Coagulation- and fibrinolysis-related antigens in plasma and dialysate of CAPD patients.

OBJECTIVE: The present study is aimed at gaining insight into coagulation and fibrinolysis in the peritoneal cavity of patients on continuous ambulatory peritoneal dialysis (CAPD). For this purpose we measured coagulation- and fibrinolysis-related antigens in plasma and dialysate, comparing patients with and without peritonitis. DESIGN: Markers of activated coagulation and fibrinolysis in plasma and dialysate of CAPD patients were determined at different time points (0 hr, 2 hr, 4 hr) after infusion of the dialysis solution in the peritoneal cavity. Prothrombin fragment (F1 + 2), thrombin-antithrombin III complex (TAT), and fibrin monomer (FM) were chosen as parameters of activated coagulation. Fibrin degradation products (FbDP), D-dimer (DD), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor type 1 (PAI-1) were measured as parameters for ongoing fibrinolysis. Beta 2-microglobulin, albumin, and IgG were used as marker proteins for the diffusion of proteins of intravascular origin into the peritoneal cavity. PATIENTS: Eleven clinically stable CAPD patients, who had not suffered from peritonitis during the last six months, and 5 CAPD patients with an acute episode of bacterial peritonitis were studied. RESULTS: In the dialysate of stable CAPD patients (n = 11) the concentration of activation markers of coagulation and fibrinolysis increased continuously with dwell time. After four hours we found remarkably high levels of the coagulation markers F1 + 2 (0.4 +/- 0.1 nmol/L), TAT (6.5 +/- 1.0 ng/mL), and FM (24.5 +/- 7.1 micrograms/mL), and the fibrinolysis markers DD (851 +/- 26 ng/mL), FbDP (1.0 +/- 0.3 microgram/mL), t-PA (3.3 +/- 0.8 ng/mL), and PAI-1 (2.6 +/- 1.2 ng/mL). The dialysate-to-plasma (D/P) ratios of all of these antigens were significantly higher compared to the D/P ratios of proteins with similar molecular weight, which are not produced intraperitoneally (beta 2-microglobulin, albumin, and IgG). These findings point to a local, thrombin-induced intraperitoneal fibrin generation during regular CAPD. Compared with clinically stable CAPD patients, the patients with bacterial peritonitis (n = 5) had significantly higher levels of F1 + 2 (5.3 +/- 1.6 nmol/L), TAT (57.8 +/- 10.7 ng/mL), FM (972 +/- 3.2 micrograms/L), FbDP (16.4 +/- 2.9 micrograms/L), and PAI-1 (7.3 +/- 2.4 ng/mL) in the dialysate (4-hr dwell time), and a 2.4-times higher ratio between FM and FbDP. These results can be interpreted as an intraperitoneal imbalance between coagulation and fibrinolysis during peritonitis. CONCLUSION: Our study demonstrates a high intraperitoneal fibrin formation, not only during peritonitis but also in clinically stable CAPD patients. The remarkably high levels of coagulation (F1 + 2, TAT, FM) and fibrinolysis (FbDP, DD, t-PA, PAI-1) related antigens in the dialysate of patients without peritonitis cannot be explained by transport from plasma into the peritoneal cavity and may reflect a high rate of intraperitoneal fibrin turnover. The balance between peritoneal generation and degradation of fibrin is obviously disturbed in CAPD patients with peritonitis, who had significantly higher levels of coagulation markers in the dialysate and a higher ratio between FM and FbDP.

Increased antibody titers against mycobacterial heat-shock protein 65 in patients with vasculitis and arteriosclerosis.

Heat shock proteins (HSPs) are a group of highly conserved proteins that show extensive homology at the DNA and protein level among bacterial and mammalian species. Furthermore, bacterial HSPs induce specific cellular and humoral immune responses in mammals. Cross-reacting antibodies may therefore be induced in chronic infections. Recently, it has been claimed that patients with arteriosclerosis (AS) of the carotid arteries have significantly elevated antibody titers to mycobacterial HSPs. In this study, we extended the spectrum of vascular diseases and analyzed sera from patients with systemic vasculitis and systemic lupus erythematosus (SLE) for the presence of anti-HSP antibodies. Anti-HSP antibodies, tested in an ELISA with recombinant mycobacterial HSP 65, were significantly elevated in patients with vasculitis (n = 56; p < 0.01) and AS (n = 29; p < 0.0001), but only marginally in patients with SLE (n = 22; p > 0.05) compared to healthy controls (n = 90). These findings further support the concept of infection-induced immune reactions playing a pathogenic role in the development of both AS and vasculitis.

Distribution of the granulocyte serine proteinases proteinase 3 and elastase in human glomerulonephritis.

The serine proteinases proteinase 3 (PR3) and elastase are target antigens of antineutrophil cytoplasmic autoantibodies (ANCAs), which are found in various systemic vasculitides with rapidly progressive glomerulonephritis (RPGN). The expression of both proteinases was studied immunohistologically (avidin-biotin complex method) with murine monoclonal antibodies against PR3 (WGM2) and elastase (NP 57) in 122 human renal biopsy specimens to investigate their role in mediating renal damage. Expression of PR3 predominated in ANCA-associated RPGN and was independent of the serologic ANCA pattern (c-/p-ANCA). The PR3 staining pattern was patchy and not always related to distint granulocytes due to antigen spreading by disintegrating cells. It was found in crescentic glomeruli and the interstitum of ANCA-positive RPGN. In contrast, glomerular and interstitial elastase staining pattern was much more granulocyte related and was even found in noncrescentic glomeruli in c-ANCA- and p-ANCA-positive pauci-immune RPGN. Endothelial cell and glomerular basement membrane-bound PR3 or elastase expression were not observed. A faint glomerular PR3/elastase expression was seen in Goodpasture's syndrome and within the interstitium in crescentic mesangioproliferative glomerulonephritis (granulocyte related). Both serine proteinases were found in the glomeruli in ANCA-negative acute postinfectious glomerulonephritis. In conclusion, this study provides evidence, for the first time, for the implication of the granulocyte serine proteinases PR3 and elastase in mediating pauci-immune ANCA-positive RPGN and different forms of proliferative glomerulonephritis. The expression of ANCA antigens in ANCA-negative glomerulonephritis suggests that this finding is a marker of neutrophil activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Limitations of pulse oral calcitriol therapy in continuous ambulatory peritoneal dialysis patients.

Calcitriol is increasingly used for therapy of secondary hyperparathyroidism in patients with end-stage renal disease. Its therapeutic efficacy, however, often has been limited by the associated increase in intestinal calcium and phosphorus absorption. Previous studies reported that these side effects could be avoided by intermittent administration of calcitriol in high doses, subsequently referred to as pulse therapy. The present study was designed to investigate pulse oral calcitriol therapy in a patient subgroup especially susceptible to the development of hypercalcemia and hyperphosphatemia under standard continuous calcitriol treatment. We examined 15 peritoneal dialysis patients with moderate degrees of hyperparathyroidism (intact parathyroid hormone [iPTH] levels, 150 to 903 pg/mL) ingesting between 1.5 and 6 g of calcium salts as the sole phosphate binders. Treatment consisted of 0.5 microgram calcitriol twice weekly. Eight of these patients had been previously converted to low calcium dialysate to tolerate the necessary doses of phosphate-binding calcium salts. During the study period, comprising 8 pretreatment weeks and 8 weeks of therapy, dialysates and doses of calcium salts were not changed, so that only calcitriol influenced the determined parameters. As expected, iPTH levels decreased rapidly in all patients (P < 0.0001). However, within 4 weeks of treatment a marked increase in calcium phosphorus products was observed (P < 0.0001). Overt hypercalcemia developed in five patients. We concluded that pulse oral calcitriol has to be carefully monitored in peritoneal dialysis patients receiving high doses of calcium salts because of the increased risk for hypercalcemia and hyperphosphatemia.

Assessment of soluble adhesion molecules (sICAM-1, sVCAM-1, sELAM-1) and complement cleavage products (sC4d, sC5b-9) in urine. Clinical monitoring of renal allograft recipients.

Increasing evidence exists that inducible adhesion molecules are involved in cell-mediated allograft rejection. In addition, complement activation during rejection has been described. This study investigated, whether specific molecules derived from either pathway are excreted into urine during rejection and whether they can provide useful diagnostic tools for the monitoring of renal transplant recipients. Urinary concentrations of soluble adhesion molecules (sICAM-1, sVCAM-1, sE-selectin) and of complement cleavage products (sC4d and sC5b-9), were determined by standardized ELISA in 30 normal controls and 80 samples from 49 recipients of renal allografts. In contrast to the low amounts of adhesion molecules and complement components uniformly excreted by healthy persons (group 0), marked differences were observed among allograft recipients. To prove the clinical relevance of these differences in excretion, patient samples were assigned to 5 categories according to clinical and histopathological criteria: group I--acute steroid-resistant rejection (n = 10); group II--acute steroid-sensitive rejection (n = 10); group III--chronic rejection (n = 23); group IV--stable graft function (n = 27); and group V--miscellaneous disorders (n = 10), including infections, CsA overdoses, and glomerulonephritis. Urinary levels of sICAM-1, sVCAM-1, and sC4d were significantly higher in group I compared with all other groups (P < 0.01). The difference in sICAM-1 excretion between groups III and IV also reached statistical significance (P < 0.05). Urinary concentrations of sICAM-1, sVCAM-1, and sC4d were reflective of their histological distribution in corresponding graft biopsies. None of the patients excreted E-selectin in detectable amounts. Excretion of the terminal membrane attack complex C5b-9 was not significantly associated with any diagnosis. It is concluded that for clinical purposes the combined evaluation of sICAM-1, sVCAM-1, and sC4d is most useful and can provide valuable information with regard to the severity and the type of allograft rejection.

Aneurysms of coronary arteries in a patient with adult polycystic kidney disease: arteriosclerosis or involvement by the primary disease?

Adult polycystic kidney disease is frequently associated with gastrointestinal and cardiovascular abnormalities. These include hypertension, mitral valve prolapse, mild dilation of the aortic root, abdominal aneurysms, and predisposition to aortic, mitral, and tricuspidal valve regurgitation reminiscent of Marfan's syndrome. Although the exact molecular mechanisms of adult polycystic kidney disease are not well established, a generalized defect of collagen structure is hypothesized. The most severe vascular problems, however, are typical intracranial aneurysms with a high incidence of subarachnoid hemorrhage and a high mortality rate. We report a case of dilated coronary arteries found incidentally in a patient with adult polycystic kidney disease and stress-induced angina pectoris. The typical angina pectoris of the patient is explained by left ventricular hypertrophy and coronary heart disease. Multiple liver cysts, mitral valve prolapse, and the coronary aneurysms in this patient with adult polycystic kidney disease appear to reflect the manifestation of a generalized connective tissue disorder in this syndrome.

[Fasciola hepatic infection in a family: diagnosis and therapy]. / Fasciola hepatica--Infektion einer Familie. Diagnostik und Therapie.

A 39-year-old man was hospitalized because of a 5-week history of feeling very ill, with fever up to 39 degrees C and nonspecific upper abdominal pain. He looked very pale and his spleen was painful on palpation. There was a blood eosinophilia of over 50% and computed tomography demonstrated hypodense areas in the liver, suggesting a parasitic infection with liver involvement. An ELISA factor of over 100 and the finding of liver fluke eggs in bile confirmed the diagnosis of Fasciola hepatica infection, which was probably acquired by eating wild watercress when visiting in the Allgäu. A fasciola infection was also proven in his 37-year-old sister who for some time had complained of colicky right-sided upper abdominal pain, her 40-year-old husband with similar symptoms and their 10-year-old daughter. All four were successfully treated for two days with 10 mg/kg triclabendazole daily by mouth. Persons eating raw vegetables and salads of wild-growing plants are at risk of being infected with Fasciola hepatica.