Continuous hemofiltration in severe sepsis: is it beneficial?
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Biomedical subjects
Publications and source records attributed to C Tielemans.
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Haemodialysis patients with iron overload sometimes develop resistance to erythropoietin therapy due to 'functional iron deficiency'. It is known that this resistance may be overcome by iron supplementation; however, the latter could worsen haemosiderosis. Therefore, we treated four iron-overloaded haemodialysis patients who had developed relative resistance to erythropoietin (among whom three had features of 'functional iron deficiency') with ascorbic acid (500 mg intravenously after haemodialysis, 1-3 times a week). The erythropoietin doses were voluntarily kept unchanged during the study. After a latency of 2-4 weeks, haematocrit and haemoglobin had increased respectively from 26.5 +/- 0.7 to 32.7 +/- 0.4 vol% and from 8.8 +/- 0.3 to 10.8 +/- 0.2 g/dl (means +/- SEM, P < 0.001). While serum ferritin remained unchanged, transferrin saturation increased from 27 +/- 7 to 54 +/- 12% (P < 0.05), suggesting that ascorbic acid supplementation had allowed mobilization of iron from tissue burdens. In one patient, haematocrit declined after withdrawal of vitamin C and increased again after rechallenge. Also, ascorbate supplementation was continued after the study in two patients and allowed the erythropoietin doses to be decreased, 8 and 11 weeks, respectively, after the start of the trial. When a control group of seven patients with normal iron status and without resistance to erythropoietin were challenged in the same manner with ascorbate, no elevation of haematocrit or transferrin saturation was noted. We conclude that ascorbate supplementation may circumvent resistance to erythropoietin that sometimes occurs in iron-overloaded patients, in particular, in the setting of 'functional iron deficiency'.
Persistent hypercalcaemia was observed in two patients with oxalate osteopathy complicating primary hyperoxaluria type 1; four other cases have been reported in the literature. In none of the six patients could hypercalcaemia be ascribed to hyper-parathyroidism secondary to renal failure. It occurred in the absence of aluminum intoxication, and was associated with normal calcitriol. Hypercalcaemia responded to mithramycin in one patient, and to corticosteroid administration in three; corticosteroid withdrawal was followed by recurrence of hypercalcaemia in the three cases. It is suggested that hypercalcaemia results from the osteoclast-stimulating activity of macrophages constituting the granulomata which invade the bone marrow in response to oxalate deposition. Whatever its pathogenesis, a trial of corticosteroid appears warranted for treating hypercalcaemia complicating oxalosis.
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Enhanced levels of soluble TNF-receptors (sTNF-R) have been reported in patients with chronic renal failure. The aim of the present study was to evaluate the effects on sTNF-R levels in plasma of haemodialysis patients of the anticoagulation method and of the type of membrane used, as well as the variability of predialysis sTNF-R levels during time. All haemodialysis patients tested (n = 35) showed increased levels of both sTNF-R55 (72.4 +/- 5.7 ng/ml, P < 0.001) and sTNF-R75 (18.2 +/- 2 ng/ml, P < 0.001) before dialysis, as compared with normal healthy controls (< 2.5 ng/ml for both sTNF-R), confirming previous observations. sTNF-R levels were determined before and during haemodialysis at different time intervals in patients receiving either heparin (2500 U, 5000 U, or 10,000 U), low molecular weight heparin, or periodic saline flushing to prevent coagulation of the extracorporal circuit. A transient, small decrease in both sTNF-R levels occurred at the beginning of haemodialysis (t = 15 min) with all anticoagulation methods used. At the end of haemodialysis, sTNF-R55 and sTNF-R75 concentrations were only minimally affected (P > 0.05). Predialysis sTNF-R levels were similar in patients dialysed on either cellulose diacetate or polyacrylonitrile. Finally, there were only minimal variations in predialysis sTNF-R levels in individual patients during the 1 week observation period. Although the biological consequences of the increased TNF-binding ability of serum from haemodialysis patients is still unclear, it could play a role in the complex immunological perturbations of uraemic patients.
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Three patients on chronic maintenance haemodialysis have progressively increased their haematocrit to reach values between 40 and 45%, a situation associated with an increased risk of thrombosis of their arteriovenous fistulae. Two of them had been submitted to repeated phlebotomies, which remained unsuccessful despite the induction of a profound iron deficiency in one of them. Hence, a trial with oral theophylline was performed in the three patients, resulting in a sustained decrease of the haematocrit (from 43.6 to 33%) and endogenous erythropoietin (from 46 to 15 mU/ml) levels. In two patients, theophylline therapy was stopped transiently due to gastrointestinal side-effects, which resulted in a rapid return to previous haematocrit levels; rechallenge with a better tolerated preparation, however, was efficient again. We conclude that oral theophylline appears to be an efficient treatment to control too high haematocrit levels in dialysis patients.
Two similar cases of rapidly progressive fibrosing interstitial nephritis in young women who followed the same slimming regimen prompted us to conduct an epidemiological survey of the nephrology centres of Brussels and to further investigate the exact nature of this slimming treatment. Seven other women under the age of 50 in terminal or preterminal renal failure were admitted for dialysis in 1991 and 1992. They had all followed a slimming regimen in the same medical clinic. Renal biopsy samples in eight of the nine cases showed extensive interstitial fibrosis without glomerular lesions. Two of the patients were seen for the first time in terminal renal failure and were started immediately on dialysis. For the seven other women, the nephropathy was characterised by a rapid deterioration in renal function, with initial serum creatinine doubling within about 3 months. The clinic had specialised in slimming treatments for the previous 15 years without any problems. In May, 1990, therapy was changed, with the introduction of two Chinese herbs (Stephania tetrandra and Magnolia officinalis). In June, 1992, three of twenty-five randomly selected women who had followed the same regimen during at least 3 months from 1990 had impaired renal function. Chemical analysis of some brands of these Chinese herbs did not show nephrotoxic contaminants of fungal or plant origin (ochratoxin or aristolochic acid) or adulteration by diuretics or antiinflammatory drugs. However, the medicinal preparation of the capsules taken by patients had different alkaloid profiles from those expected in Chinese plants. The striking relation between a specific type of fibrosing interstitial nephritis in young women and a slimming treatment involving Chinese herbs adds support to the arguments against uncontrolled therapy with herbal preparations.
To test the assumption that the previously reported abnormal 24-hour blood pressure (BP) variations in hemodialysis (HD) patients might be due to associated complications of chronic renal failure, we recorded the 24-hour noninvasive BP and heart rate (HR) patterns in 14 carefully selected chronic HD patients. No of the patients suffered from orthostatic hypotension, and all were free of any previously reported associated condition known to affect the 24-hour BP profiles. The BP and HR profiles were quantitatively analyzed using the periodogram method. The results were compared those from 14 controls matched for age, sex, and casual BP. No difference could be found between the HD patients and the controls, either in the absolute and relative amplitudes of the 24-hour systolic BP and diastolic BP variations or in the timings and levels of their respective acrophases and nadirs (except for the timings of the second systolic BP and diastolic BP acrophases; P < 0.05). The absolute levels of the HR acrophases and nadirs were higher in the HD patients than in the controls (P < 0.05 and P < 0.01, respectively), while both the absolute and relative amplitudes of the 24-hour HR profiles and the relative values and timings of the HR acrophases and nadirs were similar in both groups. Consequently, the 24-hour HR pattern was similar in the HD patients than in the controls, except that the entire profile was shifted upward.(ABSTRACT TRUNCATED AT 250 WORDS)
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Systemic hypertension as assessed by causal blood pressure measurements is a frequently reported side-effect of recombinant human erythropoietin (rHuEpo) treatment. We investigated the effect of rHuEpo treatment on the 24-h ambulatory blood pressure and heart rate profiles of 13 chronic haemodialysis patients. After 3-4 months of rHuEpo therapy it was found that the mean haematocrit had increased from 24.5 +/- 1.0% to 32.0 +/- 1.1% (P less than 0.005), while body-weight and control of uraemia as assessed by routine laboratory data remained unchanged. Despite gradual and incomplete correction of anaemia by use of low doses of rHuEpo, increases in the ambulatory systolic and diastolic blood pressure were found. The greatest increases affected day-time systolic blood pressure and night-time diastolic blood pressure, and these increases were significant (P less than 0.05). As a result, pulse pressure increased during day-time (P less than 0.05) while the night-time decline in diastolic blood pressure disappeared. An increase in peripheral resistance after partial correction of renal anaemia might explain these observations. rHuEpo therapy increased the percentage of abnormal ambulatory blood pressure measurements (defined as systolic blood pressure greater than 140 mmHg and/or diastolic blood pressure greater than 90 mmHg) from 33% to 52% (P less than 0.05) while in contrast, mean casual prehaemodialytic and posthaemodialytic blood pressure values remained unchanged. We conclude that changes in 24-h blood pressure profiles should be carefully assessed by ambulatory blood pressure monitoring in haemodialysis patients treated with rHuEpo, since these changes are likely to be missed when only causal blood pressures are measured.
ANCA antibodies represent a family of autoantibodies directed against neutrophil enzymes. Immunofluorescence patterns allow to distinguish c-ANCAs from p-ANCAs. The detection of ANCAs is often a key element for the diagnosis of Wegener's granulomatosis, microperiarteritis, Churg-Strauss syndrome and idiopathic rapidly progressive glomerulonephritis. Although the pathogenic role of ANCAs is not firmly established, their detection often allows an early therapeutic decision in necrotizing vasculitides.
We report five life-threatening anaphylactoid reactions occurring within the very first minutes of hemodialysis on polyacrylonitrile (AN69) capillary dialyzers in three patients receiving ACE inhibitors. Such reactions were not observed either in patients treated with ACE inhibitors but dialyzed on other membranes (N = 9), nor in patients on AN69 who did not receive ACE inhibitors (N = 19). These anaphylactoid reactions could be due to bradykinin accumulation, as a result of both increased synthesis--by interaction of blood with the AN69 polymer--and catabolism blockade by ACE inhibitors.
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The clinical, biochemical, radiological and scintigraphical data related to renal osteodystrophy were followed in 18 patients on CAPD for 3 to 5 years. The majority maintained normal serum calcium, bicarbonate and alkaline phosphatase concentrations; serum phosphate concentration decreased after starting CAPD but remained somewhat elevated. Only half of the patients needed phosphate binders. Serum PTH concentrations fell in those with high values at the start and remained stable in most others. Serum aluminum concentrations never exceeded 50 micrograms/l while serum 25(OH)D3 levels remained low. Bone radiology and scintigraphy were characterized by their stability over time. We think that CAPD, with the addition of calcium carbonate, phosphate binders and vitamin D analogs can achieve good control of renal osteodystrophy. In addition, joint problems are not common in CAPD patients but we present evidence that they too are at risk of dialysis amyloidosis.
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We compared plasma beta-2-microglobulin (beta 2M) at a 1-year interval in 25 CAPD patients and 25 patients haemodialysed with cuprophane membranes and matched for residual renal function and duration of renal replacement therapy. Plasma beta 2M remained lower in CAPD patients throughout the study, and increased significantly with time both in CAPD and haemodialysis patients, as renal function decreased. In both groups, plasma beta 2M was negatively correlated with residual creatinine clearance, the influence of the latter being much greater in haemodialysis, as demonstrated by comparison of the regression lines. In haemodialysis, but not in CAPD, plasma beta 2M also correlated with time on dialysis. In CAPD patients, the daily peritoneal output averaged 38 mg (range 16-59 mg), and was directly correlated with plasma beta 2M. CAPD thus allows a significant peritoneal removal of beta 2M, which progressively takes over from the declining renal function, resulting in lower plasma beta 2M than in matched haemodialysis patients. However, the peritoneal removal of beta 2M remains insufficient and values increase with time as renal function declines. Thus, if beta 2M amyloidosis is related to raised plasma levels, the risk of beta 2M amyloidosis in CAPD should simply be delayed as compared to haemodialysis.