Biomedical subjects
E Ritz
Publications and source records attributed to E Ritz.
Beta blockers in the management of chronic kidney disease.
The sympathetic nervous system modulates renal function through its receptors namely beta1 (cardiac output and renin release), alpha1 (systemic and renovascular constriction), and beta2 renovascular dilation. Sympathetic overactivity is commonly seen in chronic kidney disease (CKD) and is an important contributor to increasing the risk of cardiovascular events as well as increasing renal disease progression. Recent evaluations of drug use in people with CKD shows a remarkably low percentage of patients receiving beta-blockers, especially in more advanced stage CKD when cardiovascular risk is higher. This is in large part due to tolerability of these agents. Moreover, water-soluble beta-blockers such as atenolol and metoprolol are dialyzable and require supplementation to avoid exacerbation of arrhythmias following dialysis. Newer vasodilating beta-blockers have better tolerability and different effects on renal hemodynamics as well as metabolic variables. These effects are related to the relative alpha1-blocking effect of agents such as carvedilol and labetolol, with carvedilol having relatively greater alpha-blocking effects. Few studies evaluate beta-blockers on cardiovascular risk in CKD patients. Studies with carvedilol demonstrate attenuated increases in albuminuria as well as reduction in cardiovascular events in CKD patients with hypertension. This paper reviews the animal and clinical trial data that evaluate beta-blockers in CKD highlighting the vasodilating beta-blockers. It is apparent that greater use of this drug class for blood pressure control would further enhance reduction of risk of heart failure, the most common cause of death in the first year of starting dialysis.
[Clinical and health economic implications of early treatment with irbesartan of patients with type 2 diabetes mellitus, hypertension and nephropathy].
BACKGROUND AND OBJECTIVE: It was the aim of this study to project the long-term clinical and cost outcomes of irbesartan treatment, based on data from the irbesartan in Reduction of Microalbuminuria-2 (IRMA-2) study and the irbesartan in Diabetic Nephropathy Trial (IDNT), in hypertensive patients with type 2 diabetes and renal disease in Germany. PATIENTS AND METHODS: A Markov model adapted to the German setting simulated progression of renal disease and associated changes in mortality in patients with hypertension, type 2 diabetes and microalbuminuria. Early irbesartan 300 mg daily (initiated at microalbuminuria) and late irbesartan (initiated at overt nephropathy) were compared to a control scheme of antihypertensive standard medications with comparable blood pressure control, initiated at microalbuminuria. Cumulative incidence of ESRD, time to onset of ESRD, life expectancy (LE), quality-adjusted life years (QALY) and costs were projected over 25 years for 1,000 simulated patients, from a third party payer perspective. Clinical and cost outcomes were discounted at 5% per annum. RESULTS: When compared to standard blood pressure control, both early and late treatment with irbesartan were projected to reduce the cumulative incidence of ESRD fromm23.80.3% to 9.10.6% and 19.83%, increase discounted LE by 0.670.04 and 0.030.00 years, and improve QALY by 0.750.04 and 0.070.01 years per treated patient, respectively. Early irbesartan treatment was associated with a cost savings of i 12,658825 per patient while late irbesartan treatment was associated with a cost savings of i 4,116575 per patient compared to control over the 25-year time horizon. CONCLUSIONS: Early irbesartan treatment was projected to improve LE and QALY, and reduce the onset of ESRD, with cost savings, in hypertensive patients with type 2 diabetes and microalbuminuria in Germany. Later use of irbesartan in overt nephropathy is also superior to standard care. These findings suggest that irbesartan should be started earlier and continued long-term.
[The devil takes the hindmost].
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[Smoking -- the futile fight against the vice. A historical perspective].
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[Prevalence and pharmacotherapy of diabetes mellitus in primary care].
BACKGROUND AND OBJECTIVE: So far only incomplete epidemiological data on the management of diabetes mellitus have been available for the Federal Republic of Germany. It was the aim of this study to obtain such information from a representative cross-section of patients. PATIENTS AND METHODS: 43549 consecutive, unselected patients (52.6% females; mean age 64.9 +/- 11.7 years) of general practitioners and internists in private practice were included in this study which was based on data provided by the general practitioners or internists during September 2001. They recorded prevalence of diabetes, hypertension and 22 other diseases, and the patients' current treatment. Also recorded were associations of other patient-related variables (age, gender, associated or resulting diseases, hypertension, micro- and macrovascular complications, obesity), with medical practitioner-related variables (medical training, use of guidelines, regional factors) and with the frequency of antidiabetic treatment (total and differentiated by class of drug). RESULTS: The prevalence of diabetes mellitus in this cohort was 15.6% (18.5% for males and 13.7% for females). 67.6% of the diabetics received antidiabetic medication. There was little difference, between the different age groups and between males and females, with regard to which of the various drugs were prescribed. Patients with macrovascular complications were more intensively treated with antidiabetics than those with exclusively microvascular ones. There was hardly any correlation between patterns of prescription and various practitioner characteristics (medical training, use of guidelines, regional factors). CONCLUSION: There was little differentiation in the prescription of antidiabetic medication by general practitioners/internists among an unselected patient cohort.
Renal failure and ACE inhibition: how much is too much?
The dose-response relationship between pharmacological blockade of the renin-angiotensin system (RAS) and angiotensin II concentration in the circulation, on the one hand, and decrease of blood pressure, on the other hand, has been well established. In contrast it is currently unclear which dose of ACE inhibitors and/or angiotensin receptor blockers is optimal for nephroprotection. Clinical studies are rendered quite complex by an early decrease of glomerular filtration after RAS blockade and by side effects at higher doses such as renal sodium loss, hyperkalemia, anemia, etc. Animal experiments and recent clinical studies suggest that the doses of ACE inhibitors or angiotensin receptor blockers required for maximal reduction of proteinuria (as a surrogate marker) and for optimal nephroprotection (retardation of the loss of glomerular filtration) exceed those required for maximal lowering of blood pressure. Ongoing studies try to define the relative merits of high dose monotherapy (ACE inhibitors or angiotensin receptor blockers) versus a combination therapy of the two.
Introduction.
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Current and future challenges in anaemia management.
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Diabetic nephropathy and anaemia.
Anaemia is a frequent complication of diabetic nephropathy. It has only recently been recognised that in diabetic patients anaemia is seen not only in preterminal renal failure, but also frequently in patients with only minor derangement of renal function. At any level of glomerular filtration rate (GFR) anaemia is more frequent and severe in diabetic compared to nondiabetic patients. A major cause of anaemia is an inappropriate response of erythropoietin to anaemia. Additional factors are iron deficiency and iatrogenic factors, e.g. ACE inhibitor treatment. When serum creatinine is still normal, the erythropoietin concentration is predictive of more rapid loss of glomerular function. When serum creatinine is elevated, the haemoglobin values are predictive of the rate of progression. It is currently under investigation whether reversal of anaemia attenuates the rate of progression. Because most of the late complications of diabetes (retinopathy, neuropathy, heart disease, peripheral arterial disease) involve ischaemic tissue damage, it would be intuitively plausible that treatment with human recombinant erythropoietin should be beneficial, but definite evidence for this hypothesis is currently not available.
Impact of renal dysfunction as a cardiovascular risk factor.
This review summarizes the available evidence concerning the relationship between renal dysfunction and cardiovascular risk in non-diabetic patients. Based on numerous studies, there remains no more doubt today, that even minor renal dysfunction, as reflected by microalbuminuria and/or decreased estimated glomerular filtration rate, causes a dramatic increase in cardiovascular risk. Renal dysfunction as a novel risk indicator should be incorporated into currently used algorithms to assess risk factor profile, not to the least because evaluation of renal function helps to select the most appropriate strategy to reduce the cardiovascular risk.
[Historical roles of salt].
Recently increasing evidence has been provided pointing to a close relation of salt consumption to hypertension as well as to target organ damage. It is interesting to note that the discussion concerning salt is unusually emotional. This may be explained, at least in part, by the fact that since ancient times salt had deep symbolic significance, as exemplified, mostly subconsciously, by many customs and expressions still in current use. In the past salt was essential to preserve food. The past importance of salt as a commodity can well be compared with that of oil today. These and further historical aspects of the role of salt are briefly dealt with in this article.
[Vascular access for hemodialysis: will the tunnelled atrial catheter solve the problems?].
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[10 minute consultation: hypokalemia as incidental finding].
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ACE-inhibition is superior to endothelin A receptor blockade in preventing abnormal capillary supply and fibrosis of the heart in experimental diabetes.
AIMS/HYPOTHESIS: There is little information whether cardiac capillary supply is deranged in diabetes. Hyperglycaemia is a potent stimulus for endothelin-1 (ET-1) production. We therefore hypothesised that increased ET-1 production in Streptozotocin-induced Type 1 diabetes causes abnormalities of cardiac capillaries and the aorta. To this end we compared the effects of an ET receptor A blocker (ETA-RB) with that of an ACE-inhibitor (ACE-i) or their combination in rats with Streptozotocin (STZ) diabetes. METHODS: Sprague Dawley rats were injected with 65 mg STZ i.v. and subsequently developed diabetes. Rats were left untreated or received daily either the ACE-i Trandolapril, the ETA-RB Darusentan or a combination of both. After 6 months the experiment was terminated and the heart and the aorta were investigated using quantitative morphological techniques. RESULTS: ACE-i but not ETA-RB lowered blood pressure in STZ Type 1 diabetic rats. Capillary length density was lower in untreated STZ diabetic rats (2932+/-128 mm/mm3) compared to non-diabetic control rats (3410+/-252 mm/mm3). Treatment with ACE-i (3568+/-431 mm/mm3), but not with ETA-RB (2893+/-192 mm/mm3), prevented the decrease in capillary supply. Volume density of the myocardial interstitium was higher in untreated STZ diabetic rats (0.86+/-0.04%) compared to non-diabetic control rats (0.36+/-0.06%). In all three intervention groups the values were lower (ACE-i: 0.53+/-0.05%, ETA-RB: 0.7+/-0.08% and combination: 0.69+/-0.1). CONCLUSION/INTERPRETATION: Our study identifies a capillary defect of the heart in STZ diabetes, i.e. decreased capillary supply. This abnormality was reversed by ACE-i, but not by ETA-R blockade. A similar trend, although not complete normalisation, was seen in cardiac fibrosis.
[Health economic consequences of the use of irbesartan in patients in Germany with type 2 diabetes, nephropathy and hypertension].
BACKGROUND AND AIMS: The "Irbesartan in Diabetic Nephropathy Trial" (IDNT), demonstrated a reduction in the combined endpoint of doubling of serum creatinine, end-stage renal disease (ESRD) or death compared to control or amlodipine arms in patients with hypertension, type 2 diabetes and overt nephropathy when treated with irbesartan. Aim of this study is to compare long-term consequences in costs and outcomes of IDNT treatment alternatives from the German health care system's perspective. METHODS: A Markov model simulated progression from overt nephropathy to doubling of serum creatinine, end-stage renal disease, and death in patients with hypertension, type 2 diabetes and overt nephropathy for the three treatment arms. Treatment-specific probabilities were derived from IDNT. German-specific ESRD-related data were retrieved from published sources to reflect local management practices, ESRD outcomes and costs. A time horizon of 10 years was used. Delay in onset of ESRD and mean costs per patient were calculated. Future costs were discounted at 5 % per annum. RESULTS: The cumulative incidence of ESRD after 10 years with irbesartan (36 %) is lower compared to amlodipine (49 %) or control (45 %). Irbesartan leads to cost savings of 14 424 EUR and 8 720 EUR per patient versus amlodipine or control respectively. CONCLUSION: Treating patients with hypertension, type 2 diabetes and nephropathy using irbesartan lowers the cumulative incidence of ESRD and is cost-saving compared to amlodipine or control.
Comparison of renal morphology in the Streptozotocin and the SHR/N-cp models of diabetes.
The Streptozotocin (STZ) model of diabetes is commonly used for studies of diabetic nephropathy although the histological lesions of the kidney are mild and do not resemble those seen in diabetic patients. The SHR/N-cp rat model of type II diabetes spontaneously develops pronounced abnormalities in renal histology. In the present study, we compared renal morphology in the STZ rat and the diabetic SHR/N-cp rat. Sprague-Dawley rats received STZ, developed diabetes after 2 days and were treated with insulin. In the SHR/N-cp rat, obesity is inherited as an autosomal recessive trait. The progeny are either lean (used as controls) or obese and diabetic. After 6 months of observation, STZ and SHR/N-cp rats were killed. The renal damage was evaluated by assessing damage indices and by using stereological techniques. In addition, immunohistochemistry and electron microscopy were performed. The glomerular and tubulointerstitial changes were much more pronounced in the diabetic SHR/N-cp compared to the STZ model. In parallel glomerular PCNA+cells were significantly more frequent and expression of TGF-beta and PDGF by immunohistochemistry in glomeruli and in the tubulointerstitial space was more pronounced in SHR/N-cp compared to STZ rats. The glomeruli of SHR/N-cp contained less and larger podocytes as well as smaller mesangial cells embedded in more mesangial matrix compared to STZ. Similarly, less, but larger endothelial cells were found in SHR/N-cp than in STZ rats. The mean glomerular volume was similarly increased in the two models. Albumin excretion was only modestly increased in STZ diabetes, but pronounced in the SHR/N-cp rat. Although the STZ model of diabetes exhibits numerous biochemical sequelae of hyperglycemia, the morphological lesions are unimpressive. In contrast, the diabetic SHR/N-cp exhibits marked structural lesions, particularly podocyte damage and mesangial expansion that promise to make it a more suitable model for investigation of diabetic glomerulosclerosis.
A 63bp deletion in the promoter of rage correlates with a decreased risk for nephropathy in patients with type 2 diabetes.
Several polymorphisms have been identified in the RAGE-promoter region that might modulate the outcome of disease. Here we analyse the association of a 63bp deletion (delta63) spanning from bp - 407 to bp - 345 with diabetic nephropathy. The deletion was determined using the polymerase chain reaction (PCR) in a cross-sectional study with 1087 patients with type 1 diabetes (n = 559) and type 2 diabetes (n = 528). 475 patients with osteoporosis served as disease independent control. The prevalence of the heterozygous genotype did not significantly differ between the three groups (type 1: 2.15 %, type 2: 2.27 %, controls: 1.47 %), indicating that heterozygous delta63 is not related to the manifestation of diabetes. Homozygous carriers were not identified in this study. The heterozygous delta63 genotype, was associated with a reduced prevalence of diabetic nephropathy in patients with type 2 diabetes (OR = 0.06; 95 % CI: [0.05, 0.07]), but not in patients with type 1 (OR = 1.49; 95 % CI: [1.14, 1.94]). We conclude, that patients with type 2 diabetes and the 63bp deletion in the promoter of RAGE seem to be protected from diabetic nephropathy. The observed difference between type 1 and type 2 diabetes might point to diverse pathomechanisms of nephropathy in both types of diabetes.