Measurement of Kallikrein Activity in Urine of Rats and Man Using a Chromogenic Tripeptide Substrate. Validation of the Amidolytic Assay by Means of a Bradykinin Radioimmunoassay

Peer Reviewe

Lithium treatment reduces the renal kallikrein excretion rate

Lithium treatment reduces the renal kallikrein excretion rate. Lithium salts are widely used agents for the prophylactic treatment of affective disorders. Lithium salts may be associated with distal nephron dysfunction. Kallikrein is a protease which is generated by the distal nephron. We used an amidolytic assay of chromatographically purified enzyme to determine the urinary excretion rate of active kallikrein in relation to lithium treatment. All plasma lithium concentrations were within the therapeutic range (0.4 to 0.9 mmol/liter). In 15 patients the urinary excretion rate of active kallikrein was 267.4 65.6 mU/24 hrs before lithium treatment, and fell to 117.8 39.6 mU/24 hrs (P < 0.05) on day 14 of lithium treatment. This reduction was associated with a decrease of immunoreactive kallikrein in the same urines by 66%. In another 15 patients who had undergone lithium therapy for an average period of 5.6 years, the urinary excretion rate of active kallikrein was 86.1 14.5 mU/24 hrs, while 21 age-matched healthy controls had an excretion rate of 364.1 58.4 mU/24 hrs (P < 0.05). Measurements of immunoreactive kallikrein in the same urine samples demonstrated a reduction of kallikrein after long-term lithium treatment by 78%. These observations could not be attributed to changes in creatinine clearance, renal sodium or potassium excretion rates or plasma concentrations of aldosterone and vasopressin. Addition of lithium to the urine in vitro had no demonstrable effect on kallikrein measurement by amidolytic assay. We conclude that lithium in therapeutic plasma concentrations may directly suppress the secretion of kallikrein by renal connecting tubule cells

Risikoprädiktoren für kardiovaskuläre und zerebrovaskuläre Mortalität bei Diabetes

Recent epidemiologic studies suggest that patients with diabetes mellitus suffer from increased hospital mortality after myocardial infarction and stroke. The aim of our analysis was to compare the hospital outcome of diabetic and non-diabetic patients with cardiovascular events and to analyse the relevant risk predictors. Therefore data of the Schwabing Myocardial Infarction Registry from 1999 to 2004, the Schwabing stroke register from 2003/2004, and the Pasing stroke register from 2007/2008 were assessed. Overall, these are 3171 recorded patients, of which 1087 were diabetic patients (34.3%) and 2084 non-diabetic patients (65.7%). Diabetic patients showed, apart from CRP, comparable risk predictors (GFR OR 4.2, CI 1.7-10.6, p<0.005; heart rate OR 2.1, CI 1.1-4.0, p=0.025; hypertension OR 0.3, CI 0.2-0.6, p<0.001) as non-diabetic patients (CRP OR 4.5, CI 2.3-8.8, p<0.001; GFR OR 3.8, CI 1.8-8.1, p<0.001; heart rate OR 2.7, CI 1.6-4.9, p<0.001; hypertension OR 0.5, CI 0.3-0.8, p<0.01). In the diabetic group, the frequency of these predictors was, however, significantly higher. Hypertension on admission appeared as a favourable prognostic factor. This has also been demonstrated in previous studies in the ICU. Whether potential pre-treatment or higher blood-pressure levels per se may contribute to the observation requires further investigations. For the clinical practice we can draw the conclusion that patients with the parameters found here increased need special attention on admission and during the treatment

P-181: Fixed-dose valsartan + hydrochlorothiazide combination therapy compared with amlodipine monotherapy in hypertensive patients with additional cardiovascular risk factors: The vast study

Objectives: To determine whether the combination of valsartan 160 mg and hydrochlorothiazide (HCTZ) 25 mg once-daily (od) is more effective than amlodipine 10 mg od in reducing systolic blood pressure (BP) in patients suffering from moderate hypertension combined with at least one other cardiovascular risk factor or concomitant condition. Further, to study the effects of treatment on vascular markers. Methods: A multicenter, randomized, double-blind, active-controlled, three-arm study over 24 weeks. After a two-week single-blind placebo run-in period, 1088 stage-II hypertensive patients with additional risk factors were randomized to three groups, two receiving valsartan 160 mg od and one group receiving amlodipine 5 mg od. At Week 4, HCTZ 12.5 mg and 25 mg respectively, were added to the valsartan groups and the amlodipine dose was force-titrated to 10 mg od. Patients were followed-up for a total of 24 weeks. Results: The combination of valsartan 160 mg+HCTZ 25 mg reduced systolic BP significantly (p<0.05) more than amlodipine monotherapy (least-squares mean changes from baseline 29.7±0.7 mmHg and 27.6± 0.7 mmHg, respectively). For diastolic BP the values were 11.1±0.4 mmHg and 10.8±0.4 mmHg, respectively (differences not significant). Levels of IL-6, t-PA antigen and hs-CRP were reduced with both combination therapies at week 12 (figure). Significantly more patients discontinued because of adverse events in the amlodipine group (18.2%) than in the combination-therapy groups (4.2% and 3.5%) over the 6 months treatment period. Conclusions: Valsartan 160 mg+HCTZ 25 mg is an effective and well-tolerated therapy in this patient population with possible beneficial effects on vascular marker

Bradykinin is a mediator of anaphylactoid reactions during hemodialysis with AN69 membranes

Bradykinin is a mediator of anaphylactoid reactions during hemodialysis with AN69 membranes. Anaphylactoid reactions (AR) are the most feared complications of hemodialysis. Recently, a high incidence of AR has been reported during dialysis with AN69 membranes in patients treated with ACE inhibitors. Plasma levels of C3a, histamine and bradykinin were measured in 12 patients at the onset of AR during dialysis with AN69. We also investigated bradykinin generation in 10 symptom-free patients dialyzed with four different membranes. None of the 12 patients studied during AR displayed excessive complement activation or histamine release. In contrast, high bradykinin plasma levels (2392 53 fmol/ml; mean sem) were observed in all nine patients of whom bradykinin was measured. One patient developed two consecutive episodes of hypersensitivity on AN69 membranes even without taking ACE inhibitors. Bradykinin levels were high in both episodes (5280 and 10467.7 fmol/ml). Furthermore, this patient showed no symptoms and normal bradykinin levels (123.4 fmol/ml) when dialyzed with other membranes. The role of the membrane type in the AR is further substantiated by the observation that AN69 also provoked a significantly higher bradykinin generation (327.6 18 fmol/ml; mean SEM) during symptom-free sessions compared to other membranes like CuprophanR (5.1 7.3), HemophanR (17.2 6.3) and PolysulfoneR (39.7 6.6). Our findings strongly suggest that bradykinin is the principal mediator of AR during hemodialysis with AN69 membranes. To our knowledge it is the first time that data support the hypothesis of a more general role of bradykinin in shock-like symptoms. Furthermore, bradykinin generation must be regarded as a new marker of biocompatibility of extracorporeal treatments

Er-Ziehen durch Be-Ziehen

Entwurf eines ganzheitlichen Erziehungsmodells auf der Grundlage der Individualpsychologie und der ostasiatischen Philosophie