Peritoneal dialysate fill-volumes and hernia development in a cohort of peritoneal dialysis patients.

A retrospective case control study was performed on a cohort of 244 peritoneal dialysis patients followed over 5 years to determine whether dialysate fill-volume was associated with hernia development. The laboratory and clinical parameters of patients who developed hernias during this time period were compared with those of patients who did not develop hernias. Information on 27 patients who developed hernias was compared with that on 217 patients who did not develop hernias. Dialysate fill-volume was similar between groups (2.2 +/- .3 L for patients with hernias vs. 2.2 +/- .3 L for controls). Three patients with fill-volumes of 1.5 L developed hernias, and no patients with fill-volumes of 3 L developed hernias. Age, duration of time on dialysis, and body surface area were also similar between groups. This investigation could not find a relationship between fill-volume and hernia formation. From this study it would appear that physicians should not hesitate to increase fill-volume based on concerns of hernia development.

[Importance of 24-hour blood pressure monitoring in secondary hypertension]. / Bedeutung der 24-Stunden-Blutdruckmessung bei sekundärer Hypertonie.

A typical diurnal variation in blood pressure is observed in patients with essential hypertension. Attenuation or lack of circadian periodicity might be expected in patients with secondary hypertension. Therefore, non invasive ambulatory blood-pressure monitoring was performed in 172 patients with secondary hypertension and in 201 patients with essential hypertension. The following patients with secondary hypertension were investigated: renoparenchymatous nephropathy (n = 29), diabetic nephropathy (n = 24), morbus Conn (n = 6), renal artery stenosis (n = 32), pheochromocytoma (n = 5), hemodialysis patients (n = 30), and patients after kidney transplantation (n = 44). In addition, 36 pregnant women (17 normotensives, 19 hypertensives) were studied. 98.5% of patients with essential hypertension showed a nightly decline in blood pressure of at least 15 mmHg (systolic + diastolic), whereas 70% of patients with secondary hypertension showed either an attenuated circadian rhythm or no circadian rhythm. Patients with pheochromocytoma who had a nighttime increase in blood pressure demonstrated the greatest difference in the essential hypertension collective, followed by patients with diabetic nephropathy and 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 nighttime decline in blood pressure during 24-h-ambulatory monitoring is an indication of secondary hypertension, which should be further investigated. As a practical consequence, antihypertensive drugs should also be applied in an evening dose in secondary hypertensives. Noninvasive ambulatory blood-pressure monitoring is recommended for treatment control, especially in patients who need an efficient blood-pressure control.

Comparison of the antihypertensive efficiency of nitrendipine, metoprolol, mepindolol and enalapril using ambulatory 24-hour blood pressure monitoring.

In a randomized 6-month study of 201 patients, the antihypertensive efficiency of the calcium antagonist nitrendipine, the beta 1-selective blocker metoprolol, mepindolol, the beta blocker with intrinsic activity and the angiotensin-converting enzyme inhibitor enalapril were compared as monitored by 24-hour ambulatory blood pressure (BP) measurements. The study was designed so that a comparable decrease in casual BP values was obtained with all 4 drugs. If normotension was not achieved with monotherapy, a diuretic also was administered. Pretreatment casual BP and mean 24-hour ambulatory BP values did not differ between the 4 groups. Normotension as assessed by casual BP measurements was observed in all 4 groups after 6 months of therapy, there being no significant differences between the groups. However, significantly more diuretics were required in the mepindolol (n = 14) and in the enalapril (n = 20) groups compared to the nitrendipine (n = 5) and metoprolol (n = 7) groups. Despite comparable casual BP control, the 4 groups differed significantly in their mean 24-hour measurements. The greatest systolic and diastolic BP decreases were seen in the metoprolol group. Metoprolol was also the most effective drug in decreasing the frequency of systolic pressure peaks greater than 180 mm Hg. Both beta blockers and enalapril significantly decreased the morning BP increase compared to the values before treatment, while nitrendipine did not. These data show that casual BP measurement is not a good predictor of 24-hour BP in patients taking hypertensive therapy. Despite an equal degree of "office" BP control, different antihypertensive regimens do not confer the same degree of "nonoffice" BP control.

[Plasma endothelin in normal probands and patients with nephrologic-rheumatologic and cardiovascular diseases]. / Plasma-Endothelin bei Normalpersonen und Patienten mit nephrologisch-rheumatologischen und kardiovaskulären Erkrankungen.

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.

Low molecular weight heparin versus standard heparin. A long-term study in hemodialysis and hemofiltration patients.

The influence of low molecular weight (LMW) heparin (Braun 21-23, Mulsungen, West Germany) and unfractionated standard heparin (SH) on blood clotting and other routine laboratory parameters was investigated in a 30 week cross-over study in 30 hemodialysis patients. The LMW heparin dose necessary (anti FXa-activity) for effective anticoagulation was two thirds of the standard heparin dose. Using these doses, both substances displayed identical antithrombotic effects. Complications were not seen in either group. PTT and thrombin time were only marginally effected by LMW heparin, whereas they were markedly prolonged by SH heparin. Factor VIII activity was significantly lower in the LMW heparin group as compared to the standard heparin group after 18, 24, and 30 weeks. Antithrombin III, fibrinogen, fibrin monomers, plasminogen, and alpha 2-antiplasmin were comparable in both groups. Creatinine, urea, hemoglobin, and hematocrit were also unchanged, excluding differences in dialysis efficacy or occult blood loss. Equal numbers of blood transfusions were necessary, but bleeding complications did not occur in either group. In conclusion, safe and effective dialysis can be performed using this low molecular weight heparin for anticoagulation in hemodialysis and hemofiltration. The possible benefits of LMW heparin (reduced frequency of bleeding, alleviation of hypertriglyceridemia) were not, however, apparent, possibly because of the short observation period and the low incidence of hemorrhagic complications in routine dialyses.

[24-hour blood pressure behavior in patients with untreated and treated hypertension in comparison with normotensive patients]. / 24-h-Blutdruckverhalten bei Patienten mit unbehandelter und behandelter Hypertonie im Vergleich zu normotonen Patienten.

Blood pressure was continuously monitored over 24 h in 201 patients with mild to moderate essential hypertension using a noninvasive method. Measurements were made both before and after 6 months of antihypertensive treatment and the data were compared to results from 100 normotensive patients. The frequency with which blood pressure values above 140/90 mm Hg occurred during the 24-h period proved to be the most reliable parameter for distinguishing between hypertensive and normotensive profiles. The blood pressures of all patients could be normalized (less than 140/90 mm Hg) on single or combined drug therapy as assessed by casual measurement. However, significant differences were observed between the 24-h profiles of the treated patients and the control group. The mean 24-h blood pressure, the mean day and nighttime blood pressures, the mean hourly pressure, and the frequency of increased blood pressure values were all significantly higher in the patients on medication as compared to the normotensive controls. This would suggest that normotension, as defined by the control group, cannot be attained with antihypertensive medication. In conclusion, 24-h continuous blood pressure monitoring allows a better evaluation of blood pressure profiles and consequently, will be of greater value in assessing cardiovascular risk than occasional random measurements.

[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]. / Ambulante kontinuierliche 24 h Blutdruckregistrierung in der Diagnostik and Therapie der arteriellen Hypertonie und die Beeinflussung durch die Antihypertensiva Enalapril, Metoprolol, Mepindolol und Nitrendipin.

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.

Comparison of low molecular weight heparin to standard heparin in hemodialysis/hemofiltration.

Low molecular weight (LMW) heparin has been compared to standard unfractionated (UF) heparin in hemodialysis/hemofiltration in a 12 month, randomized study. Seventy patients with end-stage chronic renal failure starting dialysis treatment were randomly assigned to one of two groups treated with either LMW or UF heparin. The LMW and UF heparin doses used produced similar plasma anti-FXa levels, and comparable antithrombotic effectiveness was observed in the two groups as reflected in similar incidences of thrombus formation in the extracorporeal circulation: 1.59% and 1.33% for LMW and UF heparin, respectively. No bleeding complications were seen with either heparin, but significantly (P less than 0.05) fewer erythrocyte concentrates were needed in the LMW heparin patients. Mean factor VIII activities had risen significantly (P less than 0.001) after 12 months in the UF heparin group, whereas they were unchanged in the LMW heparin group. A significant (P less than 0.05) increase in plasma triglycerides was observed in the UF heparin group which was attributable to six (18.8%) of the patients in this group. Triglyceride concentrations remained relatively constant in the LMW heparin group. Post-heparin lipolytic activity, and in particular hepatic lipase activity, was not stimulated to the same extent in the LMW heparin-treated patients as compared to the UF heparin group. We conclude that LMW heparin is a suitable alternative to standard UF heparin for anticoagulation in hemodialysis/hemofiltration therapy. It may offer potential advantages with regard to a lower requirement for erythrocyte concentrates and less derangement of certain metabolic parameters, such as factor VIII, triglycerides and plasma lipase activity.

Comparison of unfractionated heparin and low molecular weight heparin during long-term use in chronic haemodialysis and haemofiltration patients.

Antithrombotic activity, necessary doses and effects on coagulation and lipid variables of the low molecular weight heparin derivative Fragmin were compared to unfractionated (UF) heparin in long-term multicentre trials. Results of more than 10,000 dialyses are reported. On the basis of preliminary studies, UF heparin and Fragmin doses were used that lead to anti-Xa activities of more than 0.5 U/ml. With this dose, sufficient antithrombotic activity was achieved with both heparins. Bleeding complications were not noticed. Partial thromboplastin time (PTT) and thrombin time were only marginally increased by Fragmin (5-8 s) in contrast to UF heparin (PTT 90-120 s, thrombin time 230-260 s). Surprisingly, the elevated levels of factor VIII strongly decreased during the 6-month treatment period with Fragmin and increased again during the following 6-month treatment period with UF heparin. Creatinine, urea, haemoglobin and transaminases did not change in both heparin groups: this excluded reduced dialysis efficiency or occult blood loss. Additionally, 15 patients with acute renal failure and high bleeding risk were dialysed with low doses of Fragmin (anti-FXa: 0.2-0.3 U/ml). No severe bleeding occurred. A continuous ambulant peritoneal dialysis patient with deep vein thrombosis was treated effectively with intraperitoneal application of Fragmin for 6 months without any problems.

Low molecular weight heparin in hemodialysis and hemofiltration patients.

Low molecular weight (LMW)-heparin was used as the sole anticoagulant during hemodialysis and hemofiltration in a pilot study on 32 patients. A LMW-heparin dose corresponding to 50% of the patients usual unfractionated, standard (UF)-heparin dose was found to produce comparable plasma heparin levels (anti-FXa-activity). No thrombosis of the extracorporal system and no bleeding complications occurred at this LMW-heparin dose. In contrast to UF-heparin, LMW-heparin produced only slight increases in PTT and thrombin time in all patients. Lipoprotein lipase was stimulated only marginally by LMW-heparin, with a correspondingly reduced release of free fatty acids. Both heparin species caused similar elevations in factor VIII and fibrin monomers, thus excluding a difference in coagulation activation. On the basis of these results, long-term studies have been started at four nephrology centers. To date, 26 patients have been treated with LMW-heparin for 6 months. A LMW-heparin dose was used that produced plasma anti-FXa-activity of 0.5 to 0.9 U/ml (initial dose: 30 to 40; dose/hr: 8 to 15 anti-FXa-units/kg body wt). PTT and thrombin time were only increased by 5 sec on average. Surprisingly, the elevated pre-dialysis levels of factor VIII and fibrin monomers decreased during this 6-month period. Bleeding complications did not occur and thrombotic complications were not observed when the anti-FXa levels were above 0.5 U/ml. LMW-heparin, therefore, appears to be a good alternative to UF-heparin for dialysis patients and may present less risk of bleeding because of its reduced effect on PTT, thrombin time, and thrombocytes.