Leptospirosis presenting as haemolytic uraemic syndrome: a case report.

BACKGROUND: Leptospirosis is a rare infectious disease especially in Western Countries. Renal involvement is a recognised complication of leptospirosis but leptospirosis-associated haemolytic uraemic syndrome is extremely rare and to our knowledge has only been reported once, in 1985. CASE PRESENTATION: A 29-year-old male was transferred to our Renal Unit with fevers, myalgia and diarrhoeal illness. Laboratory investigations revealed an acute kidney injury, acute liver injury, significantly raised lactate dehydrogenase with marked anaemia, thrombocytopenia and schistocytes on a blood film. A diagnosis of haemolytic uraemic syndrome was made. Surprisingly, the stool culture was negative which led to a suspicion of leptospirosis as one of the differential diagnoses. This was subsequently confirmed by enzyme-linked immunosorbent assay and microscopic agglutination test. He received plasma exchange and antibiotics and made a complete recovery on discharge. CONCLUSION: Leptospirosis presenting as haemolytic uraemic syndrome is rare but should be considered in the differential diagnosis especially in the presence of significant liver injury, as current evidence suggests that the disease is re-emerging.

Perioperative Plasma-Lyte use reduces the incidence of renal replacement therapy and hyperkalaemia following renal transplantation when compared with 0.9% saline: a retrospective cohort study.

BACKGROUND: Kidney transplant recipients often receive large volumes of intravenous fluid replacement in the peri-operative period. Administration of 0.9% saline has previously been associated with acidosis, hyperkalaemia and acute kidney injury. The perioperative use of physiologically balanced replacement fluids may reduce the incidence of post-operative renal replacement therapy and hyperkalaemia. METHODS: A retrospective review of consecutive renal transplants before and after a change in perioperative fluid prescription from 0.9% saline to Plasma-Lyte 148. RESULTS: A total of 97 patients were included in the study, 59 receiving exclusively 0.9% saline and 38 receiving exclusively Plasma-Lyte. Patients in the Plasma-Lyte group were less likely to require emergency postoperative dialysis than those receiving 0.9% saline [odds ratio (OR) 0.15 (95% confidence interval 0.03-0.48), P = 0.004], and these patients had more favourable biochemical parameters with less hyperkalaemia, less acidosis and better diuresis. Patients in the Plasma-Lyte group also had a shorter length of hospital stay (7 days versus 11 days; P < 0.0001) and better graft function at 3 months postoperatively (estimated glomerular filtration rate 51 versus 44 mL/min/1.73 m2; P = 0.03); however, there was no difference in graft function at 1 year. CONCLUSIONS: Plasma-Lyte in the perioperative period is safe in renal transplantation and is associated with a favourable biochemical profile, including a reduced incidence of hyperkalaemia, better diuresis and less frequent use of renal replacement therapy early after surgery. In patients receiving Plasma-Lyte, graft function was better at 3 months, but this difference did not persist up to 1 year after transplantation.

Type I interferon causes thrombotic microangiopathy by a dose-dependent toxic effect on the microvasculature.

Many drugs have been reported to cause thrombotic microangiopathy (TMA), yet evidence supporting a direct association is often weak. In particular, TMA has been reported in association with recombinant type I interferon (IFN) therapies, with recent concern regarding the use of IFN in multiple sclerosis patients. However, a causal association has yet to be demonstrated. Here, we adopt a combined clinical and experimental approach to provide evidence of such an association between type I IFN and TMA. We show that the clinical phenotype of cases referred to a national center is uniformly consistent with a direct dose-dependent drug-induced TMA. We then show that dose-dependent microvascular disease is seen in a transgenic mouse model of IFN toxicity. This includes specific microvascular pathological changes seen in patient biopsies and is dependent on transcriptional activation of the IFN response through the type I interferon α/ß receptor (IFNAR). Together our clinical and experimental findings provide evidence of a causal link between type I IFN and TMA. As such, recombinant type I IFN therapies should be stopped at the earliest stage in patients who develop this complication, with implications for risk mitigation.

Critically ill patients requiring acute renal replacement therapy are at an increased risk of long-term renal dysfunction, but rarely receive specialist nephrology follow-up.

BACKGROUND: Episodes of acute kidney injury (AKI) have been associated with the development of chronic kidney disease (CKD). However, follow-up pathways for patients who have survived AKI complicating critical illness are not well established. We hypothesised that patients who had AKI requiring renal replacement therapy (RRT) in intensive care are at risk of CKD, but are rarely referred for nephrology follow-up at hospital discharge. METHODS: We performed a retrospective analysis of all patients who survived AKI requiring renal replacement therapy in intensive care units (ICUs) in the East London region, examining renal function at baseline, hospital discharge and 3-6 months follow-up. We excluded patients who were known to renal services prior to index admission. RESULTS: From 5,544 critical care admissions, we identified 219 patients who survived to be discharged, having undergone RRT for AKI, that were not previously known to renal services. Of these, 124 (57%) had creatinine measured within 3-6 months after discharge, 104 having a pre-morbid baseline for comparison. Only 26 patients (12%) received specialist nephrology follow-up. At 3-6 months follow-up, the estimated glomerular filtration rate was significantly lower than baseline (48 vs. 60 ml/min/1.73 m(2); p < 0.001), with the prevalence of CKD stage III-V rising from 49 to 70% (p < 0.001). CONCLUSIONS: Follow-up of patients who required RRT for AKI in ICU is inconsistent despite evidence of a significant increase in the prevalence of CKD. There is strong justification for the development of robust pathways to identify survivors of AKI in order to detect and manage CKD and its complications.

Cephalic arch stenosis in autogenous haemodialysis fistulas: treatment with the viabahn stent-graft.

PURPOSE: Cephalic arch stenosis (CAS) is an important and common cause of dysfunction in autogenous haemodialysis fistulas that requires multiple reinterventions and aggressive surveillance. We evaluated the safety and efficacy of the Viabahn stent-graft for the management of CAS. METHODS: Between April 2005 and October 2011, 11 consecutive patients [four men and seven women (mean age 56.7 years)] with CAS and dysfunctional fistulas were treated with insertion of 11 Viabahn stent-grafts. Six stent-grafts were inserted due to residual stenosis after angioplasty and five for fistuloplasty-induced rupture. No patient was lost to follow-up. RESULTS: The technical and clinical success rate was 100 %. Primary access patency rates were 81.8 % [95 % confidence interval (CI) 0.482-0.977] at 6 months and 72.7 % (95 % CI 0.390-0.939) at 12 months. Secondary access patency rates were 90.9 % at 6 months (95 % CI 0.587-0.997). There were no procedure-related complications. Mean follow-up was 543.8 days (range 156-2,282). CONCLUSION: The use of the Viabahn stent-graft in the management of CAS is technically feasible and, in this small series, showed patency rates that compare favorably with historical data of angioplasty and bare stents.

Single UK centre experience on the treatment of PD peritonitis--antibiotic levels and outcomes.

BACKGROUND: There are few studies of the pharmacokinetics of vancomycin and gentamicin in peritoneal dialysis (PD) patients and the influence of antibiotic concentrations on treatment outcome. Concerns about resistance to ceftazidime and potential of aminoglycoside toxicity make the choice of empiric antibiotic difficult. METHODS: We retrospectively collected data from 613 patients on PD between 1 June 2002 and 31 December 2005. During this time, we adopted a protocol that minimized aminoglycoside exposure to patients with residual renal function and carefully monitored serum antibiotic concentrations. RESULTS: There were no statistical differences in mean day-5 vancomycin concentrations for continuous ambulatory peritoneal dialysis (CAPD) vs automated peritoneal dialysis (APD) and for anuric vs not-anuric patients. However, low levels (<12 mg/l) were recorded for 12.8% CAPD and 15% APD patients. These remained low at day 10 in 16% patients (25% if not anuric) despite incremental dosing. Vancomycin concentration did not predict cure or relapse of Gram-positive or culture-negative peritonitis. Gentamicin concentration (>2 mg/l in >50% patients) did not predict outcome of Gram-negative and culture-negative peritonitis. Moreover, cure rates were the same irrespective of whether gentamicin was continued for 14 days or was switched to ceftazidime after 5 days. CONCLUSION: We have confirmed that the International Society for Peritoneal Dialysis (ISPD) dosing guideline for vancomycin in CAPD and APD patients produces adequate serum concentrations of the antibiotics in the vast majority. However, large incremental dosing of vancomycin is needed if day-5 levels are low; especially for not-anuric patients. Whilst evidence of gentamicin toxicity in PD remains controversial, ISPD dosing regimen resulted in high levels for >50% patients. High gentamicin concentrations did not correlate with treatment success, but switching gentamicin to ceftazidime at day 5 appeared safe and limited aminoglycoside exposure. Increasing vancomycin and gentamicin concentrations do not appear to improve cure rates and alternative strategies (such as combination treatment) should be considered for future research.

New flow cytometric technique for the evaluation of circulating endothelial progenitor cell levels in various disease groups.

Circulating endothelial progenitor cells (EPC) localise to sites of ischaemia and play a role in vascular repair and re-endothelialisation of injured blood vessels. Low levels of EPCs are associated with cardiovascular disease (CVD) in the general population. It is not clear at present whether and how the numbers of circulating EPCs vary in diseases other than CVD. We have enumerated EPCs by the flow cytometric analysis of whole blood by using a novel cocktail of monoclonal antibodies. This consisted of CD2FITC, CD13FITC and CD22FITC to eliminate non-progenitor cells and VEGFR2PE and CD133-streptavidin-PeCy7 to include only EPCs. We analysed 250 patients with varying stages of uraemia, 36 patients with inflammatory bowel disease (IBD) and 9 patients with acute respiratory distress syndrome and compared this to 74 healthy controls. Using flow cytometry we were able to measure the circulating levels of EPCs, with a result available within hours of the sample being obtained. Circulating EPC numbers vary in different patient groups and healthy controls. In uraemic patients, irrespective of disease severity, there are lower numbers of circulating EPC numbers compared to normal controls (46.6+/-3.7 vs. 66.1+/-4.7; p=0.03). This new technique provides a means of monitoring patients and shows a reduction in circulating EPCs in uraemic patients; this abnormality may be a target of novel therapies.