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C Wanner

Publications and source records attributed to C Wanner.

At least 19 recordsLinked to original sources
PubMed2006

Grading evidence and recommendations for clinical practice guidelines in nephrology. A position statement from Kidney Disease: Improving Global Outcomes (KDIGO).

Considerable variation in grading systems used to rate the strength of guideline recommendations and the quality of the supporting evidence in Nephrology highlights the need for a uniform, internationally accepted, rigorous system. In 2004, Kidney Disease: Improving Global Outcomes (KDIGO) commissioned a methods expert group to recommend an approach for grading in future nephrology guidelines. This position statement by KDIGO recommends adopting the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach for the grading of evidence and guidelines on interventions. The GRADE approach appraises systematic reviews of the benefits and harms of an intervention to determine its net health benefit. The system considers the design, quality, and quantity of studies as well as the consistency and directness of findings when grading the quality of evidence. The strength of the recommendation builds on the quality of the evidence and additional considerations including costs. Adaptations of the GRADE approach are presented to address some issues pertinent to the field of nephrology, including (1) the need to extrapolate from studies performed predominantly in patients without kidney disease, and (2) the need to use qualitative summaries of effects when it is not feasible to quantitatively summarize them. Further refinement of the system will be required for grading of evidence on questions other than those related to intervention effects, such as diagnostic accuracy and prognosis.

Global Health↗
PubMed2006

[Treatment of dyslipoproteinemia in chronic renal failure].

In patients with chronic kidney disease, treatment with statins presumably not only has an influence on cardiovascular endpoints, but also delays the progression of the renal disease. Recommendations for the treatment of lipid metabolism disorders in the general population with normal renal function are based on numerous prospective, randomized and placebo-controlled studies. In contrast, recommendations for patients with pathological renal function can merely be extrapolated from the results of those studies. Post hoc analyses from the large pravastatin studies confirm a significant risk reduction of primary cardiovascular and cerebrovascular end points for the CDK stages 2 and 3. For CKD stages 4 and 5, available data are merely rudimentary, so that the results of ongoing studies will have to be awaited.

Cause of Death↗
PubMed2006

Clinical benefit of enzyme replacement therapy in Fabry disease.

Enzyme replacement therapy (ERT) with recombinant human alpha-galactosidase A (r-halphaGalA) enhances microvascular globotriaosylceramide clearance and improves clinical symptoms in patients with Fabry disease. We evaluated whether these effects are translated into a long-term benefit of kidney and heart function. We did a single center, prospective, open label study in 26 patients with Fabry disease (one early death, follow-up in 25 patients). r-Alpha-GalA was administered in a dosage of 1 mg/kg body weight every second week. The effect of therapy on clinical end points (death, cardiac and cerebrovascular event, renal failure), cardiac and renal function monitored by Doppler echocardiography, 99Tc-GFR, and proteinuria was investigated. After a mean treatment time of 23 +/- 8 months, nine patients experienced 12 end points, including two deaths. All end points occurred in patients with impaired renal function (n = 16; GFR 71 +/- 17 ml/min/1.73 m2). Despite ERT, renal function deteriorated to 60 +/- 23 ml/min/1.73 m2 (P = 0.04) and left ventricular posterior wall thickness (PWT) did not change (14.0 +/- 2.1 vs 13.4 +/- 2.3 mm). In contrast, patients without impairment of renal function (n = 9) had a more favorable outcome (no clinical events; GFR 115 +/- 18 vs 102 +/- 14 ml/min/1.73 m2, NS; PWT 11.7 +/- 1 and 10.7+/-0.7 mm, P = 0.04). Proteinuria remained unchanged (1.34 +/- 0.94 vs 1.01 +/- 0.97 g/day, n = 10). Patients with impaired renal function have a less favorable outcome and may develop cardiovascular and renal end points despite ERT.

Adult↗
PubMed2005

Morbus Fabry of the heart. Why should cardiologists care?

Fabry Disease is an X-linked lysosomal storage disorder leading to the accumulation of glycosphingolipids, mainly globotriaosylceramides in all tissues and solid organs of the body. The disease was described by Johannes Fabry and William Anderson coevally in 1898. Beside the involvement of the central nervous system, peripheral nerves, kidneys, skin and endovascular endothelium, the heart plays a major role in the disease. Left ventricular hypertrophy is one hallmark initially presenting with preserved ventricular function. However, with progression of the disease patients die due to heart failure. Though angina is often reported, the incidence of epicardial coronary stenosis is not a dominant feature, if at all small vessel disease can occur. In respect of arrhythmias a broad spectrum can be seen including shortened or prolonged PR-intervals, AV blocks of different degrees and sometimes malignant ventricular arrhythmias. In the past, women were considered to be carriers of the disease but hardly to develop clinical symptoms. In recent years there is evidence that female carriers may more often be affected with severe symptoms. In addition, a group of Fabry patients displaying mainly cardiac involvement were described as having a cardiac variant of the disease. This implied the hypothesis that some of those patients with unexplained myocardial hypertrophy do suffer from Fabry disease. Since 2002 enzyme replacement therapy is available and there is first evidence for its efficacy to reduce hypertrophy and increase myocardial function. If this is associated with a prognostic improvement has to be determined in future studies.

Cardiology↗
PubMed2004

Clinical features of migraine: a cross-sectional study in patients aged three to sixty-nine.

We investigated 260 consecutive patients classified as migraine cases aged 3-69 at two tertiary headache centres, one for children and adolescents and the other for adults to evaluate the relationship between age and clinical features of migraine cross-sectionally. We only included subjects with definite migraine without or with aura and we excluded subjects with coexisting tension-type headache, medication overuse and/or other clinically relevant disorders. The percentage of males decreased markedly from childhood to adulthood and this affected the evaluation of age-related changes in male patients, as only large differences reached the level of statistical significance. In females, the headache duration and the prevalence of unilateral, pulsating pain, photophobia and phonophobia increased, whereas the prevalence of aggravation by physical activity decreased with age. In conclusion, this cross-sectional, clinic-based study on a strictly defined sample of 260 consecutive patients with definite migraine covering a wide range of age from the very young to the old suggests marked age-related differences of the clinical features of migraine in females and failed to demonstrate similar differences in males due to the small number of adult male migraineurs.

Adolescent↗
PubMed2004

Clinical practice guidelines for managing dyslipidemias in kidney transplant patients: a report from the Managing Dyslipidemias in Chronic Kidney Disease Work Group of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative.

The incidence of cardiovascular disease (CVD) is very high in patients with chronic kidney (CKD) disease and in kidney transplant recipients. Indeed, available evidence for these patients suggests that the 10-year cumulative risk of coronary heart disease is at least 20%, or roughly equivalent to the risk seen in patients with previous CVD. Recently, the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (K/DOQI) published guidelines for the diagnosis and treatment of dyslipidemias in patients with CKD, including transplant patients. It was the conclusion of this Work Group that the National Cholesterol Education Program Guidelines are generally applicable to patients with CKD, but that there are significant differences in the approach and treatment of dyslipidemias in patients with CKD compared with the general population. In the present document we present the guidelines generated by this workgroup as they apply to kidney transplant recipients. Evidence from the general population indicates that treatment of dyslipidemias reduces CVD, and evidence in kidney transplant patients suggests that judicious treatment can be safe and effective in improving dyslipidemias. Dyslipidemias are very common in CKD and in transplant patients. However, until recently there have been no adequately powered, randomized, controlled trials examining the effects of dyslipidemia treatment on CVD in patients with CKD. Since completion of the K/DOQI guidelines on dyslipidemia in CKD, the results of the Assessment of Lescol in Renal Transplantation (ALERT) Study have been presented and published. Based on information from randomized trials conducted in the general population and the single study conducted in kidney transplant patients, these guidelines, which are a modified version of the K/DOQI dyslipidemia guidelines, were developed to aid clinicians in the management of dyslipidemias in kidney transplant patients. These guidelines are divided into four sections. The first section (Introduction) provides the rationale for the guidelines, and describes the target population, scope, intended users, and methods. The second section presents guidelines on the assessment of dyslipidemias (guidelines 1-3), while the third section offers guidelines for the treatment of dyslipidemias (guidelines 4-5). The key guideline statements are supported mainly by data from studies in the general population, but there is an urgent need for additional studies in CKD and in transplant patients. Therefore, the last section outlines recommendations for research.

Adolescent↗
PubMed2003

Pharmacokinetics of amlodipine in hypertensive patients undergoing haemodialysis.

OBJECTIVE: Amlodipine is a calcium antagonist of the dihydropyridine class. This study was performed to examine the single and multiple dose pharmacokinetics of amlodipine in hypertensive patients undergoing haemodialysis and to measure the index of accumulation during multiple dosage. An additional objective was to examine the dialysability of amlodipine by measuring its appearance in dialysate. METHODS: Seventeen hypertensive out-patients on haemodialysis were enrolled in this prospective, open, non-comparative phase-IV study. Fifteen patients completed the study. In the first part of the study, the patients were given a single oral 5-mg dose of amlodipine and blood samples taken 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 72 and 144 h later. After a 4-week wash-out period, the patients were given a daily 5-mg oral dose of amlodipine for 30 days. The trough levels of amlodipine were measured on days 8, 15, 22 and 29. On day 30, the total time course of amlodipine concentrations in plasma was measured, as in the first part of the study. In addition, on day 15, the concentrations of amlodipine in dialysate were measured at the same time as in blood. Blood pressure and heart rate were measured and adverse events monitored. Pharmacokinetic parameters [Cmax, tmax, kel and AUC(0-24)] were calculated for the single dose and for the dose on day 30 and the accumulation index calculated on the basis of AUC(0-24) and Cmax. RESULTS: The mean values of the single-dose pharmacokinetic parameters were as follows: Cmax 3.83 microg l(-1), tmax 5.01, AUC(0-24) 59.90 microg l(-1) h, kel 0.0177 h(-1). The mean accumulation index on the basis of AUC(0-24) was calculated as 3.70. Very low levels of amlodipine were detectable in dialysate fluid. The most frequently reported adverse events were hypertension, hypotension and muscle cramps. CONCLUSION: There are only minor differences in the pharmacokinetics of amlodipine between healthy subjects and hypertensive patients on haemodialysis. Comparison with literature values for healthy volunteers suggests that amlodipine is rapidly and extensively absorbed in the patient group. Amlodipine is essentially not dialysable. These findings do not indicate a need for dose adjustment in renal failure patients on haemodialysis.

Adult↗
PubMed2001

Inflammation and advanced glycation end products in uremia: simple coexistence, potentiation or causal relationship?

The causes for the high frequency of cardiovascular disease in dialysis patients are multifactorial in origin. Disturbances in the carbohydrate and lipid metabolism, the balance between oxidants and antioxidants and the immuno-inflammatory system are thought to play a role. Chronic uremia is characterized by the accumulation of advanced glycation end products (AGEs) and advanced oxidation products (AOPP) as well as activation of the acute phase response. High serum levels of these products and acute phase reactants such as C-reactive protein (CRP), fibrinogen and serum amyloid A can be found. CRP has been shown to predict cardiovascular and overall mortality in hemodialysis patients. Whether CRP is involved causally in atherosclerosis or merely represents a marker of disease is as yet unknown. Since CRP has been detected in colocalization with modified apolipoproteins or complement components in atherosclerotic lesions, a pathophysiological role seems very likely. AGEs as well have been detected in aortas of hemodialysis patients. Incubation of endothelial cells with AGEs induced expression of adhesion molecules with consecutive attraction of monocytes to the vessel wall. Thus far, clinical studies investigating the predictive effects of AGEs on cardiovascular mortality in hemodialysis patients are lacking. There is considerable debate about what factors turn on the acute phase response in this population. Proinflammatory effects of AGEs mediated through one receptor for AGEs, RAGE, have been described. We hypothesize that there may be a link between increased hepatic CRP production and the accumulation of AGEs in uremia. AGEs may stimulate CRP production in hepatocytes either directly or indirectly via interaction with monocytes.

Acute-Phase Reaction↗
PubMed2001

Dual effect of oxidized LDL on cell cycle in human endothelial cells through oxidative stress.

BACKGROUND: Oxidized low-density lipoprotein (OxLDL) exerts proliferation and apoptosis in vascular cells, depending on its concentration and the exposure time. Various steps in the cell cycle and in the apoptotic signaling cascade are modulated by O2-, and OxLDL stimulates vascular O2- formation. Here we studied the role of NADPH oxidase, a potential source for O2- formation after OxLDL stimulation, in cell proliferation, and we investigated whether OxLDL influences anti-apoptotic genes in cultured human umbilical vein endothelial cells (HUVEC). Methods and Results. OxLDL dose-dependently (10 to 300 microg/mL) stimulated O2- formation in HUVEC (detected by cytochrome c assay and by chemiluminescence of lucigenin). Low OxLDL concentrations (5 to 10 microg/mL) induced proliferation (detected by 3H-thymidine incorporation), while higher concentrations (50 to 300 microg/mL) induced apoptotic cell death (detected by Annexin assay and DNA fragmentation). Proliferation was blocked by the antioxidants SOD and catalase and by diphenyleneiodonium (10 micromol/L), an inhibitor of the O2- generating NADPH oxidase. In addition, cells transfected with antisense oligonucleotides for NADPH oxidase showed a significantly reduced O2- formation after stimulation with OxLDL. The OxLDL effect on apoptosis was also blocked by antioxidants. Since endothelial cells are protected against apoptosis through anti-apoptotic genes, we investigated whether OxLDL overcomes protection against apoptosis through suppression of the anti-apoptotic gene A20, a zinc-finger protein. OxLDL suppressed the expression of A20 in a dose-dependent manner. CONCLUSION: These data indicate that OxLDL has a dual effect on cell cycle in HUVEC, inducing proliferation at low and apoptosis at higher concentrations. Both effects are mediated by O2- formation, with NADPH oxidase being a major source for O2-. Thus, OxLDL contributes importantly to vascular cellular turnover through the induction of oxidative stress.

Apoptosis↗
PubMed2001

Abnormalities in uremic lipoprotein metabolism and its impact on cardiovascular disease.

Patients with end-stage renal disease (ESRD) suffer from a secondary form of complex dyslipidemia consisting of both quantitative and qualitative abnormalities in serum lipoproteins resulting from alterations in lipoprotein metabolism and composition. The prominant features of uremic dyslipidemia are an increase in serum triglyceride levels (due to elevated very low density lipoprotein [VLDL]-remnants and intermediate-density lipoprotein [IDL]) and low high-density lipoprotein (HDL) cholesterol. Low-density lipoprotein (LDL) cholesterol often is normal, but the cholesterol may originate from the atherogenic small and dense LDL subclass (sdLDL). The apolipoprotein B (apoB)-containing part of the lipoprotein may undergo modifications (enzymatic- and advanced glycation end-product [AGE]-peptide modification, oxidation, or glycosilation). Modifications contribute to impaired LDL receptor-mediated clearance from plasma and promote prolonged circulation. While LDL particles undergo a vicious cycle of accumulation and modification, reverse cholesterol transport is also impaired due to low lecithin:cholesterol acyltransferase (LCAT) and paraoxonase activity. Therefore, discoid HDL particles are structurally altered and hepatic cholesterol clearance is limited. The composition of HDL may also be altered during states of inflammation. The contribution of this complex and atherogenic form of dyslipidemia to cardiovascular disease in patients with renal disease is unclear at present. Most studies are negative in demonstrating the predictive power of serum lipids for the development of cardiovascular disease. This is most likely due to interference with deteriorating aspects of the activated acute-phase response. Nevertheless, patients with renal disease belong to a very high cardiovascular risk group and dyslipidemia should most likely be subjected to sufficient lipid-lowering therapy in most patients. Because it is also still unclear whether we have available therapies with sufficient impact on LDL size, remnant lipoprotein-lowering, and restoration of HDL function, we urgently need the results from large scale intervention trials such as the 4D-trial and the CHORUS study.

Apolipoproteins B↗
PubMed2001

Cardiovascular disease determinants in chronic renal failure: clinical approach and treatment.

INTRODUCTION: Cardiovascular disease (CVD), as the leading cause of morbidity and mortality in patients on renal replacement therapy (RRT), has a central role in everyday nephrological practice. METHODS: Consensus was reached on key points relating to the clinical approach and treatment of the main cardiovascular risk factors in RRT patients (hypertension, anaemia, hyperparathyroidism, dyslipidaemia, new emerging risk factors). In addition, the role of convective treatments on cardiovascular outcomes was examined. RESULTS: Hypertension should be managed by aiming at blood pressure values of < or =140/90 mmHg (< or =160/90 mmHg in the elderly), firstly by ensuring target dry body weight is achieved. No single class of drug has proved superior to others in RRT patients, provided that the blood pressure target is achieved, although ACE inhibitors have shown specific organ protection in high-risk patients (HOPE study) and are well tolerated. Anaemia should be managed by using erythropoietin and iron supplements, aiming at haemoglobin levels of 12 g/dl and keeping serum ferritin levels < 500 ng/ml. The management of hyperparathyroidism is currently unsatisfactory, as calcium supplements have the potential to increase cardiovascular calcification. While awaiting new calcium- and aluminium-free phosphate binders, it is essential to ensure dialysis adequacy. Clinical studies are in progress to assess the real impact of lipid-lowering drugs in RRT. In the meantime, serum LDL-cholesterol < 160 mg/dl and triglycerides < 500 mg/dl may be desirable targets. The impact of new emerging risk factors (inflammation and chronic infection, hyperhomocysteinaemia, metabolic waste-product accumulation) and their proper management are still under research. Convective dialysis treatments may confer some degree of protection from dialysis-related amyloidosis and mortality, but clinical data on this important issue are still controversial and no definitive conclusions can be drawn at present. CONCLUSION: CVD prevention and treatment is a great challenge for the nephrologist. Achieving evidence-based consensus can help in encouraging the implementation of best clinical practice in line with the progress of current knowledge.

Anemia↗
PubMed2001

Haemodynamic effects of valsartan in acute renal ischaemia/reperfusion injury.

BACKGROUND: Acute deterioration of renal function is an important side-effect of angiotensin-converting enzyme (ACE) inhibitors, especially if accompanied by other nephrotoxic events. Angiotensin II receptor(1) blockers (ARB) are thought to have fewer side-effects on renal perfusion and function. We examined the effects of valsartan (VAL) on kidney function as well as the contribution of the nitric oxide (NO) system in a rat model of ischaemic acute renal failure (ARF). METHODS: ARF was induced by 40 min of clamping of both renal arteries in female Sprague-Dawley rats. Renal haemodynamic and tubular parameters were determined during post-ischaemic infusion of vehicle, VAL, VAL and the NO-synthase substrate L-arginine, and VAL together with inhibition of NO synthases (NOS) by L-NMMA. RESULTS: Clamping induced acute renal failure with marked decreases in glomerular filtration rate (GFR) and renal plasma flow (RPF) accompanied by a rise in renal vascular resistance (RVR) and fractional sodium excretion. Valsartan caused a slight but significant improvement of GFR and RPF without full recovery of renal function and caused a lowering of RVR and tubular sodium loss. L-arginine-co-administration had no additive beneficial effect. Valsartan-induced changes were not significantly depressed by unspecific inhibition of NOS. CONCLUSIONS: Inhibition of the angiotensin II-receptor(1) diminishes the deleterious effects of ischaemia and reperfusion on glomerular function and on the renal microcirculation. An involvement of the NO system could not be demonstrated.

Acute Disease↗
PubMed2001

Dyslipidemia and renal disease: pathogenesis and clinical consequences.

Patients with chronic renal disease suffer from a secondary form of complex dyslipidemia. The most important abnormalities are an increase in serum triglyceride levels (elevated VLDL-remnants/IDL), small LDL particles and a low HDL cholesterol level. The highly atherogenic LDL subclass, namely LDL-6 or small dense LDL, accumulates preferentially in hypertriglyceridemic diabetic patients with nephropathy or on hemodialysis treatment. All these lipoprotein particles contain apolipoprotein B, thus the complex disorder can be summarized as an elevation of triglyceride-rich apolipoprotein B-containing complex lipoprotein particles. Growing evidence suggests that all of the components of this type of dyslipidemia are independently atherogenic. These particles, specifically the apolipoprotein B moiety, are predominantly prone to modification such as oxidation and glycosilation, which contributes to impaired clearance by the LDL receptor. These complex alterations in lipoprotein composition not only passively accompany chronic renal disease but on the contrary also promote its progression and the development of atherosclerosis. Therefore, renal patients with dyslipidemia should be subjected to lipid-lowering therapy. The effectiveness of lipid lowering on the reduction of cardiovascular endpoints or the progression of renal disease is under investigation or remains to be studied.

Apolipoproteins B↗
PubMed2001

Abnormal lipid metabolism after renal transplantation.

The evidence that lipid disorders in patients following renal transplantation play a major role in the pathogenesis of atherosclerosis and chronic renal allograft rejection is circumstantial. The high rate of clinical vascular disease and cardiovascular complications in renal transplant recipients, the high prevalence of an atherogenic dyslipidemia and the evidence from the statin regression trials in the general population suggest that lipid lowering treatment is beneficial in patients after renal transplantation. In addition, animal models and observational studies in patients have demonstrated correlations between plasma lipid levels and both acute and chronic rejection. Animal transplant models and clinical trials in heart transplant patients also suggest that statin treatment decreases the incidence of chronic rejection. However, the mechanisms behind this protective effect remain unsolved and no conclusive data exist proving that statins directly inhibit the development of chronic rejection. However, sufficient evidence exists to consider the use of these agents in the posttransplant setting for their possible effects on cardiovascular complications.

Animals↗
PubMed2000

Hormonal changes in brain death and immune activation in the donor.

Kidneys obtained from brain dead donors show inferior graft survival compared to living donation. The effects of brain death itself are thought to be partly responsible for these results. We, therefore, examined levels of catecholamines, the vasoconstricting hormones AT II, ET-1 and renin activity, pituitary hormones, and their correlation to pro-inflammatory cytokines and cytokine receptors. In 17 brain dead patients and 19 preoperative neurosurgical patients, these parameters were measured by HPLC, RIA and ELISA. Brain death resulted in massive increases in serum catecholamines, AT II and ET-1, as well as PRA, whereas thyroid and adrenal hormone levels remained unchanged. We found a significant correlation with rises in IL-6 and soluble TNF and IL-2 receptors as markers for the activation of immunological cascades. We concluded that these effects could be directly and indirectly responsible for the impaired organ perfusion and function observed in brain death.

Adult↗
PubMed2000

Tacrolimus in acute renal failure: does L-arginine-infusion prevent changes in renal hemodynamics?

Nephrotoxicity is one of the main side effects of calcineurin-inhibitors. The influence of tacrolimus on the renal vasculature has not been well described. We have therefore examined the effects of tacrolimus on renal functional parameters as well as the contribution of the NO-system in a model of ischemic acute renal failure (ARF). Induction of ARF was achieved by clamping both renal arteries of female Sprague-Dawley rats. During the experiment, RBF, GFR, MAP, RVR and FENa were determined during infusion of vehicle, TAC, TAC and the NOS-activator L-arginine, and TAC and NOS-inhibition due to L-NMMA. TAC induced a significant rise in RVR with further decrease of RBF and GFR. Simultaneous L-arginine-infusion could reverse these effects during the infusion without complete restoration to preischemic levels. NOS-inhibition increased MAP and RBF without any effect on GFR. FENa did not differ significantly between the groups. Tacrolimus in the situation of ischemic acute renal failure causes vasoconstriction of pre- and postglomerular vessels with a further deterioration of renal function. L-arginine abolishes the functional deterioration, most likely due to increased NO-liberation.

Acute Kidney Injury↗