Hypothermic Perfusion Modifies the Association Between Anti-LG3 Antibodies and Delayed Graft Function in Kidney Recipients.

We previously reported associations between autoantibodies to the LG3 fragment of perlecan, anti-LG3, and a higher risk of delayed graft function (DGF) in kidney transplant recipients. Here, we aimed to determine whether some factors that modulate ischemia-reperfusion injury (IRI) can modify this association. We performed a retrospective cohort study in kidney transplant recipients in 2 university-affiliated centers. In 687 patients, we show that high pre-transplant anti-LG3 are associated with DGF when the kidney is transported on ice (odds ratio (OR): 1.75, 95% confidence interval 1.02-3.00), but not when placed on hypothermic perfusion pump (OR: 0.78, 95% CI 0.43-1.37). In patients with DGF, high pre-transplant anti-LG3 are associated with a higher risk of graft failure (subdistribution hazard ratio (SHR): 4.07, 95% CI: 1.80, 9.22), while this was not the case in patients with immediate graft function (SHR: 0.50, 95% CI 0.19, 1.29). High anti-LG3 levels are associated with a higher risk of DGF in kidneys exposed to cold storage, but not when hypothermic pump perfusion is used. High anti-LG3 are also associated with a higher risk of graft failure in patients who experience DGF, a clinical manifestation of severe IRI.

Accuracy in precordial ECG lead placement: Improving performance through a peer-led educational intervention.

BACKGROUND AND OBJECTIVES: Inaccurate electrocardiography (ECG) lead placement may lead to erroneous diagnoses, such as poor R wave progression. We sought to assess the accuracy of precordial ECG lead placement amongst hospital staff members, and to re-evaluate performance after an educational intervention. METHODS AND RESULTS: 100 randomly selected eligible staff members placed sticker dots on a mannequin, their positions were recorded on a radar plot and compared to the correct precordial lead positions. The commonest errors were placing V1 and V2 leads too superiorly, and V5 and V6 leads too medially.Following an educational intervention with the aid of moderated poster presentations and volunteer patients, the study was repeated six months later. 60 subjects correctly placed all leads, compared to 10 in the pre-intervention cohort (P<0.0001) with the proportion achieving correct placement of any lead rising from 0.34 to 0.83, (p<0.0001 for all leads). CONCLUSION: Incorrect ECG lead placement is common. This may be addressed through regular training incorporated into annual induction processes for relevant health care professionals.

Epidemiology and outcome of antimicrobial resistance to gram-negative pathogens in bacteriuric kidney transplant recipients.

BACKGROUND: In kidney transplant recipients, episodes of bacteriuria are often treated regardless of the presence of symptoms because of the lack of clear treatment guidelines suggesting otherwise. This practice may lead to the development of antimicrobial resistance. Our aim was to determine the incidence, determinants, and impact of antimicrobial resistance in kidney transplant recipients with gram-negative bacteriuria. METHOD: We conducted a single-center, retrospective cohort study in patients who underwent kidney transplantation between January 2008 and June 2013. To identify risk factors for the development of resistance, we used a logistic regression model with generalized estimating equations to account for within-subject correlation. RESULTS: Among the 318 patients who underwent kidney transplantation during the study period, 147 patients developed 555 gram-negative episodes of bacteriuria. Resistance to trimethoprim-sulfamethoxazole and quinolones, and production of extended-spectrum ß-lactamase (ESBL) occurred in 52%, 21%, and 5% of isolated microorganisms, respectively. An increased risk of resistance to quinolones and production of ESBL were associated with concomitant diabetes (odds ratio [OR]: 2.29, 95% confidence interval [CI]: 1.11-4.74), the first year post transplantation (OR: 2.88, 95% CI: 1.36-6.09), and antibiotic treatment in the previous 6 months (OR: 3.36, 95% CI: 1.66-6.81). This resistance profile was also associated with the presence of symptoms, a longer duration of antibiotic treatment, and a higher rate of hospitalization. CONCLUSION: Antimicrobial resistance to quinolones and production of ESBL were commonly seen, and were shown to demonstrate an adverse impact on outcomes in kidney transplant recipients with gram-negative bacteriuria. The decision on treatment for asymptomatic bacteriuria should be made with caution, given the potential for the selection of resistant strains.

Spatial and Temporal Clustering of Anti-Glomerular Basement Membrane Disease.

BACKGROUND AND OBJECTIVES: An environmental trigger has been proposed as an inciting factor in the development of anti-GBM disease. This multicenter, observational study sought to define the national incidence of anti-GBM disease during an 11-year period (2003-2014) in Ireland, investigate clustering of cases in time and space, and assess the effect of spatial variability in incidence on outcome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We ascertained cases by screening immunology laboratories for instances of positivity for anti-GBM antibody and the national renal histopathology registry for biopsy-proven cases. The population at risk was defined from national census data. We used a variable-window scan statistic to detect temporal clustering. A Bayesian spatial model was used to calculate standardized incidence ratios (SIRs) for each of the 26 counties. RESULTS: Seventy-nine cases were included. National incidence was 1.64 (95% confidence interval [95% CI], 0.82 to 3.35) per million population per year. A temporal cluster (n=10) was identified during a 3-month period; six cases were resident in four rural counties in the southeast. Spatial analysis revealed wide regional variation in SIRs and a cluster (n=7) in the northwest (SIR, 1.71; 95% CI, 1.02 to 3.06). There were 29 deaths and 57 cases of ESRD during a mean follow-up of 2.9 years. Greater distance from diagnosis site to treating center, stratified by median distance traveled, did not significantly affect patient (hazard ratio, 1.80; 95% CI, 0.87 to 3.77) or renal (hazard ratio, 0.76; 95% CI, 0.40 to 1.13) survival. CONCLUSIONS: To our knowledge, this is the first study to report national incidence rates of anti-GBM disease and formally investigate patterns of incidence. Clustering of cases in time and space supports the hypothesis of an environmental trigger for disease onset. The substantial variability in regional incidence highlights the need for comprehensive country-wide studies to improve our understanding of the etiology of anti-GBM disease.

Colchicine toxicity in renal patients - Are we paying attention?

Colchicine is an approved agent in the management and prophylaxis of gout and familial Mediterranean fever but its therapeutic value is limited by its narrow therapeutic index. Multisystem toxicity is uncommonly reported; and is often associated with renal impairment and/or specific drug interactions. We report two cases of colchicine toxicity marked by severe neuromyopathy in a diabetic with stage 4 chronic kidney disease (CKD) and a renal transplant recipient. Both patients presented with diarrhea, acute on chronic kidney injury and progressive muscle weakness while on colchicine for several weeks or longer. In addition to kidney disease, risk factors for colchicine toxicity included maintenance therapy with simvastatin in the first patient and cyclosporine in the second. Creatine phosphokinase (CPK) was elevated in both cases at presentation and neurophysiologic studies showed a pattern of severe myopathy with axonal sensorimotor neuropathy. The first patient recovered from neurological weakness in a few weeks, but the second patient suffered an extraordinarily protracted and severe neuromuscular disability for a year. The two cases reinforce the need for extra vigilance in prescribing and monitoring colchicine therapy in renal patients with specific attention to drug interactions known to increase the risk of toxicity, thus avoiding such combinations in patients with renal impairment.

Rare manifestations of infective endocarditis: the long known, never to be forgotten diagnosis.

Infective endocarditis (IE) is a life-threatening condition often manifesting as a multisystem disease; its heterogeneous features present a diagnostic challenge. We report two cases of IE masquerading as rare extracardiac complications: a splenectomised patient with a periarticular ankle abscess and acute encephalopathy; and a young man with a cutaneous vasculitis following a spontaneous intracerebral haemorrhage. In both cases, the diagnosis was suspected following detection of afebrile bacteraemia and confirmed with echocardiography. Risk factors included a pneumococcal bacteraemia in the asplenic patient and a previously undiagnosed bicuspid aortic valve in the second patient. Both patients recovered well with appropriate antibiotic therapy followed by valve surgery. IE is an important diagnosis to consider in patients with systemic symptoms or organ specific, otherwise unexplained relevant pathology especially in the presence of a cardiac murmur or risk factors for IE including structural heart disease, prosthetic valves or intravascular devices, and in immunosuppressed patients.

Comparison of Percutaneous and Open Surgical Techniques for First-Time Peritoneal Dialysis Catheter Placement in the Unbreached Peritoneum.

BACKGROUND: The percutaneous Seldinger method of peritoneal dialysis catheter (PDC) insertion has gained favor over recent years whereas traditionally it was reserved for patients considered not fit for general anesthesia. This blind technique is believed to be less safe, and is hence avoided in patients with previous laparotomy incisions. Reports on the success of this method may therefore be criticized for selection bias. In those with no prior abdominal surgery the optimal method of insertion has not been established. METHODS: We retrospectively reviewed the outcomes of first-time PDC placements comparing the percutaneous (group P) and surgical (group S) insertion techniques in patients without a history of previous abdominal surgery in a single center between January 2003 and June 2010. We assessed catheter survival at 3 and 12 months post-insertion and compared complication rates between the two groups. RESULTS: A total of 63 percutaneous and 64 surgical catheter insertions were analyzed. No significant difference was noted in catheter survival rates between group P and group S (86.2% vs 80% at 3 months, p = 0.37; and 78.3% vs 71.2% at 12 months, p = 0.42 respectively). Early and overall peritonitis rates were similar (5% vs 5.3%; p = 1, and 3.5 vs 4.9 episodes per 100 patient-months; p = 0.13 for group P and group S respectively). There were also no significant differences between the two groups in exit site leaks (15.9% in group P vs 6.3% in group S; p = 0.15), poor initial drainage (9.5% in group P vs 10.9% in group S, p = 0.34) or secondary drainage failure (7.9% in group P vs 18.8% in group S, p = 0.09). CONCLUSION: This study illustrates the success and safety of percutaneous PDC insertion compared with the open surgical technique in PD naive patients without a history of prior abdominal surgery. Catheter survival was favorable with percutaneous insertion in this low-risk patient population but larger prospective studies may help to determine whether either method is superior. The percutaneous technique can be recommended as a minimally invasive, cost-effective procedure that facilitates implementing an integrated care model in nephrology practice.

A comparative analysis of percutaneous and open surgical techniques for peritoneal catheter placement.

BACKGROUND: Peritoneal dialysis (PD) is the preferred available option of renal replacement therapy for a significant number of end-stage kidney disease patients. A major limiting factor to the successful continuation of PD is the long-term viability of the PD catheter (PDC). Bedside percutaneous placement of the PDC is not commonly practiced despite published data encouraging use of this technique. Its advantages include faster recovery and avoidance of general anesthesia. METHODS: We carried out a retrospective analysis of the outcomes of 313 PDC insertions at our center, comparing all percutaneous PDC insertions between July 1998 and April 2010 (group P, n = 151) with all surgical PDC insertions between January 2003 and April 2010 (group S, n = 162). RESULTS: Compared with group P patients, significantly more group S patients had undergone previous abdominal surgery or PDC insertion (41.8% vs 9.3% and 33.3% vs 3.3% respectively, p = 0.00). More exit-site leaks occurred in group P than in group S (20.5% vs 6.8%, p = 0.002). The overall incidence of peritonitis was higher in group S than in group P (1 episode in 19 catheter-months vs 1 episode in 26 catheter-months, p = 0.017), but the groups showed no significant difference in the peritonitis rate within 1 month of catheter insertion (5% in group P vs 7.4% in group S, p = 0.4) or in poor initial drainage or secondary drainage failure (9.9% vs 11.7%, p = 0.1, and 7.9% vs 12.3%, p = 0.38, for groups P and S respectively).Technical survival at 3 months was significantly better for group P than for group S (86.6% vs 77%, p = 0.037); at 12 months, it was 77.7% and 68.7% respectively (p = 0.126). No life-threatening complications attributable to the insertion of the PDC occurred in either group. CONCLUSIONS: Our analysis demonstrates further encouraging outcomes of percutaneous PDC placement compared with open surgical placement. However, the members of the percutaneous insertion group were primarily a selected subset of patients without prior abdominal surgery or PDC insertion, therefore limiting the comparability of the groups. Studies addressing such confounding factors are required. Local expertise in catheter placement techniques may affect the generalizability of results.

Severe rhabdomyolysis as a consequence of the interaction of fusidic acid and atorvastatin.

Rhabdomyolysis is a known complication of statin therapy and may be triggered by a pharmacokinetic interaction between a statin and a second medication. Fatal statin-induced rhabdomyolysis has an incidence of 0.15 deaths/million prescriptions. We describe 4 cases of severe rhabdomyolysis with the common feature of atorvastatin use and coadministration of fusidic acid. All cases involved long-term therapy with atorvastatin; fusidic acid was introduced for treatment of osteomyelitis or septic arthritis. Three cases occurred in the setting of diabetes mellitus, with 2 in patients with end-stage renal disease, suggesting increased susceptibility to atorvastatin-fusidic acid-induced rhabdomyolysis in these patient populations. Of the 4 patients in this series, 3 died. Fusidic acid is a unique bacteriostatic antimicrobial agent with principal antistaphylococcal activity. There have been isolated reports of rhabdomyolysis attributed to the interaction of statins and fusidic acid, the cause of which is unclear. Fusidic acid does not inhibit the cytochrome P450 3A4 isoenzyme responsible for atorvastatin metabolism; increased atorvastatin levels due to inhibition of the glucuronidation pathway may be responsible. Considering the low frequency of fusidic acid use, the appearance of 4 such cases within a short time and in a small population suggests the probability that development of this potentially fatal complication may be relatively high.

Nurofen Plus toxicity-what should nephrologists be alert to? Rare complications of an increasingly misused medication.

We report the staggered clinical course of a young Caucasian female who suffered rare deleterious effects of Nurofen Plus misuse with a near fatal outcome. Several life-threatening events intervened before the underlying problem of serious dependency was identified. Effects on renal tubular acidification and bone marrow function as well as the commoner complications of acute kidney injury and peptic ulceration are described. In addition, this is the first case report in which the syndrome of reversible posterior leucoencephalopathy is linked to analgesic misuse, occurring after recovery of renal function. Recommendations for restricting availability of codeine-based analgesics are made.