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Papers by hendrik koller

Apoptosis of human polymorphonuclear neutrophils accelerated by dialysis membranes via the activa... more Apoptosis of human polymorphonuclear neutrophils accelerated by dialysis membranes via the activation of the complement system

Acta Medica Austriaca, 2001

Nephrology Dialysis Transplantation, 2004

Background. Haemodialysis (HD) with bioincompatible cellulosic membranes like Cuprophan (CU) is c... more Background. Haemodialysis (HD) with bioincompatible cellulosic membranes like Cuprophan (CU) is considered to influence negatively the clinical outcome of acute and chronic renal failure. In this effect, apart from the disturbance of phagocytosis or oxygen species production by leukocytes, increased apoptosis also has been implicated recently. The objective of this study was to study the effect of HD membranes on apoptosis induction in polymorphonuclear neutrophils (PMN). Methods. PMN from healthy donors and uraemic patients were isolated and apoptosis was induced by co-incubation with CU, Hemophan or polyamide hollow fibres in the presence of serum from healthy or uraemic humans. Apoptosis was quantified by flow cytometry using Annexin V-FITC and propidium iodide staining and was confirmed by the detection of DNA fragmentation on gel electrophoresis. The deposition of immunoglobulins (Ig) and complement factors on hollow fibres was detected by direct immunofluorescence. Results. Heat inactivation or the depletion of complement components or Ig significantly reduced apoptosis, indicating its dependence on classical complement activation. The detection of IgG on hollow CU fibres and the restored acceleration of apoptosis by the appropriate replenishment of Ig-deficient sera additionally confirmed these findings. Inhibition experiments revealed that caspases were necessary mainly, but not exclusively, for apoptosis to occur after complement activation. Uraemia led to increased PMN apoptosis in the presence of bioincompatible, but not biocompatible, membranes. Conclusions. Our results suggest that the acceleration of PMN apoptosis in the presence of CU is mediated via an antibody-dependent activation of the classical complement pathway mobilizing both caspase-dependent and -independent pathways.

Lupus, 2005

Sir — the first report in 1983 by Hughes, the antiphospholipid antibody syndrome (APS) is a well ... more Sir — the first report in 1983 by Hughes, the antiphospholipid antibody syndrome (APS) is a well known cause of arterial and venous thrombosis. In the last three years, several case reports of APS and thrombosis affecting the arterial vessels including the coronary and renal arteries have been published. While there is some consensus of the treatment of venous thrombotic complications, management of arterial thrombosis is unclear and possible strategies include oral anticoagulants, thrombolysis or percutaneous transluminal angioplasty (PTA) with or without stenting. To date, successful PTA with stenting has been mainly reported for coronary revascularization but rarely for renal artery stenosis. – 4 We report a case of a 63-year old male with a history of systemic lupus erythematosus (SLE) and secondary APS who was diagnosed with bilateral renal artery stenosis (RAS) and successfully treated with bilateral PTA and stent implantation. A 63-year old male with a history of SLE, APS and previously well controlled arterial hypertension presented with accelerating hypertension and worsening renal function. He was a former smoker with normal glycemic status and mild hypercholesterolemia. Since 1976, the patient had suffered from multiple episodes of venous thrombosis affecting the pulmonary, saphenous and cranial sinus venous system. He was subsequently diagnosed with SLE and secondary APS by the presence of IgG anticardiolipin antibodies and had been prescribed warfarin for 19 years. Other significant medical history included primary hypothyroidism after radioiodine (I) therapy for diffuse toxic goitre and mild renal insufficiency since 1995. During the outpatient clinic visit the patient reported uncontrolled blood pressure on several home blood pressure recordings. On examination, the patient was hypertensive with 160/95 mmHg. An ACE-Inhibitor (ACE-I) was added to the previous anti-hypertensive regimen, and laboratory tests after one week showed significant loss of renal function with a creatinine of 1.9 mg/dL and a creatinine clearance of 52 mL/min (compared to one week previously: 1.2 mg/dL and 75 mL/min). Additional laboratory analysis revealed no change of ANA titers or complement levels, and the urine sediment was normal with mild proteinuria of 246 mg/ day. Exacerbation of SLE with renal involvement was thought to be unlikely, and CT angiography was performed, which revealed a 10 6 mm ostial thrombus of the left renal artery occluding 70% of the lumen (Figure 1) and an almost complete obliteration of the right renal artery near the ostium. Renal ultrasound and Doppler studies were performed showing asymmetrical seized kidneys (left: 9.7 cm, right: 11.2 cm) and resistance index (RI) of 0.55 on both sides. PTA and stenting was performed on two separate sessions under distal protection and warfarin was increased to a target INR of 3.0–4.0. One and a half years after the procedure the patient is normotensive on his previous blood pressure medications and has recovered renal function with a creatinine of 1.39 mg/dL. To date, follow up Doppler studies have shown no evidence of restenosis indicating patent vessels. Loss of renal function after the administration of ACE-I is a hallmark of bilateral renal artery stenosis or unilateral stenosis in a single kidney and is potentially reversible if recognized early. In our patient, absence of evidence of lupus activity, the history of secondary APS and the recent administration of ACE-I prompted a search for this potentially treatable cause of renal dysfunction. In fact, renal artery stenosis (RAS) and APS might be more common than previously thought: Hughes reported a significantly higher prevalence (26%) of RAS in patients with APL who had difficult to control hypertension compared to otherwise young healthy hypertensive patients. The precise nature of our patients stenosis remains obscure but is likely to be atherosclerotic: CT angiography showed typical features of atherosclerotic lesions, and risk factors for atherosclerosis in our patient included former nicotine abuse, age, male gender, family history of coronary artery disease, hypercholesterolemia, former use of steroids and hypertension; nontraditional risk factors included possible atherogenic properties mediated by anticardiolipin antibodies through cross reaction with oxidized low density lipoprotein (ox-LDL) and enhanced ox-LDL uptake into monocytes/macrophages and by endothelial cell proliferation. – 9 Correspondence: Dr Hendrik Koller, Klinische Abteilung für Nephrologie, Universitätsklinik für Innere Medizin, Anichstr. 35, A 6020 Innsbruck, Austria. E-mail: hendrikkoller@yahoo.com Received 16 September 2004; accepted 21 March 2005 Lupus (2005) 14, 566–568

International Journal of Cardiology, 2006

Angina pectoris a common encountered complaint in internal medicine, and the work up includes a r... more Angina pectoris a common encountered complaint in internal medicine, and the work up includes a routine battery of tests to identify treatable causes and to exclude myocardial damage. However, rare reversible causes of angina exist which might remain undetected if additional, non-traditional tests are not applied properly. We recently encountered a patient whose unusual cause of angina could be detected and reversed by a simple blood gas analysis.

Clinical Nephrology, 2004

Parathyroidhormone (PTH) measurement is important in the evaluation of bone disease in patients w... more Parathyroidhormone (PTH) measurement is important in the evaluation of bone disease in patients with chronic renal failure. Large carboxyl-terminal PTH fragments (C-PTH) cross-react with second-generation PTH assays, lead to an overestimation of biologically active PTH, and are evaluated by a combination of second- and third-generation PTH assays. The aim of our study was to examine whether the use of 4 different PTH assays of putatively same specificity leads to comparable results detecting C-PTH fragments. In 70 chronic dialysis patients, total PTH and PTH(1-84) were measured in parallel by 4 novel PTH assays (Nichols Advantage Intact PTH and Bio-Intact PTH Chemiluminescence Assay, Nichols Institute Diagnostics, USA, DUO Total and CAP PTH IRMA, Scantibodies Laboratory, USA). The C-PTH concentration was quantitated by subtracting PTH(1-84) from total PTH. Consecutively, the PTH(1-84)/C-PTH ratio was calculated. Nichols Intact PTH and DUO Total PTH assays were highly correlated (r = 0.985), as well as Nichols Bio-Intact and DUO CAP assays (r = 0.984). However, total PTH values measured by the Nichols assay were 30% higher (median (range): 185 (9.9 - 2,332) versus 130 (2.3 - 1,271.1) pg/ml, p < 0.01). PTH(1-84) values, measured by the Nichols Bio-Intact PTH assay were 8% higher compared to the Scantibodies CAP assay (median (range): 79.6 (7.5 - 1,060.9) versus 73.7 (4.4 - 918.9) pg/ml, p = NS). Thirty-six patients had a ratio < 1 measured by the Nichols assays, whereas only 8 patients showed the same ratio when measured by the Scantibodies assays. In 28 patients (40%), contradictory PTH(1-84)/C-PTH ratios were found, showing a ratio < 1 when measured by the Nichols assays, but > 1 when the Scantibodies assays were used. In conclusion, our results suggest that the PTH(1-84)/C-PTH ratio cannot be equally used as a predictor of bone turnover when different PTH assays are used. Depending on those assays, differences in total PTH values mathematically lead to varying amounts of C-PTH fragments resulting in variable, even contradictory PTH(1-84)/C-PTH ratios.

Kidney International, 2004

We appreciate the attempts by Lowrie and others to explain the suspected gender effect as simply ... more We appreciate the attempts by Lowrie and others to explain the suspected gender effect as simply reflecting the difference in body size. In the analysis of our findings we explored functions of body size that might diminish or erase the difference between the genders in their response to the dialysis dose, expressed either as Kt or Kt/V. As detailed in our paper [1], the dependence of the dose effect on gender was not explained by differences in body size expressed as several different parameters, including weight, height, body surface area, water volume, and body mass index (Table ). The dose effect was not significantly associated with any of these size parameters. In fact, the nonsignificant weak trends that were detected were further diminished by correction for gender (Table ). Furthermore, the suggested increased mortality of males treated at the higher dose could not be explained by any consideration of body size. A non-0 intercept for a linear relationship between body size and required solute clearance is a clear mathematic concept that is difficult to understand physiologically. It implies an enormous amount of dialysis (or kidney function) for very small people, and a near infinite amount for even smaller biological organisms. Probably the relationship is nonlinear but with a 0 intercept (e.g., a power function of body mass). This is consistent with the universal scaling law that relates physiologic functions to the 3/4 power of body mass and to the current practice of correcting the creatinine clearance or GFR for body surface area (2/3 power of body mass) [2, 3, 4]. The effect of body size as an independent mortality risk factor in hemodialyzed patients reported by Lowrie et al is now commonly accepted, and was also observed in the HEMO Study (Table ). However, the marked rotation of the line depicting dose versus size in the graph provided by Lowrie et al suggests that the relationship of size with outcome can be altered by changing the dose. Post-hoc analyses of our data [1] do not support such a dependence of the effect of dose on the risk associated with body size in a range of eKt/V from 1.16 to 1.53, but do indicate that women were more responsive to the dose effect than men. The risk associated with female gender, in contrast to small body size, can be viewed as favorable because females appeared to respond to the higher dose, whereas both small patients and males did not. Finally, we must reiterate two important limitations that we noted in our paper. First, the finding of a different dose effect in men and women must be viewed as a suggestion only because the level of significance was not high in the context of multiple subgroup analyses. Second, because the power of the study to detect effects in subgroups is limited, it cannot rule out the possibility of an undetected dependence of the dose effect on body size.

Nephrology Dialysis Transplantation, 2004

Actualmente, por la falta de órganos para trasplante renal provenientes de cadáveres, y debido al... more Actualmente, por la falta de órganos para trasplante renal provenientes de cadáveres, y debido al largo tiempo de espera por un riñón, existe una tendencia a realizar trasplantes renales utilizando riñones procedentes de donadores vivos. La mayoría de los donadores son familiares del receptor. La donación de órganos debe considerarse como un regalo con un valor extraordinario y debe facilitarse a los candidatos a donación. En todo el mundo se ha observado un aumento en el número de personas en la lista de espera para un trasplante renal. El trasplante renal de donador vivo se considera actualmente como el mejor método de tratamiento en pacientes con insuficiencia renal terminal, debido a que ofrece la mayor supervivencia a corto y largo plazos. En vista de que existen diferencias significativas en los criterios de selección y evaluación de los donadores renales, en especial en un grupo selecto de pacientes añosos o con enfermedades asociadas, es indispensable establecer criterios mínimos de selección. Todos los donadores deberán contar con una historia clínica completa y exámenes de laboratorio y gabinete que permitan su evaluación integral. Estos estudios se describen con detalle en este artículo. También se discuten los criterios para donadores renales con ciertas comorbilidades (obesos, hipertensos, hiperglucémicos, con litiasis y neoplasias) que previamente se descartaban como candidatos para donación.

Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 2005

Ruf et al. report hyponatremia to be an excellent predictor of outcome in patients with advanced ... more Ruf et al. report hyponatremia to be an excellent predictor of outcome in patients with advanced cirrhosis and that the presence of hyponatremia significantly increases the efficacy of the Model for End-Stage Liver Disease (MELD) to predict waitlist mortality.1 Furthermore, they suggest hyponatremia to be incorporated into the MELD formula. However, we believe that with the emergence of aquaretics (i.e., V2-receptor antagonists) for treatment of hyponatremia these suggestions should be viewed with caution. These drugs, which are expected to be approved by the FDA this year, have been shown to reverse hyponatremia efficiently in patients with advanced liver disease.2,3 While it has yet to be shown that treatment with aquaretics increases survival in this patient population, the prevalence of hyponatremia will certainly decrease with the more widespread use of these drugs. Furthermore, it can be assumed that the management of ascites will also be affected due to the aquaretic effect of these drugs. With the emergence of these new drugs and the anticipated change of the incidence of hyponatremia in this patient population, we believe that the suggestion to incorporate serum sodium into the MELD score might be premature and will need to be reconsidered after the full impact of these drugs have been evaluated. Hendrik Koller, MD Alexander Rosenkranz Department of Nephrology Medical University Innsbruck Innsbruck, Austria

Transplant International, 2004

Clearance of C4d deposition after successful treatment of acute humoral rejection in follow-up bi... more Clearance of C4d deposition after successful treatment of acute humoral rejection in follow-up biopsies: a report of three cases Abstract Acute humoral rejection (AHR) is currently perceived as an immunological reaction against donor antigens mediated by complement-binding antibodies. C4d, a split product of complement activation and bound to endothelial cells of the peritubular capillaries, is used as a diagnostic marker for AHR. We report on three patients with biopsyproven acute humoral rejection who were treated initially with plasmapheresis (PS). As two of the patients did not recover renal function, and biopsy showed persistent C4d staining after PS, immunoadsorption (IAS) was additionally performed on them. In all patients, renal function recovered, and follow-up biopsies in two patients showed complete disappearance of C4d, 29 days and 58 days after transplantation and only minimal residual C4d deposits in one patient 48 days after transplantation. We conclude that successful treatment of AHR is followed by complete resolution of serological and histological markers of AHR, displayed by the disappearance of C4d. Keywords Transplantation. C4d. Acute rejection. Humoral rejection. Plasmapheresis .

Apoptosis of human polymorphonuclear neutrophils accelerated by dialysis membranes via the activa... more Apoptosis of human polymorphonuclear neutrophils accelerated by dialysis membranes via the activation of the complement system

Acta Medica Austriaca, 2001

Nephrology Dialysis Transplantation, 2004

Background. Haemodialysis (HD) with bioincompatible cellulosic membranes like Cuprophan (CU) is c... more Background. Haemodialysis (HD) with bioincompatible cellulosic membranes like Cuprophan (CU) is considered to influence negatively the clinical outcome of acute and chronic renal failure. In this effect, apart from the disturbance of phagocytosis or oxygen species production by leukocytes, increased apoptosis also has been implicated recently. The objective of this study was to study the effect of HD membranes on apoptosis induction in polymorphonuclear neutrophils (PMN). Methods. PMN from healthy donors and uraemic patients were isolated and apoptosis was induced by co-incubation with CU, Hemophan or polyamide hollow fibres in the presence of serum from healthy or uraemic humans. Apoptosis was quantified by flow cytometry using Annexin V-FITC and propidium iodide staining and was confirmed by the detection of DNA fragmentation on gel electrophoresis. The deposition of immunoglobulins (Ig) and complement factors on hollow fibres was detected by direct immunofluorescence. Results. Heat inactivation or the depletion of complement components or Ig significantly reduced apoptosis, indicating its dependence on classical complement activation. The detection of IgG on hollow CU fibres and the restored acceleration of apoptosis by the appropriate replenishment of Ig-deficient sera additionally confirmed these findings. Inhibition experiments revealed that caspases were necessary mainly, but not exclusively, for apoptosis to occur after complement activation. Uraemia led to increased PMN apoptosis in the presence of bioincompatible, but not biocompatible, membranes. Conclusions. Our results suggest that the acceleration of PMN apoptosis in the presence of CU is mediated via an antibody-dependent activation of the classical complement pathway mobilizing both caspase-dependent and -independent pathways.

Lupus, 2005

Sir — the first report in 1983 by Hughes, the antiphospholipid antibody syndrome (APS) is a well ... more Sir — the first report in 1983 by Hughes, the antiphospholipid antibody syndrome (APS) is a well known cause of arterial and venous thrombosis. In the last three years, several case reports of APS and thrombosis affecting the arterial vessels including the coronary and renal arteries have been published. While there is some consensus of the treatment of venous thrombotic complications, management of arterial thrombosis is unclear and possible strategies include oral anticoagulants, thrombolysis or percutaneous transluminal angioplasty (PTA) with or without stenting. To date, successful PTA with stenting has been mainly reported for coronary revascularization but rarely for renal artery stenosis. – 4 We report a case of a 63-year old male with a history of systemic lupus erythematosus (SLE) and secondary APS who was diagnosed with bilateral renal artery stenosis (RAS) and successfully treated with bilateral PTA and stent implantation. A 63-year old male with a history of SLE, APS and previously well controlled arterial hypertension presented with accelerating hypertension and worsening renal function. He was a former smoker with normal glycemic status and mild hypercholesterolemia. Since 1976, the patient had suffered from multiple episodes of venous thrombosis affecting the pulmonary, saphenous and cranial sinus venous system. He was subsequently diagnosed with SLE and secondary APS by the presence of IgG anticardiolipin antibodies and had been prescribed warfarin for 19 years. Other significant medical history included primary hypothyroidism after radioiodine (I) therapy for diffuse toxic goitre and mild renal insufficiency since 1995. During the outpatient clinic visit the patient reported uncontrolled blood pressure on several home blood pressure recordings. On examination, the patient was hypertensive with 160/95 mmHg. An ACE-Inhibitor (ACE-I) was added to the previous anti-hypertensive regimen, and laboratory tests after one week showed significant loss of renal function with a creatinine of 1.9 mg/dL and a creatinine clearance of 52 mL/min (compared to one week previously: 1.2 mg/dL and 75 mL/min). Additional laboratory analysis revealed no change of ANA titers or complement levels, and the urine sediment was normal with mild proteinuria of 246 mg/ day. Exacerbation of SLE with renal involvement was thought to be unlikely, and CT angiography was performed, which revealed a 10 6 mm ostial thrombus of the left renal artery occluding 70% of the lumen (Figure 1) and an almost complete obliteration of the right renal artery near the ostium. Renal ultrasound and Doppler studies were performed showing asymmetrical seized kidneys (left: 9.7 cm, right: 11.2 cm) and resistance index (RI) of 0.55 on both sides. PTA and stenting was performed on two separate sessions under distal protection and warfarin was increased to a target INR of 3.0–4.0. One and a half years after the procedure the patient is normotensive on his previous blood pressure medications and has recovered renal function with a creatinine of 1.39 mg/dL. To date, follow up Doppler studies have shown no evidence of restenosis indicating patent vessels. Loss of renal function after the administration of ACE-I is a hallmark of bilateral renal artery stenosis or unilateral stenosis in a single kidney and is potentially reversible if recognized early. In our patient, absence of evidence of lupus activity, the history of secondary APS and the recent administration of ACE-I prompted a search for this potentially treatable cause of renal dysfunction. In fact, renal artery stenosis (RAS) and APS might be more common than previously thought: Hughes reported a significantly higher prevalence (26%) of RAS in patients with APL who had difficult to control hypertension compared to otherwise young healthy hypertensive patients. The precise nature of our patients stenosis remains obscure but is likely to be atherosclerotic: CT angiography showed typical features of atherosclerotic lesions, and risk factors for atherosclerosis in our patient included former nicotine abuse, age, male gender, family history of coronary artery disease, hypercholesterolemia, former use of steroids and hypertension; nontraditional risk factors included possible atherogenic properties mediated by anticardiolipin antibodies through cross reaction with oxidized low density lipoprotein (ox-LDL) and enhanced ox-LDL uptake into monocytes/macrophages and by endothelial cell proliferation. – 9 Correspondence: Dr Hendrik Koller, Klinische Abteilung für Nephrologie, Universitätsklinik für Innere Medizin, Anichstr. 35, A 6020 Innsbruck, Austria. E-mail: hendrikkoller@yahoo.com Received 16 September 2004; accepted 21 March 2005 Lupus (2005) 14, 566–568

International Journal of Cardiology, 2006

Angina pectoris a common encountered complaint in internal medicine, and the work up includes a r... more Angina pectoris a common encountered complaint in internal medicine, and the work up includes a routine battery of tests to identify treatable causes and to exclude myocardial damage. However, rare reversible causes of angina exist which might remain undetected if additional, non-traditional tests are not applied properly. We recently encountered a patient whose unusual cause of angina could be detected and reversed by a simple blood gas analysis.

Clinical Nephrology, 2004

Parathyroidhormone (PTH) measurement is important in the evaluation of bone disease in patients w... more Parathyroidhormone (PTH) measurement is important in the evaluation of bone disease in patients with chronic renal failure. Large carboxyl-terminal PTH fragments (C-PTH) cross-react with second-generation PTH assays, lead to an overestimation of biologically active PTH, and are evaluated by a combination of second- and third-generation PTH assays. The aim of our study was to examine whether the use of 4 different PTH assays of putatively same specificity leads to comparable results detecting C-PTH fragments. In 70 chronic dialysis patients, total PTH and PTH(1-84) were measured in parallel by 4 novel PTH assays (Nichols Advantage Intact PTH and Bio-Intact PTH Chemiluminescence Assay, Nichols Institute Diagnostics, USA, DUO Total and CAP PTH IRMA, Scantibodies Laboratory, USA). The C-PTH concentration was quantitated by subtracting PTH(1-84) from total PTH. Consecutively, the PTH(1-84)/C-PTH ratio was calculated. Nichols Intact PTH and DUO Total PTH assays were highly correlated (r = 0.985), as well as Nichols Bio-Intact and DUO CAP assays (r = 0.984). However, total PTH values measured by the Nichols assay were 30% higher (median (range): 185 (9.9 - 2,332) versus 130 (2.3 - 1,271.1) pg/ml, p < 0.01). PTH(1-84) values, measured by the Nichols Bio-Intact PTH assay were 8% higher compared to the Scantibodies CAP assay (median (range): 79.6 (7.5 - 1,060.9) versus 73.7 (4.4 - 918.9) pg/ml, p = NS). Thirty-six patients had a ratio < 1 measured by the Nichols assays, whereas only 8 patients showed the same ratio when measured by the Scantibodies assays. In 28 patients (40%), contradictory PTH(1-84)/C-PTH ratios were found, showing a ratio < 1 when measured by the Nichols assays, but > 1 when the Scantibodies assays were used. In conclusion, our results suggest that the PTH(1-84)/C-PTH ratio cannot be equally used as a predictor of bone turnover when different PTH assays are used. Depending on those assays, differences in total PTH values mathematically lead to varying amounts of C-PTH fragments resulting in variable, even contradictory PTH(1-84)/C-PTH ratios.

Kidney International, 2004

We appreciate the attempts by Lowrie and others to explain the suspected gender effect as simply ... more We appreciate the attempts by Lowrie and others to explain the suspected gender effect as simply reflecting the difference in body size. In the analysis of our findings we explored functions of body size that might diminish or erase the difference between the genders in their response to the dialysis dose, expressed either as Kt or Kt/V. As detailed in our paper [1], the dependence of the dose effect on gender was not explained by differences in body size expressed as several different parameters, including weight, height, body surface area, water volume, and body mass index (Table ). The dose effect was not significantly associated with any of these size parameters. In fact, the nonsignificant weak trends that were detected were further diminished by correction for gender (Table ). Furthermore, the suggested increased mortality of males treated at the higher dose could not be explained by any consideration of body size. A non-0 intercept for a linear relationship between body size and required solute clearance is a clear mathematic concept that is difficult to understand physiologically. It implies an enormous amount of dialysis (or kidney function) for very small people, and a near infinite amount for even smaller biological organisms. Probably the relationship is nonlinear but with a 0 intercept (e.g., a power function of body mass). This is consistent with the universal scaling law that relates physiologic functions to the 3/4 power of body mass and to the current practice of correcting the creatinine clearance or GFR for body surface area (2/3 power of body mass) [2, 3, 4]. The effect of body size as an independent mortality risk factor in hemodialyzed patients reported by Lowrie et al is now commonly accepted, and was also observed in the HEMO Study (Table ). However, the marked rotation of the line depicting dose versus size in the graph provided by Lowrie et al suggests that the relationship of size with outcome can be altered by changing the dose. Post-hoc analyses of our data [1] do not support such a dependence of the effect of dose on the risk associated with body size in a range of eKt/V from 1.16 to 1.53, but do indicate that women were more responsive to the dose effect than men. The risk associated with female gender, in contrast to small body size, can be viewed as favorable because females appeared to respond to the higher dose, whereas both small patients and males did not. Finally, we must reiterate two important limitations that we noted in our paper. First, the finding of a different dose effect in men and women must be viewed as a suggestion only because the level of significance was not high in the context of multiple subgroup analyses. Second, because the power of the study to detect effects in subgroups is limited, it cannot rule out the possibility of an undetected dependence of the dose effect on body size.

Nephrology Dialysis Transplantation, 2004

Actualmente, por la falta de órganos para trasplante renal provenientes de cadáveres, y debido al... more Actualmente, por la falta de órganos para trasplante renal provenientes de cadáveres, y debido al largo tiempo de espera por un riñón, existe una tendencia a realizar trasplantes renales utilizando riñones procedentes de donadores vivos. La mayoría de los donadores son familiares del receptor. La donación de órganos debe considerarse como un regalo con un valor extraordinario y debe facilitarse a los candidatos a donación. En todo el mundo se ha observado un aumento en el número de personas en la lista de espera para un trasplante renal. El trasplante renal de donador vivo se considera actualmente como el mejor método de tratamiento en pacientes con insuficiencia renal terminal, debido a que ofrece la mayor supervivencia a corto y largo plazos. En vista de que existen diferencias significativas en los criterios de selección y evaluación de los donadores renales, en especial en un grupo selecto de pacientes añosos o con enfermedades asociadas, es indispensable establecer criterios mínimos de selección. Todos los donadores deberán contar con una historia clínica completa y exámenes de laboratorio y gabinete que permitan su evaluación integral. Estos estudios se describen con detalle en este artículo. También se discuten los criterios para donadores renales con ciertas comorbilidades (obesos, hipertensos, hiperglucémicos, con litiasis y neoplasias) que previamente se descartaban como candidatos para donación.

Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 2005

Ruf et al. report hyponatremia to be an excellent predictor of outcome in patients with advanced ... more Ruf et al. report hyponatremia to be an excellent predictor of outcome in patients with advanced cirrhosis and that the presence of hyponatremia significantly increases the efficacy of the Model for End-Stage Liver Disease (MELD) to predict waitlist mortality.1 Furthermore, they suggest hyponatremia to be incorporated into the MELD formula. However, we believe that with the emergence of aquaretics (i.e., V2-receptor antagonists) for treatment of hyponatremia these suggestions should be viewed with caution. These drugs, which are expected to be approved by the FDA this year, have been shown to reverse hyponatremia efficiently in patients with advanced liver disease.2,3 While it has yet to be shown that treatment with aquaretics increases survival in this patient population, the prevalence of hyponatremia will certainly decrease with the more widespread use of these drugs. Furthermore, it can be assumed that the management of ascites will also be affected due to the aquaretic effect of these drugs. With the emergence of these new drugs and the anticipated change of the incidence of hyponatremia in this patient population, we believe that the suggestion to incorporate serum sodium into the MELD score might be premature and will need to be reconsidered after the full impact of these drugs have been evaluated. Hendrik Koller, MD Alexander Rosenkranz Department of Nephrology Medical University Innsbruck Innsbruck, Austria

Transplant International, 2004

Clearance of C4d deposition after successful treatment of acute humoral rejection in follow-up bi... more Clearance of C4d deposition after successful treatment of acute humoral rejection in follow-up biopsies: a report of three cases Abstract Acute humoral rejection (AHR) is currently perceived as an immunological reaction against donor antigens mediated by complement-binding antibodies. C4d, a split product of complement activation and bound to endothelial cells of the peritubular capillaries, is used as a diagnostic marker for AHR. We report on three patients with biopsyproven acute humoral rejection who were treated initially with plasmapheresis (PS). As two of the patients did not recover renal function, and biopsy showed persistent C4d staining after PS, immunoadsorption (IAS) was additionally performed on them. In all patients, renal function recovered, and follow-up biopsies in two patients showed complete disappearance of C4d, 29 days and 58 days after transplantation and only minimal residual C4d deposits in one patient 48 days after transplantation. We conclude that successful treatment of AHR is followed by complete resolution of serological and histological markers of AHR, displayed by the disappearance of C4d. Keywords Transplantation. C4d. Acute rejection. Humoral rejection. Plasmapheresis .