Arterio-venous fistula buttonhole cannulation technique: a retrospective analysis of infectious complications.

BACKGROUND: There are two main methods of accessing arterio-venous fistulas (AVFs); the 'buttonhole' and the 'rope-ladder' cannulation technique. Several small studies have hypothesized that the buttonhole technique is associated with increased rates of fistula-associated infection. This study addresses this hypothesis. METHODS: A retrospective review of all patients attending a large outpatient haemodialysis clinic was performed. Data were collected on the method of cannulation, infection rates, implicated microorganisms, complications of infection and time on haemodialysis. RESULTS: A total of 127 patients had received haemodialysis via an AVF: 53 via the rope-ladder technique and 74 via the buttonhole technique. Nine episodes of clinically significant bacteraemia were recorded in the buttonhole group. This equated to a rate of 0.073 bacteraemia events per 1000 AVF days. There were no episodes of bacteraemia in the rope-ladder group. Eight infections were due to methicillin-sensitive Staphylococcus aureus (MSSA); one was due to Staphylococcus epidermidis. Three patients with MSSA bacteraemia subsequently developed infective endocarditis. Five patients who developed bacteraemia events had been undergoing home haemodialysis. CONCLUSIONS: This study highlights the infectious complications associated with buttonhole cannulation techniques. All organisms isolated in our cohort were known skin colonizers. The reason for the increased rates of infection is unclear. Given this high rate of often life-threatening infection, we recommend regular audit of infection rates. We currently do not recommend this technique to our patients receiving haemodialysis.

Maintenance immunosuppression with intermittent intravenous IL-2 receptor antibody therapy in renal transplant recipients.

OBJECTIVE: To report what we believe to be the first 2 cases of long-term (>24 months) intermittent intravenous interleukin-2 receptor antibody (IL-2RA) therapy for maintenance immunosuppression following renal transplantation. CASE SUMMARY: The first patient is a 52-year-old female with a history of intolerance to calcineurin inhibitors (CNIs) and sirolimus. Following her second transplant, the patient received mycophenolate mofetil 100 mg twice daily, a tapering corticosteroid regimen (initial dose of methylprednisolone 500 mg tapered over 1 week to prednisone 30 mg/day), and biweekly intravenous daclizumab 1-1.2 mg/kg/dose; 33 months after transplant the IL-2RA was changed to intravenous basiliximab 40 mg once a month. At 40 months after transplant, the patient continued to have stable renal function (estimated glomerular filtration rate 48 mL/min/1.73 m²) with excellent tolerability. The second patient is a 59-year-old female also intolerant to CNIs and sirolimus who required intermittent maintenance therapy with intravenous basiliximab 20 mg/dose. Despite an initial rejection episode, the patient tolerated more than 2 years of basiliximab therapy with good renal function (estimated glomerular filtration rate 103 months after transplant 69 mL/min/1.73 m²) and no adverse events. DISCUSSION: The IL-2RAs basiliximab and daclizumab possess several characteristics of ideal maintenance immunosuppressive agents (ie, nondepleting, long half-lives, limited adverse events). Based on a MEDLINE search (through December 31, 2010) using the search terms basiliximab, daclizumab, organ transplant, immunosuppression, and/or maintenance immunosuppression, and an advanced search in the published abstracts from the American Transplant Congress and World Transplant Congress (2000-2010), it appears that IL-2RAs have been used successfully as short-term therapy in both renal and extrarenal transplant recipients to allow for renal recovery following CNI-induced nephrotoxicity. In heart transplant recipients, the IL-2RAs have been used for <24 months as maintenance immunosuppression in patients intolerant of CNIs or sirolimus. CONCLUSIONS: To the best of our knowledge, these 2 cases are the first to demonstrate that IL-2RAs can be used as an alternative to a CNI in a de novo immunosuppressive regimen. Also, this is the first report to illustrate successful long-term use of IL-2RAs in renal transplant recipients. This alternative approach was well tolerated by our patients, with no apparent adverse events. Although the efficacy of such regimens cannot be determined with 2 case reports, the fact that intermittent intravenous IL-2RA administration was successfully accomplished in these patients provides impetus to evaluate this treatment modality in prospective studies.

A pilot study on the immunological effects of oral administration of donor major histocompatibility complex class II peptides in renal transplant recipients.

Oral tolerance is an important physiological mechanism of immune hyporesponsiveness to dietary antigens and the commensal flora of the gastrointestinal tract. Feeding of alloantigens, therefore, has the potential to suppress undesirable immune responses after transplantation. To date, there are no published reports on the effects of such an approach in human transplant recipients. In the present pilot study, we demonstrate complete suppression of baseline indirect alloreactivity in patients with chronic renal allograft dysfunction following the oral feeding of low (0.5 mg/d) but not higher (1.0 and 5.0 mg/d) doses of donor major histocompatibility complex (MHC) class II peptides. The regimen was well tolerated with no evidence for sensitization to the donor antigen. Our results indicate that oral feeding of low dose donor MHC peptide may represent a safe and effective therapy to suppress indirect alloreactivity in renal transplant recipients with chronic allograft dysfunction and warrants further clinical investigation.

Renal transplantation in patients with positive lymphocytotoxicity crossmatches: one center's experience.

BACKGROUND: Sensitization to human leukocyte antigens remains an important barrier to successful renal transplantation. MATERIALS AND METHODS: Herein we describe our center's experience with a plasmapheresis-based desensitization protocol for highly sensitized patients. Twenty-nine patients had a positive T-cell or positive B-cell lymphocytotoxicity crossmatch against their donors. In some cases, baseline crossmatches were of high titer (e.g., 11 had baseline titers > or =1:32). RESULTS: Twenty-eight of 29 patients were rendered T-cell crossmatch negative and B-cell crossmatch negative/low positive and transplanted. None had hyperacute rejection but 11 (39%) had acute antibody mediated rejection. Median follow-up is 22 months: 25 of the 28 (89%) of allografts are still functioning with mean plasma creatinine 1.5 mg/dL. There was one death because of the transplant or immunsuppression, one case of cytomegalovirus disease and no cases of lymphoproliferative disease. CONCLUSION: This series provides further evidence of the high efficacy of plasmapheresis-based desensitization protocols. Even patients with high baseline crossmatch titers can be successfully desensitized and transplanted. Short- and medium-term outcomes are encouraging but longer-term data are needed.

Transplantation across previously incompatible immunological barriers.

This article reviews recent advances, which allow the transplantation across or around previously incompatible immunological barriers such as a positive crossmatch or ABO blood group incompatibility.

Acetaminophen-induced anion gap metabolic acidosis and 5-oxoprolinuria (pyroglutamic aciduria) acquired in hospital.

A rare cause of high anion gap acidosis is 5-oxoproline (pyroglutamic acid), an organic acid intermediate of the gamma-glutamyl cycle. Acetaminophen and several other drugs have been implicated in the development of transient 5-oxoprolinemia in adults. We report the case of a patient with lymphoma who was admitted for salvage chemotherapy. The patient subsequently developed fever and neutropenia and was administered 20.8 g of acetaminophen during 10 days. During this time, anion gap increased from 14 to 30 mEq/L (14 to 30 mmol/L) and altered mental status developed. After usual causes of high anion gap acidosis were ruled out, a screen for urine organic acids showed 5-oxoproline levels elevated at 58-fold greater than normal values. Predisposing factors in this case included renal dysfunction and sepsis. Clinicians need to be aware of this unusual cause of anion gap acidosis because it may be more common than expected, early discontinuation of the offending agent is therapeutic, and administration of N -acetylcysteine could be beneficial.

Traumatic calcinosis cutis in a dialysis patient.

A patient with end-stage renal disease and refractory hyperparathyroidism was evaluated for acute-onset thickening and hardening of the skin of the lower extremities. Her clinical course and physical examination findings were consistent with the recently described entity of nephrogenic fibrosing dermopathy. However, skin biopsy results showed metastatic and dystrophic calcification, without calcific uremic arteriolopathy (calciphylaxis). The patient reported a history of self-inflicted trauma; the authors postulate that trauma, in the setting of hyperparathyroidism and an elevated serum calcium phosphorous product, resulted in the subcutaneous deposition of calcium salts. To the authors' knowledge, this is the first report of metastatic and dystrophic calcification, without calciphylaxis, in a patient with refractory hyperparathyroidism. This case underscores both the rich variety of skin conditions seen in patients undergoing dialysis and recent developments in the field of dermatologic disorders associated with end-stage renal disease.

Update in renal transplantation.

Renal transplantation is the treatment of choice for most patients with end-stage renal disease. The shortage of donor organs, however, remains a major obstacle to successful, early transplantation. This shortage has actually worsened despite an increase in living family-related and unrelated donors. On the other hand, over the last 10 years, allograft and recipient survival have significantly improved. This encouraging outcome reflects many factors, particularly a favorable shift in the balance between the efficacy and toxicity of immunosuppressive regimens. As acute rejection and early graft loss have become less common, the focus is increasingly directed toward the prevention and treatment of the long-term complications of renal transplantation. These include suboptimal allograft function, premature death, cardiovascular disease, and bone disease. Thus, a multidisciplinary approach--rather than management of immunological issues alone--is now required to optimize long-term outcomes of renal transplant recipients.

Assessment by flow cytometry of intracellular cytokine production in the peripheral blood cells of renal transplant recipients.

INTRODUCTION: There is accumulating evidence that non-invasive immune monitoring may be useful in the early period after renal transplant, particularly with regard to predicting the presence of acute rejection. It is less clear whether chronic allograft nephropathy (CAN) is also associated with consistent changes in peripheral blood or urine cells. We hypothesized that patients with CAN would manifest different patterns of cytokine production (compared with non-CAN controls), detectable in peripheral blood mononuclear cells (PBMCs). METHODS: Flow cytometry was used to quantify production within PBMCs of multiple cytokines. RESULTS: A pilot study showed significant differences in cytokine production between healthy controls and transplanted subjects. However, differences between transplanted patients with and without CAN were small and non-significant. DISCUSSION: Flow cytometry is a potentially useful method for quantifying cytokine production by PBMCs of renal transplant recipients. The technique is sensitive enough to detect differences between distinct test groups but could not find differences between recipients with and without CAN. This probably reflects the lack of a true difference because pathological changes within the long-term allograft may simply not be reflected or detected in the total population of PBMCs. Further studies should explore the usefulness of this technique in assaying more defined populations of PBMCs (such as those activated by donor allopeptides) and in serial monitoring of individual patients.

Gemcitabine-associated thrombotic microangiopathy.

BACKGROUND: Gemcitabine-associated thrombotic microangiopathy (TMA) is believed to be very rare, with an estimated incidence rate of 0.015%. Indications for gemcitabine are expanding, and comprehensive characterization of this complication is therefore important. METHODS: The authors performed a retrospective chart review of all cases with gemcitabine-associated TMA diagnosed at Partners Healthcare System (Boston, MA) between January 1997 and February 2002. RESULTS: Nine patients with gemcitabine-associated TMA were identified. Diagnosis was aided by clinical and laboratory features. Renal biopsy confirmed the diagnosis in two patients. The cumulative incidence of gemcitabine-associated TMA was 0.31% (8 cases among 2586 patients) when only the 8 patients with TMA who were treated at clinics associated with the current study were considered (1 patient with a TMA syndrome was transferred from another institution). The median patient age was 53 years, and the median time to development of a TMA syndrome after the initiation of gemcitabine was 8 months (range, 3-18 months), with a cumulative dose ranging from 9 to 56 g/m(2). New or exacerbated hypertension was a prominent feature in 7 of 9 patients and preceded the clinical diagnosis by 0.5-10 weeks. Treatment of TMA included discontinuation of gemcitabine, antihypertensive therapy, plasma exchange, and dialysis. Outcomes are known for all nine patients. Six patients remain alive, whereas three have died of disease progression. No patient died as a direct result of TMA, but two developed kidney failure requiring dialysis, and one developed chronic renal insufficiency. CONCLUSIONS: In the current series, the largest single-institution study to date, the incidence of gemcitabine-associated TMA was higher than previously reported (0.31% vs. 0.015%). Seven of nine patients developed new or exacerbated hypertension, which could be a useful early identifier of patients with gemcitabine-associated TMA syndromes.

Efficacy and safety of low-dose valganciclovir for prevention of cytomegalovirus disease in renal transplant recipients: a single-center, retrospective analysis.

STUDY OBJECTIVE: To evaluate the safety and efficacy of valganciclovir 450 mg/day for 6 months for cytomegalovirus (CMV) prophylaxis in renal transplant recipients. DESIGN: Single-center, retrospective analysis. SETTING: Urban, academic medical center. PATIENTS: Fifty-eight patients who received de novo renal transplants from August 1, 2001-November 21, 2002. INTERVENTION: Valganciclovir 450 mg/day was administered to all renal transplant recipients at risk for CMV disease. Therapy was begun postoperatively and was dose adjusted to renal function. MEASUREMENTS AND MAIN RESULTS: Data collected from renal transplant recipients were demographics, immunosuppressive and antiviral drug therapy, and occurrence of CMV disease, acute rejection, allograft loss, and hematologic adverse events. Donor (D)/recipient (R) CMV serostatus was 37.9% D+/R+, 29.3% D-/R+, 17.3% D+/R-, and 15.5% D-/R-. Antithymocyte globulin (ATG) was administered to 62.1% of patients. Most of the transplant recipients received triple immunosuppression as maintenance therapy. Median follow-up was 20 months. The frequency of CMV disease was 1.7% within 6 months after transplantation and 5.2% at any point after transplantation. All patients who developed CMV disease were D+/R- and had received ATG. Leukopenia and thrombocytopenia associated with valganciclovir were seen in 28% and 24% of patients, respectively. One patient developed acute cellular rejection. No graft losses or deaths occurred. Early discontinuation of valganciclovir occurred in 20% of patients secondary to severe, persistent leukopenia, thrombocytopenia, and/or diarrhea. None of these patients developed CMV disease. CONCLUSION: A high rate of CMV disease was noted among the D+/R- population. Administration of ATG as an induction agent also increased the frequency of CMV disease. Despite the low dosage of valganciclovir, hematologic adverse events were common. However, valganciclovir, administered at 450 mg/day for 6 months, was effective and relatively safe for prophylaxis of CMV disease in renal transplant recipients.

Calcium channel blockers as the treatment of choice for hypertension in renal transplant recipients: fact or fiction.

Posttransplantation hypertension has been identified as an independent risk factor for chronic allograft dysfunction and loss. Based on available morbidity and mortality data, posttransplantation hypertension must be identified and managed appropriately. During the past decade, calcium channel blockers have been recommended by some as the antihypertensive agents of choice in this population, because it was theorized that their vasodilatory effects would counteract the vasoconstrictive effects of the calcineurin inhibitors. With increasing data becoming available, reexamining the use of traditional antihypertensive agents, including diuretics and beta-blockers, or the newer agents, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers, may be beneficial. Transplant clinicians must choose antihypertensive agents that will provide their patients with maximum benefit, from both a renal and a cardiovascular perspective. Beta-blockers, diuretics, and ACE inhibitors have all demonstrated significant benefit on morbidity and mortality in patients with cardiovascular disease. Calcium channel blockers have been shown to possess the ability to counteract cyclosporine-induced nephrotoxicity. When compared with beta-blockers, diuretics, and ACE inhibitors, however, the relative risk of cardiovascular events is increased with calcium channel blockers. With the long-term benefits of calcium channel blockers on the kidney unknown and a negative cardiovascular profile, these agents are best reserved as adjunctive therapy to beta-blockers, diuretics, and ACE inhibitors.