Gerhard Warneke

Plasma-Endothelin bei Normalpersonen und Patienten mit nephrologisch-rheumatologischen und kardiovaskulären Erkrankungen

SummaryPlasma concentrations of the recently isolated potent vasoconstrictory peptide endothelin were measured in 382 patients. The investigations were performed by means of a sensitive radioimmunoassay specific for Endothelin-1, 2.The results from 110 healthy volunteers displayed a normal range of 44.67±3.51 pg/ml. Significantly raised levels were found in 33 patients with chronic end-stage renal failure both before and after hemodialysis. In contrast, 35 patients with compensated renal insufficiency did not differ from the normals. Sixty-five patients after kidney transplantation revealed significantly elevated levels, as did 27 patients with acute myocardial infarction, 8 after coronary bypass surgery, and 5 with liver cirrhosis. The mean values of 27 patients with untreated hypertension, 22 with secondary hypertension, of various causes and 16 with coronary artery disease were comparable to the normal population. The values were significantly decreased in 9 pregnant women with hypertension and proteinuria. A marked decline was found in 5 patients with systemic lupus erythematodes, while 20 patients with rheumatoid arthritis demonstrated only a slight decrease.The pathophysiological role of endothelin as a local or circulating hormone in regulating systemic blood pressure or release of other hormones remains to be determined.Plasma concentrations of the recently isolated potent vasoconstrictory peptide endothelin were measured in 382 patients. The investigations were performed by means of a sensitive radioimmunoassay specific for Endothelin-1, 2. The results from 110 healthy volunteers displayed a normal range of 44.67 +/- 3.51 pg/ml. Significantly raised levels were found in 33 patients with chronic end-stage renal failure both before and after hemodialysis. In contrast, 35 patients with compensated renal insufficiency did not differ from the normals. Sixty-five patients after kidney transplantation revealed significantly elevated levels, as did 27 patients with acute myocardial infarction, 8 after coronary bypass surgery, and 5 with liver cirrhosis. The mean values of 27 patients with untreated hypertension, 22 with secondary hypertension, of various causes and 16 with coronary artery disease were comparable to the normal population. The values were significantly decreased in 9 pregnant women with hypertension and proteinuria. A marked decline was found in 5 patients with systemic lupus erythematodes, while 20 patients with rheumatoid arthritis demonstrated only a slight decrease. The pathophysiological role of endothelin as a local or circulating hormone in regulating systemic blood pressure or release of other hormones remains to be determined.

Fehlender nächtlicher Blutdruckabfall in der 24-Stunden Blutdruckmessung: Hinweis auf eine sekundäre Hypertonie

SummaryNon invasive 24 hours ambulatory blood pressure monitoring was performed in 81 patients with secondary hypertension (renoparenchymatous nephropathyn=15, diabetic nephropathyn=10, Conns diseasen=4, renal artery stenosisn=15, pheochromocytoman=2, hemodialysis patientsn=15 and patients after kidney transplantationn=20). The results were compared to 201 patients with essential hypertension.The results showed that 98.5% of patients with essential hypertension have a nightly decline in blood pressure of at least 15 mmHg (systolic+diastolic), whereas 69% of patients with secondary hypertension showed either an attenuated circadian rhythm or no circadian rhythm. Patients with pheochromocytoma who had a night time increase in blood pressure demonstrated the greatest difference to the essential hypertension collective followed by patients with diabetic nephropathy, Conns disease and the group of patients after kidney transplantation. After successful treatment of the condition leading to hypertension circadian periodicity returned in some patients.In summary these results suggest that the absence of a night time decline in blood pressure during 24-hour-ambulatory monitoring is an indication of secondary hypertension.Non invasive 24 hours ambulatory blood pressure monitoring was performed in 81 patients with secondary hypertension (renoparenchymatous nephropathy n = 15, diabetic nephropathy n = 10, Conns disease n = 4, renal artery stenosis n = 15, pheochromocytoma n = 2, hemodialysis patients n = 15 and patients after kidney transplantation n = 20). The results were compared to 201 patients with essential hypertension. The results showed that 98.5% of patients with essential hypertension have a nightly decline in blood pressure of at least 15 mmHg (systolic + diastolic), whereas 69% of patients with secondary hypertension showed either an attenuated circadian rhythm or no circadian rhythm. Patients with pheochromocytoma who had a night time increase in blood pressure demonstrated the greatest difference to the essential hypertension collective followed by patients with diabetic nephropathy, Conns disease and the group of patients after kidney transplantation. After successful treatment of the condition leading to hypertension circadian periodicity returned in some patients. In summary these results suggest that the absence of a night time decline in blood pressure during 24-hour-ambulatory monitoring is an indication of secondary hypertension.

Parameters of the Kallikrein-Kinin, Coagulation and Fibrinolytic Systems as Early Indicators of Kidney Transplant Rejection

In order to find early indicators of kidney transplant rejection before clinical symptoms were noticed, parameters of the coagulation, fibrinolytic and kallikrein-kinin systems were measured. Nineteen patients were followed before and daily after kidney transplantation during the first week and every second day in the following weeks. All patients received immunosuppressive therapy with cyclosporin and corticoids. Ten patients suffered from transplant rejection. The first rejection occurred on the 7th day after transplantation. Of all the parameters measured, kallikrein inhibition, beta-FXIIa inhibition, plasminogen and antithrombin III were early indicators of kidney transplant rejections. A rise in these parameters could be demonstrated 2-3 days before clinical signs were noticed. In the other 9 patients no significant rises in antithrombin III, plasminogen, kallikrein inhibition and beta-FXIIa inhibition could be found.

[Ambulatory continuous 24-hour blood pressure monitoring in the diagnosis and therapy of arterial hypertension and modification by the antihypertensive agents enalapril, metoprolol, mepindolol and nitrendipine].

After improvement of technical equipment continuous ambulatory blood pressure monitoring is more and more used in the diagnosis of hypertension. New fully automatic systems permit a reliable registration and evaluation of 24-h blood pressure profiles. Typical circadian rhythmics of blood pressure, independent of a variability with different grades of activity, can be demonstrated in normotensive persons and also in patients with essential hypertension. Patients with secondary forms of hypertension show a nivellation or offset of circadian blood pressure rhythmics. A study was performed to examine the antihypertensive efficacy of the calcium antagonist Nitrendipine, the beta 1-adrenoceptor-selective blocker Metoprolol, the beta-blocker with intrinsic activity Mepindolol and the angiotensin converting enzyme inhibitor Enalapril in patients with mild to moderate hypertension over a period of 6 month. Continuous ambulatory blood pressure monitoring was performed before and after 6 month of therapy. 98 of 299 included patients broke off therapy, 47 of those because of side effects. Hydrochlorothiazide was given additionally if the antihypertensive effect of monotherapy was not sufficient after a period of 4 weeks. Morning blood pressure controls at the end of the treatment period showed normotensive values in all groups without significant differences between the groups before and at the end of the treatment period. The number of prescriptions of diuretics necessary to achieve normotension differed between the four treatment groups: Nitrendipine (n = 5), Metoprolol (n = 7), Mepindolol (n = 14), Enalapril (n = 20). In contrast to the morning blood pressure values the continuous 24-h blood pressure monitoring demonstrated significant differences between the therapy groups. Metoprolol turned out as most effective in lowering blood pressure and in reducing the number of systolic blood pressure peaks above 180 mmHg, but on the other hand showed the highest incidence of relative hypotension (less than 100 mmHg systolic, less than 80 mmHg diastolic). Mepindolol demonstrated a significant lower efficacy. In the Nitrendipin group least of all prescriptions of diuretics were necessary and the lowest number of hypotensive systolic blood pressure values occurred. Enalapril showed the most significant reduction of diastolic values above 100 mmHg and the lowest number of diastolic values below 80 mmHg, but the highest number of prescription of diuretics was necessary in the Enalapril group. In none of the four therapy groups a neutralisation of circadian blood pressure rhythmics was demonstrable.SummaryAfter improvement of technical equipment continuous ambulatory blood pressure monitoring is more and more used in the diagnosis of hypertension. New fully automatic systems permit a reliable registration and evaluation of 24-h blood pressure profiles. Typical circadian rhythmics of blood pressure, independent of a variability with different grades of activity, can be demonstrated in normotensive persons and also in patients with essential hypertension. Patients with secondary forms of hypertension show a nivellation or offset of circadian blood pressure rhythmics. A study was performed to examine the antihypertensive efficacy of the calcium antagonist Nitrendipine, theβ1-adrenoceptor-selective blocker Metoprolol, theβ-blocker with intrinsic activity Mepindolol and the angiotensin converting enzyme inhibitor Enalapril in patients with mild to moderate hypertension over a period of 6 month. Continuous ambulatory blood pressure monitoring was performed before and after 6 month of therapy. 98 of 299 included patients broke off therapy, 47 of those because of side effects. Hydrochlorothiazide was given additionally if the antihypertensive effect of monotherapy was not sufficient after a period of 4 weeks. Morning blood pressure controls at the end of the treatment period showed normotensive values in all groups without significant differences between the groups before and at the end of the treatment period. The number of prescriptions of diuretics necessary to achieve normotension differed between the four treatment groups: Nitrendipine (n=5), Metoprolol (n=7), Mepindolol (n=14), Enalapril (n=20).In contrast to the morning blood pressure values the continuous 24-h blood pressure monitoring demonstrated significant differences between the therapy groups. Metoprolol turned out as most effective in lowering blood pressure and in reducing the number of systolic blood pressure peaks above 180 mmHg, but on the other hand showed the highest incidence of relative hypotension (<100 mmHg systolic, <80 mmHg diastolic). Mepindolol demonstrated a significant lower efficacy. In the Nitrendipin group least of all prescriptions of diuretics were necessary and the lowest number of hypotensive systolic blood pressure values occurred. Enalapril showed the most significant reduction of diastolic values above 100 mmHg and the lowest number of diastolic values below 80 mmHg, but the highest number of prescription of diuretics was necessary in the Enalapril group. In none of the four therapy groups a neutralisation of circadian blood pressure rhythmics was demonstrable.ZusammenfassungDurch technische Verbesserungen der Meßgeräte findet die nichtinvasive kontinuierliche Blutdruckmessung in zunehmendem Umfang Anwendung in der Hypertoniediagnostik. Neue vollautomatische Meßgeräte erlauben eine zuverlässige Registrierung und Auswertung von 24 Stunden Blutdruckprofilen. Unabhängig von aktivitätsbedingten Blutdruckschwankungen findet sich bei normotonen Personen und auch bei Patienten mit primärer Hypertonie ein typischer circadianer Rhythmus des Blutdrucks. Patienten mit sekundären Hypertonieformen zeigen eine Abflachung oder Aufhebung des circadianen Blutdruckrhythmus. In einer Studie wurde die Wirksamkeit des Calciumantagonisten Nitrendipin, desβ1-selektiven Blockers Metoprolol, des ISA-β-blockers Mepindolol und des ACE-Hemmers Enalapril über einen Zeitraum von 6 Monaten bei Patienten mit leichter bis mittelschwerer Hypertonie untersucht. Eine 24 h Blutdruckregistrierung erfolgte vor und nach 6-monatiger Therapie. Von 299 eingeschlossenen Patienten brachen 98 Patienten die Studie ab, davon 47 wegen unerwünschter Wirkungen. Bei nichtausreichender Wirksamkeit der Monotherapie wurde nach 4 Wochen zusätzlich Hydrochlorothiazid verordnet. Die morgendlichen Ambulanzblutdruckwerte lagen in allen Gruppen am Ende des Beobachtungszeitraums im normotonen Bereich, ohne daß signifikante Unterschiede zwischen den Gruppen vor und am Ende der Studie bestanden. Zu diesem Therapieerfolg war eine unterschiedliche Anzahl von Diuretikaverordnungen notwendig: Nitrendipin (n=5), Metoprolol (n=7), Mepindolol (n=14) und Enalapril (n=20).Trotz der vergleichbaren morgendlichen Blutdruckwerte ergaben sich in der 24 h Blutdruck-Registrierung z.T. deutliche Unterschiede. Metoprolol zeigte den deutlichsten blutdrucksenkenden Effekt und reduzierte systolische Blutdruckspitzen über 180 mmHg am effektivsten; wies aber auch die höchste Inzidenz von relativ hypotonen Werten (<110/<80 mmHg) auf. Eine wesentlich geringere Wirkung wies Mepindolol auf. Nitrendipin benötigte die geringste Anzahl zusätzlicher Diuretikaverordnungen und wies die geringste Anzahl von hypotonen systolischen Werten auf. Enalapril wies die deutlichste Reduktion von diastolischen Werten über 100 mmHg auf, und zeigte die geringste Anzahl von diastolischen Werten unter 80 mmHg, benötigte allerdings am häufigsten ein Diuretikum. Die Blutdrucktagesrhythmik wurde in keiner der 4 Therapiegruppen aufgehoben.

Influence of CAPD and Residual Diuresis on the Serum Levels of Alpha-1-Microglobulin in End-Stage Renal Disease

The chronic retention of proteins of low molecular weight (LMWP) seems to be connected with some unsolved problems of end-stage renal disease (e.g. reduced immune function, AB amyloidosis, hormonal imbalances), irrespective of the type of renal replacement therapy. Therefore, several recently discovered LMWPs such as alpha 1-microglobulin have to be evaluated concerning their contribution to the uremic syndrome. Although we observed a considerable daily loss of total protein into the CAPD dialysate, no differences were found in the removal of small proteins (MW less than 68 kilodaltons) when compared to conventional hemodialysis. Maintenance of renal function (residual diuresis greater than 100 ml/day) seems to be more potent keeping the serum concentrations of LMWP low than CAPD or hemodialysis.

Results of Antithrombin III Treatment in Patients after Kidney Transplantation

Priv.-Doz. Dr. J. Schrader, Abteilung für Nephrologie, Universitätsspital, Robert-Koch-Strasse 40, D-3400 Göttingen (FRG) Dear Sir, Acute local intravascular coagulation is common in kidney transplant rejection [1–3]. Mostly in hyperacute rejection the pathogenetic importance of intravascular coagulation in kidney damage could be demonstrated [4, 5]. It has also been shown that antithrombin III (AT III) levels rose during the rejection process before clinical signs were noticed [6]. The raised levels of AT III during transplant rejection might reflect an acute phase response to the rejection process. Also, as the role of this protein is to protect against intravascular thrombosis, the raised levels early in and throughout the rejection period might reflect a response by the body to supply an enhanced antithrombotic potential to protect the blood supply of the transplanted organ by diminishing glomer-ular fibrin deposits [6]. According to this a therapy with AT III could imitate the natural defense reaction and could have a protective effect on kidney function. Therefore, the effect of AT III treatment had been studied in 51 patients undergoing kidney transplantation. In 14 patients the vascular system of the transplanted kidney was perfused with 2,000 U AT III (Kybernin; Behring, Marburg) before implantation. In 15 patients additionally to the AT III perfusion a daily intravenous AT III treatment of 1,000 U was performed until the onset of an urine flow above 500 ml/day, while the remaining 22 patients served as a control group. The shortest duration of intravenous treatment was 3 days, the maximum was 28 days. The mean duration of AT III therapy was 10.3 ± 8.1 days. The three patient groups did not differ in age, sex, underlying renal diseases, warm and cold ischemia times and in the numer of mismatches. In table 1 the duration of oligoanu-ria, the number of necessary hemofiltrations after transplantation and the number of detected transplant rejections are shown. The duration of oligoanuria and the Table I. Number of days of oligoanuria, of necessary hemofiltrations and of rejection episodes after kidney transplantation in the 3 groups; in the lower part mean values of AT III during the first 28 days after transplantation are shown (*p < 0.05). Control AT III AT III group perfusion perfusion (n = 22) (n = 14) and i.v. treatment (n = 15)

Deferoxamin-Therapie der renalen Osteopathie: Bilanzen von Aluminium, Eisen, Kupfer und Zink

Patienten mit dialysepflichtiger Niereninsuffizienz lagern Aluminium in Gehirn, Knochen und Erythrozyten ein, was zu Dialyse-Enzephalopathie, renaler Osteopathie und einer Zunahme der renalen Anamie fuhrt [1–3]. Deferoxamin (DFO), ein Kationen-Komplexbildner, wird bei diesen Patienten eingesetzt, um das sonst zu etwa 80–90% an Eiweis gebundene Aluminium aus seiner Eiweisbindung zu losen [4]. Der so entstehende Aluminium-DFO-Komplex (Stabilitatskonstante 1021, Molekulgrose etwa 600 Dalton) ist filtrabel und kann mittels verschiedener Dialyseverfahren aus dem Organismus entfernt werden.