First Report on the OPTN National Variance: Allocation of A2 /A2 B Deceased Donor Kidneys to Blood Group B Increases Minority Transplantation.

In 2002, the Organ Procurement and Transplantation Network (OPTN) Minority Affairs Committee (MAC) implemented a national, prospective, "variance of practice" to allow deceased donor, ABO blood group incompatible, A2 antigen, kidney transplantation into blood group B recipients; outcomes of this cohort were compared to ABO compatible recipients. The goal of the variance was to increase the number of transplants to B candidates without negatively impacting survival or compromising system equity. Only B recipients with low anti-A IgG titers (<1:8) were eligible to receive these kidneys. Across eight participating Donation Service Areas (DSA), there were 101 A2 /A2 B to B transplants through 12/31/11, of which the majority of the recipients (61%) were ethnic minorities. At 12, 24, and 36 months, Kaplan-Meier graft survival rates for the B recipients of A2 /A2 B kidneys were 95.0%, 90.6%, and 85.4%, respectively, comparable to outcomes for B recipients of B kidneys, 92.6%, 87.9%, and 82.5%, respectively (p-value = 0.48). Five DSAs increased the proportion of B transplants during 41 months postvariance, with a lesser proportional decrease in blood group A transplants. The data support the proposition that this allocation algorithm may provide a robust mechanism to increase access of blood group B minority candidates to kidney transplantation.

Determinants of discard of expanded criteria donor kidneys: impact of biopsy and machine perfusion.

We examined factors associated with expanded criteria donor (ECD) kidney discard. Scientific Registry of Transplant Recipients (SRTR)/Organ Procurement and Transplantation Network (OPTN) data were examined for donor factors using logistic regression to determine the adjusted odds ratio (AOR) of discard of kidneys recovered between October 1999 and June 2005. Logistic and Cox regression models were used to determine associations with delayed graft function (DGF) and graft failure. Of the 12,536 recovered ECD kidneys, 5139 (41%) were discarded. Both the performance of a biopsy (AOR = 1.21, p = 0.02) and the degree of glomerulosclerosis (GS) on biopsy were significantly associated with increased odds of discard. GS was not consistently associated with DGF or graft failure. The discard rate of pumped ECD kidneys was 29.7% versus 43.6% for unpumped (AOR = 0.52, p < 0.0001). Among pumped kidneys, those with resistances of 0.26-0.38 and >0.38 mmHg/mL/min were discarded more than those with resistances of 0.18-0.25 mmHg/mL/min (AOR = 2.5 and 7.9, respectively). Among ECD kidneys, pumped kidneys were less likely to have DGF (AOR = 0.59, p < 0.0001) but not graft failure (RR = 0.9, p = 0.27). Biopsy findings and machine perfusion are important correlates of ECD kidney discard; corresponding associations with graft failure require further study.

The effect of kidney size on cadaveric renal allograft outcome.

Chronic rejection is the commonest cause of long-term renal allograft loss. Though immunologic factors are thought dominant in its pathogenesis, nonimmunologic factors, in particular, hyperfiltration damage related to reduced renal mass, have also been proposed as factors in the causation of chronic allograft rejection. We assessed the influence of renal size on graft survival and function in all cyclosporine-treated cadaver donor adult renal allograft recipients engrafted at a single center between June 1989 and July 1994, whose grafts functioned for > or = to 3 months (n=169). Patients were divided into 4 groups based on the ratio of kidney volume to recipient body surface area (volume/BSA) (ml/m2), and outcome in groups compared by methods including Cox's proportional hazards and Kaplan-Meier analysis. No significant differences between groups existed for serum creatinine levels, presence of significant proteinuria, or 1- and 5-year graft survival. There was no correlation between volume/BSA and either serum creatinine or degree of proteinuria at 3, 6, 12, 36, and 60 months posttransplant. Volume/BSA was similar in patients with good or poor renal function (58 +/-21 vs. 56 +/- 28 ml/m2), with or without significant proteinuria (57 +/- 24 vs. 60 +/- 25 ml/m2) or in patients who lost their grafts to chronic rejection compared with those with stable allograft function (64 +/- 34 vs. 59 +/- 24 ml/m2). Volume/BSA was not a predictor of graft survival on multivariate regression. We conclude that donor kidney size has no apparent effect on cadaveric renal allograft outcome in the short and intermediate-term, suggesting that close matching of donor kidney size to recipient size is not presently indicated.

Diabetes mellitus after renal transplantation: as deleterious as non-transplant-associated diabetes?

BACKGROUND: Despite use of lower doses of corticosteroid hormones after renal allotransplantation in the era of cyclosporine and tacrolimus, posttransplant diabetes mellitus remains a common clinical problem. METHODS: We prospectively investigated the effect of posttransplant diabetes on long-term (mean follow-up, 9.3+/-1.5 years) graft and patient survival in the 11.8% of our renal transplant population (n = 40) who developed diabetes after kidney transplantation, and we compared outcome in 38 randomly chosen nondiabetic control patients who had received transplants concurrently. RESULTS: Twelve-year graft survival in diabetic patients was 48%, compared with 70% in control patients (P = 0.04), and Cox's regression analysis revealed diabetes to be a significant predictor of graft loss (P = 0.04, relative risk = 3.72) independent of age, sex, and race. Renal function at 5 years as assessed by serum creatinine level was inferior in diabetic patients compared to control patients (2.9+/-2.6 vs. 2.0+/-0.07 mg/dl, P = 0.05). Two diabetic patient who experienced graft loss had a clinical course and histological features consistent with diabetic nephropathy; other diabetes-related morbidity in patients with posttransplant diabetes included ketoacidosis, hyperosmolar coma or precoma, and sensorimotor peripheral neuropathy. Patient survival at 12 years was similar in diabetic and control patients (71% vs. 74%). CONCLUSIONS: Posttransplant diabetes mellitus is associated with impaired long-term renal allograft survival and function, complications similar to those in non-transplant-associated diabetes may occur in posttransplant diabetes, and, hence, as in non-transplant-associated diabetes, tight glycemic control may also be warranted in patients with posttransplant diabetes.

Effects of diabetes and uremia on mesenteric vascular reactivity.

BACKGROUND: Diabetes and uremia are comorbid conditions that have significant effects on cardiovascular physiology. These studies were designed to examine the effects of diabetes and uremia on vascular reactivity. METHODS: Sprague-Dawley rats were divided into control (C), diabetic (D), uremic (U), and diabetic/uremic (D + U) groups. Diabetes (D, D + U groups) was induced with an injection of streptozotocin. Uremic (U, D + U groups) was produced by seven-eighths nephrectomy. Serum glucose, blood urea nitrogen, creatinine, creatinine clearance, and protein excretion were measured at baseline and before microvascular studies at 4 or 8 weeks after injection. Vascular reactivity was studied in isolated, pressurized, and superfused segments of mesenteric arterioles (300 microns). Changes in internal vessel diameter were measured in response to phenylephrine (10(-8) to 10(-4) mol/L), acetylcholine (10(-9) to 10(-5) mol/L), and nitroprusside (10(-9) to 10(-2) mol/L). RESULTS: Results at 4 and 8 weeks were similar in all groups. Vasoconstrictor responses to phenylephrine and endothelium-independent vasodilator responses to nitroprusside were not altered in any experimental group. Endothelium-dependent vasodilator responses to acetylcholine were significantly depressed in both diabetic groups (D and D + U, p < 0.01 versus control), and there were no differences between the two diabetic groups. CONCLUSIONS: Streptozotocin-induced diabetes results in impairment of endothelial-dependent (nitric oxide mediated) vasodilator responses in mesenteric resistance vessels, which are unaffected by coexisting uremia. Uremia has little effect on mesenteric vascular reactivity in this model.

Delayed thromboembolectomy for subacute limb ischemia.

Arterial embolization frequently requires immediate operative intervention. Occasionally, embolic events produce subacute limb ischemia that may not be recognized as thromboembolic in origin. In October 1988, a prospective policy to attempt thromboembolectomy rather than infrainguinal bypass in all patients with delayed presentation of lower limb thromboembolism was initiated at our institution. Seven limbs in five patients were identified by history, physical examination, noninvasive study, and/or angiography as ischemic due to thromboembolism, which occurred from 3 to 10 weeks prior to presentation. Six of seven limbs were studied angiographically, and all seven were treated by femoral and/or popliteal thromboembolectomy with limb salvage. Six of seven limbs were restored to normal arterial hemodynamics as assessed by intra- and postoperative noninvasive study. One limb in a patient continued to have minimal residual occlusive disease that was recognized preoperatively. In all cases, chronic and fresh thromboemboli were found at surgery and confirmed by pathology. Chronic thromboembolism seems to be an underrecognized event. Limb salvage can be achieved readily even if extensive delay in diagnosis is present. Using preoperative angiography and intraoperative noninvasive techniques to measure the success of revascularization, as well as avoiding, when possible, complex infrainguinal reconstruction in these high-risk patients allows for an aggressive approach to limb salvage with gratifying results.

Tc-99m MAG3 evaluation of recipients with dual adult cadaveric renal allografts. Simultaneous transplantation of both kidneys from marginal donors.

PURPOSE: The application of Tc-99m mercaptoacetyl triglycine (MAG3) renal scintigraphy in patients who had simultaneous unilateral retroperitoneal transplant of both kidneys from marginal adult cadaveric donors is assessed. METHODS: Eighteen patients who had this unusual form of kidney transplant were monitored and evaluated by Tc-99m MAG3 renal scintigraphy. More than 60 of the radioisotopic studies, including immediate postoperative and subsequent follow-up examinations, were performed among these patients. RESULTS: In all the studies, the two transplanted kidneys were not equally well visualized by this scintigraphic procedure because of the inherent difference in their depth from the body surface, a feature of this particular surgical design. Despite this limitation, the efficacy of the scintigraphic procedure for such dual renal allografts appears to be similar to that established for kidney transplants performed in the conventional manner. CONCLUSION: To use the scintigraphic procedure effectively, certain sensible and logical adjustments are needed for the comparative visual and semiquantitative assessments of the two kidneys in this special form of transplantation.

Impact of human leukocyte antigen-DR mismatch status on kidney graft survival in a predominantly African-American population under the newer immunosuppressive era.

BACKGROUND: Human leukocyte antigen (HLA)-DR has been shown to be immunogenic and associated with poor long-term graft function. However, under potent induction immunosuppression with antithymocyte globulin, the impact of the HLA-DR remains unclear. METHOD: We reviewed 672 renal transplant recipients who received their transplants between 1998 and 2007. All patients received antithymocyte globulin as induction therapy followed by tacrolimus + prednisone + mycophenolate mofetil for maintenance immunosuppression. We divided the patients into three groups according to HLA-DR mismatch status (zero, one, or two mismatches). RESULTS: The three groups were different in total number of mismatches, deceased donor transplant, and delayed graft function, respectively. By Kaplan-Meier survival analysis, actuarial graft survival was significantly lower in the HLA-DR two mismatches group (72%) compared to HLA-DR zero mismatches group (78.5%) or HLA-DR one mismatch group (78.5%; P = .05, by log-rank test). Using Cox regression analysis, the risk of graft failure with two HLA-DR mismatches as compared with zero HLA-DR mismatches was 1.6 (95% confidence interval = 1.0-2.44, P = .049). When adjusted for age, wait time, race, type of transplant, retransplant status, T-cell flow crossmatch, delayed graft function, acute rejection, HLA-A and HLA-B, the effect of HLA-DR on survival was not significant (P = .55). CONCLUSION: The independent effect of HLA-DR mismatches on adverse graft survival is diminished under potent antibody induction and maintenance immunosuppression in our predominantly African-American population.

The kidney in liver transplantation.

Renal dysfunction often complicates the course of liver transplant recipients. Preoperative renal dysfunction, including hepatorenal syndrome (HRS) may be present. Assessment of renal function in the pretransplant patient with end-stage liver disease is fraught with pitfalls. Direct measurement of GFR by a method other than creatinine clearance is recommended wherever possible. Preoperative renal biopsy should also be considered in those patients with renal dysfunction in whom the diagnosis of HRS is not definite. With the routine use of veno venous bypass, renal perfusion is maintained and intraoperative events generally do not play a significant role in the development of postoperative dysfunction. Postoperatively immunosuppressive medications such as CsA or FK506 account for most of the renal dysfunction that is observed. Other factors such as graft dysfunction, sepsis, and nephrotoxic drugs may also participate in renal impairment. The exact mechanism of cyclosporine or FK506 nephrotoxicity remains unknown. In liver transplant recipients, no convincing therapeutic strategies exist to combat nephrotoxicity other than dose reduction of immunosuppressive therapy. Patients with HRS can be successfully treated by liver transplantation with recovery of renal function and with patient survival rates comparable to recipients without HRS, despite increased morbidity.

Aminoguanidine prolongs survival in azotemic-induced diabetic rats.

Toxic effects of hyperglycemia-induced advanced glycosylated end products (AGEs) may explain some vasculopathic complications of diabetes. Aminoguanidine, a known inhibitor of AGE formation, was administered by gavage to Sprague-Dawley streptozotocin-induced diabetic rats made azotemic by surgical reduction of renal mass. All rats became hyperglycemic. Renal ablation caused renal insufficiency, as evidenced by markedly reduced endogenous creatinine clearances at days 7 and 14. Aminoguanidine-treated rats had significantly (P < 0.04) superior survival to that of untreated azotemic diabetic rats. We infer from the extended life in a rat model of uremia in diabetic nephropathy that aminoguanidine may prove beneficial in human diabetes.

Unemployment in inner-city renal transplant recipients: predictive and sociodemographic factors.

Studies of dialysis patients report unemployment rates of 60% to 75%; however, it is generally believed that following transplantation, improvement in well-being and removal of time constraints imposed by the dialytic regimen afford improvement in employment status. We studied 58 stable renal transplant recipient attending an outpatient transplant clinic by questionnaire, administered anonymously. Only 25 (43%) of the patients were currently employed. Employed and unemployed patients did not differ when compared for age, gender, race, cause of renal disease, type of transplant or prior dialysis, time on dialysis or time since transplantation, years of education, or prestige score or classification ("blue collar" v "white collar") of prior job. In the employed group, 24 (96%) patients had worked before developing kidney disease compared with 23 (70%) patients in the unemployed group (P < 0.05). While on dialysis, 19 (79%) of the employed patients continued working compared with 10 (30%) of the unemployed patients (P < 0.005). Major reasons for discontinuing work after starting dialysis for both groups were subjective illness (feeling too sick, 51%), followed by interference of the dialysis regimen with time necessary for work (32%). Only 15% of the previously employed patients did not work after transplantation because of feeling too sick. By multiple logistic regression, the strongest predictors of employment posttransplant were being more than 1 year posttransplant (odds ratio, 2.35; 95% confidence interval, 1.01 to 5.5) and having been employed before transplantation (odds ratio, 3.79; 95% confidence interval, 1.60 to 9.02). Over half of the unemployed patients (20 [61%]) expressed interest in job training. Eighty percent to 90% of patients in both groups were insured by Medicare, with the second greatest number insured by Medicaid. Of the 15 unemployed patients insured by Medicaid, 67% reported that their decision not to work was related to fear of losing Medicaid benefits because they could not afford medications without it. Despite no difference in actual type of insurance carried, 17 (51%) of the unemployed patients believed their health insurance coverage was inadequate compared with four (12%) of the employed patients (P = 0.005, chi-squared test). Unemployment remains a significant problem for our population of inner-city renal transplant recipients. Attention to job retention or retraining during the early renal disease and dialysis therapy period may promote better rehabilitation following transplantation. However, for this population, with limited employment opportunities, removal of disincentives to work, including loss of Insurance and Inability to pay for medications, will be necessary before we can provide optimal rehabilitation for renal transplant recipients from all social strata.