Quantifying Individual-Level Inaccuracy in Glomerular Filtration Rate Estimation : A Cross-Sectional Study.

BACKGROUND: Although the population-level differences between estimated glomerular filtration rate (eGFR) and measured glomerular filtration rate (mGFR) are well recognized, the magnitude and potential clinical implications of individual-level differences are unknown. OBJECTIVE: To quantify the magnitude and consequences of the individual-level differences between mGFRs and eGFRs. DESIGN: Cross-sectional study. SETTING: Four U.S. community-based epidemiologic cohort studies with mGFR. PATIENTS: 3223 participants in 4 studies. MEASUREMENTS: The GFRs were measured using urinary iothalamate and plasma iohexol clearance; the eGFR was calculated from serum creatinine concentration alone (eGFRCR) and with cystatin C. All GFR results are presented as mL/min/1.73 m2. RESULTS: The participants' mean age was 59 years; 32% were Black, 55% were women, and the mean mGFR was 68. The population-level differences between mGFR and eGFRCR were small; the median difference (mGFR - eGFR) was -0.6 (95% CI, -1.2 to -0.2); however, the individual-level differences were large. At an eGFRCR of 60, 50% of mGFRs ranged from 52 to 67, 80% from 45 to 76, and 95% from 36 to 87. At an eGFRCR of 30, 50% of mGFRs ranged from 27 to 38, 80% from 23 to 44, and 95% from 17 to 54. Substantial disagreement in chronic kidney disease staging by mGFR and eGFRCR was present. Among those with eGFRCR of 45 to 59, 36% had mGFR greater than 60 whereas 20% had mGFR less than 45; among those with eGFRCR of 15 to 29, 30% had mGFR greater than 30 and 5% had mGFR less than 15. The eGFR based on cystatin C did not provide substantial improvement. LIMITATION: Single measurement of mGFR and serum markers without short-term replicates. CONCLUSION: A substantial individual-level discrepancy exists between the mGFR and the eGFR. Laboratories reporting eGFR should consider including the extent of this uncertainty to avoid misinterpretation of eGFR as an mGFR replacement. PRIMARY FUNDING SOURCE: National Institutes of Health.

Increasing organ donation and transplantation: the U.S. experience over the past decade.

The growing gap between the need for and supply of transplantable organs in the U.S. led to several initiatives over the past decade. UNOS implemented policies intended to facilitate the use of expanded criteria donor kidneys with mixed success. The U.S. government sponsored several organ donation and transplantation collaboratives, leading to significant increases in organ donation over several years. The use of organs from donors dying from cardiac death has increased steadily over the past decade, with such donors now exceeding 10% of the total. Revisions of state anatomic death acts allowed persons to declare their intention to donate by enrolling in state donor registries, facilitating the identification of willing donors by organ procurement organization. Despite these initiatives, the disparity between organ demand and supply has continued to grow, primarily as a result of marked increase in the number of candidates awaiting kidney transplantation.

Influence of arterial elasticity and vessel dilatation on arteriovenous fistula maturation: a prospective cohort study.

BACKGROUND: Arteriovenous fistula maturation requires dilatation of the anastomosed artery and vein. The factors that affect dilatation and the mechanisms by which dilatation promotes maturation are not understood. This pilot study tested two hypotheses: that low arterial elasticity is associated with maturation failure, and that vessel dilatation is required for adequate fistula blood flow during dialysis. METHODS: Thirty-two patients underwent preoperative measurement of small artery elasticity index, and pre-anastomosis measurement of artery and vein luminal diameters during fistula surgery. Fistulas were considered mature if they were used successfully in three consecutive treatments within 6 months. A mathematical model was used to determine whether vessel dilatation is needed for adequate fistula flow. RESULTS: Six fistulas were excluded from analysis of maturation because dialysis did not begin within 6 months. Twenty-one of the remaining 26 fistulas were located in the upper arm. Six of 26 failed to mature, and all 6 developed stenosis. The average small artery elasticity index was lower in failed than in matured fistulas (2.25 versus 3.71 ml/ mmHg x 100, P = 0.02). Artery and vein diameters of the 32 patients ranged from 2.5 to 5.0 and 3.5 to 7.0 mm, respectively. When the diameters were applied to the mathematical model, predicted fistula flows ranged from 412 to 1380 ml/min. CONCLUSIONS: Low arterial elasticity is associated with stenosis and fistula maturation failure. However, vessel dilatation is not needed for adequate blood flow except at the smaller diameters in this study. We speculate that low elasticity promotes development of stenosis. Larger studies are needed to confirm these promising results and to determine whether therapies directed at improving elasticity can improve maturation.

Ureteral clipping simplifies hand-assisted laparoscopic donor nephrectomy.

OBJECTIVES: We describe a technique of doubly clipping the distal ureter during hand-assisted laparoscopic donor nephrectomy (HALDN) to prevent urine accumulation, thereby simplifying renal hilar division and potentially decreasing the graft warm ischemic time. METHODS: A technique of placing polymer-locking clips across the distal ureter prior to division was developed to prevent urine accumulation and the need for suctioning during critical hilar vessel division. RESULTS: We found that ureteral clipping and the elimination of urine accumulation simplified renal hilar division. Retrospective assessment of a series of 27 sequential HALDNs (15 without and 12 with clipping) demonstrated similar estimated blood loss, total operative and warm ischemic times (P 0.13 to 0.18). No adverse impact on graft viability or recipient outcome was observed. CONCLUSION: Distal ureter clipping to prevent urine accumulation around the renal hilum during HALDN is safe and helpful.

Arterial revascularization for upper extremity ischemia in patients with chronic kidney disease.

Surgical revascularization of the upper extremity is uncommon, comprising only 4 to 18 per cent of all vascular surgical interventions. Patients with renal failure have higher rates of atherosclerotic cardiovascular and peripheral arterial disease resulting from chronic inflammation, endothelial damage associated with hemodialysis, and vascular trauma. Upper extremity arterial disease with chronic ischemia may be underrecognized in these patients. We reviewed our experience with upper extremity revascularization in patients with renal failure presenting with chronic ischemia. Four patients with longstanding chronic kidney disease developed chronic severe ischemia affecting the forearm or hand. All had previous dialysis access in the symptomatic arm, although none had a functional ipsilateral access at the time of presentation. All patients had successful revascularization with resolution of symptoms and patent bypass grafts at follow up. There was one death 4 months postoperatively and one patient has not returned for follow up. Patients with renal failure with symptomatic upper extremity arterial occlusion should be considered for revascularization of the infrabrachial arteries.

Effect of changing the priority for HLA matching on the rates and outcomes of kidney transplantation in minority groups.

BACKGROUND: HLA typing and the time a patient has spent on the waiting list are the primary criteria used to allocate cadaveric kidneys for transplantation in the United States. Candidates with no HLA-A, B, and DR mismatches are given top priority, followed by candidates with the fewest mismatches at the HLA-B and DR loci; this policy contributes to a higher transplantation rate among whites than nonwhites. We hypothesized that changing this allocation policy would affect graft survival and the racial balance among transplant recipients. METHODS: We estimated the relative rates of kidney transplantation according to race resulting from the current allocation policy and racial differences in HLA antigen profiles, using a Cox model for the time from placement on the waiting list to transplantation. Another model, also adjusted for HLA-B and DR antigen profiles, estimated the relative rates of kidney transplantation that would result if the distribution of these antigen profiles were identical among the racial and ethnic groups. We also investigated the effect of HLA matching on the risk of graft failure, using a Cox model for the time from the first transplantation to graft failure. The results of the two analyses were used to estimate the change in the racial balance of transplantation and graft-failure rates that would result from the elimination of HLA-B matching or HLA-B and DR matching as a means of assigning priority. RESULTS: Eliminating the HLA-B matching as a priority while maintaining HLA-DR matching as a priority would decrease the number of transplantations among whites by 4.0 percent (166 fewer transplantations over a one-year period), whereas it would increase the number among nonwhites by 6.3 percent and increase the rate of graft loss by 2.0 percent. CONCLUSIONS: Removing HLA-B matching as a priority for the allocation of cadaveric kidneys could reduce the existing racial imbalance by increasing the number of transplantations among nonwhites, with only a small increase in the rate of graft loss.

Early mortality rates in older kidney recipients with comorbid risk factors.

BACKGROUND: There are over 60,000 candidates on the deceased donor kidney wait-list and the percentage of candidates over age 50 years continues to grow each year. National data have not previously been used to evaluate the association of comorbidities with mortality in older patients. METHODS: A multivariate analysis of 30,262 deceased donor primary kidney recipients aged 18-59 years and 8,895 aged >or=60 years evaluated the association of six recipient comorbidities on 90- and 365-day patient mortality rates. The additional effects of expanded criteria donors (ECD) and development of delayed graft function (DGF) were also evaluated. RESULTS: The 365-day mortality rate for recipients aged >or=60 years (10.5%) was more than twice that of recipients aged 18-59 years (4.4%) and comorbidities significantly increased mortality rates even higher (10.6-21.4%). The 365-day mortality rate for recipients aged >or=60 years who received an ECD kidney was 14.4% and who developed DGF was 15.9% while recipients with comorbidities but no DGF and no ECD ranged from 16.0 to 42.3%. The 365-day transplant mortality rate of recipients aged >or=60 years with comorbidities is higher than the 365-day wait-list mortality for patients with the same comorbidities, suggesting a lack of survival benefit from transplantation. CONCLUSIONS: Mortality rates for patients aged >or=60 years with comorbidities are higher than for those without comorbidities, significantly higher than for younger patients, and higher than for wait-listed patients. Thus, utility may be poorly served by allocating kidneys to older patients with comorbidities, and perhaps discussion of exclusionary listing criteria is warranted.

Impact of fellowship training in initiating a laparoscopic donor nephrectomy program.

OBJECTIVES: Laparoscopic donor nephrectomy (LDN) is the current standard of care, but remains a challenging procedure. A urologist at our center performed 6 months of standard and hand-assisted laparoscopic nephrectomy (HALN) fellowship (46 cases, 30 as surgeon). He subsequently performed 30 HAL renal surgeries prior to initiating our hand-assisted laparoscopic donor nephrectomy (HALDN) program. METHODS: We reviewed the intra- and postoperative outcomes of the first 20 HALDNs performed at our center. We examined demographics, estimated blood loss (EBL), operative time, complications, change in hemoglobin and creatinine, length of hospital stay, warm ischemic time, and recipient outcome. RESULTS: Twenty (20) patients underwent HALDN between November 2003 and December 2005. The mean operative time was 277 minutes. EBL averaged 176 mL. An expected rise in creatinine of 0.1-0.8 mg/dL occurred in all patients. One (1) patient had a splenic abrasion and was transfused intraoperatively. Two (2) patients' courses were complicated by ileus. The remaining patients were discharged on postoperative days 2-6. There were no other complications. Warm ischemia time averaged 3.7 minutes. Two (2) recipients experienced acute or delayed rejection episodes, requiring increased immunosuppression. One (1) recipient had good renal function until he developed sepsis 3 months later and died. All recipients were discharged with functioning grafts, and there have been no ureteral strictures. CONCLUSIONS: Six (6) months of laparoscopic nephrectomy training plus a 30-case HAL/LRN surgical experience sufficiently prepares a surgeon to initiate a HALDN program. Even at a lower volume transplant center, positive operative results and long-term graft outcomes can be achieved.

Socioeconomic Factors Associated with Readmission after Deceased Donor Renal Transplantation.

Early hospital readmissions after kidney transplantation pose a significant financial burden and hardship for patients and health-care institutions alike. We sought to identify the risk factors associated with increased likelihood of readmission after transplantation, and examined to determine whether patient socioeconomic demographics impacted the likelihood of perioperative readmissions. We evaluated all deceased donor renal transplants performed at our institution between August 2011 and December 2015. In a cohort of 325 transplant operations that met our inclusion criteria, 117 (36%) were readmitted to the hospital within 90 days of discharge. In univariable analyses, length of stay and pretransplant disabled status were associated with increased likelihood of readmission within 90 days of transplant. When placed into multivariable models, there was a suggestion association with length of stay and disability status. Kidney donor profile index, estimated posttransplant survival, employment, race, age, and payor status were not associated with readmission. In conclusion, the factors associated with posttransplant readmission are not necessarily influenced by socioeconomic factors in our study population. The data collected in this single center study indicate that the factors associated with increased rates of readmission are likely clinical in nature.

Survival of mandatorily shared cadaveric kidneys and their paybacks in the zero mismatch era.

BACKGROUND: The United Network for Organ Sharing has mandated the national sharing of well-matched cadaveric kidneys with payback to the national pool. On March 6, 1995, the policy was extended to include sharing of cadaveric kidneys for which there is a recipient with a 0-HLA mismatch (0-MM). However, the beneficial effects of this policy have been questioned. To address these concerns, we analyzed the effects of this system on graft survival, cold ischemia time, and the transplantation of highly sensitized patients during the 0-MM era. METHODS: We analyzed cadaveric solitary kidney transplant data in the OPTN/The United Network for Organ Sharing database. Cox proportional hazards analyses were conducted on 29,401 transplants performed between March 6, 1995 and December 31, 1998 to assess the effects of mandatory sharing and paybacks on graft outcome. We also compared the outcome of pairs of kidneys in which one was shared as either an 0-MM kidney (n=833) or as a payback (n=440) and the mate was transplanted locally. RESULTS: Overall, 36% of kidneys were shared, 15.6% as 0-MM and 20.4% as paybacks or other shares. Although the sharing of 0-MM kidneys significantly increased cold ischemia time, the risk of graft loss was significantly decreased. The survival of payback kidneys was not significantly different from other shared kidneys. Sharing 0-MM kidneys appeared to increase the chances of transplantation of sensitized patients and 47% of the kidneys transplanted in patients with a panel reactive antibody of more than 80% were from 0-MM donors. CONCLUSIONS: National sharing of 0-MM kidneys appears to lead to a small but significant improvement in intermediate-term graft survival despite increasing cold ischemia time. The current policy also increases access of highly sensitized patients to transplantation.

Donor characteristics associated with reduced graft survival: an approach to expanding the pool of kidney donors.

BACKGROUND: Availability of cadaveric kidneys for transplantation is far below the growing need, leading to longer waiting time and more deaths while waiting. METHODS: Using national data from 1995 to 2000, we evaluated graft survival by donor characteristics and the rate of discard of retrieved organs, with the goal of increasing use of kidneys that are associated with increased risk of graft failure, that is, expanded donor kidneys. RESULTS: Cox models identified four donor factors that independently predicted significantly higher relative risk of graft loss compared with a low-risk group. These factors included donor age, cerebrovascular accident as the cause of death, renal insufficiency (serum creatinine >1.5 mg/dL), and history of hypertension. Expanded donor kidneys were defined as those with relative risk of graft loss greater than 1.70 and included all donors aged 60 years and older and those aged 50 to 59 years with at least two of the other three conditions (cerebrovascular cause of death, renal insufficiency, hypertension). The expanded donor group accounted for 14.8% of transplanted kidneys. Among organs procured from expanded donors, 38% were discarded versus 9% for all other kidneys. The risk of graft loss of expanded donor kidneys was increased in both older and younger recipients but to a greater extent in those recipients older than 50 years. CONCLUSION: By identifying donor factors associated with graft failure, these analyses may help to expand the number of transplanted kidneys by increasing the utilization of retrieved cadaveric kidneys.

Protein kinase C and Src family kinases mediate angiotensin II-induced protein kinase D activation and acute aldosterone production.

Recent evidence has shown a role for the serine/threonine protein kinase D (PKD) in the regulation of acute aldosterone secretion upon angiotensin II (AngII) stimulation. However, the mechanism by which AngII activates PKD remains unclear. In this study, using both pharmacological and molecular approaches, we demonstrate that AngII-induced PKD activation is mediated by protein kinase C (PKC) and Src family kinases in primary bovine adrenal glomerulosa cells and leads to increased aldosterone production. The pan PKC inhibitor Ro 31-8220 and the Src family kinase inhibitors PP2 and Src-1 inhibited both PKD activation and acute aldosterone production. Additionally, like the dominant-negative serine-738/742-to-alanine PKD mutant that cannot be phosphorylated by PKC, the dominant-negative tyrosine-463-to-phenylalanine PKD mutant, which is not phosphorylatable by the Src/Abl pathway, inhibited acute AngII-induced aldosterone production. Taken together, our results demonstrate that AngII activates PKD via a mechanism involving Src family kinases and PKC, to underlie increased aldosterone production.

Program directors' views on general surgery resident travel for transplant rotations.

BACKGROUND: Some program directors in surgery (PDs) must maintain transplant rotations at nonintegrated (away) hospitals. This study investigated the opinions of PDs related to resident travel for transplant surgery experience. METHODS: An Internet-based survey was e-mailed to 251 PDs in the United States. RESULTS: Altogether, 131 PDs (52%) responded. Of those, 66% have a transplant service at integrated hospitals. Small majorities of PDs believed transplant rotations offer a good educational experience (59%) and comply with duty hours (71%). Few PDs believed transplant rotations provide excellent operative experience (47%) and mandate service over education (38%). PDs leading community-affiliated and smaller programs employed away rotations more commonly. Affected PDs used commuting (48%) and purchased temporary housing (52%). Most believed travel is a poor aspect of the experience (78%) and transplant rotations should become an optional component of residency training (60%). PDs using away hospitals more often believed this content area should be eliminated. CONCLUSIONS: Although away transplant rotations minimally impact opinions of PDs related to select educational issues, most PDs challenge the existing paradigm of transplant surgery as essential content.

Kidney and pancreas transplantation.

Data from the Scientific Registry of Transplant Recipients offer a unique and comprehensive view of US trends in kidney and pancreas waiting list characteristics and outcomes, transplant recipient and donor characteristics, and patient and allograft survival. Important findings from our review of developments during 2002 and the decade's transplantation trends appear below. The kidney waiting list has continued to grow, increasing from 47,830 in 2001 to 50,855 in 2002. This growth has occurred despite the increasing importance of living donor transplantation, which rose from 28% of total kidney transplants in 1993 to 43% in 2002. Policies and procedures to expedite the allocation of expanded criteria donor (ECD) kidneys were developed and implemented during 2002, when 15% of deceased donor transplants were performed with ECD kidneys. Unadjusted 1- and 5-year deceased donor kidney allograft survivals were 81% and 51% for ECD kidney recipients, and 90% and 68% for non-ECD kidney recipients, respectively. Although more patients have been placed on the simultaneous kidney-pancreas waiting list, the number of these transplants dropped from a peak of 970 in 1998 to 905 in 2002. This decline may be due to competition for organs from increasing numbers of isolated pancreas and islet transplants.

The report of a national conference on the wait list for kidney transplantation.

In March, 2002, over 100 members of the transplant community assembled in Philadelphia for a meeting designed to address problems associated with the growing number of patients seeking kidney transplantation and added to the waiting list each year. The meeting included representatives of nine US organizations with interests in these issues. Participants divided into work groups addressing access to the waiting list, assigning priority on the list, list management, and identifying appropriate candidates for expanded criteria donor kidneys. Each work group outlined problems and potential remedies within each area. This report summarized the issues and recommendations regarding the waiting list for kidney transplantation addressed in the Philadelphia meeting.