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Dustri-Verlag
Volume 63, No. 2/2005(February)
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Originals
Association of C-509T and T869C polymorphisms of transforming growth factor-b1 gene with susceptibility to and progression of IgA nephropathy
61
32$
Abstract
Aims: Transforming growth factor (TGF)-b1 is a cytokine with both beneficial anti-inflammatory effects and detrimental profibrotic activity in the pathophysiology and progression of glomerulonephritides. The transcriptional activity of the gene for TGF-b1 and the plasma levels of TGF-b1 protein are associated with C-509T polymorphism at the promoter region, and with T869C (Leu10Pro) polymorphism at codon 10, of the TGF-b1 gene. Methods: Using PCR-RFLP and the amplification refractory mutation system PCR, we investigated the C-509T and T869C polymorphisms, respectively, to elucidate whether allele frequency differences exist between IgA nephropathy (IgAN) patients who were followed up for at least 3 years (n = 108) and a normal population (n = 55). We also determined the correlations between the TGF-b1 polymorphisms and the progression of IgAN. Results: In C-509T polymorphism, there were significant differences in genotype frequency between IgAN patients and normal controls (CC : CT : TT, 20 : 29 : 33 vs. 11 : 31 : 13, c2 = 6.299, p = 0.043). In Kaplan-Meier survival analysis, the patients with TT genotype showed a poorer renal survival than those with CC + CT genotypes (p = 0.042). In T869C polymorphism, there were also significant differences in genotype frequency between IgAN patients and normal controls (TT : TC : CC, 4 : 79 : 25 vs. 0 : 52 : 2, c2 = 12.552, p = 0.002). The initial serum creatinine (Scr) level was higher in the patients with CC genotype than in those with TT + TC genotypes. In Kaplan-Meier survival analysis, the patients with CC genotype showed a poorer renal survival than those with TT + TC genotypes, but not to a statistically significant extent (p = 0.076). In the combined survival analyses, the high TGF-b1 producer group showed a poor renal survival rate (p = 0.014). Conclusion: Compared to normal population, the frequencies of genotypes producing high TGF-b1 protein were higher in IgAN patients. Moreover, patients with genotypes producing high TGF-b1 plasma levels showed a poor renal survival rate.
Correspondence to:
S. Kim, MD Department of Internal Medicine Seoul National University College of Medicine 28 Yongon-dong, Jongno-gu Seoul 110-744, Korea
Email: cslimjy@snu.ac.kr
C.S. Lim, Y.S. Kim, D.W. Chae, C. Ahn, J.S. Han, S. Kim, J.S. Lee and I.S. Kim
1Department of Internal Medicine, Seoul National University Boramae Hospital, 2Department of Internal Medicine, and 3Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Korea Aims: Transforming growth factor (TGF)-b1 is a cytokine with both beneficial anti-inflammatory effects and detrimental profibrotic activity in the pathophysiology and progression of glomerulonephritides. The transcriptional activity of the gene for TGF-b1 and the plasma levels of TGF-b1 protein are associated with C-509T polymorphism at the promoter region, and with T869C (Leu10Pro) polymorphism at codon 10, of the TGF-b1 gene. Methods: Using PCR-RFLP and the amplification refractory mutation system PCR, we investigated the C-509T and T869C polymorphisms, respectively, to elucidate whether allele frequency differences exist between IgA nephropathy (IgAN) patients who were followed up for at least 3 years (n = 108) and a normal population (n = 55). We also determined the correlations between the TGF-b1 polymorphisms and the progression of IgAN. Results: In C-509T polymorphism, there were significant differences in genotype frequency between IgAN patients and normal controls (CC : CT : TT, 20 : 29 : 33 vs. 11 : 31 : 13, c2 = 6.299, p = 0.043). In Kaplan-Meier survival analysis, the patients with TT genotype showed a poorer renal survival than those with CC + CT genotypes (p = 0.042). In T869C polymorphism, there were also significant differences in genotype frequency between IgAN patients and normal controls (TT : TC : CC, 4 : 79 : 25 vs. 0 : 52 : 2, c2 = 12.552, p = 0.002). The initial serum creatinine (Scr) level was higher in the patients with CC genotype than in those with TT + TC genotypes. In Kaplan-Meier survival analysis, the patients with CC genotype showed a poorer renal survival than those with TT + TC genotypes, but not to a statistically significant extent (p = 0.076). In the combined survival analyses, the high TGF-b1 producer group showed a poor renal survival rate (p = 0.014). Conclusion: Compared to normal population, the frequencies of genotypes producing high TGF-b1 protein were higher in IgAN patients. Moreover, patients with genotypes producing high TGF-b1 plasma levels showed a poor renal survival rate.
Correspondence to:
S. Kim, MD Department of Internal Medicine Seoul National University College of Medicine 28 Yongon-dong, Jongno-gu Seoul 110-744, Korea
Email: cslimjy@snu.ac.kr
Originals
Initial functional status predicts infections during steroid therapy for renal diseases
68
28$
Abstract
Background and aim: Corticosteroid therapy is an effective way of treatment for many renal diseases, however, it is sometimes associated with infections. Our aim is to identify useful predictive markers of infection during steroid therapy. Methods: We examined 121 patients (M/F = 71/50, mean age 43.8, range 15 – 82 years) who were treated with corticosteroids (IgA nephropathy in 51, minimal-change disease in 17, membranous nephropathy in 16 rapidly progressive glomerulonephritis (RPGN) in 13, lupus nephritis in 12 and other disorders in 12). Karnofsky’s performance score (KPS) was employed to assess the physical functional status at the time of diagnosis. Infections were defined as conditions that required more than 1-week care, and those that caused the patient’s death. Results: Nineteen patients (15.7%) had infections during treatment. A logistic multivariate analysis showed significant correlations between infection and the use of immunosuppressive agents (relative risk RR = 7.7, p = 0.0265), ages of 52.9 years or more (RR = 13.5, p = 0.0026), initial number of lymphocytes (Lym) less than 1.250/ml (RR = 14.2, p = 0.0011), and KPS less than 77.4 (RR = 12.1, p = 0.0020). All correlations with infection were independent of all the other variables listed above. Conclusion: KPS, along with age, Lym and the use of immunosuppressive agents, are useful for the prediction of infectious complications during steroid therapy.
Correspondence to:
T. Katoh, MD
Department of Internal Medicine III
Fukushima Medical University School of Medicine
1 Hikarigaoka
Fukushima, 960-1295 Japan
Email: t-katoh@fmu.ac.jp
Y. Sakuma, T. Katoh, K. Owada, H. Suzuki, K. Sakurai, M. Eiro, K. Asahi and T. Watanabe
Department of Internal Medicine III, Fukushima Medical University School of Medicine, Fukushima, Japan Background and aim: Corticosteroid therapy is an effective way of treatment for many renal diseases, however, it is sometimes associated with infections. Our aim is to identify useful predictive markers of infection during steroid therapy. Methods: We examined 121 patients (M/F = 71/50, mean age 43.8, range 15 – 82 years) who were treated with corticosteroids (IgA nephropathy in 51, minimal-change disease in 17, membranous nephropathy in 16 rapidly progressive glomerulonephritis (RPGN) in 13, lupus nephritis in 12 and other disorders in 12). Karnofsky’s performance score (KPS) was employed to assess the physical functional status at the time of diagnosis. Infections were defined as conditions that required more than 1-week care, and those that caused the patient’s death. Results: Nineteen patients (15.7%) had infections during treatment. A logistic multivariate analysis showed significant correlations between infection and the use of immunosuppressive agents (relative risk RR = 7.7, p = 0.0265), ages of 52.9 years or more (RR = 13.5, p = 0.0026), initial number of lymphocytes (Lym) less than 1.250/ml (RR = 14.2, p = 0.0011), and KPS less than 77.4 (RR = 12.1, p = 0.0020). All correlations with infection were independent of all the other variables listed above. Conclusion: KPS, along with age, Lym and the use of immunosuppressive agents, are useful for the prediction of infectious complications during steroid therapy.
Correspondence to:
T. Katoh, MD
Department of Internal Medicine III
Fukushima Medical University School of Medicine
1 Hikarigaoka
Fukushima, 960-1295 Japan
Email: t-katoh@fmu.ac.jp
Originals
No effect of fluvastatin on the bone mineral density of children with minimal change glomerulonephritis and some focal mesangial cell proliferation, other than an ameliorating effect on their proteinuria
74
28$
Abstract
Aim: There are conflicting data regarding the clinical benefit of the effect of HMG-CoA reductase inhibitors (statins) in osteoporosis. We have reported that fluvastatin (a statin) is effective in improving proteinuria and renal function in childhood IgA nephropathy with mild histological findings and moderate proteinuria. The aim of the present study was to clarify the effect of fluvastatin on the bone mineral density, bone metabolic markers, proteinuria, and renal function of children with minimal change glomerulonephritis with some focal mesangial cell proliferation whose glomeruli did not stain positive for IgA and on moderate proteinuria. Patients and methods: We conducted a prospective controlled study of 36 children who had recently been diagnosed with normocholesterolemic minimal change glomerulonephritis with some focal mesangial cell proliferation and moderate proteinuria, and in whom strenuous exercise was restricted. The 36 patients were randomly assigned to receive 20 mg of fluvastatin (group 1) or 5 mg/kg of dipyridamole (group 2) for two years. Results: By the end of the trial, there was no difference in BMD between the groups, and there were no changes in the four bone metabolic parameters. However, the urinary protein, hematuria and BUN levels had significantly decreased in group 1 compared to baseline, and the serum total protein and albumin levels and creatinine clearance had significantly increased in group 1 compared to baseline and group 2. Conclusions: The results of this study suggest that fluvastatin therapy has an antiproteinuric effect and improves renal function in moderately proteinuric patients with mild histological glomerulonephritis, but does not increase BMD.
Correspondence to:
K. Kano, MD Department of Pediatrics Dokkyo University School of Medicine 880 Kitakobayashi Mibu Shimotsuga-gun, Tochigi 321-0293, Japan
Email: k-kano@dokkyomed.ac.jp
K. Kano, K. Nishikura, Y. Yamada and O. Arisaka
Department of Pediatrics, Dokkyo University School of Medicine, Tochigi, Japan Aim: There are conflicting data regarding the clinical benefit of the effect of HMG-CoA reductase inhibitors (statins) in osteoporosis. We have reported that fluvastatin (a statin) is effective in improving proteinuria and renal function in childhood IgA nephropathy with mild histological findings and moderate proteinuria. The aim of the present study was to clarify the effect of fluvastatin on the bone mineral density, bone metabolic markers, proteinuria, and renal function of children with minimal change glomerulonephritis with some focal mesangial cell proliferation whose glomeruli did not stain positive for IgA and on moderate proteinuria. Patients and methods: We conducted a prospective controlled study of 36 children who had recently been diagnosed with normocholesterolemic minimal change glomerulonephritis with some focal mesangial cell proliferation and moderate proteinuria, and in whom strenuous exercise was restricted. The 36 patients were randomly assigned to receive 20 mg of fluvastatin (group 1) or 5 mg/kg of dipyridamole (group 2) for two years. Results: By the end of the trial, there was no difference in BMD between the groups, and there were no changes in the four bone metabolic parameters. However, the urinary protein, hematuria and BUN levels had significantly decreased in group 1 compared to baseline, and the serum total protein and albumin levels and creatinine clearance had significantly increased in group 1 compared to baseline and group 2. Conclusions: The results of this study suggest that fluvastatin therapy has an antiproteinuric effect and improves renal function in moderately proteinuric patients with mild histological glomerulonephritis, but does not increase BMD.
Correspondence to:
K. Kano, MD Department of Pediatrics Dokkyo University School of Medicine 880 Kitakobayashi Mibu Shimotsuga-gun, Tochigi 321-0293, Japan
Email: k-kano@dokkyomed.ac.jp
Originals
Assessment of glomerular and tubular functions in renal transplant patients receiving cyclosporine A in combination with either sirolimus or everolimus
80
32$
Abstract
2Service d’Explorations Fonctionnelles Physiologiques, CHU Rangueil,
Toulouse Cedex, France
Aims: The aim of this study was to examine the glomerular filtration rate (GFR) and tubular function at three months after renal transplantation in two groups of patients receiving cyclosporine A associated with either sirolimus (SRL) (n = 18) or everolimus (RAD) (n = 12), two structurally similar immunosuppressant drugs. Results: Donors’ and recipients’ characteristics and mean cyclosporine A trough levels were similar in the two groups. The mean sirolimus trough level was 12.01 ± 1.6 ng/ml whereas the mean everolimus trough level was 4.23 ± 0.36 ng/ml. GFR, equated by the clearance of inulin, was higher in RAD patients (64 ± 4 ml. min–1.1.73 m–2) than in SRL patients (49 ± 4 ml.min–1.1.73 m–2) (p < 0.05). The significant difference in GFR between the groups was not affected by differences in mean arterial blood pressures, or by differences in daily prednisone dosages, cyclosporine trough levels, or SRL and RAD trough levels. Phosphatemia, renal phosphate threshold (TmPO4/ GFR ratio) and uric acid clearance were significantly lower in the SRL than in the RAD group, despite similar levels of parathyroid hormone. Finally, urinary acid excretion was significantly lower in the RAD group. Conclusion: In conclusion, regarding nephrotoxicity, our preliminary data suggest that it seems to be preferable to combine cyclosporine with RAD rather than with sirolimus in renal transplant patients. However, long-term renal effects of this combination are still to be determined in a larger cohort.Correspondence to:
Dr. N. Kamar
Department of Nephrology, Dialysis and Transplantation
CHU Rangueil
1 avenue Jean Poulhès, TSA 50032
31059 Toulouse, Cedex 9, France
Email: kamar.n@chu-toulouse.fr
N. Kamar, J. Allard, D. Ribes, D. Durand, J.L. Ader and L. Rostaing
1Department of Nephrology, Dialysis and Transplantation, and2Service d’Explorations Fonctionnelles Physiologiques, CHU Rangueil,
Toulouse Cedex, France
Aims: The aim of this study was to examine the glomerular filtration rate (GFR) and tubular function at three months after renal transplantation in two groups of patients receiving cyclosporine A associated with either sirolimus (SRL) (n = 18) or everolimus (RAD) (n = 12), two structurally similar immunosuppressant drugs. Results: Donors’ and recipients’ characteristics and mean cyclosporine A trough levels were similar in the two groups. The mean sirolimus trough level was 12.01 ± 1.6 ng/ml whereas the mean everolimus trough level was 4.23 ± 0.36 ng/ml. GFR, equated by the clearance of inulin, was higher in RAD patients (64 ± 4 ml. min–1.1.73 m–2) than in SRL patients (49 ± 4 ml.min–1.1.73 m–2) (p < 0.05). The significant difference in GFR between the groups was not affected by differences in mean arterial blood pressures, or by differences in daily prednisone dosages, cyclosporine trough levels, or SRL and RAD trough levels. Phosphatemia, renal phosphate threshold (TmPO4/ GFR ratio) and uric acid clearance were significantly lower in the SRL than in the RAD group, despite similar levels of parathyroid hormone. Finally, urinary acid excretion was significantly lower in the RAD group. Conclusion: In conclusion, regarding nephrotoxicity, our preliminary data suggest that it seems to be preferable to combine cyclosporine with RAD rather than with sirolimus in renal transplant patients. However, long-term renal effects of this combination are still to be determined in a larger cohort.Correspondence to:
Dr. N. Kamar
Department of Nephrology, Dialysis and Transplantation
CHU Rangueil
1 avenue Jean Poulhès, TSA 50032
31059 Toulouse, Cedex 9, France
Email: kamar.n@chu-toulouse.fr
Originals
Dipyridamole for renal phosphate leak in successfully renal transplanted hypophosphatemic patients
87
24$
Abstract
Cukurova University, Adana, Turkey
Aim and background: Hyphosphatemia can be seen in renal transplant recipients. Hyperparathyroidism, glucocorticoid treatment, renal denervation and impairment of renal tubular phosphate reabsorption are the most common causes of hyphosphatemia in these patients. It is well-known that dipyridamole enhances renal tubular phosphate reabsorption in some clinical conditions. We did not find any information about the effect of dipyridamole in renal transplant recipients (RTRs) with hypophosphatemia. For this reason, we decided to give dipyridamole 11 RTRs with hypophosphatemia. Patients and methods: Eleven RTRs whose serum phosphate and creatinine levels were below 2.5 mg/dl and 2 mg/dl, respectively, were included in this study. None of the patients received drugs altering phosphate metabolism and they did not change their routine diets. Urinary phosphate excretion and tubular phosphate reabsorption (TPR) were calculated before and 3 weeks after dipyridamole treatment. Results: The mean levels of serum-urine (daily) phosphate and TPR before dipyridamole treatment were 1.94 ± 0.46 mg/dl, 7,187.5 ± 1,833.49 mg/day and –2.78 ± 0.62, respectively. After treatment, the mean levels of serum-urine phosphate and TPR were 2.73 ± 0.46 mg/dl, 4,845.27 ± 1,138.99 mg/day and –1.48 ± 0.80, respectively. Serum and urine phosphate levels and TPR were found to be significantly different before and after dipyridamole therapy (p < 0.05). Conclusion: Short-term dipyridamole therapy increased TPR and serum phosphate levels and decreased urinary phosphate excretion. We did not observe negative effect on renal functions in these cases. Although the number of the cases included in this study is small, dipyridamole is an effective choice in management of hypophosphatemic RTRs.Correspondence to:
Prof. Dr. S. Paydas
Cukurova University
Faculty of Medicine
Department of Nephrology
01330 Adana, Turkey
M. Balal, S. Paydas, N. Seyrek, Y. Sertdemir and I. Karayaylali
Departments of 1Nephrology and 2Biostatistics, Faculty of Medicine,Cukurova University, Adana, Turkey
Aim and background: Hyphosphatemia can be seen in renal transplant recipients. Hyperparathyroidism, glucocorticoid treatment, renal denervation and impairment of renal tubular phosphate reabsorption are the most common causes of hyphosphatemia in these patients. It is well-known that dipyridamole enhances renal tubular phosphate reabsorption in some clinical conditions. We did not find any information about the effect of dipyridamole in renal transplant recipients (RTRs) with hypophosphatemia. For this reason, we decided to give dipyridamole 11 RTRs with hypophosphatemia. Patients and methods: Eleven RTRs whose serum phosphate and creatinine levels were below 2.5 mg/dl and 2 mg/dl, respectively, were included in this study. None of the patients received drugs altering phosphate metabolism and they did not change their routine diets. Urinary phosphate excretion and tubular phosphate reabsorption (TPR) were calculated before and 3 weeks after dipyridamole treatment. Results: The mean levels of serum-urine (daily) phosphate and TPR before dipyridamole treatment were 1.94 ± 0.46 mg/dl, 7,187.5 ± 1,833.49 mg/day and –2.78 ± 0.62, respectively. After treatment, the mean levels of serum-urine phosphate and TPR were 2.73 ± 0.46 mg/dl, 4,845.27 ± 1,138.99 mg/day and –1.48 ± 0.80, respectively. Serum and urine phosphate levels and TPR were found to be significantly different before and after dipyridamole therapy (p < 0.05). Conclusion: Short-term dipyridamole therapy increased TPR and serum phosphate levels and decreased urinary phosphate excretion. We did not observe negative effect on renal functions in these cases. Although the number of the cases included in this study is small, dipyridamole is an effective choice in management of hypophosphatemic RTRs.Correspondence to:
Prof. Dr. S. Paydas
Cukurova University
Faculty of Medicine
Department of Nephrology
01330 Adana, Turkey
Originals
Recombinant human erythropoietin independence in chronic hemodialysis patients: clinical features, iron homeostasis and erythropoiesis
92
28$
Abstract
Aims: Recombinant human erythropoietin (r-HuEPO) is widely used to correct renal anemia in uremic patients. Interestingly, some chronic hemodialysis (HD) patients can maintain high hemoglobin level without the need of r-HuEPO. The aim of this study is to investigate clinical features, iron metabolism and erythropoiesis of these r-HuEPO-independent HD patients. Methods: r-HuEPO independence was defined in dialysis patients as hemoglobin greater than 12 g/dl and no use of r-HuEPO for at least 6 months. An age- and sex-matched group was selected for comparison. Their underlying diseases, duration of hemodialysis therapy, efficacy of dialysis (Kt/V), normalized protein catabolic rate (nPCR) and body mass index (BMI) were recorded. Laboratory data including: hemoglobin, albumin, high sensitivity C-reactive protein, serum iron, total iron binding capacity, transferrin saturation, ferritin, intact parathyroid hormone, soluble transferrin receptor (sTfR), serum EPO, cortisol, testosterone, aluminum and leptin levels were measured. Renal sonography was also performed in each patient to evaluate renal cyst formation. Results: About 2.3% of all HD patients (21/888; M : F = 18 : 3) were r-HuEPO-independent. These patients had significantly longer HD duration and higher serum EPO and sTfR levels, and lower transferrin saturation rate than dependent groups. Correlation analysis revealed that hemoglobin level strongly correlated with HD duration, serum sTfR and EPO levels. Levels of sTfR were positively related with serum EPO levels and BMI. Multivariate regression analysis showed that level of sTfR was the only independent factor related to r-HuEPO independence. Conclusion: R-HuEPO independence is rare among chronic hemodialysis patients. Factors contributing to this dependence are complex and multiple. Level of serum sTfR parallels erythropoiesis and is the most significant factor associated with r-HuEPO independence in chronic HD patients.
Correspondence to:
Dr. C.-T. Lee Division of Nephrology Department of Internal Medicine 123, Ta-Pei Road Niao-Sung Shang, Kaohsiung Hsien 833, Taiwan
Email: ctlee33@adm.cgmh.org.tw
C.-C. Kuo, C.-T. Lee, C.-H. Chuang, Y. Su and J.-B. Chen
1Division of Nephrology, Department of Internal Medicine, Chang-Gung Memorial Hospital, and 2Department of International Trade, Cheng Shiu Institute of Technology, Kaohsiung, Taiwan Aims: Recombinant human erythropoietin (r-HuEPO) is widely used to correct renal anemia in uremic patients. Interestingly, some chronic hemodialysis (HD) patients can maintain high hemoglobin level without the need of r-HuEPO. The aim of this study is to investigate clinical features, iron metabolism and erythropoiesis of these r-HuEPO-independent HD patients. Methods: r-HuEPO independence was defined in dialysis patients as hemoglobin greater than 12 g/dl and no use of r-HuEPO for at least 6 months. An age- and sex-matched group was selected for comparison. Their underlying diseases, duration of hemodialysis therapy, efficacy of dialysis (Kt/V), normalized protein catabolic rate (nPCR) and body mass index (BMI) were recorded. Laboratory data including: hemoglobin, albumin, high sensitivity C-reactive protein, serum iron, total iron binding capacity, transferrin saturation, ferritin, intact parathyroid hormone, soluble transferrin receptor (sTfR), serum EPO, cortisol, testosterone, aluminum and leptin levels were measured. Renal sonography was also performed in each patient to evaluate renal cyst formation. Results: About 2.3% of all HD patients (21/888; M : F = 18 : 3) were r-HuEPO-independent. These patients had significantly longer HD duration and higher serum EPO and sTfR levels, and lower transferrin saturation rate than dependent groups. Correlation analysis revealed that hemoglobin level strongly correlated with HD duration, serum sTfR and EPO levels. Levels of sTfR were positively related with serum EPO levels and BMI. Multivariate regression analysis showed that level of sTfR was the only independent factor related to r-HuEPO independence. Conclusion: R-HuEPO independence is rare among chronic hemodialysis patients. Factors contributing to this dependence are complex and multiple. Level of serum sTfR parallels erythropoiesis and is the most significant factor associated with r-HuEPO independence in chronic HD patients.
Correspondence to:
Dr. C.-T. Lee Division of Nephrology Department of Internal Medicine 123, Ta-Pei Road Niao-Sung Shang, Kaohsiung Hsien 833, Taiwan
Email: ctlee33@adm.cgmh.org.tw
Originals
Peripheral vascular disease and serum phosphorus in hemodialysis: a nested case-control study
98
36$
Abstract
4Biochemistry Laboratory, 6Instititute of Nephrology, E. Wolfson Medical Center, Holon, 2Department of Epidemiology and Preventive Medicine, 3Department of Nephrology, Rabin Medical Center, Go
Background: Serum phosphorus (P) and the product of serum calcium × serum P (Ca × P), are frequently elevated in end-stage renal disease patients on maintenance hemodialysis (HD). Elevated P and Ca × P have been associated with vascular calcification in dialysis patients. Objective: To examine the role of P and Ca × P as risk factors for incident peripheral vascular disease (PVD) in HD patients with pre-existing CVD. Methods: This nested case-control study is drawn from the 11 incident PVD events reported in the cohort of the Secondary prevention with antioxidants of cardiovascular disease in end-stage renal disease (SPACE): a randomized placebo-controlled trial. PVD was defined clinically and confirmed ultrasonographically. Each individual with a PVD event was matched for SPACE treatment group (vitamin E or placebo), age (in 4-year categories) and gender with two individuals who had no CVD end point during the follow-up period. Results: Serum P and Ca × P levels were significantly higher in PVD patients than in controls. In univariate logistic regression analysis, only serum P predicted PVD in this population (OR 2.02, 95% CI 1.07 – 3.81, p = 0.03). In multivariate analysis, adjustment was made for variables dissimilar by PVD status including underlying renal disease, diabetes, smoking, history of angina pectoris, prescription for vitamin D3, erythropoietin, calcium channel blockers and aspirin. In this model, serum P remained the only significant predictor of incident PVD (OR 2.4, 95% CI 1.01 – 5.74, p = 0.04). Conclusions: Findings of the present study are consistent with a role for serum P and Ca × P in the pathogenesis of PVD in HD patients.Correspondence to:
Dr. M. Boaz
Epidemiology Unit,
E. Wolfson Medical Center
Holon 58100, Israel
Email: mboaz8@yahoo.com
M. Boaz, T. Weinstein, Z. Matas, M.S. Green and S. Smetana
1Epidemiology Unit and Brunner Institute of Medical Research,4Biochemistry Laboratory, 6Instititute of Nephrology, E. Wolfson Medical Center, Holon, 2Department of Epidemiology and Preventive Medicine, 3Department of Nephrology, Rabin Medical Center, Go
Background: Serum phosphorus (P) and the product of serum calcium × serum P (Ca × P), are frequently elevated in end-stage renal disease patients on maintenance hemodialysis (HD). Elevated P and Ca × P have been associated with vascular calcification in dialysis patients. Objective: To examine the role of P and Ca × P as risk factors for incident peripheral vascular disease (PVD) in HD patients with pre-existing CVD. Methods: This nested case-control study is drawn from the 11 incident PVD events reported in the cohort of the Secondary prevention with antioxidants of cardiovascular disease in end-stage renal disease (SPACE): a randomized placebo-controlled trial. PVD was defined clinically and confirmed ultrasonographically. Each individual with a PVD event was matched for SPACE treatment group (vitamin E or placebo), age (in 4-year categories) and gender with two individuals who had no CVD end point during the follow-up period. Results: Serum P and Ca × P levels were significantly higher in PVD patients than in controls. In univariate logistic regression analysis, only serum P predicted PVD in this population (OR 2.02, 95% CI 1.07 – 3.81, p = 0.03). In multivariate analysis, adjustment was made for variables dissimilar by PVD status including underlying renal disease, diabetes, smoking, history of angina pectoris, prescription for vitamin D3, erythropoietin, calcium channel blockers and aspirin. In this model, serum P remained the only significant predictor of incident PVD (OR 2.4, 95% CI 1.01 – 5.74, p = 0.04). Conclusions: Findings of the present study are consistent with a role for serum P and Ca × P in the pathogenesis of PVD in HD patients.Correspondence to:
Dr. M. Boaz
Epidemiology Unit,
E. Wolfson Medical Center
Holon 58100, Israel
Email: mboaz8@yahoo.com
Originals
Hemodiafiltration with post-dilution reinfusion of the regenerated ultrafiltrate: a new on-line technique
106
32$
Abstract
Aims: All convective hemodiafiltration techniques require a replacement fluid, which must have an adequate electrolytic composition and must be sterile and pyrogen-free. Using an integrated adsorption cartridge, the ultrafiltrate can be “regenerated” and used as a replacement fluid (hemo-filtrate reinfusion; HFR). The aim of this study was to evaluate whether the HFR technique as suggested in its original configuration could be improved by inverting the purification sequence (post-dilution HFR; PDHFR) in order to increase the purification efficiency of the whole system. Methods: We performed standard HFR in 6 uremic patients during 6 months and, subsequently, during further 6 months, PDHFR. The dialytic efficacy of the two techniques and the filter blood loss were evaluated. Moreover, we studied how both techniques affected cytokine levels. Results: We observed a significant increase of urea extraction and of Kt/V values in PDHFR. An equally significant improvement was observed in regard to the extraction of b2-m and the blood loss. Furthermore, IL6 and TNFa decreased significantly after PDHFR treatment. Conclusions: HFR has proven to be an easy-to-perform hemodiafiltration technique, capable of resolving the typical problem of the other hemodiafiltration technique, the availability and production of a sterile and ultrapure reinfusion solution. The inversion of its configuration has allowed us to improve three aspects that have characterized, in our experience, the treatments performed in the original geometry: the removal of both urea and b2-m, and the filter. Finally, it’s notable that the decrease in cytokines levels achieved with PDHFR might attenuate the uremic micro-inflammatory state.Correspondence to:
Dr. S. Cipriani
c/o Clinica Chirurgica
Ospedale S. Eugenio
Piazzale dell’Umanesimo, 10
00144 Rome, Italy
Email: silvia.cipriani@tiscali.it
C. Meloni, P.M. Ghezzi, S. Cipriani, S. Petroni, C. Tozzo, P. Tatangelo, B. Rossini, V. Rossi, A. Cecilia and C.U. Casciani
1Nephrology and Dialysis Unit, St. Eugenio Hospital, Rome, 2Nephrology and Dialysis Unit, S. Croce Hospital, Cuneo, and 3Department of Surgical Clinic, Tor Vergata University, Rome, Italy Aims: All convective hemodiafiltration techniques require a replacement fluid, which must have an adequate electrolytic composition and must be sterile and pyrogen-free. Using an integrated adsorption cartridge, the ultrafiltrate can be “regenerated” and used as a replacement fluid (hemo-filtrate reinfusion; HFR). The aim of this study was to evaluate whether the HFR technique as suggested in its original configuration could be improved by inverting the purification sequence (post-dilution HFR; PDHFR) in order to increase the purification efficiency of the whole system. Methods: We performed standard HFR in 6 uremic patients during 6 months and, subsequently, during further 6 months, PDHFR. The dialytic efficacy of the two techniques and the filter blood loss were evaluated. Moreover, we studied how both techniques affected cytokine levels. Results: We observed a significant increase of urea extraction and of Kt/V values in PDHFR. An equally significant improvement was observed in regard to the extraction of b2-m and the blood loss. Furthermore, IL6 and TNFa decreased significantly after PDHFR treatment. Conclusions: HFR has proven to be an easy-to-perform hemodiafiltration technique, capable of resolving the typical problem of the other hemodiafiltration technique, the availability and production of a sterile and ultrapure reinfusion solution. The inversion of its configuration has allowed us to improve three aspects that have characterized, in our experience, the treatments performed in the original geometry: the removal of both urea and b2-m, and the filter. Finally, it’s notable that the decrease in cytokines levels achieved with PDHFR might attenuate the uremic micro-inflammatory state.Correspondence to:
Dr. S. Cipriani
c/o Clinica Chirurgica
Ospedale S. Eugenio
Piazzale dell’Umanesimo, 10
00144 Rome, Italy
Email: silvia.cipriani@tiscali.it
Originals
Anxiety and depression in chronic hemodialysis: some somatopsychic determinants
113
28$
Abstract
Aims: Depression and anxiety are so common in hemodialysis (HD) patients that we found it useful to study the respective contributions of the subjective somatic sensations and of the objective medical comorbidity to psychological distress. We also hypothesized that denial has a protective effect against anxiety and depression, and that alexithymia is, on the contrary, a risk factor. Material and methods: In a cross-sectional design, we investigated relationships between psychological distress and somatic complaints, Charlson comorbidity index, denial and alexithymia, in a group of 54 patients on incenter HD. They filled psychometric self-rated questionnaires in (State Anxiety Inventory, Hospital Anxiety and Depression Scale, 13-item Short Beck Depression Inventory, Kidney Disease Quality of Life Short Form, 20-item Toronto Alexithymia Scale). A principal component analysis allowed us to focus on HADS-total score, which was confirmed to be representative of anxio-depression. Then, correlational analyses and a stepwise regression analysis were performed. Results: HADS-total score is inversely associated with the use of denial as a psychological defence mechanism (p < 0.001), and positively correlated with difficulties in identifying emotions (p < 0.001), with difficulties in expressing feelings (p < 0.05), and with the intensity of subjective somatic complaints (p < 0.001). On the contrary, it is not related to the somatic comorbidity. In the stepwise regression, the somatic complaints, the denial and the difficulties in recognizing emotions emerge as the three main variables related to the HADS-total score (p < 0.001). Conclusions: Subjective physical complaints are here associated with psychological distress in chronic HD patients, while objective organic comorbidity does not seem to influence their mood and anxiety status. Denial is an efficient coping style against negative emotions, but it can diminish compliance. So, the subjective perception of the disease seems to have an important impact on the anxiety and mood levels, which can also be influenced by the emotional regulation abilities.
Correspondence to:
Dr. V. Jadoulle
Rue du Bassinia 19
1348 Louvaine-la-Neuve, Belgium
Email: Vincent.Jadoulle@psp.ucl.ac.be
V. Jadoulle, P. Hoyois and M. Jadoul
1Department of Psychopathology, 2Epidemiology Unit, and 3Department of Nephrology, Cliniques universitaires Saint Luc and Université Catholique de Louvain, Brussels, Belgium Aims: Depression and anxiety are so common in hemodialysis (HD) patients that we found it useful to study the respective contributions of the subjective somatic sensations and of the objective medical comorbidity to psychological distress. We also hypothesized that denial has a protective effect against anxiety and depression, and that alexithymia is, on the contrary, a risk factor. Material and methods: In a cross-sectional design, we investigated relationships between psychological distress and somatic complaints, Charlson comorbidity index, denial and alexithymia, in a group of 54 patients on incenter HD. They filled psychometric self-rated questionnaires in (State Anxiety Inventory, Hospital Anxiety and Depression Scale, 13-item Short Beck Depression Inventory, Kidney Disease Quality of Life Short Form, 20-item Toronto Alexithymia Scale). A principal component analysis allowed us to focus on HADS-total score, which was confirmed to be representative of anxio-depression. Then, correlational analyses and a stepwise regression analysis were performed. Results: HADS-total score is inversely associated with the use of denial as a psychological defence mechanism (p < 0.001), and positively correlated with difficulties in identifying emotions (p < 0.001), with difficulties in expressing feelings (p < 0.05), and with the intensity of subjective somatic complaints (p < 0.001). On the contrary, it is not related to the somatic comorbidity. In the stepwise regression, the somatic complaints, the denial and the difficulties in recognizing emotions emerge as the three main variables related to the HADS-total score (p < 0.001). Conclusions: Subjective physical complaints are here associated with psychological distress in chronic HD patients, while objective organic comorbidity does not seem to influence their mood and anxiety status. Denial is an efficient coping style against negative emotions, but it can diminish compliance. So, the subjective perception of the disease seems to have an important impact on the anxiety and mood levels, which can also be influenced by the emotional regulation abilities.
Correspondence to:
Dr. V. Jadoulle
Rue du Bassinia 19
1348 Louvaine-la-Neuve, Belgium
Email: Vincent.Jadoulle@psp.ucl.ac.be
Highlights of the Bamberg Bone Symposium
Cellular and molecular mechanisms of secondary hyperparathyroidism
119
52$
Abstract
The objective of this review is to share important basic research insights into the mechanisms of secondary hyperparathyroidism. An understanding of these mechanisms is essential to more effectively treating the disease. Central underlying abnormalities are increased parathyroid hormone (PTH) gene expression and secretion, and parathyroid cell proliferation. Significant progress has been made in understanding these abnormalities at the cellular and molecular level, particularly their regulation. Studies point to a prominent role of calcium, phosphate and vitamin D as regulators of PTH and parathyroid cell proliferation. 1,25[OH]2 vitamin D3 decreases PTH synthesis and secretion. Small decreases in serum calcium and prolonged increases in serum phosphate as may occur in patients with chronic failure, increase PTH secretion, PTH gene expression, and parathyroid cell proliferation. Regulation at the level of PTH gene expression is particularly significant given the limited amount of preformed mature PTH. It is now known that calcium and phosphate regulate PTH gene expression through changes in protective parathyroid cytosolic proteins that bind to an instability element in the PTH mRNA 3’-untranslated region and influence transcript stability. These findings may help guide the development of novel therapies for secondary hyperparathyroidism.Correspondence to:
Prof. J. Silver
Nephrology and Hypertension Services
Hadassah University Hospital
Jerusalem 91120, Israel
Email: silver@cc.huji.ac.il
J. Silver and R. Levi
Department of Nephrology and Hypertension Services, Hadassah University Hospital, Jerusalem, Israel The objective of this review is to share important basic research insights into the mechanisms of secondary hyperparathyroidism. An understanding of these mechanisms is essential to more effectively treating the disease. Central underlying abnormalities are increased parathyroid hormone (PTH) gene expression and secretion, and parathyroid cell proliferation. Significant progress has been made in understanding these abnormalities at the cellular and molecular level, particularly their regulation. Studies point to a prominent role of calcium, phosphate and vitamin D as regulators of PTH and parathyroid cell proliferation. 1,25[OH]2 vitamin D3 decreases PTH synthesis and secretion. Small decreases in serum calcium and prolonged increases in serum phosphate as may occur in patients with chronic failure, increase PTH secretion, PTH gene expression, and parathyroid cell proliferation. Regulation at the level of PTH gene expression is particularly significant given the limited amount of preformed mature PTH. It is now known that calcium and phosphate regulate PTH gene expression through changes in protective parathyroid cytosolic proteins that bind to an instability element in the PTH mRNA 3’-untranslated region and influence transcript stability. These findings may help guide the development of novel therapies for secondary hyperparathyroidism.Correspondence to:
Prof. J. Silver
Nephrology and Hypertension Services
Hadassah University Hospital
Jerusalem 91120, Israel
Email: silver@cc.huji.ac.il
Highlights of the Bamberg Bone Symposium
Assessment of effects of lanthanum carbonate with and without phosphate supplementation on bone mineralization in uremic rats
127
48$
Abstract
Aims: Previous studies have indicated that impaired bone mineralization in 5/6th nephrectomized rats given high doses of lanthanum carbonate is due to phosphorus depletion caused by excessive binding to, and reduced absorption of, dietary phosphate. This study aimed to test this hypothesis by: 1) directly comparing the effects of a supratherapeutic dose of lanthanum carbonate or dietary phosphorus restriction on bone mineralization in a rodent model of chronic renal failure (CRF); and 2) investigating whether phosphorus supplementation would prevent the bone mineralization defect associated with lanthanum carbonate treatment. Methods and materials: Male Sprague-Dawley rats were subjected to sham surgery or a two-step 5/6th nephrectomy to induce CRF and randomized across five treatment groups: sham, CRF, CRF + dietary phosphorus deficiency, CRF + lanthanum carbonate (1000 mg/kg/ day), and CRF + lanthanum carbonate + parenteral phosphorus repletion. Results: Rats with 5/6th nephrectomy had elevated serum creatinine, blood urea concentration, and urine volume and protein, consistent with impaired renal function, and increased urinary phosphorus and serum parathyroid hormone, consistent with hyperparathyroidism. Lanthanum carbonate and dietary phosphate insufficiency induced parallel changes in serum and urine markers of phosphate homeostasis and increased osteoid formation. These changes induced by lanthanum carbonate were normalized by systemic phosphate supplementation. Conclusions: These findings provide further support for the concept that supratherapeutic doses of lanthanum carbonate induce effects on bone mineralization in uremic rats via an indirect pharmacological mechanism (phosphate depletion) and not via direct bone toxicity.Correspondence to:
Dr. S. Damment
Shire Pharmaceutical Development Ltd.
Hampshire International Business Park
Chineham, Basingstoke, Hampshire, RG24 8EP, UK
S.J.P. Damment1 and V. Shen2
1Department of Biosciences, Shire Pharmaceutical Development Ltd., Basingstoke, UK, and 2SkeleTech Inc., Seattle, WA, USA Aims: Previous studies have indicated that impaired bone mineralization in 5/6th nephrectomized rats given high doses of lanthanum carbonate is due to phosphorus depletion caused by excessive binding to, and reduced absorption of, dietary phosphate. This study aimed to test this hypothesis by: 1) directly comparing the effects of a supratherapeutic dose of lanthanum carbonate or dietary phosphorus restriction on bone mineralization in a rodent model of chronic renal failure (CRF); and 2) investigating whether phosphorus supplementation would prevent the bone mineralization defect associated with lanthanum carbonate treatment. Methods and materials: Male Sprague-Dawley rats were subjected to sham surgery or a two-step 5/6th nephrectomy to induce CRF and randomized across five treatment groups: sham, CRF, CRF + dietary phosphorus deficiency, CRF + lanthanum carbonate (1000 mg/kg/ day), and CRF + lanthanum carbonate + parenteral phosphorus repletion. Results: Rats with 5/6th nephrectomy had elevated serum creatinine, blood urea concentration, and urine volume and protein, consistent with impaired renal function, and increased urinary phosphorus and serum parathyroid hormone, consistent with hyperparathyroidism. Lanthanum carbonate and dietary phosphate insufficiency induced parallel changes in serum and urine markers of phosphate homeostasis and increased osteoid formation. These changes induced by lanthanum carbonate were normalized by systemic phosphate supplementation. Conclusions: These findings provide further support for the concept that supratherapeutic doses of lanthanum carbonate induce effects on bone mineralization in uremic rats via an indirect pharmacological mechanism (phosphate depletion) and not via direct bone toxicity.Correspondence to:
Dr. S. Damment
Shire Pharmaceutical Development Ltd.
Hampshire International Business Park
Chineham, Basingstoke, Hampshire, RG24 8EP, UK
Highlights of the Bamberg Bone Symposium
Utilization of bone histomorphometry in renal osteodystrophy: demonstration of a new approach using data from a prospective study of lanthanum carbonate
138
36$
Abstract
Aim: The aim of this study was to develop a novel approach to the analysis of bone histomorphometric data and outcomes presentation that would simplify the characterization of renal osteodystrophy and facilitate clinical decision-making. Methods and materials: Data were derived from a randomized trial of dialysis patients treated for one year with a dose of lanthanum carbonate or calcium carbonate (up to 3750 mg/day and 9000 mg/day, respectively). Histomorphometric analyses of baseline and end-of-study bicortical transiliac bone biopsies were performed. Activation frequency, bone formation rate/bone surface, osteoclast surface/ bone surface, osteoblast surface/bone surface, mineralization lag time, and osteoid thickness were determined to provide a measure of overall bone cell activity (bone formation, bone resorption, bone turnover) and risk of developing osteopenia (bone balance). A novel approach of qualitatively grouping these numerical data as “improved”, “unchanged”, or “worsened” based on deviation from normal was used to facilitate interpretation of clinical relevance. Results: Using our method, lanthanum carbonate was shown to improve histomorphometric parameters measured. These improvements were superior to those produced by calcium carbonate. These data add valuable clinical relevance to the previously published qualitative data from the same cohort [D’Haese et al. 2003]. Lanthanum carbonate moderated extreme forms of renal osteodystrophy, whereas calcium carbonate treatment increased the incidence of adynamic and predominant hyperparathyroid bone disease. Conclusions: This study provides an approach to the prospective evaluation of bone disease progression with therapy, and its application supports the safety and greater efficacy of one-year lanthanum carbonate versus calcium carbonate therapy as a means to normalize bone turnover in dialysis patients.Correspondence to:
Dr. H.H. Malluche, MD, FACP
Robert G. “Robin” Luke Chair in Nephrology
Division of Nephrology
Bone and Mineral Metabolism
Department of Medicine
University of Kentucky Chandler Medical Center
800 Rose Street, Room 564
Lexington, KY 40536-0298, USA
Email: hhmall@uky.edu
T. Freemont and H.H. Malluche
1Division of Laboratory and Regenerative Medicine, University of Manchester, England, and 2Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, Lexington, KY, USA Aim: The aim of this study was to develop a novel approach to the analysis of bone histomorphometric data and outcomes presentation that would simplify the characterization of renal osteodystrophy and facilitate clinical decision-making. Methods and materials: Data were derived from a randomized trial of dialysis patients treated for one year with a dose of lanthanum carbonate or calcium carbonate (up to 3750 mg/day and 9000 mg/day, respectively). Histomorphometric analyses of baseline and end-of-study bicortical transiliac bone biopsies were performed. Activation frequency, bone formation rate/bone surface, osteoclast surface/ bone surface, osteoblast surface/bone surface, mineralization lag time, and osteoid thickness were determined to provide a measure of overall bone cell activity (bone formation, bone resorption, bone turnover) and risk of developing osteopenia (bone balance). A novel approach of qualitatively grouping these numerical data as “improved”, “unchanged”, or “worsened” based on deviation from normal was used to facilitate interpretation of clinical relevance. Results: Using our method, lanthanum carbonate was shown to improve histomorphometric parameters measured. These improvements were superior to those produced by calcium carbonate. These data add valuable clinical relevance to the previously published qualitative data from the same cohort [D’Haese et al. 2003]. Lanthanum carbonate moderated extreme forms of renal osteodystrophy, whereas calcium carbonate treatment increased the incidence of adynamic and predominant hyperparathyroid bone disease. Conclusions: This study provides an approach to the prospective evaluation of bone disease progression with therapy, and its application supports the safety and greater efficacy of one-year lanthanum carbonate versus calcium carbonate therapy as a means to normalize bone turnover in dialysis patients.Correspondence to:
Dr. H.H. Malluche, MD, FACP
Robert G. “Robin” Luke Chair in Nephrology
Division of Nephrology
Bone and Mineral Metabolism
Department of Medicine
University of Kentucky Chandler Medical Center
800 Rose Street, Room 564
Lexington, KY 40536-0298, USA
Email: hhmall@uky.edu
Highlights of the Bamberg Bone Symposium
Mechanisms of vascular calcification in renal disease
146
52$
Abstract
Vascular calcification is commonplace in patients with end-stage renal disease where it develops rapidly and predicts a variety of adverse outcomes. The processes responsible for vascular calcification have been the focus of much research, aided in recent decades by molecular genetic techniques and in vitro models. Converging evidence now suggests that vascular calcification is an active, regulated process, with abundant similarities to the process of skeletal mineralization. Using an in vitro model of calcifying vascular smooth muscle cells (VSMCs), we have shown that a mineral imbalance induces VSMC apoptosis, and that VSMC apoptotic bodies and vesicles can nucleate basic calcium phosphate in the form of hydroxyapatite, the same mineral found in bone. Gene expression studies suggest that the normal vessel wall expresses proteins such as matrix Gla protein that inhibit calcification. In addition, circulating proteins such as fetuin-A are produced at remote sites and act to inhibit soft tissue calcification systemically. However, down-regulation or perturbation of these proteins may lead to a phenotypic transformation of VSMCs to osteo/chondrocytic-like cells while the calcified environment may stimulate macrophages to adopt osteoclastic properties. Both clinical and basic research findings indicate an inverse relationship between bone mineralization and vascular calcification. The mechanisms linking these two processes are a topic for further investigation, with current theories proposing a role for lipids, common regulatory molecules, and calcium and bone turnover. We have synthesized these findings into a theoretical model offering a putative pathway for the development of severe vascular calcification in end-stage renal disease.Correspondence to:
Dr. C.M. Shanahan
Department of Medicine
Box 110, Addenbrooke’s Hospital, Hills Road
Cambridge CB2 2QQ, U.K.
Email: cs131@mole.bio.cam.ac.uk
C.M. Shanahan
Department of Medicine, University of Cambridge, Cambridge, UK Vascular calcification is commonplace in patients with end-stage renal disease where it develops rapidly and predicts a variety of adverse outcomes. The processes responsible for vascular calcification have been the focus of much research, aided in recent decades by molecular genetic techniques and in vitro models. Converging evidence now suggests that vascular calcification is an active, regulated process, with abundant similarities to the process of skeletal mineralization. Using an in vitro model of calcifying vascular smooth muscle cells (VSMCs), we have shown that a mineral imbalance induces VSMC apoptosis, and that VSMC apoptotic bodies and vesicles can nucleate basic calcium phosphate in the form of hydroxyapatite, the same mineral found in bone. Gene expression studies suggest that the normal vessel wall expresses proteins such as matrix Gla protein that inhibit calcification. In addition, circulating proteins such as fetuin-A are produced at remote sites and act to inhibit soft tissue calcification systemically. However, down-regulation or perturbation of these proteins may lead to a phenotypic transformation of VSMCs to osteo/chondrocytic-like cells while the calcified environment may stimulate macrophages to adopt osteoclastic properties. Both clinical and basic research findings indicate an inverse relationship between bone mineralization and vascular calcification. The mechanisms linking these two processes are a topic for further investigation, with current theories proposing a role for lipids, common regulatory molecules, and calcium and bone turnover. We have synthesized these findings into a theoretical model offering a putative pathway for the development of severe vascular calcification in end-stage renal disease.Correspondence to:
Dr. C.M. Shanahan
Department of Medicine
Box 110, Addenbrooke’s Hospital, Hills Road
Cambridge CB2 2QQ, U.K.
Email: cs131@mole.bio.cam.ac.uk
Highlights of the Bamberg Bone Symposium
Contrasting mammalian PTH promoters: identification of transcription factors controlling PTH gene expression
158
24$
Abstract
Parathyroid hormone (PTH) is a key component in the maintenance of calcium and phosphate homeostasis. The steady-state expression of the PTH gene can be modeled as a balance between transcriptional activators and repressors. During renal failure, the gradual loss of kidney function is often accompanied by increased circulating concentrations of PTH and decreased synthesis of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). The latter finding results in impaired calcium absorption and the removal of a known repressor of PTH gene transcription. Current regimens for treating secondary hyperparathyroidism associated with renal insufficiency are focused on boosting activities that repress PTH gene transcription or secretion of the hormone, and involve the use of vitamin D and its analogues or calcimimetic agents. However, in recent years, concerns have arisen over the use of the steroid hormone and alternative treatments are being sought. Here, we present new information regarding transcription factors controlling PTH gene expression, which include the specificity proteins (Sp) and the nuclear factor Y (NF-Y) complex. A highly conserved DNA response element for the Sp proteins has been identified in mammalian promoters, while an NF-Y binding site is uniquely positioned in the human promoter. Both of these factors are expressed in the parathyroid gland and their DNA elements appear to be functioning as activators of PTH gene expression. Further elucidation of such pathways may offer novel approaches for treating hyperparathyroidism associated with renal failure via suppression of transcriptional activators. That work is currently in progress.Correspondence to:
Dr. N.J. Koszewski Department of Internal Medicine Division of Nephrology, Bone & Mineral Metabolism University of Kentucky Medical Center 800 Rose Street, Room MN562 Lexington, KY 40536-0298, USA
Email: njhosz0@uky.edu
N.J. Koszewski, A.P. Alimov, M.C. Langub, O.-K. Park-Sarge and H.H. Malluche
1Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky Medical Center, Lexington, KY, 2National Institute of Health for Scientific Reviews, Bethesda, MD and 3Department of Physiology, University of Kentucky Medical Center, Lexington, Parathyroid hormone (PTH) is a key component in the maintenance of calcium and phosphate homeostasis. The steady-state expression of the PTH gene can be modeled as a balance between transcriptional activators and repressors. During renal failure, the gradual loss of kidney function is often accompanied by increased circulating concentrations of PTH and decreased synthesis of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). The latter finding results in impaired calcium absorption and the removal of a known repressor of PTH gene transcription. Current regimens for treating secondary hyperparathyroidism associated with renal insufficiency are focused on boosting activities that repress PTH gene transcription or secretion of the hormone, and involve the use of vitamin D and its analogues or calcimimetic agents. However, in recent years, concerns have arisen over the use of the steroid hormone and alternative treatments are being sought. Here, we present new information regarding transcription factors controlling PTH gene expression, which include the specificity proteins (Sp) and the nuclear factor Y (NF-Y) complex. A highly conserved DNA response element for the Sp proteins has been identified in mammalian promoters, while an NF-Y binding site is uniquely positioned in the human promoter. Both of these factors are expressed in the parathyroid gland and their DNA elements appear to be functioning as activators of PTH gene expression. Further elucidation of such pathways may offer novel approaches for treating hyperparathyroidism associated with renal failure via suppression of transcriptional activators. That work is currently in progress.Correspondence to:
Dr. N.J. Koszewski Department of Internal Medicine Division of Nephrology, Bone & Mineral Metabolism University of Kentucky Medical Center 800 Rose Street, Room MN562 Lexington, KY 40536-0298, USA
Email: njhosz0@uky.edu
Case reports
Spontaneous rupture of a left gastroepiploic artery aneurysm in a patient with autosomal-dominant polycystic kidney disease
163
20$
Abstract
Autosomal-dominant polycystic kidney disease (ADPKD) has been known to be associated with a variety of vascular diseases. We present a hemodialysis patient with ADPKD who died of a massive intraperitoneal hemorrhage caused by the spontaneous rupture of a left gastroepiploic artery aneurysm. A 64-year-old male was admitted to our hospital with acute upper abdominal pain and hemorrhagic shock. An abdominal angiography showed three aneurysms and the source of hemorrhage was assumed to be the left gastroepiploic artery aneurysm. The patient died of severe metabolic acidosis and disseminated intravascular coagulation (DIC) on the second hospital day. At autopsy, there was massive bleeding into the abdominal cavity, and pathological examination of the left gastroepiploic artery aneurysm revealed a dissecting aneurysm. This is the first case describing a rupture of a gastroepiploic aneurysm in a patient with ADPKD.
Correspondence to:
Y. Nagaba, MD Department of Internal Medicine Kitasato University, School of Medicine 1-15-1 Kitasato Sagamihara city, Kanagawa 228-8555, Japan
Email: yanagaba@med.kitasato-u.ac.jp
Y. Nagaba, H. Nishimaki, M. Ichinoe, Y. Okuwaki, M. Hamura, T. Makino, T. Sano, M. Higashihara, K. Kamata and K. Soma
1Department of Internal Medicine, 2Departments of Emergency and Critical Care Medicine, and 3Department of Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan Autosomal-dominant polycystic kidney disease (ADPKD) has been known to be associated with a variety of vascular diseases. We present a hemodialysis patient with ADPKD who died of a massive intraperitoneal hemorrhage caused by the spontaneous rupture of a left gastroepiploic artery aneurysm. A 64-year-old male was admitted to our hospital with acute upper abdominal pain and hemorrhagic shock. An abdominal angiography showed three aneurysms and the source of hemorrhage was assumed to be the left gastroepiploic artery aneurysm. The patient died of severe metabolic acidosis and disseminated intravascular coagulation (DIC) on the second hospital day. At autopsy, there was massive bleeding into the abdominal cavity, and pathological examination of the left gastroepiploic artery aneurysm revealed a dissecting aneurysm. This is the first case describing a rupture of a gastroepiploic aneurysm in a patient with ADPKD.
Correspondence to:
Y. Nagaba, MD Department of Internal Medicine Kitasato University, School of Medicine 1-15-1 Kitasato Sagamihara city, Kanagawa 228-8555, Japan
Email: yanagaba@med.kitasato-u.ac.jp
Case reports
Hypercreatininemia and hyperglycemia: diabetic nephropathy or “inverted peritoneal auto-dialysis”?
167
16$
Abstract
3Department of Surgery, Catholic University, Rome, Italy
We describe a case of 51-year-old male with fever, abdominal pain and inguino-scrotal hernia. Laboratory examination revealed hypercreatininemia and hyperglycemia, firstly interpreted as diabetic nephropathy. US and CT scan showed a hernia of the bladder into the scrotum. Surgery revealed multiple bladder perforations with peritoneal diffusion of urine. So, hypercreatininemia was caused by peritoneal reabsorption of urea and creatinine, a condition that may be described as “inverted peritoneal auto-dialysis”. Surgical reposition and repairment of the bladder led to rapid normalization of serum urea and creatinine. Discharged diagnosis was intraperitoneal rupture of inguino-scrotal hernia of the bladder in patient with recent onset of diabetes mellitus.Correspondence to:
Dr. R. Manna
Istituto di Medicina Interna
Università Cattolica del Sacro Cuore
Largo A. Gemelli, 8
00168 Rome, Italy
Email: rmanna@rm.unicatt.it
R. Manna, P. Mirk, G. Sallustio, G. Brisinda, D. Izzi, M. La Regina, G. Nucera, G. Maria, M. Montalto and G. Ghirlanda
1Department of Internal Medicine, 2Department of Radiology, and3Department of Surgery, Catholic University, Rome, Italy
We describe a case of 51-year-old male with fever, abdominal pain and inguino-scrotal hernia. Laboratory examination revealed hypercreatininemia and hyperglycemia, firstly interpreted as diabetic nephropathy. US and CT scan showed a hernia of the bladder into the scrotum. Surgery revealed multiple bladder perforations with peritoneal diffusion of urine. So, hypercreatininemia was caused by peritoneal reabsorption of urea and creatinine, a condition that may be described as “inverted peritoneal auto-dialysis”. Surgical reposition and repairment of the bladder led to rapid normalization of serum urea and creatinine. Discharged diagnosis was intraperitoneal rupture of inguino-scrotal hernia of the bladder in patient with recent onset of diabetes mellitus.Correspondence to:
Dr. R. Manna
Istituto di Medicina Interna
Università Cattolica del Sacro Cuore
Largo A. Gemelli, 8
00168 Rome, Italy
Email: rmanna@rm.unicatt.it
Letter to the Editor
Spontaneous remission in frequently relapsing minimal-change disease
170
8$
Abstract
I.S. Meisels
Letter to the Editor
Nephrotic syndrome associated with hidradenitis suppurativa
171
12$
Abstract
Y. Caliskan, H. Yazici, M. Kucuk, S. Alisir, I. Kilicaslan and T. Ecder
