Risk of heparin lock-related bleeding when using indwelling venous catheter in haemodialysis.

BACKGROUND: The indwelling venous catheter such as Dual-Cath or Twin-Cath is widely used in haemodialysis. Although the manufacturer recommends filling the catheter lumen with heparin after the dialysis session to prevent clotting, little is known about the systemic effects of such a procedure. METHODS: Twenty haemodialysis patients with Dual-Cath were studied. Dialysis anticoagulation was achieved by injecting a bolus of dalteparin. The patient/control ratio of activated partial thromboplastin time (aPTT) was determined at the end of the session immediately before and 10 min after locking with 2 ml of undiluted heparin (10,000 U/catheter). We also determined the catheter volume for each patient and measured aPTT immediately before and 10 min after heparin locking with this patient-specific volume. Catheter patency was followed over a 2-week period. RESULTS: The aPTT values determined at the end of two consecutive dialysis sessions were nearly normal, respectively 1.29 (+/-0.17) and 1.33 (+/-0.22), whereas all patients had uncoagulable blood (aPTT >3.75) 10 min after locking with 2 ml of heparin. When catheter volumes were individually calculated, they were found to be substantially lower than 2.0 ml (1.21+/-0.12 for the arterial branch and 1.27+/-0.13 for the venous branch). aPTT was only 2.42+/-0.73 10 min after locking with the estimated volumes except in one patient (aPTT >3.75). No catheter clotting was observed despite these smaller locking volumes. CONCLUSIONS: A risk of inducing serious bleeding does indeed exist with Dual-Cath heparin locking, especially in postoperative patients. This risk can be reduced by measuring catheter length at the time of placement in order to ensure an appropriate lock volume. Sodium citrate, polygeline, or urokinase are possible alternatives to heparin.

Plasma levels and metabolism of AcSDKP in patients with chronic renal failure: relationship with erythropoietin requirements.

N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is a physiological inhibitor of hematopoiesis that is maintained at stable levels in normal plasma. Its degradation in vivo and in vitro by angiotensin-converting enzyme (ACE) accounts for the high plasma concentrations of AcSDKP in patients treated with ACE inhibitors. Because ACE inhibitors can induce anemia in some patients, we measured plasma AcSDKP concentrations in 176 patients with chronic renal failure: 120 hemodialysis (HD) and 56 nondialysis (nD) patients, 39 of whom were administered ACE inhibitors. We studied the relationships between AcSDKP levels, hematologic parameters, and recombinant human erythropoietin (rHuEPO) requirements in these patients. AcSDKP levels were significantly greater in HD (10.3 +/- 3.9 pmol/mL) and nD (3.1 +/- 1.8 pmol/mL) patients not administered ACE inhibitors than controls (1.8 +/- 0.2 pmol/mL). In all patients, treatment with ACE inhibitors significantly increased these levels fourfold. HD sessions significantly decreased AcSDKP concentrations by 66% and reduced the predialysis in vitro half-life of AcSDKP (270 +/- 109 minutes) to values (182 +/- 67 minutes) not significantly different from those of controls or nD patients. Most HD patients treated with ACE inhibitors had AcSDKP levels greater than 24 pmol/mL (the greatest concentration found in other nD and HD patients). Only in this group of patients did weekly doses of rHuEPO correlate with AcSDKP levels. Our results show that renal function is essential to maintain stable AcSDKP plasma levels, and at high levels, AcSDKP acts as a uremic toxin causing partial resistance to erythropoietin and inhibiting erythropoiesis.

Factors predicting the long-term success of maintenance cyclosporine monotherapy after kidney transplantation.

BACKGROUND: The theoretical aim of maintenance cyclosporine monotherapy (mCsA) after kidney transplantation is to reduce the incidence of the metabolic complications of corticosteroids and to minimize the adverse effects of excessive long-term immunosuppression. This study was performed in low-immunological-risk cadaveric kidney transplant recipients to evaluate the risks and benefits of mCsA and the long-term graft survival, and to determine the factors predicting success of this policy. METHODS: The multicenter retrospective study was conducted in 329 Caucasian patients receiving mCsA out of 728 first cadaveric kidney transplant recipients. The inclusion criteria were: HLA antibodies < or =25%, serum creatinine <200 micromol/L, and no rejection or only one rejection episode. At the end of the study, we compared the group of patients successfully treated with mCsA (successful group) with those requiring additional immunosuppressive agents (unsuccessful mCsA group). RESULTS: Overall patient and graft survival rates for the 728 first cadaveric graft were 92% and 64%, respectively, at 8 years. Out of 329 patients enrolled in mCsA, 240 were maintained on this treatment and 89 were withdrawn (3 deaths, 18 graft losses, 68 functional grafts). The 8-year graft survival in the 329 enrolled mCsA patients was 84%, 95% in the successful mCsA group, and 70% in the unsuccessful mCsA group. Multivariate analysis showed that the factors predicting success of mCsA were: donor age <40 years (P = 0.001), serum creatinine at mCsA initiation <125 micromol/L (P = 0.02), no rejection episode before mCsA initiation (P = 0.005), and glomerulopathy as the primary renal disease (P = 0.001). CONCLUSION: Numerous kidney transplant recipients with a low immunological risk and good and stable renal function may benefit from discontinuation of prednisone and azathioprine in order to reduce the complications related to these drugs. This therapeutic approach had no adverse impact on the overall long-term graft survival for "low risk" and successful patients.

Whole blood production of monocytic cytokines (IL-1beta, IL-6, TNF-alpha, sIL-6R, IL-1Ra) in haemodialysed patients.

BACKGROUND: The production of monocytic cytokines by isolated mononuclear cells after stimulation by phytohaemagglutinin (PHA) and lipopolysaccharide (LPS) is generally increased in haemodialysed (HD) patients. We performed whole blood (WB) cultures to evaluate cytokine production by blood cells inside their complex cellular and humoral network. METHODS: Diluted whole blood from HD patients (collected before dialysis) and controls was cultured alone with PHA (2.5 microg/ml) or LPS (1 and 3 microg/ml). Supernatants were collected after 24 and 48 h of culture, and concentrations of IL-1 beta, IL-6, TNF-alpha, sIL-6R and IL-1Ra were determined by ELISA. RESULTS: The low spontaneous production of IL-1beta, IL-6 and TNF-alpha in both patients and controls was not significantly modified by PHA. The lower dose of LPS (1 microg/ml) induced a significant but lower increase in production of IL-1beta, IL-6 and TNF-alpha in patients than in controls. In contrast, while it did not further increase their production in controls, the higher concentration of LPS (3 microg/ml) still increased their production in patients to the same level than in controls. The plasma concentrations of sIL-6R were higher in patients than in controls. In both groups, the sIL-6R concentration did not vary during the culture period whether the cells were stimulated or not with LPS or PHA. This suggests that the increased plasma levels of sIL-6R were not produced by blood cells. Despite a similar significant LPS and PHA induced production of IL-1Ra, the IL-1Ra/IL-1beta ratio was always higher in patients than in controls. CONCLUSION: Monocytes from HD patients in WB cultures are hyporesponsive to PHA and LPS for their IL-1beta, TNFalpha and IL-6 production in contrast to isolated monocytes that demonstrate signs of activation. If it reflects the in vivo situation it could partly explain the immune defect in uraemic and haemodialysed patients. Higher sIL-6R/IL-6 and IL-1Ra/IL-1beta ratios could also participate to the complex immune disturbances of HD patients by reducing the biological activity of two cytokines playing a major role in the immune and inflammatory network.

[A little known cause of chronic renal insufficiency in the adult: systemic tuberous sclerosis]. / Une cause mal connue d'insuffisance rénale chronique de l'adulte: la sclérose tubéreuse systémique.

BACKGROUND: Angiomyolipomas and renal cysts are commonly observed in patients with systemic tuberous sclerosis. Hemorrhagic complications related to the angiomyolipomas are well known. CASE REPORT: A 63-year old woman was hospitalized for severe chronic renal failure. Physical examination revealed skin manifestations of systemic tuberous sclerosis, which the patient had hidden to date. The radiographic work-up demonstrated complete disorganization of the renal parenchyma in both kidneys due to multiple cysts and angiomyolipomas. DISCUSSION: Chronic renal failure can be the inaugural manifestation in low-grade cases of systemic tuberous sclerosis which may go undiagnosed for years allowing progressive destruction of the kidneys.

Decrease of serum paraoxonase activity in chronic renal failure.

Paraoxonase is an esterase that hydrolyzes organophosphate compounds. The enzyme is associated with HDL and could protect LDL against peroxidation, which suggests a possible involvement of paraoxonase in the antiatherogenic properties of HDL. Paraoxonase activity has been shown to be low in patients with myocardial infarction, diabetes mellitus, or familial hypercholesterolemia. Because cardiovascular disease is the main cause of death in chronic renal failure, serum paraoxonase activity was measured by spectrophotometry using three synthetic substrates (phenyl acetate, paraoxon, and 4-nitrophenyl acetate) in 305 patients with kidney disease, including 47 patients with non-end-stage chronic renal failure, 104 patients treated with hemodialysis, 22 patients treated with peritoneal dialysis, and 132 renal transplant patients. Patients were compared with two groups of aged-matched control subjects (total number = 195). Especially with 4-nitrophenyl acetate, paraoxonase activity was lower in patients with some degree of renal insufficiency (chronic renal failure [P < 0.05], chronic hemodialysis [P < 10(-4)], chronic peritoneal dialysis [P < 10(-4)]) than in control subjects. In transplant patients, paraoxonase activity was not found to be different from that in control subjects. The decrease of paraoxonase activity and thus the reduction of its antiatherogenic properties in renal failure could be an essential factor of premature vascular aging, especially when dialysis is used. Renal transplantation seems to restore paraoxonase activity.

[Lymphoproliferative syndromes after renal transplantation]. / Syndromes lymphoprolifératifs après transplantation rénale.

UNLABELLED: Following kidney transplantation, lymphoproliferative disorders (LD) are encountered at a frequency of 1%. The onset of these LD is correlated with the degree of immunosuppression. The mortality is elevated (> 50%) especially in late forms. Since 1984 we have performed two hundred and seventeen kidney transplantations. The patients received sequential quadruple-drug immunosuppressive therapy: antilymphocyte globulin (ALG), azathioprine, corticosteroids and cyclosporine. A diagnosis of LD was established in ten patients, four were of early onset (within twelve months of transplantation) and six late (after five to nine years). Rejection occurred in two patients, one of which was steroid resistant requiring ALG. Three LD arose from the graft hilum, four had a voluminous tumor mass with extranodal sites: the graft (1), stomach (2), gingiva (1), meninges (1), and bone marrow (1). Histologically there were eight cases of large-cell B lymphoma, 1 mononucleosis-like LD, and a MALT lymphoma. A search for EBV was positive seven times. Treatment consisted of decreasing immunosuppressive therapy only (1), combined with antiviral treatment (1), or with surgical removal of the graft (3), and/or chemotherapy (5). Nine patients are still alive, in complete remission, graft loss occurred in four cases. CONCLUSION: In our series, we found a high frequency of LD. Despite 4 LD with a voluminous tumor mass and unfavorable histological prognosis requiring chemotherapy, all the LD in our series had a favorable outcome.

Macrophage colony stimulating factor involvement in uremic patients.

The immunodeficiency of patients with chronic renal failure (CRF) is related to multiple and complex alterations of the cytokine network and of its target cells such as T or B lymphocytes, monocytes, fibroblasts or endothelial cells. Chronic activation of monocytic functions is recognized as a key factor in these immunological disorders. Since macrophage colony stimulating factor (M-CSF) is essential for the activation of several functions of monocytes and macrophages and their production of cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor alpha, we investigated its involvement in patients with CRF. When measured by ELISA, M-CSF serum levels were significantly higher in patients with progressive CRF and those on hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) than in controls. M-CSF serum levels did not correlate with the degree of renal insufficiency and were probably related to complex alterations in its production and/or degradation by the specific M-CSF receptors of macrophages. In HD patients the M-CSF serum concentrations inversely correlated with the number of circulating lymphocytes and were significantly higher in anemic patients requiring treatment with erythropoietin. Our results suggest that M-CSF may play a role in altering the immune system in uremic patients by maintaining in the circulation and tissues permanently primed monocytes and/or macrophages that can then be triggered to an activated state by secondary stimuli such as endotoxins, complement components, other cytokines or contact with foreign surfaces.

Renal infarction and thrombosis of the infrarenal aorta in a 35-year-old man with primary antiphospholipid syndrome.

Renal manifestations of the "primary" antiphospholipid syndrome are rare. We report the case of an athletic 35-year-old man with an unremarkable medical history who suddenly developed hypertension and a renal infarction. Laboratory and radiological investigations showed a complete thrombosis of the infrarenal aorta, extensive collateral circulation arising from the superior mesenteric artery, and the primary antiphospholipid syndrome. Eight cases of renal infarction have previously been reported in the primary antiphospholipid syndrome. To our knowledge, this represents the first case of an infrarenal aortic thrombosis attributable to this syndrome.

Calcium oxalate crystalluria in elderly patients and treatment with naftidrofuryl oxalate.

Crystalluria is important in the evaluation of patients with urinary stone and is more frequently encountered in elderly than in younger adults. After noting that calcium oxalate monohydrate crystalluria was higher in elderly patients, we undertook a study to determine if oral treatment with naftidrofuryl oxalate, a drug frequently prescribed for elderly patients in France, was associated with crystalluria. The presence of early morning crystalluria was assessed in non-stone-forming patients hospitalized in a geriatric department. We studied 251 patients without a history of nephrolithiasis (mean age; 81.6 +/- 8.5 years) of whom 49 had been treated orally with naftidrofuryl oxalate at a mean dosage of 485 +/- 120 mg/24h. We identified and quantified the crystals in one early morning urine sample kept at room temperature. The frequency of crystalluria in elderly patients without stones who were not taking naftidrofuryl oxalate was 31.7% compared with only 6% in the general adult population. In this group, mainly calcium phosphate crystals were found. In patients who received naftidrofuryl oxalate, the frequency of crystalluria was 51% of which the major component was calcium oxalate monohydrate and not calcium phosphate. Naftidrofuryl oxalate may enhance crystal formation in elderly patients. This should be taken into account, particularly when other predisposing factors for nephrolithiasis are present, and a preventive increase in fluid intake considered.

Uraemia is necessary for erythropoietin-induced hypertension in rats.

1. There is no experimental proof that renal insufficiency is a necessary condition for hypertension during erythropoietin treatment. 2. The present study compares the effect of 3 weeks treatment with r-hu EPO (50 i.u./kg) on systolic blood pressure (SBP), haematocrit and plasma cGMP in an animal model of chronic renal failure (remnant kidney model excision) and sham-operated rats. 3. Sub-total nephrectomy induced a significant fall in haematocrit and a significant increase in plasma creatinine levels. Treatment with r-hu EPO resulted in a significant haematocrit increase in uraemic as well as in non-uraemic rats. Despite this effect, r-hu EPO treatment had no effect on SBP in sham-operated rats. On the contrary, this treatment caused significant SBP elevation in uraemic rats; in these rats, SBP increase did not correlate with haematocrit increase. 4. Plasma cGMP concentrations were significantly higher in uraemic compared to sham-operated rats and were not modified by r-hu EPO treatment. 5. This study provides evidence that renal insufficiency in rats is a prerequisite for the development of hypertension during erythropoietin treatment.

[Vaccination against hepatitis B virus. Value of intradermal administration in dialysed patients non responsive to intramuscular approach]. / Vaccination contre le virus de l'hépatite B. Intérêt de l'administration intradermique chez les dialysés non répondeurs par voie intramusculaire.

OBJECTIVES: Approximately 16-27% of dialysis patients (DP) have no detectable antibodies after 5 intramuscular injections of hepatitis B vaccine and represent a group at high risk to contract hepatitis B virus. We report the efficacy of the intradermal route of a recombinant hepatitis B vaccine (r-HBV) in non-responsive dialysis patients in our dialysis unit. METHODS: Intradermal vaccinations were performed in 20 dialysis patients (mean age 62 years) non-responsive to the intramuscular injections (mean 6.8). Five micrograms of r-HBV (Engerix B, SK and F) were administered intradermally every two weeks (maximum 70 micrograms) until a level of anti-HBV antibodies (anti-HBs) arbitrarily choosen of > or = 230 mUI/ml was attained. Anti-HBs was determined after the fourth and subsequent intradermal injections (IMX, Abbott). RESULTS: Fourteen dialysis patients (70%) developed anti-HBs > 10 mUI/ml (geometric mean titers of 330 mIU/ml). Among these, 9 developed seroprotective levels before the fifth injection. Five patients developed anti-HBs > or = 1000 mUI/ml and 6 others developed anti-HBs > or = 230 mUI/ml. After the intradermal injections were discontinued, 11 patients were monthly monitored for at least 3 months, and 6 for one year. The geometric mean antibody level was at 3 months: 157 (n = 11), at 6 months: 122 (n = 8), at nine months: 117 (n = 6), and at 12 months: 66 mIU/ml (n = 6). The age and the sex, haemodialysis duration, albumin levels or treatment by erythropoietin did not seem to play a role in appearance of anti-HBs. CONCLUSIONS: Our experience in 20 dialysis patients shows that repeated low-dose intradermal injections resulted in long-term seroprotection in a substantial number of dialysis patients non-responsive to the intramuscular vaccinations.