Bacterial meningitis--complication from a dialysis catheter.

Various infective complications associated with dialysis catheter infection have been reported in the literature previously. We report a case of a hemodialysis patient presented with confusion and dysarthria secondary to Staphylococcus aureus septicemia and meningitis originating from a tunneled catheter used for providing dialysis. Blood cultures from the periphery, central venous catheter and culture of the line tip grew methicillin-sensitive Staphylococcus aureus. Lumbar puncture after CT brain confirmed Staphylococcus aureus. He was treated with high dose of an appropriate parenteral antibiotic and also removal of the infected line. In spite of optimal treatment, he died 15 days following his admission. The ideal option will be to use a definitive access like a fistula or AV graft, but in practice a significant proportion of hemodialysis patients is dialyzed with temporary or tunneled catheters all over the world, and infection poses a serious threat to dialysis patients resulting in significant mortality and morbidity. In patients with dialysis catheter-related sepsis, removal of the infected catheters and appropriate antibiotic treatment will prevent serious metastatic complications. Planning definitive access well ahead in chronic kidney disease patients and minimizing the use of temporary access is the only way forward.

A 5-year audit of haemodialysis access.

This is a review of our experience with vascular access procedures over a 5-year period at Derriford Hospital, Plymouth, UK. The aims of the study were to examine the outcome of vascular access procedures and factors influencing access survival. Between April 1995 and March 2000, 151 patients who underwent 221 vascular access procedures were studied. Of these, 136 had autogenous arteriovenous fistulae, whereas 85 had prosthetic AV grafts (41% in the thigh). The overall primary failure rate was 21% whereas the 1- and 5-year cumulative access survival rates were 60 and 41%, respectively. Thigh grafts have a mean survival of 36 months compared with 32 months for prosthetic upper limb and 43 months for autogenous fistulae. Age, diabetes and predialysis status did not significantly influence access survival. Thrombosis was responsible for access failure in 62 cases (28%). Avoiding subclavian vein canulation and performing vessel mapping prior to access placement should reduce the risk of access failure due to outflow obstruction.

Effect of fluvastatin on acute renal allograft rejection: a randomized multicenter trial.

BACKGROUND: Statin therapy has been reported to reduce the acute rejection rate following renal transplantation in a pilot study. The present study is the first randomized, double-blind and adequately powered study to examine the effect of statins on acute rejection of renal allografts. METHODS: A total of 364 patients were randomly assigned to receive either fluvastatin 40 mg or placebo in combination with conventional cyclosporine-based immunosuppressive therapy. The primary end point was treated first acute rejection. Secondary end points included biopsy-proven rejection, histological severity of rejection, occurrence of steroid-resistant rejection, and serum creatinine at three months following transplantation. RESULTS: Fluvastatin was well tolerated; no patients developed myositis or rhabdomyolysis. There was no difference in the acute rejection rate [86 (47.3%) fluvastatin vs. 87 (47.8%) placebo] and no significant difference in the severity of rejection, steroid resistant rejection or mean serum creatinine at three months (160 micromol/L vs. 160 micromol/L). Total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol and triglyceride levels increased following renal transplantation. With the exception of the increase in HDL-C, which was augmented, the increases in lipid parameters were significantly reduced by fluvastatin (total cholesterol +17.5% vs. 35.7%; LDL-C +6.3% vs. 46.7%; HDL-C +43.3% vs. 38.1%; triglyceride +52.2% vs 77.6%). CONCLUSIONS: Contrary to the reported effects of statins, fluvastatin had no effect on the incidence or severity of acute rejection following renal transplantation. There were no increases in adverse events. A significant and potentially beneficial alteration in the lipid profile was observed in the early post transplant period. We conclude that fluvastatin may be used safely to correct dyslipidemia in patients with end-stage renal failure through the peri-transplant period.

A study of cytokine gene polymorphisms and protein secretion in renal transplantation.

Although there is evidence that cytokine gene polymorphisms are associated with varying quantities of cytokine protein production, the exact role of these polymorphisms in allograft rejection remains unclear. In a previous study, we demonstrated a significant association between high IL-10 secretion in mixed lymphocyte culture (MLC), together with HLA mismatching for at least 4-6 antigens, with the occurrence of acute rejection following renal transplantation. We, therefore, wished to ascertain whether cytokine gene polymorphisms are associated with varying levels of protein secretion and/or allograft rejection in the same group of patients. Cytokine protein secretion in MLC for IL-4, IL-6, IL-10 and IFN-gamma was measured by ELISA in 49 patient-donor pairs. Protein secretion for the above cytokines was also measured in phytohaemagglutinin (PHA) stimulated cultures in 30 normal controls. In both patient and control groups, single nucleotide polymorphism analysis for IL-4 G(-590)T, IL-6 G(-174)C, IL-10 G(-1082)A, IL-10 C(-819)T, IL-10 C(-592)A, TNF-alpha G(-308)A and microsatellite analysis for IFNG (CA repeat) was performed. No correlation was found between cytokine gene polymorphisms and cytokine protein secretion in either mitogen stimulated cultures (control group) or MLC (patient group). In addition, no correlation was demonstrated between cytokine gene polymorphisms and renal allograft rejection.

Cytokine secretion in mixed lymphocyte culture: a prognostic indicator of renal allograft rejection in addition to HLA mismatching.

We have previously demonstrated significant inter-individual variations in cytokine protein secretion between normal individuals and patients prior to renal transplantation. In this study, pre-transplant patient vs. donor mixed lymphocyte cultures (MLC) were set up between 57 renal allograft patient/donor pairs, and secretion of cytokine protein (IL-2, IL-4, IL-6, IL-10 and IFN-gamma) into the culture supernatant measured by ELISA. Significant inter-individual variations in protein secretion in MLC were observed for all cytokines studied. Univariate analysis demonstrated that high levels of IFN-gamma and IL-10 in MLC and spontaneous IL-4, together with female donor sex and a high degree of HLA mismatching (especially HLA-DR) were significantly associated with rejection. However, multivariate analysis revealed the greatest risk of rejection (RR = 25.5, P = 0.003) was associated with a combination of high IL-10 secretion in MLC and mismatching for at least four HLA antigens (HLA-A, -B and -DR). It remains to be determined whether cytokine secretion in MLC is linked to cytokine gene polymorphisms. In future, assays for measuring either cytokine secretion or genetic polymorphisms may prove to be useful in aiding donor selection and tailoring immunosuppressive therapy.

Ranitidine reduces phosphate binding in dialysis patients receiving calcium carbonate.

BACKGROUND: In a previous controlled study we showed that ranitidine significantly reduced the phosphate binding of aluminium hydroxide in patients with renal failure, probably increasing intragastric pH. METHODS: In this study we have investigated the effect of ranitidine on the phosphate binding of calcium carbonate in fifteen dialysis patients. Ranitidine 300 mg or a placebo tablet was taken before breakfast for two 4-week periods in a double-blind crossover trial with no washout period. The mean daily dose of calcium carbonate was 2 g and neither the dose nor the patient's diet was changed during the study period. Blood was taken at 2-weekly intervals for serum phosphate, calcium, albumin, and alkaline phosphatase measurements, and at the end of each treatment period for parathyroid hormone (PTH) level. RESULTS: Serum phosphate concentrations were significantly higher during the ranitidine than the placebo phase, 1. 78 (+/-0.43 SD) versus 1.59 (+/-0.49 SD) mmol/l (P<0.001). Serum calcium, albumin, PTH, and alkaline phosphatase concentrations did not differ between the two treatment periods. CONCLUSION: This study shows that ranitidine has a significant adverse effect on the phosphate binding of calcium carbonate in patients with renal failure.

Long-term use of the low molecular weight heparin tinzaparin in haemodialysis.

Fifty-two patients with chronic renal failure undergoing hospital haemodialysis were given a single bolus dose of tinzaparin (Innohep, Leo Laboratories, UK) into the arterial side of the dialyser, for up to 43 consecutive dialyses. The mean tinzaparin dose at the beginning was 2,139 IU anti-Xa and at the end 2,186 IU anti-Xa. Overall, tinzaparin proved a satisfactory anticoagulant for 1,370 (96.0%) out of 1,427 dialyses. Significant clot formation was prevented in 1,326 (92.8%) out of 1,429 dialyses. The clinically effective dose was associated with a mean plasma anti-Xa activity 1 h after dosing of 0.4 IU/ml and suppressed fibrinopeptide A formation for up to 4 h. Bleeding, from the skin or mucous membranes, was recorded at 27 (1.9%) of 1,408 dialyses. Prolonged fistula bleeding on completion of dialysis was recorded on only 20 occasions. Other haemorrhagic events included haematemesis, bruising and subconjunctival haemorrhage (each in 1 patient) and epistaxis (2 patients). Three patients died during the study of causes considered unrelated to tinzaparin therapy, myocardial infarction (2 patients) and multiple myeloma. Other adverse events reported included vomiting (3 patients) and hypotension (3 patients). Three patients ceased treatment due to haematemesis, prolonged bleeding from fistula puncture and thrombosis of the arteriovenous access, respectively. A small, but statistically significant, increase within the normal reference range was recorded in the mean values for aspartate aminotransferase and alanine aminotransferase.

Treatment of postrenal transplant erythrocytosis. Long-term efficacy and safety of angiotensin-converting enzyme inhibitors.

Fifty-two patients with postrenal transplant erythrocytosis were treated with an angiotensin-converting enzyme inhibitor (lisinopril or enalapril) for a median of 13 months (range 0-44). A significant fall in haemoglobin of 1.8 +/- 1.6 g dl-1 (range - 0.8 to 6.6) occurred over the first 3 months (p < 0.0001). The haemoglobin then remained stable for as long as 3 years. Both enalapril and lisinopril were equally effective. Therapy was withdrawn in 16 patients (31%) because of decline in renal function (6), anaemia (5), hypotension (3), hyperkalaemia (1) or erectile impotence (1) - complications which were all reversible. Angiotensin-converting enzyme inhibitors in low dose are a safe and effective long-term therapy for postrenal transplant erythrocytosis.

Nursing involvement in research: an academic pursuit or relevant to nursing practice?

It is said that nursing is 'informed by research'. We evaluated the effect a clinical research project had on the nursing procedure of a nonrotating, permanent continuous ambulatory peritoneal dialysis (CAPD) team involved primarily in patient care. A trial of the overnight solute clearance as a simple measure of the adequacy of CAPD was carried out and its effect on the following aspects of nursing practice was assessed: 1. Teamwork-Can research be successfully incorporated within the team's work structure in a clinical environment? 2. Nurse's role-Duties of the nurse involved in the research (selection of patients, organization of appointments, collection of samples, and calculation of results). 3. Nurse/patient relationship-Individual knowledge of patients' needs and communication skills employed (necessity for true informed consent). The experience showed us that the participation in research is not only possible, but also interesting from the nurses' viewpoint and of direct benefit to the patients.

Polymorphisms in angiotensin-converting-enzyme gene and progression of IgA nephropathy.

We have investigated the influence of the functional insertion (I) and deletion (D) polymorphism in intron 16 of the gene for angiotensin-converting enzyme (ACE) in a retrospective study of 100 patients with IgA nephropathy. There was no difference in genotype frequency compared with normal subjects. However, patients homozygous for the D allele tended to present at an earlier age (medians: DD, 33; ID, 34; II, 42 years) and to require renal replacement therapy at a younger age (medians 37, 42, and 48 years, respectively). The rate of progression was significantly worse in patients homozygous for the D allele. The DD genotype is associated with increased severity of disease in patients with IgA nephropathy.

Renal transplant vein occlusion: an early diagnostic sign?

We report new Doppler ultrasound findings in two patients with renal vein thrombosis and obstruction following renal transplantation. In both cases there was a marked reduction in the systolic peak with relatively normal diastolic flow in the intrarenal arterial waveforms. Venous flow was still detectable at the renal hilum in both cases, and throughout the graft in one case. We suggest that, in the absence of signs of proximal renal artery stenosis, small amplitude arterial waveforms with a depressed systolic peak and maintained diastolic flow, despite intrarenal venous flow, represent renal vein thrombosis in evolution or renal vein obstruction. These findings merit early surgical exploration.

Long-term outcome of the use of OKT3 to treat steroid-resistant acute renal allograft rejection.

OKT3 was used to treat steroid-resistant acute renal allograft rejection in 30 of 496 adult patients transplanted over a 6-year period. Rejection was reversed (defined as a fall in serum creatinine by 50% or more within 30 days of treatment with OKT3) in 40% of cases. Successful reversal was significantly more likely when rejection occurred shortly after transplantation (t ratio -2.53; P = 0.019). The long-term outcome was disappointing; the actuarial graft survival at 1 year from the start of treatment with OKT3 was 42%, and no grafts have thus far survived longer than 3 years. Graft survival was shorter in older patients (coefficient/standard error 2.226; P < 0.05), and no other predictor of long-term outcome was identified. Patient survival at 3 years was 88%. Serious infection occurred in 33% of patients, with two deaths. Our experience suggests that treatment with OKT3 is unlikely to reverse acute renal allograft rejection in more than half of patients where rejection is resistant to steroids. Although long-term graft survival occurred in a few cases, the overall long-term outcome was disappointing, particularly in older patients. Finally, our analysis indicates the difficulty of predicting which patients will derive long-term benefit when OKT3 is used to treat steroid-resistant rejection.

Ophthalmic features of fourteen cases of Goodpasture's syndrome.

Juxtapapillary subretinal neovascular membranes developed in both eyes of a patient who had been treated for Goodpasture's syndrome for 4 years. These lesions caused visual impairment but were successfully treated by laser photocoagulation. Subretinal neovascularisation has not been reported before in association with Goodpasture's syndrome, but diverse ocular abnormalities have been described. It is not certain whether these lesions were caused by anti-basement-membrane auto-antibodies. The eyes of 13 other patients with Goodpasture's syndrome were examined, in order to detect other unsuspected ocular pathology. In 1 further patient, both retinae contained a few unexplained superficial retinal haemorrhages. During follow-up, the original patient developed bilateral peripheral retinoschisis. From this short series and from cases previously described, we conclude that sight-threatening ocular abnormalities are rare in Goodpasture's syndrome. It is, however, particularly important to be aware of the possibility of treatable eye disease in Goodpasture's syndrome, since the introduction of effective treatment with immunosuppression and plasmapheresis has made long-term survival likely.

Effect of Helicobacter pylori infection on intragastric urea and ammonium concentrations in patients with chronic renal failure.

AIM: To assess the value of measuring the gastric juice urea:ammonium ratio in detecting Helicobacter pylori infection in patients with chronic renal failure. METHODS: Twenty three (12 men) patients with established chronic renal failure and dyspepsia were studied. Gastric juice (2 ml) was aspirated during endoscopy to measure urea and ammonium. The upper gastrointestinal tract was routinely inspected and two antral biopsy specimens obtained. The 14C-urea breath test was conducted within 14 days of endoscopic examination to determine H pylori antibody response. RESULTS: The median (range) serum urea concentration in 11 patients with renal failure and H pylori infection was similar to that in 12 without H pylori infection. The median gastric juice urea concentration in subjects with infection was lower than that in the subjects without infection (p < 0.01). The median gastric juice ammonium concentration in subjects with the infection was higher compared with subjects without infection (p < 0.01). There was an overlap of the urea and ammonium concentrations in gastric juice from both H pylori positive and negative subjects. The urea:ammonium ratio was 0.16 (0.01-1.11) for subjects with H pylori compared with 1.63 (1.0-18.9) in subjects without infection (p < 0.001). CONCLUSION: The urea:ammonium ratio differentiated both groups, with the exception of one false negative result. The urea:ammonium ratio proved almost as effective in identifying the presence of H pylori infection in subjects with chronic renal failure as it had in subjects with normal renal function.

Human leucocyte antigen (HLA) and malaria morbidity in a Gambian community.

Human leucocyte antigen (HLA) class I and class II typing was performed on 177 children in a rural area of The Gambia who were followed for 2 years in a longitudinal study of malaria morbidity. A comparison was made between those who experienced an episode of clinical malaria in one or both years and those who showed no evidence of infection in either year. No convincing association was found between morbidity and class I phenotype. An overall association of morbidity with the distribution of class II haplotypes was seen, but association with individual DR-DQ haplotypes were not conclusive.