[The therapy of vasculitis].
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Anti-Inflammatory Agents↗
Biomedical subjects
E Ritz
Publications and source records attributed to E Ritz.
[The forms and diagnosis of vasculitis].
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Diagnosis, Differential↗
Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group.
BACKGROUND: Drugs that inhibit angiotensin-converting enzyme slow the progression of renal insufficiency in patients with diabetic neuropathy. Whether these drugs have a similar action in patients with other renal diseases is not known. We conducted a study to determine the effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of renal insufficiency in patients with various underlying renal diseases. METHODS: In a three-year trial involving 583 patients with renal insufficiency caused by various disorders, 300 patients received benazepril and 283 received placebo. The underlying diseases included glomerulopathies (in 192 patients), interstitial nephritis (in 105), nephrosclerosis (in 97), polycystic kidney disease (in 64), diabetic nephropathy (in 21), and miscellaneous or unknown disorders (in 104). The severity of renal insufficiency was classified according to the base-line creatinine clearance: 227 patients had mild insufficiency (creatinine clearance, 46 TO 60 ml per minute), and 356 had moderate insufficiency (creatinine clearance, 30 to 45 ml per minute). The primary end point was a doubling of the base-line serum creatine concentration or the need for dialysis. RESULTS: At three years. 31 patients in the benazepril group and 57 in the placebo group had reached the primary end point (P<0.001). In the benazepril group, the reduction in the risk of reaching the end point was 53 percent overall (95 percent confidence interval, 27 to 70 percent), 71 percent (95 percent confidence interval, 21 to 90 percent) among the patients with mild renal insufficiency, and 46 percent (95 percent confidence interval, 12 to 67 percent) among those with moderate renal insufficiency. The reduction in risk was greatest among the male patients; those with glomerular diseases, diabetic nephropathy, or miscellaneous or unknown causes of renal disease; and those with base-line urinary protein excretion above 1 g per 24 hours. Benazepril was not effective in patients with polycystic disease. Diastolic pressure decreased by 3.5 to 5.0 mm Hg in the benazepril group and increased by 0.2 to 1.5 mm Hg in the placebo group. CONCLUSIONS: Benazepril provides protection against the progression of renal insufficiency in patients with various renal diseases.
Adult↗
Immunochemiluminometric assay with two monoclonal antibodies against the N-terminal sequence of human parathyroid hormone.
We have developed an immunochemiluminometric assay (ICMA) with two monoclonal antibodies for the N-terminal sequence of human parathyroid hormone (hPTH). One monoclonal antibody (A1-70) was physically adsorbed onto polystyrene beads, the other (B1-70) was labelled with acridinium ester and synthetic hPTH (1-38) was used as standard. This assay has cross-reactions with synthetic hPTH (1-34) and hPTH (1-84) but no cross-reactions with hPTH (4-16), (28-48), (39-84), (44-68), (53-84) and hPTH-rP (1-86). The assay detection limit is 0.4 pmol/l. The normal range is 1.3-12 pmol/l based on 72 normal volunteers. About 91% of study patients (n = 58) with surgically proven primary hyperparathyroidism (1 degree HPT) had PTH values above normal and one of them showed a low normal intact PTH value but elevated PTH values with use of this assay. After immunoabsorption of plasma samples from patients with secondary hyperparathyroidism (2 degrees HPT) on hemodialysis with polystyrene beads containing antibodies against hPTH (39-84), some patients still showed significant amounts of PTH in this new ICMA but not intact PTH. The data reveal that significant amounts of amino-terminal immunoreactive PTH fragments rarely exist in 1 degree HPT but are present in some patients with 2 degrees HPT. The major advantage of this assay is to measure both amino-terminal PTH fragments and intact PTH with no interference from carboxy-terminal PTH fragments because two anti-N-terminal hormone sequence monoclonal antibodies are used.
Adult↗
Bradykinin excretion is increased in severely hyperglycemic streptozotocin-diabetic rats.
The renal kallikrein-kinin system (KKS) was studied in pair-fed streptozotocin (STZ)-induced diabetic rats and compared with age-matched controls. Twelve weeks after STZ injection, rats were normotensive, showed hyperglycemia, proteinuria, polydipsia and reduced glomerular filtration rate (GFR) and body weight. The activities of urinary prekallikrein (PKLK) and kallikrein (KLK) were reduced accompanied by an up to 3-fold increase of bradykinin (BK) excretion compared to controls. The increased BK excretion suggests that the renal KKS in STZ-diabetes is activated and that the reduction in urinary PKLK and KLK activity may be due to an increased consumption of these enzymes or to a negative feedback mechanism. The stimulation of the renal KKS in STZ-diabetes could reflect an attempt of the organism to balance glomerular hypertension.
Animals↗
Antibodies to neutrophil elastase: a study in patients with vasculitis.
Whether antibodies to elastase (EL) exist in autoimmune disease is controversial, due in part to inadequate methods used to determine antibody titers. We have developed a highly sensitive and specific enzyme-linked immunosorbent assay, using immobilized EL and mouse monoclonal antibodies for standardization. The specificity of the enzyme-linked immunosorbent assay was confirmed by absorption studies and Western blot analysis. Using this enzyme-linked immunosorbent assay, antibodies to EL were found in antineutrophil cytoplasmic antibody-positive vasculitis patients to a higher degree than reported in the literature (in eight of 108 patients with Wegener's granulomatosis and in 15 of 78 patients with microscopic polyangiitis). Patients with Wegener's granulomatosis or microscopic polyangiitis and antibodies to EL had significantly more severe renal involvement, as indicated by the higher frequency of dialysis dependency. Also in contrast to reported data, antibodies to EL were found less frequently in patients with systemic lupus erythematosus (nine of 64 patients). Binding of systemic lupus erythematosus sera to uncoated plates, giving a nonspecific reaction, was seen quite frequently, which might explain the discrepancy.
Adult↗
Diabetic nephropathy in type II diabetes.
The incidence of end-stage renal failure in patients with type II diabetes has dramatically increased in recent years, both in the United States and, with some delay, in some European countries. These epidemiologic observations have thoroughly dispelled the mistaken belief that renal prognosis was benign in type II diabetes. Recent interest has focused on the early stages of nephropathy in type II diabetes. With respect to renal hemodynamics, renal morphology, and progression of established diabetic nephropathy, there are no substantial differences between types I and type II diabetes. There is good evidence that preventive measures are effective, ie, glycemic control, blood pressure control, protein restriction, and discontinuation of smoking. The high prevalence of the disease (which in principle is preventable) calls for intense efforts to (1) educate the medical community, (2) substantially improve patient education and medical care, and (3) intensify research in this field.
Animals↗
Inhibitory effect of calcium channel blockers on human mesangial cell growth: evidence for actions independent of L-type Ca2+ channels.
Calcium channel blockers (CCB) are known to affect the outcome of glomerulosclerosis in vivo and to suppress mesangial cell proliferation and cytokine production in vitro. It is uncertain, however, whether (i) human adult mesangial cells (HMC) express L-type Ca2+ channels and (ii) whether the effect of CCB on HMC is mediated by inhibition of L-type Ca2+ channels. In single cell preparations of HMC, the L-type Ca2+ channel agonist Bay K 8644 and K+-depolarization of the cell membrane caused a transient increase of cytosolic free Ca2+ ([Ca2+]i) in 60 to 80% of the cells. The CCB verapamil and nifedipine partially inhibited the effect of Bay K 8644 and K+-depolarization on [Ca2+]i. Binding experiments confirmed these functional studies by showing specific binding at the phenylalkylamine binding site of L-Type Ca2+ channels. Quiescent HMC were stimulated with fetal calf serum (FCS) or growth factors (platelet derived growth factor A/B, epidermal growth factor, angiotensin II, endothelin 1) in the presence of various concentrations (10(-10) to 10(-5) M) of different CCB: either (R)-verapamil, (S)-verapamil or the raceme of verapamil, and nifedipine or diltiazem, respectively. In addition, the enantiomers of devapamil were studied, because their action on the L-type Ca2+ channel is more stereoselective than that of the enantiomers of verapamil. At high concentrations (10(-6) to 10(-5) M) (R,S)-verapamil decreased cell numbers in cultures of quiescent HMC, increased LDH in the supernatant, and caused loss of trypan blue exclusion (cytotoxicity). At lower concentrations (R,S)-verapamil showed no cytotoxicity, but had two effects: (1.) concentration dependent (down to 10(-8) M) inhibition of indices of cell proliferation, that is, (i) stimulated (FCS or growth factor) 3H-thymidine incorporation and (ii) increment in cell number; and (2.) inhibition of indices of cell or matrix protein synthesis, that is, (i) stimulated 3H-methionine incorporation and (ii) 3H-proline incorporation. At equimolar concentrations the dihydropyridine nifedipine was equipotent with verapamil, whereas the benzothiazepine diltiazem was conspicuously less effective. Even at the lowest effective concentration (10(-8) M) comparison of (R)- and (S)-verapamil showed no significant difference between the enantiomer with weak or with strong effect on L-type Ca2+ channels, and this was true even when the more stereoselective enantiomers of devapamil were tested. These observations argue against the notion that effects of CCB result from specific interaction with L-type Ca2+ channels. The data are more consistent with the idea that interactions with targets other than L-type Ca2+ channels are involved.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Endocrine disturbances of calcium metabolism in uremia: renal causes and systemic consequences.
The genesis of the hormonal disturbances in calcium metabolism of renal failure is complex, but can be understood basically as the consequence of the deranged endocrine function of the kidney, that is, failing biosynthesis of the renal secosterol hormone 1,25 OH2D3. It is of interest to note how our concepts concerning the genesis of these disturbances, and the role of 1,25 OH2D3 therein, have changed with time. We illustrate this using three examples: (i) the signals activating the parathyroid gland in early renal failure; (ii) the genesis of parathyroid hyperplasia; and (iii) the actions of 1,25 OH2D3 in renal failure unrelated to calcium control.
Animals↗
Early increase in blood pressure and diastolic left ventricular malfunction in patients with glomerulonephritis.
In patients with diabetic nephropathy blood pressure increases progressively before the conventional threshold of normal blood pressure (140/90 mm Hg) is transgressed. In patients with glomerulonephritis, no information on this point is available. To clarify this issue we sequentially examined 20 untreated patients with biopsy-proven primary chronic glomerulonephritis (GN) who had casual blood pressure below 140/90 mm Hg and normal GFR by inulin clearance. Patients were compared with normotensive healthy controls who were matched for BMI, gender and age. We measured ambulatory 24-hour blood pressure (SpaceLab system), echocardiography (ASE criteria, Acuson 128 XP 10), CIn and CPAH, urinary Na excretion, PRA and insulin concentration. In patients with GN, the median 24 hour (P < 0.0005), daytime (P < 0.001) and nocturnal sleeping time (P < 0.0001) MAP values were significantly higher than in matched controls (daytime, mean 97 mm Hg, 85 to 106 GN vs. 89 controls range 82 to 102; nocturnal sleeping time, mean 80.3 mm Hg, 71 to 89.5 GN vs. 73 controls, range 63 to 84). Echocardiographic examination showed significantly greater posterior wall thickness (P < 0.01) and ventricular septal thickness (P < 0.003). In addition the early diastolic to late diastolic (E/A) ratio of mitral valve peak inflow velocity was significantly (P < 0.0008) lower in patients. The data point to left ventricular wall thickening accompanied by LV diastolic malfunction. The study documents elevated ambulatory blood pressure in patients with primary chronic glomerulonephritis despite normal body weight and normal GFR. This is associated with evidence of target organ damage in the heart. The findings suggest that in patients with glomerulonephritis blood pressure increases initially within the normotensive range. This observation in conjunction with evidence of early target organ changes provides an argument for early antihypertensive intervention, but controlled trials to test efficacy and safety of this proposal are necessary.
Adult↗
Vena cava diameter measurement for estimation of dry weight in haemodialysis patients.
A correct estimation of volume status and so-called dry weight in dialysis patients remains a difficult clinical problem. Clinical status and chest X-ray are not sensitive enough, while invasively measured central venous pressures are not routinely available. Recently, the sonographic determination of the diameter and collapse of the inferior vena cava (IVC) has been proposed as a noninvasive method for estimating intravascular volume. We tried to evaluate the clinical relevance of this method in dialysis patients by comparing it with central venous pressures (CVP) and atrial natriuretic peptide (ANP). To establish a normal range and to control for confounding variables, we examined a large number of healthy controls. Furthermore, the influence of tricuspid insufficiency was examined echocardiographically. Measurements of the IVC diameters were well reproducible, with a coefficient of variation for interobserver error of 2.2%, and a coefficient of variation of 1.4% for intraobserver error. The collapse index was less well reproducible and therefore not used for further analysis. In 86 normal controls (age 18 to 76 years), IVC diameters showed a wide variation, and they were not correlated to age, height, weight, or body surface area. However, there was a significant correlation of IVCex to heart rate (r = 0.63, P < 0.001). Therefore, we calculated percentiles of the heart rate-IVCex relation in normals, and compared the results in patients to these. In 10 overhydrated haemodialysis patients, CVP was closely correlated to IVCex (r = 0.72, P < 0.001), but there was a wide interindividual variation of the slope of this relation. An IVCex above the 95th percentile of normal was a good predictor of an elevated CVP (i.e. > 12 cmH2O). In another 39 stable, chronic haemodialysis patients, there was a significant correlation of the intradialytic decrease of ANP and IVCex (r = 0.69, P < 0.001). However, this correlation existed only in patients without tricuspid insufficiency. In summary, sonography of the inferior vena cava is a valuable tool for estimating dry weight in dialysis patients, provided that some caveats are kept in mind: (i) there is a wide variation of IVC diameters in normals, and single measurements are not helpful in individual patients; (ii) there is a significant, inverse correlation between IVC diameters and heart rate, and the precision of intravascular volume assessment is enhanced by interpreting heart rate corrected diameters; (iii) the presence of tricuspid insufficiency leads to unreliable results, as it influences IVC diameters per se. Intravascular volume changes are reflected by IVC measurements, as shown by the correlation to other indices of intravascular volume, such as CVP and alpha-hANP. IVC sonography is noninvasive and easily available; serial measurements allow an estimation of changes of intravascular volume in patients without cardiac filling impairment. However, unlike with body impedance, interstitial volume is not reflected by IVC diameters.
Adolescent↗
New insights into mechanisms of blood pressure regulation in patients with uraemia.
There is no doubt that in patients with endstage renal failure sodium/water retention and (often unrecognized) hypervolaemia is the single most important determinant for elevated blood pressure. More detailed analysis reveals that in the renal patient susceptibility to hypervolaemia is increased due to inappropriately elevated activity of pressor systems (and/or decreased activity of depressor systems). These abnormalities comprise inappropriately activated renin-angiotensin system (RAS) (circulating and local) as well as sympathetic activity, but more hypothetical possibilities must also be considered, e.g. abnormalities of renal vasodilators (medullipin), L-arginine-derived agmatin, endothelin and NO.
Blood Pressure↗
What is the appropriate dialysate calcium concentration for the dialysis patient?
Recently, there has been a trend to lower dialysate calcium concentrations because of the frequent occurrence of hypercalcaemia with the use of calcium-containing phosphate binders. No single dialysate calcium concentration is available which suits all dialysis patients. The risk of hypercalcaemia depends on intradialytic (diffusive and convective) calcium transport and interdialytic calcium balance (negative or positive intestinal balance). Low dialysate calcium concentrations expose the patient to the risks of negative calcium balance and increase in parathyroid hormone concentration, particularly if patients are non-compliant with the intake of calcium-containing phosphate binders.
Calcium↗
Expression of receptors for advanced glycation end-products in occlusive vascular and renal disease.
Formation and deposition of advanced glycation end-products (AGEs) has been linked to late diabetic complications. Interactions of AGEs are at least partly mediated by binding of AGEs to their cellular surface receptor RAGE. This review summarizes the immunohistological data obtained for RAGE distribution in vessel segments of diabetic and non-diabetic patients with peripheral occlusive vascular disease and in kidneys of patients with diabetic nephropathy, and inflammatory and non-inflammatory renal disease. It is demonstrated that increased RAGE expression is not restricted to diabetes mellitus but contributes to a range of vascular and renal disorders.
Diabetic Angiopathies↗
Autosomal dominant polycystic kidney disease--the patient on renal replacement therapy.
In Europe approximately 6% of all patients on chronic renal replacement therapy suffer from polycystic kidney disease. Survival of patients with polycystic kidney disease on renal replacement therapy is better than for other primary renal diseases, despite a similar cardiovascular risk profile. We documented a significantly higher erythropoietin level in polycystic patients even in advanced uraemia and on dialysis. A better haemoglobin level seems to improve long-term survival because of a possible beneficial effect on cardiac function. There is no increased risk of renal cell carcinoma in patients with autosomal dominant polycystic kidney disease. Polycystic patients on dialysis should be followed for cardiac valve abnormalities and cerebral aneurysms.
Cardiovascular Diseases↗
Renal haemodynamics in the elderly.
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Aged↗
Nephropathy of type II diabetes mellitus.
In recent years there has been a dramatic increase of almost epidemic proportions in the incidence of patients with type II diabetes mellitus who reach end-stage renal failure and enter renal replacement programmes. This is mainly due to the greater prevalence and better survival of patients with type II diabetes and diabetic nephropathy. Against this background measures to prevent the appearance and progression of diabetic nephropathy are of immense interest. Apart from the undoubted role of hyperglycaemia, the importance of genetic determinants of nephropathy has recently been recognized. Factors of proven or suspected efficacy in attenuating progression include: hypertension, hyperglycaemia, smoking and proteinuria. The role of dietary protein intake is less well documented. Nephropathy in type II diabetes has become the single most common cause of end-stage renal failure in Germany and is today a major challenge to clinical nephrology.
Blood Pressure↗
Prevalence of dialysis-related amyloidosis in diabetic patients. Diabetes Amyloid Study Group.
It has recently been shown that beta 2-microglobulin isolated from amyloid deposits in dialysis patients is modified by advanced glycation (AGE). In this context it appeared of interest to examine in a cross-sectional multicentre study whether dialysis-related amyloidosis, as evaluated by X-ray assessment of cysts in the metacarpal bones, was different in diabetic patients on maintenance haemodialysis for more than 5 years time compared with matched non-diabetic controls. We evaluated the hand skeleton of 75 diabetic patients (9 type I, 66 type II; 35 male, 40 female; median age 64 years, range 31-86; median duration of dialysis 7 years, range 5-17). They were compared with 150 patients without diabetes mellitus who were matched for age, gender and duration of dialysis. Hand X-rays were centrally evaluated by one radiologist unaware of the underlying clinical diagnosis. The overall frequency of amyloid cysts was 9/75 (12%) in diabetic patients (95% confidence interval 4.6-19.3%) and 28/150 (19%) in matched controls (95% confidence interval 12.4-24.9%). The results indicate that diabetes mellitus does not confer an increased risk of dialysis-related amyloid cysts. The results are of interest with respect to the mechanism of amyloid formation.
Adult↗