Real-time assessment of in vivo renal ischemia using laser autofluorescence imaging.

Potentially transplantable kidneys experience warm ischemia, and this injury is difficult to quantify. We investigate optical spectroscopic methods for evaluating, in real time, warm ischemic kidney injury and reperfusion. Vascular pedicles of rat kidneys are clamped unilaterally for 18 or 85 min, followed by 18 or 35 min of reperfusion, respectively. Contralateral, uninjured kidneys serve as controls. Autofluorescence and cross-polarized light scattering images are acquired every 15 s using 335-nm laser excitation (autofluorescence) and 650+/-20-nm linearly polarized illumination (light scattering). We analyze changes of injured-to-normal kidney autofluorescence intensity ratios during ischemia and reperfusion phases. The effect of excitation with 260 nm is also explored. Average injured-to-normal intensity ratios under 335-nm excitation decrease from 1.0 to 0.78 at 18 min of ischemia, with a return to baseline during 18 min of reperfusion. However, during 85 min of warm ischemia, average intensity ratios level off at 0.65 after 50 min, with no significant change during 35 min of reperfusion. 260-nm excitation results in no autofluorescence changes with ischemia. Cross-polarized light scattering images at 650 nm suggest that changes in hemoglobin absorption are not related to observed temporal behavior of the autofluorescence signal. Real-time detection of kidney tissue changes associated with warm ischemia and reperfusion using laser spectroscopy is feasible. Normalizing autofluorescence changes under 335 nm using the autofluorescence measured under 260-nm excitation may eliminate the need for a control kidney.

Pretransplant recipient cytomegalovirus seropositivity and hemodialysis are associated with decreased renal allograft and patient survival.

BACKGROUND: Pretransplant systemic inflammation has been associated with decreased renal allograft survival, and infectious agents such as cytomegalovirus (CMV) may play a role. We hypothesized that pretransplant CMV seropositivity is a risk factor for decreased patient and allograft survival after cadaveric renal transplantation and that other factors believed to modulate systemic inflammation, such as dialysis modality, might act synergistically with CMV to decrease patient and allograft survival. METHODS: The United Network for Organ Sharing database was reviewed to identify all patients undergoing cadaveric renal transplantation in the United States from 1988 to 1997. Outcomes for CMV seropositive and seronegative recipients of organs from CMV seronegative donors were analyzed. Subgroup analysis was performed to identify any synergistic influence on outcome between CMV serostatus and known determinants of risk, including degree of human leukocyte antigen mismatch, pretransplant dialysis, and cold ischemia time. RESULTS: Of 29,875 patients who underwent transplantation, 12,239 were CMV seronegative and 17,636 were CMV seropositive. Patient survival was decreased by pretransplant seropositivity (relative risk [RR] 1.11, P =0.001). In addition, this group demonstrated worse overall allograft survival (RR 1.05, P =0.029), although this adverse effect disappeared when patients who died with a functioning graft were censored. Decreased allograft survival was most pronounced in patients who were on hemodialysis before transplantation (RR 1.62, P =0.004). CONCLUSIONS: Pretransplant CMV seropositivity is associated with decreased patient survival. Pretransplant CMV seropositivity and hemodialysis have a synergistic adverse effect on graft survival, independent of patient mortality. Additional studies are required to define mechanisms by which pretransplant CMV infection and dialysis modality may contribute to decreased allograft survival.

Occult pretransplantation systemic inflammation and posttransplantation vascular changes in a primate arterial allograft model.

BACKGROUND: Occult systemic inflammation, as manifested by increased levels of C-reactive protein (CRP), identify patients at increased risk for renal allograft rejection. The mechanisms linking occult systemic inflammation to these adverse outcomes remain unclear. The purpose of this study was to examine the anatomic and physiologic effects of occult pretransplantation systemic inflammation on posttransplantation allograft outcome in a nonhuman primate model. METHODS: Seventy-one healthy male Rhesus macaques were stratified into quartiles based on serum CRP. Five high quartile and six low quartile animals underwent common iliac artery transplantation from male donors. Duplex ultrasound measured graft flow at 3 weeks postoperatively; luminal narrowing was assessed by graft/femoral peak systolic velocity ratio. At 6 weeks, the grafts were harvested and morphometry studies were performed. Vessel wall changes were assessed by measuring the intimal medial area. RESULTS: The allografts placed in high CRP quartile animals had more luminal narrowing by 3 weeks than those placed in low quartile animals, as evidenced by a higher mean graft/femoral peak systolic velocity ratio (1.6 vs. 0.90, P=0.006). Morphometry studies after graft harvest showed increased vessel wall area in the high quartile group versus the low quartile group (1.39 mm vs. 1.03 mm, P=0.018). CONCLUSIONS: Occult pretransplantation systemic inflammation is associated with increased intimal thickening and stenosis after arterial allograft transplantation in a primate model. Additional studies are needed to confirm these results and to further investigate potential mechanisms linking pretransplantation systemic inflammation to adverse outcomes after transplantation.

Intra-access blood flow in patients with newly created upper-arm arteriovenous native fistulae for hemodialysis access.

BACKGROUND: The upper-arm native arteriovenous fistula for hemodialysis (HD) vascular access is an important option in the long-term HD population. This single-center cohort study evaluated intra-access blood flow (Q AC) in 3 variants of newly created upper-arm fistulae. METHODS: Fifty-three patients with mature, working, upper-arm fistulae composed of brachial artery to cephalic vein (n = 27), brachial artery to basilic vein (n = 13), and brachial artery to median antecubital vein (n = 13) fistulae were included. Nine of 13 brachio-median antecubital fistulae were of the Gracz type and used the deep perforating vein. Q AC was measured by means of ultrasound velocity dilution during HD. In brachio-median antecubital fistulae, additional flow in the alternate draining vein was measured by means of duplex ultrasound, with 9 of 11 studied patients showing a patent alternate outflow, of whom 7 patients showed substantial flow (median, 0.7 L/min). RESULTS: Q AC in the HD-used primary vein in brachio-median antecubital fistulae (0.85 L/min) was significantly less than those of brachiocephalic and brachiobasilic fistulae (1.4 and 1.7 L/min, respectively). However, when the additional flow provided by the patent alternate vein in brachio-median antecubital fistulae was considered, flow rates provided by all 3 variants of fistulae appeared similar. The inverse correlation between alternate-vein and primary-vein flows (r = -0.70; P = 0.017) suggested there was competitive flow between the 2 venous outlets. There was no instance of access recirculation. CONCLUSION: Upper-arm fistulae, regardless of type, provide excellent blood flows and should be considered routinely if a wrist fistula is not feasible. The patent alternate vein in the brachio-median antecubital or Gracz fistula may continue to drain a substantial amount of blood.

Outcomes of upper arm arteriovenous fistulas for maintenance hemodialysis access.

HYPOTHESIS: Radiocephalic fistulas for maintenance hemodialysis access are not feasible in all patients with end-stage renal disease. Our aim was to review our experience with 3 types of upper arm arteriovenous fistula (AVF) to ascertain whether they are reasonable alternatives to radiocephalic fistulas and which, if any, have superior performance. PATIENTS AND METHODS: Patient medical records were retrospectively reviewed. The main outcomes were maturation rate, time to maturation, assisted maturation rate, complication rates, reintervention rates, primary and assisted primary patency rates, and effects of comorbidities. RESULTS: Eighty-six patients with end-stage renal disease underwent creation of a brachiocephalic, brachiobasilic, or brachial artery-to-median antecubital vein AVF. Overall, 80% matured, with 23% requiring an intervention to achieve maturity. The mean time to maturation was 3.8 months; 47% had a complication (inability to access, thrombosis, and so on), and 43% required additional interventions. The overall primary patency and assisted primary patency rates at 12 months were 50% and 74%, respectively. Brachiobasilic AVFs not superficialized immediately often needed a second operation. There were no significant differences in patency rates among the 3 AVF types. The AVFs in patients with diabetes took 2 months longer to mature than did those in patients without diabetes. CONCLUSIONS: An upper arm AVF is a reasonable alternative for maintenance hemodialysis access when a radiocephalic AVF is not possible. There are 3 valid options from which to choose to best accommodate each patient's antecubital anatomy. Diabetes may adversely affect outcomes. Our data suggest that brachiobasilic AVFs should be superficialized at the initial procedure, if feasible.

Spectroscopic imaging for detection of ischemic injury in rat kidneys by use of changes in intrinsic optical properties.

It is currently impossible to consistently predict kidney graft viability and function before and after transplantation. We explored optical spectroscopy to assess the degree of ischemic damage in kidney tissue. Tunable UV laser excitation was used to record autofluorescence images, at different spectral ranges, of injured and contralateral control rat kidneys to reveal the excitation conditions that offered optimal contrast. Autofluorescence and near-infrared cross-polarized light-scattering imaging were both used to monitor changes in intensity and spectral characteristics, as a function of exposure time to ischemic injury. These two modalities provided different temporal behaviors, arguably arising from two different mechanisms providing direct correlation of intrinsic optical signatures to ischemic injury time.

Upper arm arteriovenous fistula versus forearm looped arteriovenous graft for hemodialysis access: a comparative analysis.

If an autogenous wrist radiocephalic arteriovenous fistula cannot be created, the next choice for chronic hemodialysis access may be a prosthetic forearm looped arteriovenous graft (FAL-AVG) or a native upper arm arteriovenous fistula (UA-AVF). We reviewed our experience with these two forms of dialysis access to determine which is preferable. Patient medical records were retrospectively reviewed. The main outcomes were time to first use, complications, and reinterventions as well as primary and assisted primary patency. Eighty-six patients underwent creation of UA-AVF, and 60 patients underwent placement of FAL-AVG. Time to first use was 3.8 months for UA-AVFs vs. 1.8 months for FAL-AVGs (p < 0.018). Complication rates were 42% vs. 65% for UA-AVFs vs. FAL-AVGs, respectively (p = 0.006). Thrombosis was more common in FAL-AVGs than UA-AVFs (42% vs. 17%, p = 0.001), as was nonelective reintervention (50% vs. 30%, p = 0.016). Patency rates were similar at 1 and 2 years. Although UA-AVFs and FAL-AVGs share similar early patency rates, UA-AVFs may be a better choice for chronic hemodialysis access because of a lower incidence of complications and nonelective reinterventions. To maximize the benefits of UA-AVFs, however, early surgical referral is required.

Pre-transplant elevations of interleukin-12 and interleukin-10 are associated with acute rejection after renal transplantation.

BACKGROUND: Methods for predicting patients at higher risk for rejection before transplantation may help improve outcomes. We hypothesized that pre-transplant elevations of serum interleukin-12 (IL-12), a pro-inflammatory cytokine, would predict acute rejection, while pre-transplant IL-10, an immunoregulatory cytokine, would be down-regulated in patients subsequently experiencing acute rejection. MATERIALS AND METHODS: Thirty patients experiencing acute rejection after cadaveric renal allograft transplantation and a control group of 30 patients, undergoing the same procedure but without the occurrence of rejection, were identified. Serum samples taken before transplantation from each patient were then analyzed quantitatively for IL-12 and IL-10 using ELISA assays. RESULTS: The mean pre-transplant serum IL-12 level was higher in patients who subsequently underwent acute rejection vs. those who did not (181 +/- 143 pg/mL vs. 81.2 +/- 71.5 pg/mL, respectively, p = 0.007). Unexpectedly, pre-transplant serum IL-10 levels were also elevated in patients who underwent rejection (559 +/- 293 pg/mL vs. 332 +/- 163 pg/mL, respectively, p = 0.002). Multivariate analysis demonstrated that elevations of IL-12 and IL-10 were independent risk factors for rejection when adjusted for confounding variables. CONCLUSIONS: Pre-transplant elevations of IL-12 and, unexpectedly, IL-10 are associated with acute rejection after cadaveric renal transplantation and may be useful in predicting which patients are at increased immunological risk at the time of transplantation. Further studies are necessary to assess the role of occult systemic inflammation in contributing to poor outcomes after transplantation.

Assessment of renal ischemia by optical spectroscopy.

INTRODUCTION: No reliable method currently exists for quantifying the degree of warm ischemia in kidney grafts before transplantation. We describe a method for evaluating pretransplant warm ischemia time using optical spectroscopic methods. METHODS: Lewis rat kidney vascular pedicles were clamped unilaterally in vivo for 0, 5, 10, 20, 30, 60, 90, or 120 min; eight animals were studied at each time point. Injured and contralateral control kidneys were then flushed with Euro-Collins solution, resected, and placed on ice. 335 nm excitation autofluorescence as well as cross-polarized light scattering images were then taken of each injured and control kidney using filters of various wavelengths. The intensity ratio of the injured to normal kidneys was compared to ischemia time. RESULTS: Autofluorescence intensity ratios through a 450-nm filter and light scattering intensity ratios through an 800-nm filter both decreased significantly with increasing ischemia time (P < 0.0001 for each method, one-way analysis of variance). All adjacent and nonadjacent time points between 0 and 90 min were distinguishable using one of these two modalities by Fisher's protected least significant difference. CONCLUSIONS: Optical spectroscopic methods correlate with warm ischemia time in kidneys that have been subsequently hypothermically preserved. Further studies are needed to correlate results with physiological damage and posttransplant performance.