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Biomedical subjects

Ralf Dikow

Publications and source records attributed to Ralf Dikow.

At least 19 recordsLinked to original sources
PubMed2006

Salt--a potential 'uremic toxin'?

It has been known for decades that salt (NaCl) determines extracellular volume as well as blood pressure and is one cause of hypertension. The difficulty to control the NaCl balance and thus treat sodium overload and hypertension in patients on dialysis has been recognized by Scribner in the early days of dialysis. In recent years, an impressive body of evidence has accumulated indicating that in essential hypertension, NaCl--blood pressure independently--causes target organ damage such as left ventricular hypertrophy, microalbuminuria, and increased aortic stiffness. It has further been recognized that NaCl increases oxidative stress and, again blood pressure independently, amplifies tissue injury induced by aldosterone. In renal damage models, progression is dramatically accelerated by high NaCl intake. Sodium as a potential culprit in progression to target organ damage in terminal renal failure has not been well investigated so far. However, it is possible, and indeed likely, that sodium plays an adverse role in the genesis of target organ damage in terminal renal failure.

Albuminuria↗
PubMed2005

Pathophysiology of cardiovascular disease and renal failure.

This article discusses the epidemiology of cardiovascular (CV) events in end-stage and early renal disease, summarizes the profile of classic and nonclassic CV risk factors in renal patients, highlights recent evidence documenting accelerated atherogenesis in renal disease, and provides information on the central arteries and heart as target organs for CV damage in renal disease.

Aorta↗
PubMed2005

Diabetic nephropathy: recent insights into the pathophysiology and the progression of diabetic nephropathy.

Diabetes has become the single most frequent comorbid condition in patients admitted for renal replacement therapy. This is the result of a greater prevalence of type 2 diabetes and better survival of diabetic patients. Progress has been made in pinpointing the predisposition to diabetes on metabolic abnormalities of muscle mitochondrial metabolism, but the long sought genes predisposing to diabetes and to diabetic nephropathy have not yet been identified. Of great concern are experimental studies documenting that maternal hyperglycemia causes nephron underdosing in the offspring. Relevant to pathogenesis and treatment of diabetic nephropathy are, among others, recent insights that hyperglycemia sensitizes target organs to blood pressure-induced damage, and that local renin-angiotensin systems play an important role in genesis and progression of diabetic nephropathy.

Diabetes Mellitus, Type 2↗
PubMed2005

Role of calcium-phosphorous disorders in the progression of renal failure.

Among factors related to disturbed calcium-phosphate metabolism in chronic kidney disease, the following must be mainly considered as potential culprits in the progression of renal dysfunction: hyperphosphatemia, hyperparathyroidism, lack of active vitamin D, and possibly excess of the phosphaturic hormone FGF 23. Early experimental work suggested a parathyroid hormone (PTH)-independent beneficial role of phosphate restriction on progression in rats (animals with physiologic hyperphosphatemia), so that the generalization of the data is uncertain. Recent observational studies also found a correlation between S-phosphate and progression, but it remains uncertain whether the relationship is causal. There is very little direct experimental or clinical evidence for a role of PTH in accelerating progression, although the PTH1 receptor is expressed in podocytes and PTH affects podocyte function (i.e., Kf). It is undoubtedly a candidate that requires more sophisticated investigation. Recently, it has been shown that progression is significantly attenuated by calcimimetics (and equally by parathyroidectomy), but it is currently impossible to exclude a confounding effect of lower blood pressure values. The most solid evidence for an impact on progression exists for active vitamin D. In the past, it was widely assumed that vitamin D was "nephrotoxic." In retrospect, nephrotoxicity was the result of hypercalcemia. Recent evidence is overwhelming that 1,25(OH)2D3 and its analogues attenuate progression in noninflammatory and inflammatory models of chronic kidney disease. The main target cells identified so far are podocytes and mesangial cells. It is currently unknown whether the novel phosphaturic hormones have an impact on progression.

Aniline Compounds↗
PubMed2005

Hemodialysis--from early days to tomorrow.

The Nestor of chronic dialysis, Belding Scribner, was well aware of most problems which plague hemodialysis to this day, but the major problem we are confronted with today has emerged much later, i.e. excessive cardiovascular mortality. Apart from modulating duration and frequency of dialysis, there is currently no logistic or technological solution immediately apparent to solve this problem. Elucidating and correcting the cardiovascular risk is the most important challenge to clinical nephrology today.

Cardiovascular Diseases↗
PubMed2004

Compelling drug indications in diabetic and nondiabetic nephropathy.

To halt progression of renal disease, the combination of several interventional strategies is recommended. The most important components comprise lowering of systolic blood pressure to approximately 120 mm Hg; providing pharmacologic blockade of the renin-angiotensin system by angiotensin-converting enzyme inhibitors or angiotensin receptor blockers; and reducing proteinuria to rates of less than 1 g/d.

Angiotensin Receptor Antagonists↗
PubMed2004

Renal disease: value of functional magnetic resonance imaging with flow and perfusion measurements.

PURPOSE: To differentiate healthy kidneys from diseased kidneys, we propose a combined magnetic resonance (MR) examination that includes measurements of renal arterial blood flow and parenchymal perfusion. MATERIALS AND METHODS: A total of 130 kidneys (patients/healthy volunteers: 83/47) were examined using renal artery MR flow measurements and renal parenchymal perfusion measurements, as well as contrast-enhanced MR angiography. Cine phase-contrast-flow measurements were performed using an ECG-gated fast low angle shot pulse sequence; perfusion was measured with an arterial spin labeling flow-sensitive alternating inversion recovery technique. Contrast-enhanced MR angiography was performed with a fast 3D gradient echo sequence in a single breath hold. For evaluation, kidneys were divided into groups based on nephrologic diagnosis of the patient. Recursive partitioning and Wilcoxon rank-sum tests were used to separate the different groups. RESULTS: Significant differences in mean renal artery flow and parenchymal perfusion were found in kidneys with renal artery stenosis as well as parenchymal disease as compared with healthy kidneys. Using a classification tree derived from the recursive partitioning, a specificity of 99% and sensitivity of 69% with a positive/negative predictive value of 97%/84% was achieved for the separation of healthy kidneys from kidneys with vascular, parenchymal or combined disease. The overall accuracy was 88%. CONCLUSION: The combination of cine PC flow measurements and MR perfusion measurements offers a comprehensive assessment of both renovascular and renoparenchymal disease and provide a noninvasive approach to differentiate between these kidneys and normal kidneys.

Adult↗
PubMed2004

Increased infarct size in uremic rats: reduced ischemia tolerance?

In patients with renal failure, myocardial infarction (MI) is more frequent and the rate of death from acute MI is very high. It has been argued that ischemia tolerance of the heart is reduced in uremia, but direct evidence for this hypothesis has not been provided. It was the purpose of this study (1) to ligate the left coronary artery and to measure the nonperfused area (risk area: total infarction plus penumbra) as well as the area of total infarction in subtotally nephrectomized (SNX) rats compared with sham-operated pair-fed control rats and (2) to examine the effects of potential confounders such as BP, sympathetic overactivity, and salt retention. The left coronary artery was ligated for 60 min, followed by reperfusion for 90 min. For visualizing perfused myocardium, lissamine green ink was injected. The nonperfused area (lissamine exclusion) and the area of total infarction (triphenyltetrazolium chloride stain) were assessed in sections of the left ventricle using image analysis. Groups of SNX rats also received: antihypertensive treatment (nadolol plus hydralazine); moxonidine; high salt diet or low salt diet (1.58% versus 0.015%). In surviving animals, the nonperfused area at risk (as the proportion of total left ventricular area), presumably determined by the geometry of vascular supply, was similar in sham-operated and SNX animals (0.38 +/- 0.13 versus 0.45 +/- 0.09; NS). In contrast, the infarcted area, given as a proportion of the nonperfused risk area, was significantly (P < 0.003) higher in SNX (0.68 +/- 0.09) compared with sham-operated (0.51 +/- 0.11) rats and was not altered by any of the above interventions. The finding that a greater proportion of nonperfused myocardium undergoes total necrosis is consistent with the hypothesis of reduced ischemia tolerance of the heart in renal failure. The findings could explain the high rate of death from MI in patients with impaired renal function.

Animals↗
PubMed2002

Renal dysfunction as a cardiovascular risk factor.

Indices of altered renal function (eg, microalbuminuria, increased serum creatinine concentration, or decrease in estimated creatinine clearance, particularly overt proteinuria) are independent predictors of cardiovascular morbidity and mortality. These parameters should be routinely evaluated in the elderly and in high cardiovascular risk populations, particularly when hypertension is present. Hypertensive kidney damage should be prevented by early aggressive treatment of hypertensive patients with microalbuminuria. To avoid further aggravation of high cardiovascular risk, antihypertensive agents devoid of unwanted metabolic side effects should be used. Epidemiologic information suggests that renal and cardiovascular outcome run parallel in this segment of the population.

Antihypertensive Agents↗
PubMed2002

Kidney and hypertension.

There is a unique relationship between the kidney and blood pressure (BP): on the one hand, renal dysfunction and particularly renal disease cause an increase in BP, while on the other hand, high BP accelerates loss of function of the diseased kidney. Transplantation studies, both in experimental animals and humans, documented that "blood pressure goes with the kidney," a normotensive recipient of a kidney genetically programmed for hypertension (HT) will develop HT, while conversely hypertensive patients with renal failure receiving the kidney of a normotensive donor may develop normotension. Family studies showed higher BP values and more frequent HT in first degree relatives of patients with primary glomerulonephritis or diabetic nephropathy, both type 1 and type 2. The notion that HT accelerates the loss of renal function has been proposed at the turn of the century, but definite evidence by observational and interventional studies has only been provided in the last two decades. The issue has been much confounded by the mistaken believe that damaged kidneys require higher BP values in order to function properly. The mechanisms of BP increase in renal disease comprise: salt retention, inappropriate activity of the renin-angiotensin system (RAS) and of the sympathetic nerve system as well as impaired endothelial cell-mediated vasodilatation. There is ample evidence both in primary renal disease (AIPRI and REIN trials) and in nephropathy of type 1 and type 2 diabetes (IDNT, RENAAL) that pharmacological blockade of the RAS by angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers has BP-independent renoprotective effects. More recently, it has also been shown that blockade of the sympathetic nerve system has BP-independent effects on albuminuria and on glomerulosclerosis.

Humans↗
PubMed2002

Angiotensin receptor antagonists in patients with nephropathy due to type 2 diabetes.

In the past few years diabetes has become the leading cause of end-stage renal disease in all Western countries. A correlation between blood pressure and rate of progression in diabetic nephropathy was noted very early, and increased local activity of the renin angiotensin system was identified as a major pathophysiological mechanism for proteinuria and nephrosclerosis in diabetic patients. Angiotensin converting enzyme (ACE) inhibitors have been shown to slow progression of nephropathy in type 1 diabetic patients. The majority of diabetic patients with nephropathy, however, are suffering from type 2 diabetes and until last year there was no convincing evidence of ACE inhibitors being able to slow progression in type 2 diabetic patients with nephropathy. Three new studies now fill this gap, showing that angiotensin receptor blockers (ARB) are nephroprotective in patients with type 2 diabetes, independently of blood pressure. This review provides an in-depth discussion of the results of these studies and provides recommendations for patient management.

Angiotensin II↗
PubMed2002

How should we manage anaemia in patients with diabetes?

Anaemia is an important component of diabetic nephropathy but only recently has it attracted the attention of diabetologists and nephrologists. In diabetic patients, anaemia is the result of diminished erythropoietin production and, to a lesser degree, of increased excretion of erythropoietin in the urine, whereas erythropoietin responsiveness remains unchanged. Although erythropoietin concentrations are predictive of the rate of progression of renal disease, epidemiological studies have failed to show lower haemoglobin concentrations in patients with diabetic compared with non-diabetic renal disease with impaired renal function. However, inappropriately low erythropoietin concentrations and anaemia have been reported in subcohorts of diabetic patients. Further studies are required to determine whether reversal of anaemia has beneficial effects on microvascular and macrovascular diabetic complications, particularly cardiac disease, retinopathy and peripheral arterial disease.

Anemia↗
PubMed2000

Opposing effects of angiotensin II on muscle and renal blood flow under euglycemic conditions.

Angiotensin II (Ang II) enhances insulin sensitivity in humans, and this is associated with a paradoxical increase in skeletal muscle blood flow. It is unclear whether these effects are mediated via subtype 1 receptors of Ang II, because these receptors are thought to mediate vasoconstriction. Insulin-stimulated glucose uptake (euglycemic clamp technique) and leg muscle blood flow (plethysmography) were measured in nine healthy male volunteers (mean age, 24 +/- 2 yr) on three occasions using a double-blind, placebo-controlled study design. The subjects were allocated in random order to (1) placebo premedication per os plus placebo infusion, (2) placebo premedication per os plus infusion of 5 ng Ang II/kg per min, and (3) premedication with 300 mg of the angiotensin II-1-receptor antagonist irbesartan per os plus infusion of 5 ng Ang II/kg per min. In addition, GFR and effective renal plasma flow were assessed using the steady-state inulin- and paraaminohippurate clearance. Insulin sensitivity (i.e., M value) and muscle blood flow after infusion of Ang II (9.3 +/- 1.8 mg/kg per min; 17.7 +/- 2.1 ml/100 g per min) were significantly higher than after placebo infusion (7.2 +/- 1.6 mg/kg per min, P: < 0.02; 13.5 +/- 1.8 ml/100 g per min, P: < 0.01). In contrast, after premedication with irbesartan, they were not significantly different (7.5 +/- 1.7 mg/kg per min; 14.3 +/- 1.9 ml/100 g per min) as compared with placebo infusion. Mean GFR and effective renal plasma flow were significantly lower (P: < 0.01), and renal vascular resistance was significantly higher (P: < 0.01) with Ang II infusion as compared with the placebo infusion study. Premedication with irbesartan almost completely blocked the vasoconstrictive effect of Ang II on renal vasculature. Under hyperinsulinemic euglycemic conditions, infusion of Ang II has opposing effects on regional arterial blood flow, i.e., an increase in skeletal muscle blood flow, but vasoconstriction of renal vasculature. Both effects are antagonized by blockade of subtype 1 Ang II receptors.

Adult↗
PubMedDate not supplied

Do AV fistulas contribute to cardiac mortality in hemodialysis patients?

Potential fistula-related problems which may impact on patient survival include high fistula flow with hyperkinetic circulation and cardiac failure, low fistula flow with the risks of underdialysis and fistula thrombosis, vascular access infection with local or systemic manifestations, and possibly induction and maintenance of a microinflammatory state (at least for synthetic grafts). All these complications are much more common with prosthetic grafts than with native arteriovenous (AV) fistulas. Fistula flow should be monitored (e.g., by duplex sonography) to guarantee adequate flow and permit preemptive intervention to avoid fistula thrombosis.

Arteriovenous Shunt, Surgical↗
PubMedDate not supplied

Cardiovascular abnormalities and hypertension in the elderly dialysis patient.

Elderly individuals comprise an ever-increasing proportion of patients on renal replacement therapy (RRT). As in younger patients, cardiovascular events are the major cause of death in the elderly on RRT, although the relative proportion succumbing to cardiovascular events is similar to that in young patients. An important observation is that the elderly are particularly likely to experience higher mortality if dialysis technique is suboptimal; they also experience particular benefit from successful renal transplantation. The latter observation has led to an "old for old" program in Europe.

Aged↗