Multi-center experience of 164 consecutive Hemodialysis Reliable Outflow [HeRO] graft implants for hemodialysis treatment.

OBJECTIVE: To report a multi-center experience with the novel Hemodialysis Reliable Outflow (HeRO) vascular access graft. MATERIALS AND METHODS: Four centers conducted a retrospective review of end stage renal disease patients who received the HeRO device from implant to last available follow-up. Data is available on 164 patients with an accumulated 2092.1 HeRO implant months. RESULTS: At 6 months, HeRO primary and secondary patency is 60% and 90.8%, respectively and at 12 months, 48.8% and 90.8%, respectively. At 24 months, HeRO had a primary patency of 42.9% and secondary patency was 86.7%. Interventions to maintain or re-establish patency have been required in 71.3% of patients (117/164) resulting in an intervention rate of 1.5/year. Access related infections have been reported in 4.3% patients resulting in a rate of 0.14/1000 implant days. CONCLUSIONS: In our experience the HeRO device has performed comparably to standard AVGs and has proven superior to TDCs in terms of patency, intervention, and infection rates when compared to the peer-reviewed literature. As an alternative to catheter dependence as a means for hemodialysis access, this graft could reduce the morbidity and mortality associated with TDCs and have a profound impact on the costs associated with catheter related infections and interventions.

Familial hypocalciuric hypercalcemia in the donor and recipient of a living related donor kidney transplant.

Familial hypocalciuric hypercalcemia (FHH) is caused by heterozygous inactivation of the calcium-sensing receptor, which is notably expressed in parathyroid and kidney. FHH is characterized by asymptomatic hypercalcemia and hypophosphatemia and confers minimal, if any, morbidity. Renal transplantation in patients with FHH has not been described previously. This report describes a patient with FHH who developed end-stage renal disease from another cause and subsequently received a living related donor kidney transplant from her FHH-affected daughter. The excellent posttransplant clinical course of both recipient and donor is emphasized.

Obesity predicts increased overall complications following pancreas transplantation.

PURPOSE: We sought to evaluate the role of recipient body mass index (BMI) on postoperative complications in patients receiving pancreas transplants. METHODS: A single-institution retrospective study of 145 consecutive patients undergoing either simultaneous kidney pancreas (SPK) or pancreas after kidney (PAK) transplantation from January 1997 through December 2003. Variables analyzed included: age, sex, BMI, number of prior transplants, cytomegalovirus status of donor and recipient, postoperative insulin resistance, complications, and overall patient and graft survival. Differences in continuous variables and dichotomous variables were evaluated using two-tailed t test and Fisher exact test, respectively. Univariate and multivariate logistic regression analyses were employed to identify predictors of overall complications following surgery. RESULTS: Obesity was defined by a BMI > or = 30. Of the 145 patients, 33 (23%) had a BMI > or = 30 and 112 (77%) had a BMI < 30. There was no significant difference in age or sex between obese and nonobese patients (P = .98 and P = .56, respectively). The type of transplantation, SPK or PAK, did not affect the complication rate (P = .36). Overall complications (infection, dehiscence, evisceration, ventral hernia, allograft failure, gangrene, necrotizing fasciitis, postoperative bleeding, or death) were significantly higher in the obese group (81% vs 40%, P < .001). Obesity was specifically associated with increased frequency of dehiscence, ventral hernia, intra-abdominal infection, gangrene, necrotizing fasciitis, and repeat laparotomy. Obese patients also had a threefold higher rate of graft pancreatitis/enteric leak. Multivariate logistic regression analysis identified age > or = 50 and BMI > or = 30 as independent predictors of overall complications following surgery (odds ratio 4.0, P = .014 and OR 6.8, P < .001, respectively). There was no difference identified between groups with regards to allograft failure, posttransplant insulin resistance, and death. CONCLUSION: Obese patients are at increased risk of overall complications following pancreas transplantation. Specifically, obese patients experience higher frequency of dehiscence, ventral hernia, intra-abdominal infection, gangrene, and necrotizing fasciitis. This study demonstrates the need for careful postoperative monitoring in the obese patient.

Comparison of transposed brachiobasilic fistulas to upper arm grafts and brachiocephalic fistulas.

BACKGROUND: Renewed interest in transposed brachiobasilic fistulas has occurred since the release of the National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI) guidelines because it is an alternative method to achieve an upper arm fistula in patients who cannot achieve a functional brachiocephalic fistula. The objective of this study was to compare outcomes among transposed brachiobasilic fistulas, upper arm grafts, and brachiocephalic fistulas. METHODS: A cohort of patients with upper arm accesses was retrospectively identified. Access outcomes were determined from medical records and contact with physicians, dialysis providers, and patients. Primary outcome was thrombosis-free survival. Secondary outcomes were primary failure, time to use, risk of catheter-related bacteremia, need for intervention, incidence of access-related complications, cumulative, and functional patency. Group differences in age, sex, race, diabetes, peripheral vascular disease, and number of previous accesses were adjusted for in the analysis where appropriate. RESULTS: Transposed brachiobasilic fistulas, upper arm grafts, and brachiocephalic fistulas were compared in 59, 82, and 56 patients, respectively. Compared with transposed brachiobasilic fistulas, upper arm grafts were more likely to thrombose with an adjusted relative risk (RR) of 2.6 (95% CI, 1.3 to 5.3) excluding primary failures and 1.6 (95% CI, 1.0 to 2.7) when accounting for the lower risk of primary failure for grafts. Transposed brachiobasilic fistulas also required less intervention (0.7 vs. 2.4 per access-year, P < 0.01) and were less likely to become infected (0 vs. 13%, P < 0.05) than grafts. Mature brachiocephalic fistulas were less likely to fail (RR 0.3, 95% CI, 0.1 to 1.0) and showed a trend for less thrombosis (RR 0.3, 0.1 to 1.1) than mature brachiobasilic fistulas. There was no significant difference in cumulative patency (failure-free survival) among the three types of access if primary failure was included at the median follow-up of 594 days. Transposed brachiobasilic fistulas provided catheter-free access one month sooner than brachiocephalic fistulas and one month later than upper arm grafts. CONCLUSIONS: Transposed brachiobasilic fistulas provide cumulative patency equivalent to upper arm grafts and brachiocephalic fistulas. They are less likely to thrombose and become infected than upper arm grafts. Compared with brachiocephalic fistula, they are more likely to mature but are at increased risk of thrombosis after maturation. Transposed brachiobasilic fistulas should be considered before placing an upper arm graft for patients that cannot achieve a functional brachiocephalic fistula.

Viral infections after renal transplantation.

Viral infections are a leading cause of posttransplantation morbidity and mortality. A number of recent developments have altered our understanding and management of these disorders. The pathogenetic roles of several viruses, including human herpesviruses 6 and 8, have been newly established. Molecular-based diagnostic tests now make more rapid diagnosis possible. The licensing of new potent antiviral agents offers a wider choice of drugs for viral prophylaxis and treatment. The use of more potent immunosuppressive agents is responsible in part for the increasing incidence of some viral infections, but this varies among drugs, and individual viruses differ in their sensitivity to immunosuppressive agents. This review summarizes the natural history, diagnosis, prevention, and treatment of many common viral infections after renal transplantation.

Catheter access for hemodialysis: an overview.

The provision of hemodialysis requires repeated, reliable access to the central circulatory system. Long-term hemodialysis has best been provided by arteriovenous fistulae and arteriovenous grafts. In recent years, more and more patients have been chronically dialyzed with tunneled dialysis catheters. These catheters, which were originally developed as a short-term bridge to permanent vascular access, have made up an increasing percentage of maintenance vascular access. While these catheters have the advantage of ease of placement and are immediately ready for use, they substantially increase the risk of bacteremia, stenosis of central veins, and even mortality.

Dialysis access infections.

Infections and specifically infectious complications of vascular access remain a major cause of morbidity and mortality in the hemodialysis population. Primary arteriovenous fistulas have the lowest rates of infections and are the access of choice whenever vascular anatomy allows. The dialysis outcomes quality initiative (DOQI) guidelines have thus stressed the need for increasing the utilization of arteriovenous fistulas. Unfortunately, comorbid disease processes and late referrals for vascular access have maintained our dependence on synthetic grafts and indwelling catheters. Indwelling catheters, in particular, have the highest rate of infection and are often associated with more serious metastatic complications. Appropriate antibiotics along with aggressive surgical debridement remain crucial in bacteremia occurring in arteriovenous fistulas or synthetic grafts (polytetrafluoroethylene). Catheter related bacteremia necessitates catheter removal with either guidewire exchange or replacement after a period of antibiotic therapy. Measures to increase our utilization of primary fistulas whenever possible will lower the risk of these complications in our patients.

A role for leukotrienes in cyclosporine nephrotoxicity.

BACKGROUND: Nephrotoxicity associated with cyclosporine A (CsA) administration is characterized by marked renal vasoconstriction, interstitial fibrosis, and arteriolar hypertrophy. While the molecular mechanisms of CsA toxicity are not well characterized, previous studies have demonstrated that altered arachidonic acid (AA) metabolism plays a role its pathogenesis. Using a rat renal transplant model, the purpose of this study was to examine the effects of CsA on the 5-lipoxygenase (5-LO) pathway of AA metabolism. METHODS: The PVG (RT1c) strain of rats underwent kidney transplantation, and recipients of nonrejecting kidney transplants were treated with either 50 mg/kg/day CsA or vehicle (N = 24). To determine the physiologic significance of increased leukotriene (LT) production, the peptidoleukotriene receptor antagonist SKF 106203 was administered to CsA-treated animals for six days. RESULTS: CsA caused a substantial reduction in glomerular filtration rate (GFR) in the transplanted rats compared with the vehicle-treated controls (1.5 +/- 0.6 vs. 4.1 +/- 0.8 mL/min/kg, P < 0.05). The reduction in renal function was associated with enhanced urinary excretion of the peptidoleukotriene metabolites LTE4 (1431 +/- 207 vs. 953 +/- 125 pg/24 h, P < 0.05) and N-acetyl-LTE4 (4411 +/- 848 vs. 463 +/- 70 pg/24 h, P < 0.001). LT receptor blockade had a significant protective effect on renal transplant function in CsA-treated animals (GFR, 4.8 +/- 1.1 vs. 1.7 +/- 0.9 mL/min/kg, P < 0.05), such that CsA-treated animals that received SKF106203 maintained GFR at levels similar to controls that never received CsA (4.1 +/- 0.8 mL/min/kg). Peptidoleukotriene receptor blockade also prevented the histomorphological abnormalities caused by CsA, including tubular vacuolization. CONCLUSIONS: These studies identify a critical role for LTs in the pathophysiology of CsA nephrotoxicity and suggest that LT antagonists may be useful in preventing CsA-associated kidney toxicity.

Diagnosis and management of BK polyomavirus interstitial nephritis in renal transplant recipients.

BACKGROUND: Interstitial nephritis caused by BK polyomavirus is a recognized complication of renal transplantation. A study of renal transplant recipients at Duke University Medical Center was undertaken to evaluate diagnostic modalities and assess clinical outcomes in transplant polyomavirus infections. METHODS: Polyomavirus nephritis was identified in 6 of 240 patients who received renal transplants between January 1996 and June 1998 and an additional patient who underwent transplantation in 1995. The clinical records of these seven patients were reviewed, as were all renal biopsy and nephrectomy specimens. Electron microscopy (EM) was performed on negatively stained urine samples from 6 patients with polyomavirus infection and 23 patients with other diagnoses. RESULTS: Patients with polyomavirus infection shared several clinical features, including ureteral obstruction (5/7 patients), lymphocele (3/7), bacterial urinary tract infection (3/7), hematuria (3/7), cytomegalovirus infection (3/7), and immunosuppression with mycophenolate mofetil (6/7). All patients experienced elevations in serum creatinine, which stabilized or decreased in four patients with altered or decreased immunosuppression. The diagnosis of polyomavirus infection was established by renal biopsy and EM of urine in five patients, by biopsy alone in one, and by EM alone in one. Sequential examinations of urine by EM were used to monitor the course of infection in six patients. CONCLUSIONS: Interstitial nephritis due to BK polyomavirus occurred in 2.5% of patients receiving renal transplants at our center since 1996. Polyomavirus infection can cause transplant dysfunction and graft loss, but progression of the infection can frequently be abrogated with alterations in immunosuppressive therapy. Both renal biopsy and EM of urine samples are useful in the diagnosis and monitoring of polyomavirus infections.

Focal segmental glomerulosclerosis: a need for caution in live-related renal transplantation.

Focal segmental glomerulosclerosis (FSGS) has increasingly been recognized to occur in a familial pattern. We have observed the development of biopsy-confirmed FSGS and subsequent end-stage renal disease (ESRD) in one live related kidney donor and ESRD without biopsy in another. Both donors had family members with ESRD secondary to FSGS. Both donors were apparently healthy by routine physical examination, urinalysis, and serum creatinine at the time of evaluation as live related donors. We believe these cases emphasize the need for great caution when evaluating siblings as potential live related donors.

Proton-decoupled phosphorus-31 magnetic resonance spectroscopy in the evaluation of native and well-functioning transplanted kidneys.

RATIONALE AND OBJECTIVES: To evaluate whether decoupling improves signal-to-noise ratio and frequency resolution of in vivo kidney spectra, and to compare native and well-functioning transplant kidneys. METHODS: Proton decoupling in conjunction with three-dimensional chemical shift imaging (3D-CSI) in phosphorus-31 magnetic resonance (MR) spectroscopy was used with a spatial resolution of 64 cm3 and 17-minute acquisition time to compare native (n = 10) and well-functioning transplant (n = 9) kidneys. RESULTS: Proton decoupling improved peak amplitudes by almost 30%, as well as chemical shift resolution of in vivo kidney spectra. No statistically significant differences in phosphometabolite ratios and renal spectra were observed between healthy volunteers and patients with nonrejecting transplants. The phosphodiester-phosphomonoester ratio was 3.02 +/- 0.88, phosphomonoester-inorganic phosphate ratio was 1.07 +/- 0.44, and inorganic phosphate-adenosine triphosphate ratio was 0.58 +/- 0.22 after correction for saturation effects. CONCLUSION: Improved spectra of native and transplant kidneys can be obtained in vivo with MR spectroscopy by using a short acquisition time.

A clustering of epidural abscesses in chronic hemodialysis patients: risks of salvaging access catheters in cases of infection.

The objective of this study was to investigate factors that might increase the risk of epidural abscesses in hemodialysis patients. The charts of all hemodialysis patients presenting with an epidural abscess over a period of 5 yr at Duke University Hospital and the Durham Veterans Administration Medical Center were reviewed for patient demographics, months on dialysis, vascular access, recently treated infections, signs and symptoms at presentation, and results of any surgical intervention. Ten patients developed an epidural abscess during a 5-yr period. Severe, debilitating back pain was the only consistent initial complaint. Eight patients had dual-lumen intravenous catheters for hemodialysis access, and five patients had or were receiving parenteral antibiotics for catheter salvage. There were no consistent physical, clinical, or laboratory findings. Surgical drainage of the abscess with removal of the hemodialysis catheters and parenteral antibiotics were required for cure in six patients. It was concluded that attempts at catheter salvage with parenteral antibiotics has significant risks for complications. Hemodialysis patients with recently treated or ongoing bacteremia who complain about severe and debilitating back pain with or without neurologic findings should raise the suspicion of an occult epidural abscess.

Hemodialysis vascular access: effect on urea kinetics and the dialysis prescription.

The effective delivery of dialysis requires repeated reliable access to the central circulation capable of providing rapid blood flow. This access to the circulation continues to be the 'weak link' in the provision of long-term renal replacement therapy. Dialysis access malfunction is a major cause of inadequate dialysis delivery and venous stenosis is the leading cause of access malfunction and thrombosis. Careful monitoring of venous dialysis pressures and recirculation along with urea kinetic modeling and physical examination of the graft can prospectively identify the malfunctioning vascular access. When these indicators are used for referral for fistulogram, venous stenosis can be identified and corrected before graft thrombosis. Not only can preemptive repair of the vascular access prevent thrombosis, it also allows for more efficient dialysis delivery to the patient.

Late withdrawal of cyclosporine in stable renal transplant recipients.

The use of cyclosporine (CsA) in renal transplantation has been associated with an improvement in 1-year graft survival, but has not changed the rate of late graft loss. We sought to determine whether the intent to withdraw CsA late after renal transplantation affects renal transplant survival and whether there is a racial difference in the effect of CsA withdrawal. This retrospective study included 384 consecutive patients receiving a renal transplant during the 1984 to 1991 period who were treated with CsA/azathioprine/prednisone and who had a functioning allograft 6 months following transplantation. Of these, 97 were electively withdrawn from CsA at a median of 22 months following transplantation. Factors significantly associated with the decision to withdraw CsA included white race, older age, and lower serum creatinine. Acute rejection within 6 months of stopping CsA occurred in 12 patients (12.4%), including nine of 78 (11.5%) white patients and three of 19 (15.8%) black patients. For the group of 287 patients who were not withdrawn from CsA, the 6-year graft survival rate was 59% (95% confidence interval, 52%, 66%). For the group of patients taken off of CsA, the 6-year graft survival rate was 84% (95% confidence interval, 76%, 92%). Cox proportional hazard survival analysis indicated that the intent to discontinue CsA was associated with better graft survival, with a hazard ratio of 0.37 (95% confidence interval, 0.20, 0.70), independent of other variables that may affect graft survival. A separate analysis controlling for waiting time bias also favored the CsA withdrawal group. There was no detectable racial difference in the effect of CsA withdrawal on graft survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of platelet activating factor in kidney transplant rejection in the rat.

Platelet activating factor (PAF) is a potent lipid mediator with a broad range of biologic activities. Experimental evidence suggests that PAF plays a role in the pathogenesis of a variety of inflammatory processes including allograft rejection. In this study, we evaluated the effects of the PAF antagonist BN52021 on the course of renal allograft rejection in a rat model. Kidneys from ACI (RT1a) rats were transplanted into fully allogeneic PVG (RT1c) rat recipients. Animals received 60 mg/kg/day of the PAF antagonist or vehicle beginning immediately prior to the transplantation procedure. In rats treated with the PAF antagonist, allograft GFR and plasma flow were maintained at levels that were significantly greater than controls. Despite the improvement in renal allograft function, BN52021 had no effect on allograft histomorphology and both groups manifested intense inflammatory cell infiltration consistent with acute cellular rejection. PAF antagonism reduced urinary excretion of thromboxane metabolites and decreased thromboxane production by homogenates prepared from kidney allografts. The PAF antagonist had no effect on urinary excretion of peptidoleukotriene metabolites or on the production of LTB4 by allografts. These data support a role for PAF in the pathophysiology of acute renal allograft rejection, and they suggest that the hemodynamic effects of PAF during rejection may be mediated through stimulation of thromboxane A2. In view of the beneficial effects of PAF blockade in rejection as well as recent reports describing efficacy in models of cyclosporine nephrotoxicity, PAF antagonists may have clinical applications in human renal allograft recipients.

A quality improvement program for hemodialysis vascular access.

The effective delivery of dialysis requires repeated reliable access to the central circulation capable of providing rapid extracorporeal blood flow. Unfortunately, this access to the circulation continues to be the "weak link" in the effective delivery of long-term hemodialysis therapy. This will likely become an even greater problem in the future as increasing numbers of patients with limited access sites secondary to advanced age and atherosclerosis enter the end-stage renal program. Therefore, the preservation of these limited vascular access sites is imperative. Vascular access thrombosis is the leading cause of graft loss and venous stenosis is the major cause of graft thrombosis. Early detection of venous stenosis through careful inspection of the graft combined with measurements of venous outflow pressure and urea recirculation can identify venous access stenosis. Identification of these lesions combined with preemptive repair improves dialysis efficiency and preserves vascular access. When these techniques are used, a dramatic impact on dialysis fistula patency and function can be seen.