Chlamydia pneumoniae IgA seropositivity is associated with increased risk for atherosclerotic vascular disease, myocardial infarction and stroke in dialysis patients.

BACKGROUND: Atherosclerotic cardiovascular disease is the major cause of morbidity and mortality in patients with chronic renal failure undergoing dialysis therapy. Aim of the study was to evaluate whether there is a correlation between a past infection with Chlamydia pneumoniae inducing antibody production and the manifestation of symptomatic atherosclerotic disease in patients with chronic renal failure on hemodialysis. METHODS: A retrospective study was designed including 151 dialysis patients with a clinical apparent atherosclerotic disease (case subjects) and 116 dialysis patients without any symptomatic atherosclerotic manifestation (control group). An ELISA was used to measure seropositivity for IgA and IgG titers. RESULTS: Elevated IgA titers against Chlamydia pneumoniae were found in 67% of the case subjects, but only in 29% of the controls (OR 5.34, CI 2.98-9.56). Forty-five patients of the case subjects had a history of myocardial infarction (OR 5.14, CI 2.38-11.09). Prior stroke was found in 30 patients in case subjects (OR 4.37, CI 1.73-11.01). The follow-up after 3 years showed that only 20 patients died from cardiovascular disease in the control group in comparison to 57 patients in the case group (OR 2.51). IgG seropositivity revealed an OR of 1.02 (CI 1.0-2.1). CONCLUSION: These results indicate that IgA seropositivity is associated with an increased frequency of symptomatic atherosclerotic manifestations. Especially an increased number of patients was found with prior myocardial infarction or stroke when elevated IgA titers were detected. IgA positivity seems to be a separate prospective risk factor in patients with chronic renal failure and hemodialysis for premature cardiovascular death.

Cellular interleukin-1 receptor antagonist production in patients receiving on-line haemodiafiltration therapy.

BACKGROUND: Repetitive exposure to cytokine-inducing substances (pyrogens) results in chronic inflammation, which may significantly contribute to some of the long-term complications in dialysis patients. On-line dialysis modalities, such as on-line haemodiafiltration (HDF), raise particular concerns because of the administration of infusate prepared from potentially contaminated dialysis fluid. Hence, great retention capability for pyrogens is of critical importance for the safe performance of on-line systems. METHODS: The microbiological safety of a novel on-line system, ONLINEplus(TM), was assessed in clinical practice in five centres for 3 months. Infusate and dialysis fluid were regularly monitored for microbial counts, endotoxins, and cytokine-inducing activity. Levels of interleukin-1 receptor antagonist (IL-1Ra) were determined in supernatants of whole blood incubated either under pyrogen-free conditions (spontaneous cytokine production) or following low-dose endotoxin exposure (LPS-stimulated cytokine production). RESULTS: We failed to detect microorganisms or endotoxin contamination of infusate during the entire study period. Moreover, neither infusate nor dialysis fluid demonstrated cytokine-inducing activity. Intradialytic IL-1Ra induction was not detected, as there was no difference between pre- and post-session values for both spontaneous and LPS-stimulated IL-1Ra production (115+/-26 vs 119+/-27 and 2445+/-353 vs 2724+/-362 pg/10(6) white blood cells (WBC), respectively). Neither the number of immunocompetent cells nor their capacity to produce IL-1Ra declined during this period, indicating that cells were not significantly stimulated during treatment. Spontaneous and LPS-induced exvivo IL-1Ra generation remained unchanged after 3 months of on-line HDF therapy as compared with the start of the study (71+/-30 pre- vs 48+/-14 post-study, and 2559+/-811 vs 2384+/-744 pg/10(6) WBC, respectively). CONCLUSIONS: The present on-line system performed safely from a microbiological view-point as both the dialysis fluid and infusate were consistently free of microorganisms, endotoxins, and cytokine-inducing substances. As a result, on-line HDF therapy had no effect upon the chronic inflammatory responses in end-stage renal disease patients.

Formation of thrombin-antithrombin III complex using polyamide and hemophan dialyzers.

The recently developed ELISA for the thrombin-antithrombin III complex (TAT) is a sensitive, specific, and simplified means of detecting intravascular coagulation. For further evaluation of the thrombogenicity of a polyamide (P) and a Hemophan (H) hollow-fibre dialyzer a cross-over study was done in ten stable patients on maintenance hemodialysis. At the same doses of heparin (mean bolus of 30 U/kg bw and maintenance doses of 86 U/kg bw), thrombin time and partial thromboplastin time were significantly lower using H. At the end of dialysis TAT was significantly higher in H (mean +/- SEM before HD 3.57 +/- .56, at 240 min 14.9 +/- 6.5 ng/ml, p less than 0.05, Wilcoxon-test) than in P (before HD 4.36 +/- .98, at 240 min 8.95 +/- 3.0 ng/ml, p less than 0.05 H 240 vs. P 240, Wilcoxon-test). Visible clotting was more pronounced in the H filter. Among other favourable features of blood compatibility the polyamide/polyvinylpyrrolidone copolymer with a hydrophilic/hydrophobic microdomain structure has less thrombogenicity. The modified cellulosic membrane H has advantages in complement activation and leukocyte depression, but thrombogenicity seems less favourable since the incorporated diethyl-amino-ethyl groups with their positive charge bind and inactivate negatively charged heparin.

[Oncogenic hypophosphatemic osteomalacia]. / Onkogene hypophosphatätmische Osteomalazie.

In the courses of six years a severe hypophosphataemic osteomalacia, painful motor impairment and multiple rib fractures developed in a 51-year-old man. The symptoms gradually improved within one year under treatment with 3 micrograms daily of 1,25-dihydroxycholecalciferol, 3 g phosphorus and 3 g calcium, and biochemical parameters and the bone scintigram became normal. Ultimately, computed tomography, scintigraphy and digital subtraction angiography revealed a highly vascularized tumour in the condylar aspect of the right femur, and it was chiselled out. Histologically it was a mesenchymal phosphaturic tumour of haemangiopericytoma type of questionable benignity. After the operation the patient was symptom-free for some weeks without any drug treatment, but the latter was then resumed because of renewed bone pain. By now, two years later, he is essentially without pain and has full mobility. However, repeat scintigraphy and angiography revealed renewed tumour growth in the right femoral condyle.

Eicosanoid release as laboratory indicator of biocompatibility.

Biocompatibility evaluation of extracorporeal devices requires the establishment of sensitive indicators of blood cells/surface interactions. Among others, arachidonic acid derivatives, such as prostaglandins and thromboxanes, play an important role in the cell control systems. Hence, the release of eicosanoids during blood exposure to dialyzer membranes was investigated. Experiments included in vitro incubation of human blood with flat membranes (FM), as well as ex vivo perfusion of hollow fiber membranes (HFM) with blood from healthy volunteers in single-pass fashion. In both models, a significant release of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) was detected. In addition, the amount of eicosanoid release depended on the type of membrane tested. After a 10-min FM incubation with fresh blood, plasma concentrations of TXB2 and PGE2 were pronounced by polycarbonate when compared to Cuprophan and polyacrylonitrile. During 10 min of open loop perfusion of HFM, polymethylmethacrylate was the most active biomaterial, whereas the reactivity of Cuprophan was significantly lower. Among HFM, Hemophan was by far the less active. These results indicate that the release of eicosanoids represents a sensitive parameter of blood cells/membrane reactivity. Thus, the question arises as to whether or not the extracorporeal process of cyclooxygenase activity could contribute to the clinical side effects of chronical hemodialysis.

Effect of dialyzer membranes on in vitro generation of eicosanoids.

Eicosanoids are potent substances released from blood cells after contact with foreign materials. Eicosanoid generation, in addition to complement fragment formation, may be a valuable indicator of the biocompatibility of dialyzer membranes. In the present in vitro study, eicosanoid generation induced by several different flat dialyzer membranes [polyacrylonitrile (PAN), cuprammonium cellulose (CC), and polycarbonate (PC)] was evaluated and compared using blood from non-uremic healthy volunteers. Generation of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) was greatest with PC followed by PAN and CC. The formation of C3a des arg with PAN was less than with either CC or PC. Our results suggest that dialyzer membranes affect complement activation and eicosanoid generation differently; biocompatibility as expressed by a low level of complement fragment formation does not necessarily translate into biocompatibility when considering eicosanoid generation.

Amelioration of postischemic acute renal failure by prostacyclin analogue (iloprost): long-term studies with chronically instrumented conscious dogs.

The potential therapeutic value of the chemically stable carbacyclin analogue iloprost on the course of postischemic acute renal failure was studied in six conscious chronically instrumented dogs and compared with five controls. Immediately after temporary ischemia (180-min cessation of blood flow by inflation of a pneumatic cuff), the investigational group PC received a continuous intraaortal infusion of iloprost (50 ng X min-1 X kg-1) over a period of seven days, whereas the control group C received 0.9% saline. The glomerular filtration rate [( 51Cr]EDTA clearance, endogenous creatinine clearance) was less decreased in the prostacyclin analogue group than in the control group [3rd day, 18 +/- 2.5 vs. 12 +/- 1 ml X min-1 (p less than 0.05); 7th day, 23 +/- 3 vs. 12 +/- 2 ml X min-1 (p less than 0.05)]. On day 1, renal blood flow (electromagnetic flow probe) was markedly lower in the control group (129 +/- 29 ml X min-1) than in the PC group (212 +/- 29 ml X min-1; p less than 0.05), even exceeding baseline levels in the latter group. Accordingly, the excessive rise in renal vascular resistance in the control group (+136%) was abolished in the PC group (-32%; p less than 0.01). Nitrogen retention was also markedly improved. Osmolar clearance was markedly lower in the control group (0.58 +/- 0.2 ml X min-1) than in the PC group (1.41 +/- 0.17 ml X min-1; p less than 0.05). It is suggested that the beneficial effect of iloprost is mediated by preservation of renal perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of long-term infusion of the calcium antagonist diltiazem on postischemic acute renal failure in conscious dogs.

The influence of long-term infusion of the calcium-entry blocker diltiazem on postischemic acute renal failure was investigated in conscious dogs monitored by implanted instruments. In 18 uninephrectomized beagle dogs on a salt-rich diet, an electromagnetic flow probe and an inflatable plastic cuff were placed around the renal artery. Acute renal failure was induced by inflating the cuff for 180 min in the conscious animal. Group A (n = 5, control) received an intraaortic injection of 0.9% NaCl (5 ml/day) from the 3rd day before until the 7th day after ischemia and group B (n = 6, posttreatment) an intra-aortic injection of diltiazem (5 micrograms X min-1 X kg-1) beginning at the end of ischemia until the 7th day. Group C (n = 7, pre- and posttreatment) received diltiazem from the 3rd day before until the 7th day after ischemia. In group A, renal blood flow dropped from 149 +/- 16 (preischemic) to 129 +/- 29 ml X min-1 on the 1st day after ischemia. In contrast, renal blood flow increased on the 1st postischemic day in both treatment groups by 29 +/- 15% (group B, P 0.05) and 14 +/- 13% (group C). In the following days, there was no significant difference in renal blood flow between groups A, B and C. In group B, the reduction of the glomerular filtration rate was similar to that in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Does captopril reduce renal function in renovascular disease by postglomerular vasodilatation?

In hypertensive patients with bilateral renal artery stenosis (RAS) or RAS of a solitary kidney, reversible decrease of glomerular filtration rate (GFR) or acute renal failure has been observed following captopril administration. Decrease of GFR has been ascribed to preferential efferent vasodilatation. To test this hypothesis, acute changes of mean arterial pressure (MAP), renal plasma flow (RPF), GFR, plasma renin activity (PRA) and PGE2-excretion after 50 mg captopril orally were measured in post-transplant hypertensives with and without transplant renal artery stenosis (TRAS) during treatment with diuretics. The fall in MAP was similar in both groups; RPF did not change significantly; GFR decreased from 58 +/- 14 (s.d.) to 49 +/- 14 ml/min (TRAS, n = 8) and from 60 +/- 15 to 50 +/- 16 ml/min (without TRAS, n = 8). There was no evidence of postglomerular dilatation in patients with TRAS, and filtration fraction decreased only in patients without TRAS. Increase of PRA after captopril was not significantly different between the two groups. PGE2-excretion did not change significantly. In one patient with severe TRAS, long term angiotensin converting enzyme (ACE) inhibition and acute normalization of MAP with sodium nitroprusside both induced a comparable decrease of GFR. The results demonstrate that acute postglomerular vasodilatation does not necessarily occur after ACE inhibition in patients with TRAS and a high-renin state.