Increased coagulation factor levels leading to allograft renal vein thrombosis.

A patient with end-stage kidney disease is described, who lost his renal allograft in the early post-transplant period due to allograft renal vein thrombosis. Prior to transplantation, he had been treated by hemodialysis and lost several vascular accesses because of thrombosis. A search for potential thrombophilic factors disclosed a unique combination of increased clotting factor levels, i.e. FVIII, FIX, FXI and homocysteine. More common hereditary and acquired hypercoagulability factors have been excluded in this patient. While clotting factor deficiencies are well known causes of hemophilia, their levels should also be measured in the workup of transplant candidates with a history of multiple vascular access thrombosis.

Gel clot LAL assay in the initial management of peritoneal dialysis patients with peritonitis: a retrospective study.

BACKGROUND: Indiscriminate use of broad-spectrum antibiotic treatment of peritonitis in peritoneal dialysis patients may have either unwanted side-effects or contribute to the development of antibiotic resistance. This may be avoided by improved diagnosis at presentation. The Limulus amoebocyte lysate assay is a convenient test detecting bacterial endotoxins or fungal beta glucans. This study evaluates a qualitative Limulus amoebocyte lysate test as a diagnostic tool used at presentation of a peritoneal dialysis patient with peritonitis. METHODS: One-hundred and eleven episodes of peritonitis in peritoneal dialysis patients have been analysed retrospectively. Limulus amoebocyte lysate results at presentation were compared with culture results. A Limulus amoebocyte lysate assay was performed using a commercial kit by incubating a mixture of dialysate effluent and Limulus amoebocyte lysate reagent at 37 degrees C. The development of a stable solid clot was considered positive. The specificity and sensitivity of the test were calculated. RESULTS: The specificity of the Limulus amoebocyte lysate assay was found to be 98% and the sensitivity 74%. Limulus amoebocyte lysate assay was false-negative in 13 cases of Gram-negative peritonitis (22%). Limulus amoebocyte lysate was positive in three of seven cases of fungal peritonitis. The study included one case each with false-positive Limulus amoebocyte lysate and with culture-negative peritonitis. CONCLUSIONS: The Limulus amoebocyte lysate assay is a convenient and valuable diagnostic tool for excluding Gram-positive peritonitis in peritoneal dialysis patients. This allows more specific antibiotic treatment at presentation and may avoid the development of bacterial resistance. A negative Limulus amoebocyte lysate test is not reliable for the exclusion of Gram-negative peritonitis. In the absence of a positive culture result 48 h after presentation, accompanied by a delayed response to treatment, a positive Limulus amoebocyte lysate assay may indicate the presence of fungus. This justifies early empiric antifungal treatment before definitive culture results are made available. Routine Limulus amoebocyte lysate assay of dialysate effluent from continuous ambulatory peritoneal dialysis patients presenting with peritonitis is recommended.

Accessory role of human peritoneal mesothelial cells in antigen presentation and T-cell growth.

BACKGROUND: To assess the role of human peritoneal mesothelial cells (HPMCs) in the generation of an immune response during peritonitis, we tested their ability to activate T-cells by antigen presentation (AP) and by the secretion of interleukin-15 (IL-15). IL-15 is a potent leukocyte activator that stimulates the proliferation of CD4+, CD8+, and B and natural killer (NK) cells. METHODS: HPMCs and mononuclear cells were derived from six volunteer patients who underwent elective abdominal surgery. Flow cytometry was used to analyze human lymphocyte antigen-DR (HLA-DR), intercellular adhesion molecule-1 (ICAM-1), and B7 molecules on HPMCs. Affinity-purified CD4 cells were used for AP assays. We used a specific enzyme-linked immunosorbent assay to detect interferon-gamma (IFN-gamma), IL-2, and IL-15 protein and reverse transcription-polymerase chain reaction for mRNA analysis. RESULTS: HPMCs expressed HLA-DR molecules following IFN-gamma treatment. ICAM-1 molecules were expressed at high levels, and B7-1 and B7-2 molecules could not be detected. The accessory function of HPMCs was assayed by T-cell stimulation using anti-CD3 antibodies (OKT3). HPMCs were essential for a significant OKT3-induced T-cell proliferation. Anti-ICAM-1 antibodies blocked OKT3-induced proliferation. HPMCs served as effective antigen-presenting cells when Tetanus toxoid (TT) or Staphylococcus aureus-alpha-toxin were used as antigens. IFN-gamma, IL-2, and IL-15 accumulated during AP reactions. We found that IL-15 is produced by HPMCs, and IFN-gamma up-regulated its mRNA levels and protein secretion in a dose-dependent manner. We also detected IL-15 in the peritoneal effluent of patients undergoing continuous peritoneal dialysis treatment. In patients suffering from peritonitis, IL-15 levels were elevated (35.0 +/- 6.0 pg/mL, N = 10) as compared with noninfected patients (16.2 +/- 4.0 pg/mL, N = 7). CONCLUSIONS: HPMCs participate in the peritoneal immune response against invading pathogens by AP. For this process, ICAM-1 is the major accessory molecule. In addition, HPMCs may contribute to T-cell activation by secretion of IL-15.

Interleukin-15, a leukocyte activator and growth factor, is produced by cortical tubular epithelial cells.

Many renal diseases, including transplant rejection, are mediated by mononuclear cells. Interleukin-15 (IL-15) has been recently described as a cytokine with IL-2-like activity. IL-15 is an effective leukocyte growth factor, activator, and chemoattractant. In rejected human kidney allografts, elevated IL-15, but not IL-2, mRNA is expressed, suggesting a role for IL-15 in the rejection process. The aim of this study was to investigate whether human cortical tubular epithelial cells (HTC) are able to produce IL-15 and whether IL-15 expression is regulated by inflammatory mediators. HTC were isolated and characterized, and IL-15 expression was analyzed by reverse transcription-PCR, enzyme-linked immunosorbent assay, and bioactivity. It was found that HTC constitutively express IL-15. Upon stimulation of HTC with interferon-gamma (IFN gamma), the levels of both mRNA and protein increased up to twofold. In contrast, lipopolysaccharide, IL-1, IL-2, and tumor necrosis factor-alpha had no detectable effect. IFN gamma action on HTC was dose-dependent from concentrations of 5 U/ml, reaching a plateau at 50 U/ml. HTC supernatants induced proliferation of the T cell line CTLD, which could be partially blocked (50%) by specific IL-15 antibodies. This study shows that IL-15 is secreted by HTC and that the Th1-cytokine IFN gamma upregulates IL-15 expression. This suggests that HTC play a role in cell-mediated renal diseases by releasing IL-15.

Effect of bicarbonate-based dialysis solutions on intracellular pH (pHi) and TNFalpha production by peritoneal macrophages.

OBJECTIVE: To compare the effect of Dianeal and two newly-formulated bicarbonate-based peritoneal solutions on intracellular pH (pHi), tumor necrosis factor-alpha (TNFalpha) mRNA level, and TNFalpha secretion by peritoneal macrophages (PMphi). DESIGN AND MEASUREMENTS: Peritoneal macrophages were isolated from dialysates collected after overnight dwells in peritonitis-free continuous ambulatory peritoneal dialysis patients. Dialysis solutions contained 1.5% or 4.25% dextrose. HCO3 concentrations of bicarbonate-(TB) and bicarbonate/lactate-buffered (TBL) solution were 38 mM and 25 mM, respectively. TBL also contained lactate at a concentration of 15 mM. pCO2 levels were 78 mmHg and 51 mmHg, respectively. In all experiments pCO2 was carefully maintained at a stable level. The pHi was measured by spectrofluorometry in BCECF-loaded PMphi exposed to different dialysis solutions or Hank's balanced salt solution. TNFalpha levels were measured by ELISA in the supernatant of lipopolysaccharide- (LPS) stimulated PMphi after their incubation in different solutions for 15 and 30 minutes. TNFalpha mRNA was measured by reverse transcriptase polymerase chain reaction (RT-PCR) of total RNA extracted from LPS-stimulated PMphi after their incubation in different solutions for 30 minutes. beta-actin mRNA was used as the control. RESULTS: Dianeal caused a profound drop in pHi to below 6.2. Following an initial drop, pHi stabilized after 4 minutes at levels of 6.96 and 6.8 after incubation in TB and TBL, respectively. In comparison to the control solution, a fall of 11% and 21% in TNFalpha secretion was seen after incubation in TB for 15 and 30 minutes, respectively, and 15% and 26% after incubation in TBL. Under identical conditions, Dianeal (Baxter, McGaw Park, IL, U.S.A.) caused 59% and >95% suppression of TNFalpha secretion. Accordingly, TNFalpha mRNA level in PMphi was severely depressed by Dianeal but no detectable inhibition was observed following incubation for 30 minutes in TB and TBL. When dextrose concentration in TB and TBL was increased from 1.5% to 4.25%, TNFalpha secretion by PMphi was not suppressed by more than 49%, even after 30 minutes incubation. Moreover, suppression of TNFalpha mRNA levels could not be detected with TB or TBL even at high dextrose concentrations. CONCLUSIONS: In contrast to Dianeal, both bicarbonate-based solutions caused only a mild drop in pHi of PMphi. We postulate this effect to be responsible for the improved capacity of PMphi to secrete TNFalpha when incubated in bicarbonate-based solutions compared to Dianeal. Reflecting its known cytotoxicity, dextrose in high concentrations diminishes the protective effect of TB and TBL on immune function of PMphi. TBL is as effective as TB in preventing the deleterious effect of Dianeal on PMphi function.

The prognostic importance of two easily obtainable noninvasive markers after intravenous thrombolytic therapy in acute myocardial infarction.

The predictability of left ventricular function, short- and long-term prognosis, assessed by means of two easily obtainable noninvasive markers, was prospectively studied in 110 consecutive patients undergoing thrombolytic therapy for acute myocardial infarction. Positive noninvasive markers were defined as follows: a) > 50% reduction in ST segment elevation within 120 min of initiating therapy, and b) early peak of creatine kinase (CK) activity < 12h after the start of thrombolysis. Seventy-five (68%) of the patients had two positive markers and are classified as the responder group. The nonresponder group consisted of 35 patients (32%) who had 0-1 positive markers. Left ventricular function was assessed 6-12 weeks after therapy by equilibrium radionuclide ventriculography. Left ventricular ejection fraction (LVEF) and survival rates at 1 month and 36 months were significantly higher in the responder group compared to the nonresponder group (54 +/- 12% vs. 43 +/- 11%, P < 0.05; 99% vs. 89%, P < 0.06; and 95% vs. 80%, P < 0.05 respectively). Thus, the combined analysis of two easily obtainable noninvasive markers can predict post-treatment preservation of left ventricular function and survival up to 36 months in patients with acute myocardial infarction undergoing thrombolytic therapy.

Short- and long-term comparative study of anistreplase versus streptokinase in acute myocardial infarction.

Streptokinase is well established as an effective thrombolytic. Anistreplase, a new thrombolytic drug, is a complex of streptokinase and acylated human plasminogen that can be administered by intravenous bolus and activates plasminogen at the clot site. Although both streptokinase and anistreplase are effected in treating myocardial infarction (MI), they have different pharmacologic properties. This study was designed to identify short- and long-term differences in their clinical effectiveness, safety in use, and survival rates in patients with acute MI. One hundred ten successive patients under seventy years of age admitted within three hours after onset of sustained chest pain suggestive of acute MI were randomized to receive either 30 units of anistreplase intravenously over five minutes or intravenous injection of 750,000 units of streptokinase over thirty to sixty minutes. Reperfusion was achieved in 34 of the 52 (65%) patients treated with anistreplase and in 41 of the 58 (71%) patients treated with streptokinase (p = NS). The two drugs were equally effective in preserving left ventricular ejection fraction, which was found to be significantly better in patients with anterior wall MI who had achieved reperfusion than it was in those who did not (p less than 0.02). One-month, twelve-month, and thirty-six-month survival rates were high (96% to 88%) with no significant difference between the two treatment groups. The authors conclude that the two drugs are equally effective thrombolytic agents but that anistreplase has the advantage that it can be administered as a bolus injection.

[Calcific periarthritis in patients with endstage renal disease on chronic dialysis].

2 patients with end-stage renal disease undergoing dialysis developed calcific periarthritis. A 25-year-old man on hemodialysis developed arthritis of 2 right metacarpophalangeal joints and a 65-year-old man on chronic ambulatory peritoneal dialysis suffered from pain and tenderness in the left buttock. Treatment with nonsteroidal antiinflammatory drugs in the first case and periarticular injection of methylprednisolone (Depomedrol) in the second were successful.

[Heat stroke associated with massive hepatic necrosis].

Heat stroke in a 21-year-old soldier was complicated by acute renal failure with rhabdomyolysis, hypophosphatemia, hypocalcemia, sinus bradycardia and massive liver necrosis. Treatment included general supportive measures, forced alkaline diuresis and IV fresh frozen plasma and cryoprecipitate and was followed by complete recovery.

Case report: serendipitous Gaucher's disease presenting as elevated erythrocyte sedimentation rate due to monoclonal gammopathy.

Immunoglobulin abnormalities have not been previously noted in totally asymptomatic patients with Gaucher's disease. We report a 40-year-old woman in whom Gaucher's disease was diagnosed during investigation for incidentally discovered elevated erythrocyte sedimentation rate. Further studies revealed IgG(lambda) monoclonal gammopathy. Physical examination and a bone survey disclosed none of the features of Gaucher's disease or multiple myeloma. We conclude that in contrast with previous observations, paraproteinemia may occur with Gaucher's disease even in the absence of splenomegaly or any one of the other features of the disease.