dose ARB (n = 43), normal dose ACEI (n = 61) and low-dose ACEI (n = 40), patients on high Dose ARB had significantly higher eGFR (p < 0.0005) and lower proteinuria (p < 0.005) at the end of the study. The loss in eGFR was 0.7 ml/min/year for high-dose ARB compared to 3.2 – 3.5 ml/ min/year for the other 3 groups (p = 0.0005). There were more patients on high-dose ARB with improvement in eGFR compared to other 3 groups (p < 0.001). Conclusion: Data from this study suggest that high-dose ARB therapy is more efficacious in reducing proteinuria and preserving renal function when compared with normal dose ARB and ACEI. In Year 5, patients on high-dose ARB had a gain in eGFR suggesting that there is possibility of recovery of renal function in these patients on long-term high-dose therapy.Correspondence to:
K.T. Woo, FRACP
Department of Renal Medicine
Singapore General Hospital
Outram Road
169608 Singapore
Email: woo.keng.thye@sgh.com.sg
Original
Efficacy of methylprednisolone, cyclophosphamide in pediatric IgA nephropathy assessed by renal biopsy
X.-Y. Jiang, Y. Mo, L.-Z. Sun, Z.-H. Yue, S.-M. Chen and W. Wu
625
32$
Abstract
Aims: IgA nephropathy is one of the most common glomerular diseases in children. The aim of this study was to investigate the clinical and pathologic efficacy of methylprednisolone and cyclophosphamide in the treatment of primary pediatric IgA nephropathy. Methods: 11 patients with renal-biopsy-diagnosed Grade IV IgA nephropathy were treated with methylprednisolone and cyclophosphamide. Pathological changes were evaluated by post-treatment renal biopsies. Results: At follow-up (18 – 60 months post-treatment), 6 patients were in complete remission. For the remaining 5, treatment was rated “markedly effective.” Renal biopsies showed less mesangial proliferation, significantly decreased crescent formation, reduced segmental sclerosis, and significantly reduced mesangial IgA deposition. Conclusions: Methylprednisolone and cyclophosphamide in children with Grade IV IgA nephropathy stabilized renal function and significantly reduced hematuria, proteinuria, mesangial IgA deposition, and the renal pathological activity index.Correspondence to:
X.-Y. Jiang MD,
associate Prof. of Pediatrics
Department of Pediatrics
First Affiliated Hospital of Sun Yat-Sen University
58 zhongshan Road 2
Guangzhou 510080, P.R. China
Email: xyjiang-3208@163.com
X.-Y. Jiang, Y. Mo, L.-Z. Sun, Z.-H. Yue, S.-M. Chen and W. Wu
Department of Pediatrics, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China Aims: IgA nephropathy is one of the most common glomerular diseases in children. The aim of this study was to investigate the clinical and pathologic efficacy of methylprednisolone and cyclophosphamide in the treatment of primary pediatric IgA nephropathy. Methods: 11 patients with renal-biopsy-diagnosed Grade IV IgA nephropathy were treated with methylprednisolone and cyclophosphamide. Pathological changes were evaluated by post-treatment renal biopsies. Results: At follow-up (18 – 60 months post-treatment), 6 patients were in complete remission. For the remaining 5, treatment was rated “markedly effective.” Renal biopsies showed less mesangial proliferation, significantly decreased crescent formation, reduced segmental sclerosis, and significantly reduced mesangial IgA deposition. Conclusions: Methylprednisolone and cyclophosphamide in children with Grade IV IgA nephropathy stabilized renal function and significantly reduced hematuria, proteinuria, mesangial IgA deposition, and the renal pathological activity index.Correspondence to:
X.-Y. Jiang MD,
associate Prof. of Pediatrics
Department of Pediatrics
First Affiliated Hospital of Sun Yat-Sen University
58 zhongshan Road 2
Guangzhou 510080, P.R. China
Email: xyjiang-3208@163.com
Original
Effect of overweight/obesity on recovery after post-infectious glomerulonephritis
M.N. Lee, U. Shaikh and L. Butani
632
24$
Abstract
Background: Children with post-infectious glomerulonephritis (PIGN) rapidly recover and have excellent long-term outcomes. After encountering several overweight/obese children with persistent urinary abnormalities during recovery from PIGN, we conducted this retrospective study to determine if overweight/obese status prolonged time to resolution of renal abnormalities after PIGN. Methods: Records of 20 children with PSGN evaluated between 1/98 and 12/05 were abstracted for demographics, clinical and laboratory data. Primary outcome measures were time to resolution of hypertension, proteinuria, microhematuria, and low complement C3. The effect of overweight/obese status on outcomes was determined using Kaplan Meier Survival and the log-rank test. Results: The median age was 8 years; 30% were overweight/obese. At presentation, 17 (85%) were hypertensive, 10 (50%) had impaired glomerular filtration (GFR), and 18 (90%) had proteinuria. At last follow-up (median 2.8 months) 12% had hypertension, 55% had microhematuria, 5% had proteinuria but none had low GFR. Median time to normalize was: 30 days (GFR), 45 days (blood pressure), 6 weeks (C3) and 6 months (microhematuria). Log rank test showed that proteinuria-, hypertension-, and hematuria-free survival were all lower in children who were overweight/obese although none of the differences were statistically significant. Time to normalization of C3 was shorter in obese/ overweight children. Conclusion: In conclusion, overweight/obese children appear to have greater residual renal injury after PIGN. The earlier C3 normalization in overweight/ obese children may indicate that the adverse effect of weight on recovery is from hemodynamic rather than inflammatory factors. Close follow-up of overweight/obese children who develop PIGN is warranted to ensure optimal long-term outcomes.Correspondence to:
L. Butani, MD
Section of Pediatric Nephrology
University of California Davis Medical Center
2516 Stockton Boulevard
Sacramento, CA 95817, USA
Email: lavjay.butani@ucdmc.ucdavis.edu
M.N. Lee1, U. Shaikh1 and L. Butani2
1Department of Pediatrics, and 2Section of Pediatric Nephrology, Department of Pediatrics, University of California Davis Medical Center, Sacramento, CA, USA Background: Children with post-infectious glomerulonephritis (PIGN) rapidly recover and have excellent long-term outcomes. After encountering several overweight/obese children with persistent urinary abnormalities during recovery from PIGN, we conducted this retrospective study to determine if overweight/obese status prolonged time to resolution of renal abnormalities after PIGN. Methods: Records of 20 children with PSGN evaluated between 1/98 and 12/05 were abstracted for demographics, clinical and laboratory data. Primary outcome measures were time to resolution of hypertension, proteinuria, microhematuria, and low complement C3. The effect of overweight/obese status on outcomes was determined using Kaplan Meier Survival and the log-rank test. Results: The median age was 8 years; 30% were overweight/obese. At presentation, 17 (85%) were hypertensive, 10 (50%) had impaired glomerular filtration (GFR), and 18 (90%) had proteinuria. At last follow-up (median 2.8 months) 12% had hypertension, 55% had microhematuria, 5% had proteinuria but none had low GFR. Median time to normalize was: 30 days (GFR), 45 days (blood pressure), 6 weeks (C3) and 6 months (microhematuria). Log rank test showed that proteinuria-, hypertension-, and hematuria-free survival were all lower in children who were overweight/obese although none of the differences were statistically significant. Time to normalization of C3 was shorter in obese/ overweight children. Conclusion: In conclusion, overweight/obese children appear to have greater residual renal injury after PIGN. The earlier C3 normalization in overweight/ obese children may indicate that the adverse effect of weight on recovery is from hemodynamic rather than inflammatory factors. Close follow-up of overweight/obese children who develop PIGN is warranted to ensure optimal long-term outcomes.Correspondence to:
L. Butani, MD
Section of Pediatric Nephrology
University of California Davis Medical Center
2516 Stockton Boulevard
Sacramento, CA 95817, USA
Email: lavjay.butani@ucdmc.ucdavis.edu
Original
Case series of idiopathic membranous nephropathy with long-term beneficial effects of ACTH peptide 1-24
T. Rauen, A. Michaelis, J. Floege and P.R. Mertens
637
28$
Abstract
Background: In patients with idiopathic membranous nephropathy (IMN), immunosuppressive therapy is usually considered when severe nephrotic syndrome or risk for progressive renal failure exist. Recently, several studies showing beneficial effects of synthetic adrenocorticotropic hormone (ACTH) under such circumstances have been published. The objective of the present case series was to evaluate long-term ACTH effects on proteinuria and renal function. Methods: Four patients with biopsy-proven membranous nephropathy and nephrotic syndrome were enrolled (median age 50 years (range 38 – 61), median GFR 39.5 ml/min (range 20 – 62), median proteinuria 9.6 g/d (range 6.0 – 20.0). Prior immunosuppressive treatment regimens included steroids, cyclosporine A, cyclophosphamide, mycophenolate mofetil or azathioprine. The patients received a synthetic ACTH analogue intramuscularly for a median duration of 8 months (range 3 – 24). ACTH dosage was adjusted according to side effects between 0.25 and 2.25 mg/week. Follow-up lasted between 24 and 82 months after therapy initiation. Results: All 4 patients exhibited partial (n = 2) or complete (n = 2) remissions of their nephrotic syndrome within the first year. After discontinuation of ACTH therapy, proteinuria remained low in 3 of 4 cases, whereas 1 patient exhibited undulating proteinuria. Glomerular function (as assessed by glomerular filtration rate, GFR) was maintained in all patients. Side effects were minor and included weight gain, elevated blood pressure and hyperglycemia. Conclusion: In all 4 cases with IMN, ACTH treatment induced a lasting disease remission with relatively few side effects.Correspondence to:
Prof. Dr. med.
P.R. Mertens
Department of Nephrology and Hypertension
Otto-von-Guericke University Magdeburg
Leipziger Straße 44
39120 Magdeburg, Germany
Email: Pmertens@ukaachen.de
T. Rauen1, A. Michaelis1, J. Floege and P.R. Mertens2
1Department of Nephrology and Clinical Immunology, RWTH-University Hospital, Aachen, and 2Department of Nephrology and Hypertension, Otto-von-Guericke University, Magdeburg, Germany Background: In patients with idiopathic membranous nephropathy (IMN), immunosuppressive therapy is usually considered when severe nephrotic syndrome or risk for progressive renal failure exist. Recently, several studies showing beneficial effects of synthetic adrenocorticotropic hormone (ACTH) under such circumstances have been published. The objective of the present case series was to evaluate long-term ACTH effects on proteinuria and renal function. Methods: Four patients with biopsy-proven membranous nephropathy and nephrotic syndrome were enrolled (median age 50 years (range 38 – 61), median GFR 39.5 ml/min (range 20 – 62), median proteinuria 9.6 g/d (range 6.0 – 20.0). Prior immunosuppressive treatment regimens included steroids, cyclosporine A, cyclophosphamide, mycophenolate mofetil or azathioprine. The patients received a synthetic ACTH analogue intramuscularly for a median duration of 8 months (range 3 – 24). ACTH dosage was adjusted according to side effects between 0.25 and 2.25 mg/week. Follow-up lasted between 24 and 82 months after therapy initiation. Results: All 4 patients exhibited partial (n = 2) or complete (n = 2) remissions of their nephrotic syndrome within the first year. After discontinuation of ACTH therapy, proteinuria remained low in 3 of 4 cases, whereas 1 patient exhibited undulating proteinuria. Glomerular function (as assessed by glomerular filtration rate, GFR) was maintained in all patients. Side effects were minor and included weight gain, elevated blood pressure and hyperglycemia. Conclusion: In all 4 cases with IMN, ACTH treatment induced a lasting disease remission with relatively few side effects.Correspondence to:
Prof. Dr. med.
P.R. Mertens
Department of Nephrology and Hypertension
Otto-von-Guericke University Magdeburg
Leipziger Straße 44
39120 Magdeburg, Germany
Email: Pmertens@ukaachen.de
Original
Insulin resistance is a risk factor for the progression of chronic kidney disease
H. Kobayashi, G. Tokudome, Y. Hara, N. Sugano, S. Endo, Y. Suetsugu, S. Kuriyama and T. Hosoya
643
40$
Abstract
Objective: Insulin resistance may contribute to the pathogenesis of hypertension and progressive chronic kidney disease (CKD), however, few clinical studies have explored the role of insulin resistance in predicting the deterioration of renal function in CKD patients. Materials and methods: Enrolled in the study were non-diabetic hypertensive patients with CKD Stage 3. Insulin resistance was assessed by a homeostasis model assessment of insulin resistance (HOMA-R) measured at the entry to the study. Patients were followed for 3 years and comparisons of renal and metabolic parameters were made in conjunction with HOMA-R between entry and the end of the study period. The insulin-resistant (IR) group was defined as patients with HOMA-R 2.0 and more, and the insulin-sensitive (IS) group as those with HOMA-R < 2.0. Results: Blood pressure in both groups was equally controlled below 130/80 mmHg throughout the observation period. The degree of insulin resistance HOMA-R and immunoreactive insulin (IRI) remained unchanged in the IS group, however, both were ameliorated in the IR group (HOMA-R, from 3.4 ± 1.5 – 3.0 ± 1.1, p = 0.022 and IRI, from 14.4 ± 6.1 µU/ml – 12.6 ± 6.8 µU/ml, p = 0.012). Creatinine clearance (CCr) and estimated glomerular filtration rate (e-GFR) decreased and serum creatinine (Cr) concentration increased in all patients. The decline in CCr calculated as the slope of the reciprocal of serum Cr concentration (1/Cr) was greater in the IR group (0.007 ± 0.004 (1/Cr/dl/mg/month) than in the IS group (0.003 ± 0.002 (1/Cr/dl/mg/month), p < 0.001). Linear regression analysis showed that the slope of 1/Cr was negatively correlated with HOMA-R, IRI, BMI, respectively. Furthermore, stepwise regression analysis showed that the independent variables to explain the decline in renal function were HOMA-R and IRI. Conclusion: Insulin resistance is a significant risk factor for the deterioration of renal function in hypertensive non-diabetic patients with CKD.Correspondence to:
S. Kuriyama, MD
Division of Nephrology
Saiseikai Central Hospital
1-4-17, Mita, Minato-ku, Tokyo, Japan
Email: kuriyamas218@yahoo.co.jp
H. Kobayashi1, G. Tokudome1, Y. Hara1, N. Sugano1, S. Endo1, Y. Suetsugu1, S. Kuriyama2 and T. Hosoya1
1Hypertension Research Unit, Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, and 2Division of Nephrology, Saiseikai Central Hospital, Tokyo, Japan Objective: Insulin resistance may contribute to the pathogenesis of hypertension and progressive chronic kidney disease (CKD), however, few clinical studies have explored the role of insulin resistance in predicting the deterioration of renal function in CKD patients. Materials and methods: Enrolled in the study were non-diabetic hypertensive patients with CKD Stage 3. Insulin resistance was assessed by a homeostasis model assessment of insulin resistance (HOMA-R) measured at the entry to the study. Patients were followed for 3 years and comparisons of renal and metabolic parameters were made in conjunction with HOMA-R between entry and the end of the study period. The insulin-resistant (IR) group was defined as patients with HOMA-R 2.0 and more, and the insulin-sensitive (IS) group as those with HOMA-R < 2.0. Results: Blood pressure in both groups was equally controlled below 130/80 mmHg throughout the observation period. The degree of insulin resistance HOMA-R and immunoreactive insulin (IRI) remained unchanged in the IS group, however, both were ameliorated in the IR group (HOMA-R, from 3.4 ± 1.5 – 3.0 ± 1.1, p = 0.022 and IRI, from 14.4 ± 6.1 µU/ml – 12.6 ± 6.8 µU/ml, p = 0.012). Creatinine clearance (CCr) and estimated glomerular filtration rate (e-GFR) decreased and serum creatinine (Cr) concentration increased in all patients. The decline in CCr calculated as the slope of the reciprocal of serum Cr concentration (1/Cr) was greater in the IR group (0.007 ± 0.004 (1/Cr/dl/mg/month) than in the IS group (0.003 ± 0.002 (1/Cr/dl/mg/month), p < 0.001). Linear regression analysis showed that the slope of 1/Cr was negatively correlated with HOMA-R, IRI, BMI, respectively. Furthermore, stepwise regression analysis showed that the independent variables to explain the decline in renal function were HOMA-R and IRI. Conclusion: Insulin resistance is a significant risk factor for the deterioration of renal function in hypertensive non-diabetic patients with CKD.Correspondence to:
S. Kuriyama, MD
Division of Nephrology
Saiseikai Central Hospital
1-4-17, Mita, Minato-ku, Tokyo, Japan
Email: kuriyamas218@yahoo.co.jp
Original
The effect of RANKL and OPG on bone mineral density in pre-dialysis chronic renal failure
A. Fahrleitner-Pammer, H. Dobnig, H.P. Dimai, H. Holzer, T. Benesch, K. Borchhardt, D. Cejka and M. Haas
652
36$
Abstract
Aims: The influence of pre-dialysis chronic kidney disease (CKD) on bone is ill defined. Isolation of specific pathogenic mechanisms would improve the understanding and therapeutic options. We therefore investigated whether parathyroid dysfunction, altered vitamin D and hormonal status, or RANKL and OPG have an influence on bone mineral density (BMD) in patients with pre-dialysis renal failure. Material: 132 patients with chronic renal failure stage 1 – 5 (not yet on dialysis) were investigated in a cross sectional study. Osteoprotegerin (OPG), receptor activator of nuclear factor kB ligand (RANKL), parathyroid hormone (whole, intact and 7-84 fragment), bone markers, sex hormones, and vitamin D status were assessed together with femoral neck and trochanter z-score. Correlation and multivariate analyses were performed between the different parameters and BMD. Results: In the multivariate analysis a significant association was found between the femoral neck z-score and sRANKL (B = –0.45; p < 0.001), and OPG (B = 0.20; p < 0.05). A significant negative association was also found between the trochanter z-score and sRANKL (B = –0.32; p < 0.001). No associations were found between the trochanter z-score and OPG or the sRANKL/OPG ratio. The body mass index was the only additional marker associated with both FN z-score (B = 0.20, p < 0.05) and TR z-score (B = 0.20, p < 0.05). Neither markers of osteoblast nor osteoclast activity, or intact PTH, whole PTH, the PTH 7-84 fragment or vitamin D status were related to bone mineral density. Conclusion: Our results demonstrate that the RANKL/RANK/OPG system is associated with bone mineral density in pre-dialysis chronic renal failure.Correspondence to:
M. Haas, MD
Department of Internal Medicine III
Division of Nephrology and Dialysis
Medical University of Vienna
Währinger Gürtel 18-20
1090 Vienna, Austria
Email: martin.haas@meduniwien.ac.at
A. Fahrleitner-Pammer1, H. Dobnig1, H.P. Dimai1, H. Holzer2, T. Benesch3, K. Borchhardt4, D. Cejka4 and M. Haas4
1Division of Endocrinology and Nuclear Medicine, 2Division Nephrology and Dialysis, Department of Internal Medicine, Medical University of Graz, 3Department of Medical Statistics, Medical University of Vienna, and 4Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Austria Aims: The influence of pre-dialysis chronic kidney disease (CKD) on bone is ill defined. Isolation of specific pathogenic mechanisms would improve the understanding and therapeutic options. We therefore investigated whether parathyroid dysfunction, altered vitamin D and hormonal status, or RANKL and OPG have an influence on bone mineral density (BMD) in patients with pre-dialysis renal failure. Material: 132 patients with chronic renal failure stage 1 – 5 (not yet on dialysis) were investigated in a cross sectional study. Osteoprotegerin (OPG), receptor activator of nuclear factor kB ligand (RANKL), parathyroid hormone (whole, intact and 7-84 fragment), bone markers, sex hormones, and vitamin D status were assessed together with femoral neck and trochanter z-score. Correlation and multivariate analyses were performed between the different parameters and BMD. Results: In the multivariate analysis a significant association was found between the femoral neck z-score and sRANKL (B = –0.45; p < 0.001), and OPG (B = 0.20; p < 0.05). A significant negative association was also found between the trochanter z-score and sRANKL (B = –0.32; p < 0.001). No associations were found between the trochanter z-score and OPG or the sRANKL/OPG ratio. The body mass index was the only additional marker associated with both FN z-score (B = 0.20, p < 0.05) and TR z-score (B = 0.20, p < 0.05). Neither markers of osteoblast nor osteoclast activity, or intact PTH, whole PTH, the PTH 7-84 fragment or vitamin D status were related to bone mineral density. Conclusion: Our results demonstrate that the RANKL/RANK/OPG system is associated with bone mineral density in pre-dialysis chronic renal failure.Correspondence to:
M. Haas, MD
Department of Internal Medicine III
Division of Nephrology and Dialysis
Medical University of Vienna
Währinger Gürtel 18-20
1090 Vienna, Austria
Email: martin.haas@meduniwien.ac.at
Original
Comparison of oral falecalcitriol and intravenous calcitriol in hemodialysis patients with secondary hyperparathyroidism: a randomized, crossover trial
H. Ito, H. Ogata, M. Yamamoto, K. Takahashi, K. Shishido, J. Takahashi, S. Taguchi and E. Kinugasa
660
40$
Abstract
Background: Falecalcitriol is a novel vitamin D analog, which has a greater potential to suppress parathyroid hormone (PTH) and a longer half-life. There are few studies to compare clinical effects of oral falecalcitriol treatment with those of intravenous calcitriol treatment. Methods: Twenty-one patients with moderate to severe SHPT were included in a random 2 × 2 crossover trial with the two vitamin D analogs (12 weeks for each treatment). The primary endpoint measure was a decrease in serum intact PTH (iPTH) level, and the secondary outcome measures included changes in serum calcium (Ca), phosphate (P), and metabolic bone marker levels. Results: Both treatments decreased iPTH and whole PTH (wPTH) levels by similar degrees (iPTH, –200.1 ± 107.0 with falecalcitriol vs. –200.8 ± 114.9 pg/ml with calcitriol, p = 0.9895; wPTH, –137.1 ± 73.1 with falecalcitriol vs. –120.4 ± 81.1 pg/ml with calcitriol, p = 0.5603). Serum Ca, P, and Ca × P product levels at the end of each treatment were comparable and the frequencies of hypercalcemia and hyperphosphatemia were also similar during each treatment period. Although intravenous calcitriol treatment significantly changed intact osteocalcin and cross-linked N-telopeptide of type I collagen after 12 weeks, oral falecalcitriol treatment did not change any bone metabolic marker level. Conclusion: The present study showed that oral falecalcitriol treatment is effective for PTH suppression, and Ca and P metabolism in hemodialysis patients with moderate to severe SHPT, as well as intravenous calcitriol administration.Correspondence to:
H. Ogata, MD, PhD
35-1 Chigasaki-chuo
Tsuzuki, Yokohama, 224-8503, Japan
Email: ogatah@med.showa-u.ac.jp
H. Ito1, H. Ogata1, M. Yamamoto1, K. Takahashi2, K. Shishido2, J. Takahashi3, S. Taguchi1 and E. Kinugasa1
1Department of Internal Medicine, Showa University Northern Yokohama Hospital, Yokohama, 2Internal Medicine, Sekishin-kai Kawasaki Clinic, Kawasaki, and 3Internal Medicine, Sohwa-kai Eda Clinic, Yokohama, Japan Background: Falecalcitriol is a novel vitamin D analog, which has a greater potential to suppress parathyroid hormone (PTH) and a longer half-life. There are few studies to compare clinical effects of oral falecalcitriol treatment with those of intravenous calcitriol treatment. Methods: Twenty-one patients with moderate to severe SHPT were included in a random 2 × 2 crossover trial with the two vitamin D analogs (12 weeks for each treatment). The primary endpoint measure was a decrease in serum intact PTH (iPTH) level, and the secondary outcome measures included changes in serum calcium (Ca), phosphate (P), and metabolic bone marker levels. Results: Both treatments decreased iPTH and whole PTH (wPTH) levels by similar degrees (iPTH, –200.1 ± 107.0 with falecalcitriol vs. –200.8 ± 114.9 pg/ml with calcitriol, p = 0.9895; wPTH, –137.1 ± 73.1 with falecalcitriol vs. –120.4 ± 81.1 pg/ml with calcitriol, p = 0.5603). Serum Ca, P, and Ca × P product levels at the end of each treatment were comparable and the frequencies of hypercalcemia and hyperphosphatemia were also similar during each treatment period. Although intravenous calcitriol treatment significantly changed intact osteocalcin and cross-linked N-telopeptide of type I collagen after 12 weeks, oral falecalcitriol treatment did not change any bone metabolic marker level. Conclusion: The present study showed that oral falecalcitriol treatment is effective for PTH suppression, and Ca and P metabolism in hemodialysis patients with moderate to severe SHPT, as well as intravenous calcitriol administration.Correspondence to:
H. Ogata, MD, PhD
35-1 Chigasaki-chuo
Tsuzuki, Yokohama, 224-8503, Japan
Email: ogatah@med.showa-u.ac.jp
Original
Natural history and impact on outcomes of acute kidney injury in patients with road traffic injury
F. Yuan, F.F. Hou, Q. Wu, P.Y. Chen, D. Xie and X. Zhang
669
48$
Abstract
Introduction: The incidence and outcomes of posttraumatic acute kidney injury (AKI) have not been well-established because of the alterations in the definition used to characterize renal dysfunction. The natural history of AKI after road traffic injury (RTI) has not been studied. Materials and Methods: We conducted a retrospective analysis of a tertiary care medical center database, on 3,945 RTI patients admitted between 2002 and 2006. Results: AKI as defined by RIFLE criteria developed in 423 (10.7%) RTI patients, with maximum RIFLE class risk, injury and failure in 43.0%, 28.6%, and 28.4% respectively. A total of 59 patients (13.9% of AKI cohort) required renal replacement therapy and 77.5% of patients surviving AKI had complete renal recovery before discharge. Infusing vasopressors >= 4 h, using high-dose diuretics, and delayed transport time were identified as the independent risk factors for occurrence of AKI. Patients with maximum RIFLE class risk, injury and failure had hospital mortality rates of 37.4, 52.9 and 79.2%, respectively, compared with 7.1% for patients without AKI. RIFLE classification was also associated with the probability of making a complete renal recovery. Conclusions: Development of AKI in RTI patients represents a substantial risk for mortality in this population. Shortening the transport time and appropriate early intervention may reduce the risk of AKI. RIFLE provides a well-balanced classification system for determining AKI and predicting its outcome in this population.Correspondence to:
Dr. F.F. Hou
Division of Nephrology
Nanfang Hospital
Southern Medical University
1838 North Guangzhou Avenue
Guangzhou, 510515, P.R. China
Email: ffhou@public.guangzhou.gd.cn
F. Yuan1, F.F. Hou1, Q. Wu1, P.Y. Chen2, D. Xie1 and X. Zhang1
1Division of Nephrology, Nanfang Hospital, and 2Department of Biostatistics, Southern Medical University, Guangzhou, P.R. China Introduction: The incidence and outcomes of posttraumatic acute kidney injury (AKI) have not been well-established because of the alterations in the definition used to characterize renal dysfunction. The natural history of AKI after road traffic injury (RTI) has not been studied. Materials and Methods: We conducted a retrospective analysis of a tertiary care medical center database, on 3,945 RTI patients admitted between 2002 and 2006. Results: AKI as defined by RIFLE criteria developed in 423 (10.7%) RTI patients, with maximum RIFLE class risk, injury and failure in 43.0%, 28.6%, and 28.4% respectively. A total of 59 patients (13.9% of AKI cohort) required renal replacement therapy and 77.5% of patients surviving AKI had complete renal recovery before discharge. Infusing vasopressors >= 4 h, using high-dose diuretics, and delayed transport time were identified as the independent risk factors for occurrence of AKI. Patients with maximum RIFLE class risk, injury and failure had hospital mortality rates of 37.4, 52.9 and 79.2%, respectively, compared with 7.1% for patients without AKI. RIFLE classification was also associated with the probability of making a complete renal recovery. Conclusions: Development of AKI in RTI patients represents a substantial risk for mortality in this population. Shortening the transport time and appropriate early intervention may reduce the risk of AKI. RIFLE provides a well-balanced classification system for determining AKI and predicting its outcome in this population.Correspondence to:
Dr. F.F. Hou
Division of Nephrology
Nanfang Hospital
Southern Medical University
1838 North Guangzhou Avenue
Guangzhou, 510515, P.R. China
Email: ffhou@public.guangzhou.gd.cn
Original
Predictive role of duplex Doppler ultrasonography in the diagnosis of acute renal obstruction in patients with unilateral renal colic
A. Granata, S. Andrulli, M.Q. Bigi, P. Pozzoni, F. Fiorini, F. Logias, M. Figuera, A. Basile and C.E. Fiore
680
32$
Abstract
Objective: The aim of our study was to assess the role of Doppler ultrasonography (DU) by resistive index (RI) and the difference of the RI (DeltaRI) in patients with acute unilateral renal obstruction. Patients and methods: We studied 36 consecutive patients (12 female, 24 male; mean age 45.6 ± 8.4 years) with suspected renal colic by intravenous pyelography (IVP) and DU with determination of the RI and the Delta RI. A RI of >= 0.70 and a DRI of >= 0.06 were considered suggestive of obstruction. IVP was considered as the “gold standard”. Results: In the studied population, RI was 0.664 ± 0.060 in the affected kidney site of symptoms and 0.614 ± 0.025 in the contralateral one, with an overall Delta RI of 0.049 ± 0.062. At IVP, 14 patients resulted within normal range (Group A; 39%), 6 patients showed lithiasis without obstruction (Group B; 17%), 8 patients showed delayed excretion of the contrast medium (Group C; 22%), and 8 patients showed a functional exclusion of the kidney (Group D; 22%). One-way analysis of variance showed the IVP group significantly related to Delta RI with the highest values in Groups C (DRI of 0.093 ± 0.051; p <0.001) and D (Delta RI of 0.116 ± 0.030; p < 0.001) in comparison with Group A (Delta RI of 0.001 ± 0.038) and Group B (Delta RI of 0.015 ± 0.024). No differences were detected between Groups C and D (p = 0.223) and between Groups A and B (p = 0.472). Delta RI measurement with DU permitted to predict the renal obstruction with a sensitivity of 93.8%, a specificity of 95.0% and an accuracy of 94.4%. Conclusions: Intrarenal Doppler ultrasonography represents a sensitive and highly specific test that can significantly contribute to the diagnosis of obstruction in patients with acute renal colic. It should be used as the first line imaging method in suspected acute renal colic, as well as for patients with renal insufficiency, pregnant women or for patients with adverse reactions to contrast media.Correspondence to:
Dr. A. Granata
Via F. Paradiso n°78/a
95024 Acireale (CT), Italy
Email: antonio.granata4@tin.it
A. Granata1, S. Andrulli2, M.Q. Bigi2, P. Pozzoni2, F. Fiorini3, F. Logias4, M. Figuera1, A. Basile1 and C.E. Fiore1
1Departments of Nephrology-Dialysis, Internal Medicine and Radiology, Vittorio Emanuele Ferrarollo Hospital, Catania, 2Department of Nephrology and Dialysis, A. Manzoni Hospital, Lecco, 3Department of Nephrology and Dialysis, ASUL 1 San Remo, Imperia, and 4Department of Nephrology and Dialysis, AO S. Camillo, Sorgono (Nuoro), Italy Objective: The aim of our study was to assess the role of Doppler ultrasonography (DU) by resistive index (RI) and the difference of the RI (DeltaRI) in patients with acute unilateral renal obstruction. Patients and methods: We studied 36 consecutive patients (12 female, 24 male; mean age 45.6 ± 8.4 years) with suspected renal colic by intravenous pyelography (IVP) and DU with determination of the RI and the Delta RI. A RI of >= 0.70 and a DRI of >= 0.06 were considered suggestive of obstruction. IVP was considered as the “gold standard”. Results: In the studied population, RI was 0.664 ± 0.060 in the affected kidney site of symptoms and 0.614 ± 0.025 in the contralateral one, with an overall Delta RI of 0.049 ± 0.062. At IVP, 14 patients resulted within normal range (Group A; 39%), 6 patients showed lithiasis without obstruction (Group B; 17%), 8 patients showed delayed excretion of the contrast medium (Group C; 22%), and 8 patients showed a functional exclusion of the kidney (Group D; 22%). One-way analysis of variance showed the IVP group significantly related to Delta RI with the highest values in Groups C (DRI of 0.093 ± 0.051; p <0.001) and D (Delta RI of 0.116 ± 0.030; p < 0.001) in comparison with Group A (Delta RI of 0.001 ± 0.038) and Group B (Delta RI of 0.015 ± 0.024). No differences were detected between Groups C and D (p = 0.223) and between Groups A and B (p = 0.472). Delta RI measurement with DU permitted to predict the renal obstruction with a sensitivity of 93.8%, a specificity of 95.0% and an accuracy of 94.4%. Conclusions: Intrarenal Doppler ultrasonography represents a sensitive and highly specific test that can significantly contribute to the diagnosis of obstruction in patients with acute renal colic. It should be used as the first line imaging method in suspected acute renal colic, as well as for patients with renal insufficiency, pregnant women or for patients with adverse reactions to contrast media.Correspondence to:
Dr. A. Granata
Via F. Paradiso n°78/a
95024 Acireale (CT), Italy
Email: antonio.granata4@tin.it
Original
Contrast-induced acute kidney injury in renal transplant recipients after cardiac catheterization
V. Agrawal, A. Swami, R. Kosuri, M. AlSabbagh, M. Agarwal, D. Samarapungavan, L.L. Rocher and P.A. McCullough
687
44$
Abstract
Renal transplant (RTX) recipients remain at high-risk for acute kidney injury (AKI) despite having improved renal function and quality of life after transplantation. We sought to identify the incidence and risk factors for contrast-induced AKI in RTX recipients after cardiac catheterization at our institute as identified by electronic records. After excluding patients on dialysis at time of procedure due to failed transplant and who did not have post-exposure creatinine values within 3 days, we reviewed 77 procedures on 57 patients. We studied one case per patient (the most recent procedure). Among the 57 patients, 42 were male, 42 were Caucasian and mean age was 58.2 ± 10.1 years. Mean serum creatinine 24 h pre-procedure was 1.7 ± 0.8 mg/dl. Contrast-induced AKI, defined as rise in serum creatinine of 25% or 0.5 mg/dl within 3 days post-catheterization, occurred in 9 procedures (15.8%). One procedure was complicated by AKI requiring dialysis. AKI occurred more frequently with use of low-osmolar contrast (ioxaglate or iohexol) in comparison with iso-osmolar contrast (iodixanol) (9/36 vs. 0/21, p = 0.019). Patients who received prophylactic N-acetylcysteine had lower incidence of AKI than those who did not (4/41 vs. 5/16, p = 0.046). Exact logistic regression analysis revealed odds ratio of developing AKI with use of low-osmolar vs. iso-osmolar contrast to be 7.747 (1.101 – ¥); p = 0.0381). Contrast-induced AKI was common in RTX recipients after cardiac catheterization. Iso-osmolar contrast was associated with a lower risk of contrast-induced AKI in comparison with low-osmolar contrast.Correspondence to:
V. Agrawal, MD
Department of Internal Medicine
William Beaumont Hospital
3601 West 13 Mile Road
Royal Oak, MI 48073, USA
Email: varunagrawal1996@yahoo.com
V. Agrawal1, A. Swami1, R. Kosuri1, M. AlSabbagh1, M. Agarwal1, D. Samarapungavan2, L.L. Rocher2 and P.A. McCullough3
1Department of Medicine, 2Division of Nephrology, and 3Divisions of Cardiology, Nutrition and Preventive Medicine, William Beaumont Hospital, Royal Oak, MI, USA Renal transplant (RTX) recipients remain at high-risk for acute kidney injury (AKI) despite having improved renal function and quality of life after transplantation. We sought to identify the incidence and risk factors for contrast-induced AKI in RTX recipients after cardiac catheterization at our institute as identified by electronic records. After excluding patients on dialysis at time of procedure due to failed transplant and who did not have post-exposure creatinine values within 3 days, we reviewed 77 procedures on 57 patients. We studied one case per patient (the most recent procedure). Among the 57 patients, 42 were male, 42 were Caucasian and mean age was 58.2 ± 10.1 years. Mean serum creatinine 24 h pre-procedure was 1.7 ± 0.8 mg/dl. Contrast-induced AKI, defined as rise in serum creatinine of 25% or 0.5 mg/dl within 3 days post-catheterization, occurred in 9 procedures (15.8%). One procedure was complicated by AKI requiring dialysis. AKI occurred more frequently with use of low-osmolar contrast (ioxaglate or iohexol) in comparison with iso-osmolar contrast (iodixanol) (9/36 vs. 0/21, p = 0.019). Patients who received prophylactic N-acetylcysteine had lower incidence of AKI than those who did not (4/41 vs. 5/16, p = 0.046). Exact logistic regression analysis revealed odds ratio of developing AKI with use of low-osmolar vs. iso-osmolar contrast to be 7.747 (1.101 – ¥); p = 0.0381). Contrast-induced AKI was common in RTX recipients after cardiac catheterization. Iso-osmolar contrast was associated with a lower risk of contrast-induced AKI in comparison with low-osmolar contrast.Correspondence to:
V. Agrawal, MD
Department of Internal Medicine
William Beaumont Hospital
3601 West 13 Mile Road
Royal Oak, MI 48073, USA
Email: varunagrawal1996@yahoo.com
Original
Parameters for successful monthly extended dosing of darbepoetin-alpha in patients undergoing hemodialysis
J. Trachsler, Z. Glück, M. Dickenmann, T. Gauthier, M. Brünisholz, P.-Y. Martin, M. Burnier, C. Wahl and R.P. Wüthrich
697
28$
Abstract
Aim: To document the feasibility and report the results of dosing darbepoetin-alpha at extended intervals up to once monthly (QM) in a large dialysis patient population. Material: 175 adult patients treated, at 23 Swiss hemodialysis centres, with stable doses of any erythropoiesis-stimulating agent who were switched by their physicians to darbepoetin-alpha treatment at prolonged dosing intervals (every 2 weeks [Q2W] or QM). Method: Multicentre, prospective, observational study. Patients’ hemoglobin (Hb) levels and other data were recorded 1 month before conversion (baseline) to an extended darbepoetin-alpha dosing interval, at the time of conversion, and once monthly thereafter up to the evaluation point (maximum of 12 months or until loss to follow-up). Results: Data for 161 evaluable patients from 23 sites were included in the final analysis. At 1 month prior to conversion, 73% of these patients were receiving darbepoetin-alpha weekly (QW) and 27% of the patients biweekly (Q2W). After a mean follow-up of 9.5 months, 34% received a monthly (QM) dosing regimen, 52% of the patients were receiving darbepoetin-alpha Q2W, and 14% QW. The mean (SD) Hb concentration at baseline was 12.3 ± 1.2 g/dl, compared to 11.9 ± 1.2 g/dl at the evaluation point. The corresponding mean weekly darbepoetin-alpha dose was 44.3 ± 33.4 µg at baseline and 37.7 ± 30.8 µg at the evaluation point. Conclusions: Conversion to extended darbepoetin-alpha dosing intervals of up to QM, with maintenance of initial Hb concentrations, was successful for the majority of stable dialysis patients.Correspondence to:
Dr. med. J. Trachsler
Stadtspital Waid, Nephrologie
Tièchestrasse 99
8037 Zürich, Switzerland
Email: johannes.trachsler@waid.zuerich.ch
J. Trachsler1, Z. Glück2, M. Dickenmann3, T. Gauthier4, M. Brünisholz5, P.-Y. Martin6, M. Burnier7, C. Wahl8 and R.P. Wüthrich1
1Universitätsspital Zürich, Nephrologie, Zürich, 2Spitalzentrum Biel, Nephrologie, Biel/Bienne, 3Universitätsspital Basel, Nephrologie, Basel, 4Hôpital Riviera, Samaritain, Service de Néphrologie, Vevey, 5Hôpital du Jura, Site de Porrentruy, Porrentruy, 6Hôpitaux Universitaires de Genève, Service de Néphrologie, Genève, 7CHUV, Service de Néphrologie et Hypertension, Lausanne, and 8Praxis und Dialysestation Dr. C. Wahl und Dr. A. Binkert, Nephrologie, Hochfelden, Switzerland Aim: To document the feasibility and report the results of dosing darbepoetin-alpha at extended intervals up to once monthly (QM) in a large dialysis patient population. Material: 175 adult patients treated, at 23 Swiss hemodialysis centres, with stable doses of any erythropoiesis-stimulating agent who were switched by their physicians to darbepoetin-alpha treatment at prolonged dosing intervals (every 2 weeks [Q2W] or QM). Method: Multicentre, prospective, observational study. Patients’ hemoglobin (Hb) levels and other data were recorded 1 month before conversion (baseline) to an extended darbepoetin-alpha dosing interval, at the time of conversion, and once monthly thereafter up to the evaluation point (maximum of 12 months or until loss to follow-up). Results: Data for 161 evaluable patients from 23 sites were included in the final analysis. At 1 month prior to conversion, 73% of these patients were receiving darbepoetin-alpha weekly (QW) and 27% of the patients biweekly (Q2W). After a mean follow-up of 9.5 months, 34% received a monthly (QM) dosing regimen, 52% of the patients were receiving darbepoetin-alpha Q2W, and 14% QW. The mean (SD) Hb concentration at baseline was 12.3 ± 1.2 g/dl, compared to 11.9 ± 1.2 g/dl at the evaluation point. The corresponding mean weekly darbepoetin-alpha dose was 44.3 ± 33.4 µg at baseline and 37.7 ± 30.8 µg at the evaluation point. Conclusions: Conversion to extended darbepoetin-alpha dosing intervals of up to QM, with maintenance of initial Hb concentrations, was successful for the majority of stable dialysis patients.Correspondence to:
Dr. med. J. Trachsler
Stadtspital Waid, Nephrologie
Tièchestrasse 99
8037 Zürich, Switzerland
Email: johannes.trachsler@waid.zuerich.ch
Case Report
A prolonged course of Group A streptococcus-associated nephritis: a mild case of dense deposit disease (DDD)?
E. Sawanobori, A. Umino, H. Kanai, K. Matsushita, S. Iwasa, H. Kitamura, T. Oda, N. Yoshizawa, K. Sugita and K. Higashida
703
24$
Abstract
We herein report the case of a 12-year-old boy with dense deposit disease (DDD) evoked by streptococcal infection. He had been diagnosed to have asymptomatic hematuria syndrome at the age of 6 during school screening. At 12 years of age, he was found to have macrohematuria and overt proteinuria with hypocomplementemia 2 months after streptococcal pharyngitis. Renal biopsy showed endocapillary proliferative glomerulonephritis with double contours of the glomerular basement membrane. Hypocomplementemia and proteinuria were sustained for over 8 weeks. He was suspected to have dense deposit disease due to intramembranous deposits in the first and the second biopsies. 1 month after treatment with methylprednisolone pulse therapy, proteinuria decreased to a normal level. Microscopic hematuria disappeared 2 years later, but mild hypocomplementemia persisted for more than 7 years. Nephritis-associated plasmin receptor (NAPlr), a nephritic antigen for acute poststreptococcal glomerulonephritis, was found to be positive in the glomeruli for more than 8 weeks. DDD is suggested to be caused by dysgeneration of the alternative pathway due to C3NeF and impaired Factor H activity. A persistent deposition of NAPlr might be one of the factors which lead to complement dysgeneration. A close relationship was suggested to exist between the streptococcal infection and dense deposit disease in this case.Correspondence to:
E. Sawanobori, MD
Department of Pediatrics
Interdisciplinary Graduate School of Medicine and Engineering
University of Yamanashi
Chuo, Yamanashi 409-3898, Japan
Email: sawanobori@kmh.kofu.yamanashi.jp
E. Sawanobori1, A. Umino1, H. Kanai1, K. Matsushita1, S. Iwasa2, H. Kitamura3, T. Oda4, N. Yoshizawa5, K. Sugita1 and K. Higashida1
1Department of Pediatrics, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 2Department of Anatomic Pathology, University of Yamanashi Hospital, Chuo, Yamanashi, 3Division of Immunopathology, Clinical Research Center, Chiba-East National Hospital, Chiba-City, 4Department of Internal Medicine, National Defense Medical College, and 5Department of Medicine, Hirose Hospital, Saitama, Japan We herein report the case of a 12-year-old boy with dense deposit disease (DDD) evoked by streptococcal infection. He had been diagnosed to have asymptomatic hematuria syndrome at the age of 6 during school screening. At 12 years of age, he was found to have macrohematuria and overt proteinuria with hypocomplementemia 2 months after streptococcal pharyngitis. Renal biopsy showed endocapillary proliferative glomerulonephritis with double contours of the glomerular basement membrane. Hypocomplementemia and proteinuria were sustained for over 8 weeks. He was suspected to have dense deposit disease due to intramembranous deposits in the first and the second biopsies. 1 month after treatment with methylprednisolone pulse therapy, proteinuria decreased to a normal level. Microscopic hematuria disappeared 2 years later, but mild hypocomplementemia persisted for more than 7 years. Nephritis-associated plasmin receptor (NAPlr), a nephritic antigen for acute poststreptococcal glomerulonephritis, was found to be positive in the glomeruli for more than 8 weeks. DDD is suggested to be caused by dysgeneration of the alternative pathway due to C3NeF and impaired Factor H activity. A persistent deposition of NAPlr might be one of the factors which lead to complement dysgeneration. A close relationship was suggested to exist between the streptococcal infection and dense deposit disease in this case.Correspondence to:
E. Sawanobori, MD
Department of Pediatrics
Interdisciplinary Graduate School of Medicine and Engineering
University of Yamanashi
Chuo, Yamanashi 409-3898, Japan
Email: sawanobori@kmh.kofu.yamanashi.jp
Case Report
Bilateral renal-cell carcinoma associated with an acquired VHL mutation and long-term trichloroethylene exposure
G.M. Wells, W. Schroth, H. Brauch and E.A. Ross
708
28$
Abstract
Background/aims: The genetic basis for clear-cell renal carcinomas has been established in familial and many sporadic forms. Whether the latter can be induced by environmental carcinogens remains controversial, with concern over solvents such as trichloroethylene (TCE). To study this putative relationship, we analyzed the VHL gene from a patient with long-term TCE exposure. Methods: PCR amplification and sequencing of VHL exons 1 – 3 were performed on peripheral blood and tumor tissue. Results: The tumor alone had a previously undescribed mutation in exon 1 of the VHL gene: deletion of a cytidine residue at position 291 relative to the first ATG start codon of the wild-type sequence. This deletion causes a frameshift and predicts an altered protein sequence from position 98 onwards. Conclusion: The affected amino acids are in the functionally important beta-domain of the VHL protein that is implicated in substrate binding for ubiquitylation, and we hypothesize the mutation lowers that affinity. There is loss of suppressor function when substrates such as hypoxia-inducible factor have impaired degradation: they accumulate and ultimately cause uncontrolled cell turnover. This association of a proposed occupational cause and occurrence of renal-cell carcinoma emphasizes the availability and use of VHL sequencing for both studying the pathophysiology of malignant transformation and potentially playing a clinical role in genetic counseling or risk assessment.Correspondence to:
E.A. Ross, MD
Division of Nephrology, Hypertension and Transplantation
University of Florida
Box 100224
Gainesville, FL 32610-0224, USA
Email: Rossea@medicine.ufl.edu
G.M. Wells1, W. Schroth2, H. Brauch2 and E.A. Ross1
1Division of Nephrology, Hypertension and Transplantation, University of Florida, Gainesville, FL, USA, and 2Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart and University Tübingen, Germany Background/aims: The genetic basis for clear-cell renal carcinomas has been established in familial and many sporadic forms. Whether the latter can be induced by environmental carcinogens remains controversial, with concern over solvents such as trichloroethylene (TCE). To study this putative relationship, we analyzed the VHL gene from a patient with long-term TCE exposure. Methods: PCR amplification and sequencing of VHL exons 1 – 3 were performed on peripheral blood and tumor tissue. Results: The tumor alone had a previously undescribed mutation in exon 1 of the VHL gene: deletion of a cytidine residue at position 291 relative to the first ATG start codon of the wild-type sequence. This deletion causes a frameshift and predicts an altered protein sequence from position 98 onwards. Conclusion: The affected amino acids are in the functionally important beta-domain of the VHL protein that is implicated in substrate binding for ubiquitylation, and we hypothesize the mutation lowers that affinity. There is loss of suppressor function when substrates such as hypoxia-inducible factor have impaired degradation: they accumulate and ultimately cause uncontrolled cell turnover. This association of a proposed occupational cause and occurrence of renal-cell carcinoma emphasizes the availability and use of VHL sequencing for both studying the pathophysiology of malignant transformation and potentially playing a clinical role in genetic counseling or risk assessment.Correspondence to:
E.A. Ross, MD
Division of Nephrology, Hypertension and Transplantation
University of Florida
Box 100224
Gainesville, FL 32610-0224, USA
Email: Rossea@medicine.ufl.edu
Case Report
A tumor-like manifestation of extrapulmonary tuberculosis in a hemodialysis patient
P. Kriki, E. Thodis, S. Deftereos, S. Panagoutsos, M. Theodoridis, K. Kantartzi, E. Mourvati, P. Prassopoulos, P. Passadakis and V. Vargemezis
714
24$
Abstract
Though pulmonary tuberculosis (TBC) remains the commonest clinical presentation, extrapulmonary TBC is an increasingly important clinical problem. Among the extrapulmonary sites, primary liver tuberculosis seems to be an extremely rare location. Fewer than 100 cases of TBC hepatic abscesses have been reported whereas most of them have been originated from other sites, usually the lung and the gastrointestinal track. Therefore, in the absence of any particular symptom this infrequent location may lead to a delayed or missing diagnosis. The present study reports the difficulties in early diagnosis of an extrapulmonary TBC case, as it happened to a 53-year-old man with diabetic nephropathy who started on regular hemodialysis for 5 months. In such “atypical presentations” the clinicians should bear in their mind the possibility of the TBC occurrence, which usually responds well to the conventional antituberculous therapy.Correspondence to:
Dr. P. Passadakis
Department of Nephrology
Medical School
University Hospital of Alexandroupolis
Democritus University of Thrace Dragana
26 Vizvizi street
68100 Alexandroupolis, Greece
Email: ploumis@med.duth.gr
P. Kriki1, E. Thodis1, S. Deftereos2, S. Panagoutsos1, M. Theodoridis1, K. Kantartzi1, E. Mourvati1, P. Prassopoulos2, P. Passadakis1 and V. Vargemezis1
1Department of Nephrology, and 2Department of Radiology, Medical School, University Hospital of Alexandroupolis, Democritus University of Thrace, Dragana, Alexandroupolis, Greece Though pulmonary tuberculosis (TBC) remains the commonest clinical presentation, extrapulmonary TBC is an increasingly important clinical problem. Among the extrapulmonary sites, primary liver tuberculosis seems to be an extremely rare location. Fewer than 100 cases of TBC hepatic abscesses have been reported whereas most of them have been originated from other sites, usually the lung and the gastrointestinal track. Therefore, in the absence of any particular symptom this infrequent location may lead to a delayed or missing diagnosis. The present study reports the difficulties in early diagnosis of an extrapulmonary TBC case, as it happened to a 53-year-old man with diabetic nephropathy who started on regular hemodialysis for 5 months. In such “atypical presentations” the clinicians should bear in their mind the possibility of the TBC occurrence, which usually responds well to the conventional antituberculous therapy.Correspondence to:
Dr. P. Passadakis
Department of Nephrology
Medical School
University Hospital of Alexandroupolis
Democritus University of Thrace Dragana
26 Vizvizi street
68100 Alexandroupolis, Greece
Email: ploumis@med.duth.gr
Case Report
Rapid onset of diabetic nephropathy in three renal allografts despite normoglycemia
D. Wojciechowski, M.L. Onozato and J. Gonin
719
28$
Abstract
Diabetes mellitus is the leading cause of end-stage renal disease in the United States. Renal transplantation is currently the treatment of choice for diabetic patients on renal replacement therapy. Current immunosuppression includes medications that are diabetogenic and place nondiabetic transplant recipients at risk for developing post-transplant diabetes mellitus and subsequent de novo diabetic nephropathy in the allograft. Here we present three patients who underwent a deceased donor renal transplant and developed posttransplant diabetes mellitus. In all three patients despite excellent glycemic control (HbA1c <= 7%) and average tacrolimus trough levels less than 10 ng/ml, clinical and histologic de novo diabetic nephropathy developed within 2 years of the diagnosis of posttransplant diabetes mellitus. This is in contrast to other reported data in which the average time to onset of de novo diabetic nephropathy was approximately 10 years. Additionally, in other case series the average HbA1c was 8.4% in patients who developed diabetic nephropathy. It is possible that the metabolic milieu of transplant recipients warrants tighter glycemic control. The allograft is also susceptible to hyperfiltration injury which may accelerate the diabetic lesions even at normal glucose levels. Further studies are warranted to determine the optimum glycemic control in posttransplant diabetes mellitus.Correspondence to:
D. Wojciechowski, DO
Georgetown University Hospital
3800 Reservoir Rd. NW, 6-PHC
Washington, DC 20007, USA
Email: davidwojciechowski@yahoo.com
D. Wojciechowski, M.L. Onozato and J. Gonin
Georgetown University Hospital, Department of Internal Medicine, Division of Nephrology and Hypertension, Washington, DC, USA Diabetes mellitus is the leading cause of end-stage renal disease in the United States. Renal transplantation is currently the treatment of choice for diabetic patients on renal replacement therapy. Current immunosuppression includes medications that are diabetogenic and place nondiabetic transplant recipients at risk for developing post-transplant diabetes mellitus and subsequent de novo diabetic nephropathy in the allograft. Here we present three patients who underwent a deceased donor renal transplant and developed posttransplant diabetes mellitus. In all three patients despite excellent glycemic control (HbA1c <= 7%) and average tacrolimus trough levels less than 10 ng/ml, clinical and histologic de novo diabetic nephropathy developed within 2 years of the diagnosis of posttransplant diabetes mellitus. This is in contrast to other reported data in which the average time to onset of de novo diabetic nephropathy was approximately 10 years. Additionally, in other case series the average HbA1c was 8.4% in patients who developed diabetic nephropathy. It is possible that the metabolic milieu of transplant recipients warrants tighter glycemic control. The allograft is also susceptible to hyperfiltration injury which may accelerate the diabetic lesions even at normal glucose levels. Further studies are warranted to determine the optimum glycemic control in posttransplant diabetes mellitus.Correspondence to:
D. Wojciechowski, DO
Georgetown University Hospital
3800 Reservoir Rd. NW, 6-PHC
Washington, DC 20007, USA
Email: davidwojciechowski@yahoo.com
Letter to the Editor
A pediatric case of severe proteinuric purpura nephritis with predominantly subepithelial IgA deposits
K. Tsuruga, I. Hanada, E. Oki, K. Suzuki, E. Ito, T. Echizenya and H. Tanaka
725
12$
Abstract
K. Tsuruga, I. Hanada, E. Oki, K. Suzuki, E. Ito, T. Echizenya and H. Tanaka
Erratum
727
8$
Abstract
Obituary
William B. Schwartz
D. Weiner, MD, MS
728
8$
Abstract
D. Weiner, MD, MS
