The Incremental Cost of Incompatible Living Donor Kidney Transplantation: A National Cohort Analysis.

Incompatible living donor kidney transplantation (ILDKT) has been established as an effective option for end-stage renal disease patients with willing but HLA-incompatible living donors, reducing mortality and improving quality of life. Depending on antibody titer, ILDKT can require highly resource-intensive procedures, including intravenous immunoglobulin, plasma exchange, and/or cell-depleting antibody treatment, as well as protocol biopsies and donor-specific antibody testing. This study sought to compare the cost and Medicare reimbursement, exclusive of organ acquisition payment, for ILDKT (n = 926) with varying antibody titers to matched compatible transplants (n = 2762) performed between 2002 and 2011. Data were assembled from a national cohort study of ILDKT and a unique data set linking hospital cost accounting data and Medicare claims. ILDKT was more expensive than matched compatible transplantation, ranging from 20% higher adjusted costs for positive on Luminex assay but negative flow cytometric crossmatch, 26% higher for positive flow cytometric crossmatch but negative cytotoxic crossmatch, and 39% higher for positive cytotoxic crossmatch (p < 0.0001 for all). ILDKT was associated with longer median length of stay (12.9 vs. 7.8 days), higher Medicare payments ($91 330 vs. $63 782 p < 0.0001), and greater outlier payments. In conclusion, ILDKT increases the cost of and payments for kidney transplantation.

Key role for CD4 T cells during mixed antibody-mediated rejection of renal allografts.

We utilized mouse models to elucidate the immunologic mechanisms of functional graft loss during mixed antibody-mediated rejection of renal allografts (mixed AMR), in which humoral and cellular responses to the graft occur concomitantly. Although the majority of T cells in the graft at the time of rejection were CD8 T cells with only a minor population of CD4 T cells, depletion of CD4 but not CD8 cells prevented acute graft loss during mixed AMR. CD4 depletion eliminated antidonor alloantibodies and conferred protection from destruction of renal allografts. ELISPOT revealed that CD4 T effectors responded to donor alloantigens by both the direct and indirect pathways of allorecognition. In transfer studies, CD4 T effectors primed to donor alloantigens were highly effective at promoting acute graft dysfunction, and exhibited the attributes of effector T cells. Laser capture microdissection and confirmatory immunostaining studies revealed that CD4 T cells infiltrating the graft produced effector molecules with graft destructive potential. Bioluminescent imaging confirmed that CD4 T effectors traffic to the graft site in immune replete hosts. These data document that host CD4 T cells can promote acute dysfunction of renal allografts by directly mediating graft injury in addition to facilitating antidonor alloantibody responses.

Quantifying the risk of incompatible kidney transplantation: a multicenter study.

Incompatible live donor kidney transplantation (ILDKT) offers a survival advantage over dialysis to patients with anti-HLA donor-specific antibody (DSA). Program-specific reports (PSRs) fail to account for ILDKT, placing this practice at regulatory risk. We collected DSA data, categorized as positive Luminex, negative flow crossmatch (PLNF) (n = 185), positive flow, negative cytotoxic crossmatch (PFNC) (n = 536) or positive cytotoxic crossmatch (PCC) (n = 304), from 22 centers. We tested associations between DSA, graft loss and mortality after adjusting for PSR model factors, using 9669 compatible patients as a comparison. PLNF patients had similar graft loss; however, PFNC (adjusted hazard ratio [aHR] = 1.64, 95% confidence interval [CI]: 1.15-2.23, p = 0.007) and PCC (aHR = 5.01, 95% CI: 3.71-6.77, p < 0.001) were associated with increased graft loss in the first year. PLNF patients had similar mortality; however, PFNC (aHR = 2.04; 95% CI: 1.28-3.26; p = 0.003) and PCC (aHR = 4.59; 95% CI: 2.98-7.07; p < 0.001) were associated with increased mortality. We simulated Centers for Medicare & Medicaid Services flagging to examine ILDKT's effect on the risk of being flagged. Compared to equal-quality centers performing no ILDKT, centers performing 5%, 10% or 20% PFNC had a 1.19-, 1.33- and 1.73-fold higher odds of being flagged. Centers performing 5%, 10% or 20% PCC had a 2.22-, 4.09- and 10.72-fold higher odds. Failure to account for ILDKT's increased risk places centers providing this life-saving treatment in jeopardy of regulatory intervention.

The pathogenesis of acute allograft dysfunction in desensitized renal transplant recipients.

BACKGROUND: Acute allograft rejection after HLA desensitization is common early post-transplant but the sequence of histopathologic changes leading to graft dysfunction has not been well defined. METHODS: We evaluated the early pathogenesis and sequence of antibody-mediated graft damage of 35 desensitized living donor kidney recipients by studying the course of biopsies taken in the very early post-transplant period (<1 month). RESULTS: A total of 14 of the 35 patients met criteria for acute antibody-mediated rejection (AMR). In these patients, the chronologic sequence of pathologic changes was C4d peritubular capillary deposition, acute tubular injury, and peritubular capillaritis, followed by glomerulitis and interstitial inflammation. Classic AMR lesions occurred early, followed by mononuclear cellular infiltration, which comprised CD4 and CD8 T cells and monocytes. Development of graft dysfunction in most patients occurred concurrently with the emergence of graft cellular infiltration, rather than at the earlier time of antibody deposition as detected via C4d deposition. CONCLUSION: These data provide novel insight into the sequence of pathologic changes in patients with AMR post-transplant after HLA desensitization.

Human allograft acceptance is associated with immune regulation.

The ultimate goal of transplantation is drug-free allograft acceptance, which is rarely encountered in transplant recipients. Using a novel human-to-mouse "trans vivo" delayed-type hypersensitivity assay, we assessed donor-reactive cell-mediated immune responses in kidney and liver transplant patients, four of whom discontinued all immunosuppression. One of these subjects (J.B.) rejected his graft after 7 years of stable function, while the others (D.S., R.D., M.L.) continue to have excellent graft function 5, 28, and 4 years after the cessation of immunosuppression. PBMCs from J.B. exhibited strong responses to both donor and recall antigens whereas PBMCs from patients D.S., R.D., and M.L. responded strongly to recall, but not donor, antigens. Furthermore, when donor and recall antigens were colocalized, the recall response in these three patients was inhibited. This donor antigen-linked nonresponsiveness was observed in four other patients who are still maintained on immunosuppression. The weakness of donor-reactive DTH responses in these patients is due to donor alloantigen-triggered regulation that relies on either TGF-beta or IL-10. In D.S., regulation is triggered by a single donor HLA Class I antigen, either in membrane-bound or soluble form. This demonstrates that allograft acceptance in humans is associated with an immune regulation pattern, which may be useful in the diagnosis and/or monitoring of transplant patients for allograft acceptance.

Chronic remodeling pathology in grafts.

The theoretical basis of chronic allograft rejection remains poorly defined, but is clearly associated with the development of a relatively unique vasculopathy, transplant vascular sclerosis (TVS). The hypothesis that TVS is the cause of chronic rejection has yet to be proven, although it is widely accepted. Accumulating data suggest that, at best, the hypothesis is incomplete. The challenge for transplant investigators is to review the currently available data and to develop a testable, revised version of the hypothesis that explains both the antigen-dependent and antigen-independent contributions to graft vascular remodeling, and that encompasses all reasonable alternative mechanisms of graft failure.

Case Report: Treatment of Renal Artery Aneurysms by Ex Vivo Renal Artery Aneurysm Repair and Transplantation.

BACKGROUND: Renal artery aneurysms are increasingly being detected incidentally during diagnostic imaging using magnetic resonance imaging, computed tomography, or angiography performed for evaluation of other diseases. Our understanding of their natural history and surgical management has evolved significantly during the past two decades. PATIENTS AND METHODS: Three patients with incidentally identified renal artery aneurysms have been referred to our renal transplantation program in the last 3 years. All three had aneurysms located at renal artery branches making endovascular repair challenging and thus underwent hand-assisted laparoscopic nephrectomy with ex vivo aneurysmectomy, with heterotopic autotransplantation in two cases and allotransplantation in the third case. RESULTS: All three cases resulted in successful renal artery aneurysm repair and reimplantation and good renal function of the implanted kidney. CONCLUSIONS: Laparoscopic nephrectomy with ex vivo aneurysm repair and reimplantation can be a successful approach to surgical management, especially in cases where the aneurysm involves multiple artery branches and endovascular repair is challenging. Given the excellent results with this surgical approach, living and deceased donor kidneys with aneurysms should be strongly encouraged if deemed reparable.

Treatment of mice with anti-CD3 mAb induces endothelial vascular cell adhesion molecule-1 expression.

In vivo treatment of mice with anti-CD3 mAb causes polyclonal T cell activation and cytokine release. Since several cytokines are known to alter expression of MHC molecules and adhesion molecules on endothelia, we hypothesized that anti-CD3 mAb treatment should result in activation of vascular endothelia. In previous studies, we established that vascular endothelial cells in murine heterotopic cardiac grafts can develop at least 2 stable inflammatory phenotypes: cardiac allograft endothelia characteristically develop reactivity with MECA-32 mAb (undefined endothelial epitope) and M/K-2 mAb (murine vascular cell adhesion molecule-1 [VCAM-1]), whereas cardiac isografts develop reactivity with MECA-32, but not M/K-2 mAb. We now report that a single treatment of cardiac isograft recipients with the anti-CD3 mAb 145-2C11 caused expression of VCAM-1 on all cardiac isograft endothelia, including the microvascular endothelia. In contrast, expression of endothelial VCAM-1 in the native heart of the isograft recipient was limited to patchy areas of larger arteries. This patchy, arterial pattern of VCAM-1 expression was observed in lung, liver, kidney, and thymus of all mice treated with 145-2C11, whether or not they were implanted with a cardiac isograft, and was dissociated from expression of MECA-32 mAb reactivity. Hence, treatment of mice with anti-CD3 mAb causes systemic endothelial activation (VCAM-1 expression), and endothelial cells of recently implanted cardiac isografts appear to be hypersensitive to induction of VCAM-1 by anti-CD3 mAb treatment. Further studies showed that (1) treatment with 145-2C11 F(ab)'2 fragments did not induce endothelial activation, (2) intravenous pretreatment with pentoxifylline eliminated all endothelial effects of 145-2C11 treatment, (3) induction of endothelial activation by 145-2C11 mAb always paralleled the expression of adverse physiologic symptoms, and (4) mice exhibit strain-specific differences in endothelial responses to 145-2C11 treatment. We propose that anti-CD3 mAb treatment causes simultaneous activation of circulating T cells and systemic vascular endothelial cells which may facilitate systemic lymphocyte-endothelial interactions, and may explain the rapid disappearance of T cells from the circulation that is associated with anti-CD3 treatment in mouse and man.

Treatment with anti-vascular cell adhesion molecule 1 monoclonal antibody induces long-term murine cardiac allograft acceptance.

Daily in vivo treatment of murine H-2d --> H-2b cardiac allograft recipients with 400 micrograms/day i.p. of M/K-2, a mAb to the endothelial adhesion molecule VCAM-1, resulted in prolongation of graft survival. The surviving allografts showed little of the histologic changes observed in acutely rejecting control allografts. When antibody treatment was discontinued after 20 days, grafts continued to function for at least 40 more days. This was approximately 30 days after mAb was no longer detectable by ELISA in the circulation, or by immunoperoxidase staining at the graft site. The most notable feature of grafts that survived 60 days was the presence of mild interstitial fibrosis. Endothelial reactivity was minimal with the mAbs MECA-32 and M/K-2, which have been used in previous studies to visualize the extensive endothelial inflammation that develops during untreated acute rejection. There was a mild cellular infiltrate containing T cells, but few macrophages. However, infiltrating T cells appeared to be inactive in that IL-2R+ cells were immunohistologically undetectable and mRNA for IL-2, IL-4, or IFN-gamma was undetectable by polymerase chain reaction. In general, the immunologic conditions in these long-term grafts differed from those seen in normal cardiac tissue, cardiac isografts, or cardiac allografts. These data demonstrate that M/K-2 mAb can suppress cardiac allograft rejection and induce long-term graft acceptance. This graft survival appears to be associated with the development of a unique state of immunity at the graft site.

Alloantigen-dependent endothelial phenotype and lymphokine mRNA expression in rejecting murine cardiac allografts.

Recent studies suggest that graft microvascular endothelia may play an important role in the regulation of rejection. Alloantigen-dependent changes in microvascular endothelial phenotype may be associated with differences in infiltrate function in allografts vs. isografts, as reflected in alloantigen-specific CTL accumulation and cytokine production. To correlate cytokine production with differences in microvascular endothelial phenotype during allograft inflammation, we used PCR to identify cytokine mRNAs isolated from pooled cardiac isografts and allografts on days 1, 3, and 5 after transplantation. Graft microvascular endothelia express an inflamed phenotype associated with wound healing and the repair of tissue damage due to mechanical trauma, ischemia, and/or reperfusion injury--i.e., high levels of ICAM-1 expression and MECA-32 mAb reactivity. By day 1 in both isografts and allografts, mRNAs for the cytokines IL1 alpha, IL6, TNF, LT, and TGF beta are upregulated or induced. By the third day in cardiac allografts, an antigen-dependent endothelial phenotype is expressed, characterized by the presence of cell surface VCAM-1. Concomitantly, mRNAs for the lymphokines IL2 and IFN gamma are detected, followed by IL4 mRNA by day 5. The expression of VCAM-1 by allograft endothelia may influence the inflammatory process, by physically recruiting specific T cell subpopulations into the response and/or by delivering additional signals to the infiltrating cells. Eventually, these and other regulatory events occurring at these early times initiate a process that later results in alloreactive tissue destruction.

Patterns of inflammatory vascular endothelial changes in murine liver grafts.

We have investigated the vascular endothelial phenotypes found at various times posttransplant in murine B10-->C3H liver grafts. In this model, liver allografts are spontaneously accepted, and survive indefinitely unless the recipient is first allosensitized with a skin allograft, in which case the liver allografts are rejected within five days. In our previous studies, allograft inflammation was associated with the development of vascular endothelial reactivity with the mAbs MECA-32 and M/K-2 (anti-VCAM-1). We observed that vascular endothelia in both liver isografts and allografts develop reactivity with MECA-32 mAb within two days of transplantation, indicating endothelial activation in both situations. In contrast, only the endothelia in liver allografts develop VCAM-1 expression, as detected with M/K-2 mAb. VCAM-1 was expressed in both rejecting and accepting liver allografts, demonstrating that endothelial VCAM-1 expression is indicative of ongoing graft inflammation but not necessarily graft rejection. Liver parenchymal cells did not appear to develop reactivity with either antibody under any of the conditions tested. In contrast, bile duct epithelia developed M/K-2 reactivity (VCAM-1 expression), but not MECA-32 reactivity in liver allografts, but not isografts. These data demonstrate alloantigen-dependent and alloantigen-independent patterns of endothelial behavior in murine liver grafts that are quite similar to those found in murine cardiac grafts. Further, they demonstrate that the expression of VCAM-1 by graft endothelia is not diagnostic for acute rejection of liver allografts.

Analysis of inflammatory endothelial changes, including VCAM-1 expression, in murine cardiac grafts.

We have employed a murine model of cardiac transplantation and two monoclonal antibodies, M/K-2 and MECA-32, to study the responses of graft endothelia during allograft rejection. Using immunohistologic techniques, we demonstrate that the monoclonal antibody M/K-2, which binds to the murine cellular adhesion molecule VCAM-1, reacts with an inducible endothelial epitope found in rejecting cardiac allografts, but not in cardiac isografts, normal cardiac tissues, or extracardiac vasculature from allografted mice. Similar, but focal, M/K-2 reactivity is also found in nontransplanted hearts undergoing virally induced myocarditis. M/K-2 reactivity does not develop in the nonrejecting cardiac allografts from nu/nu mice, and M/K-2 reactivity is found only in grafts that develop CD25+ graft-infiltrating cells--i.e., allografts but not isografts. PCR analyses of grafts during development of VCAM-1 expression indicate that allografts, but not isografts, contain mRNA for the cytokines IL-2 and IFN-gamma, and either of these cytokines may be associated with the expression of M/K-2 reactivity in rejecting allografts. Unlike M/K-2, MECA-32 identifies an inducible epitope that is observed on myocardial endothelia of both isografts and allografts, but not normal cardiac tissues. Further, expression of the MECA-32 epitope can occur in grafts that do not develop CD25+ infiltrating lymphocytes, since it is observed in isografts and the native hearts of transplanted or sham-operated mice. Indeed, MECA-32 reactivity may be T cell independent, since it is also found in nonrejecting allografts of nu/nu mice. PCR analyses of grafts during development of MECA-32 reactivity indicate that cardiac isografts contain mRNA for IL-1, IL-6, TNF, and lymphotoxin. One or more of these might be associated with induction of MECA-32 reactivity.

Impact of acute rejection and early allograft function on renal allograft survival.

Both acute rejection and the function of a renal allograft early after transplantation correlate with long-term graft survival. In this study we assessed the relationship between these two factors in 843 adult recipients of first cadaveric renal grafts, transplanted at a single institution and followed for a minimum of 3.5 years. Patients were divided into four groups according to (1) history of acute rejection (AR) during the first 6 months after transplantation, and (2) concentration of serum creatinine at 6 months after transplantation (SCr(6mo) < or > or = 2 mg/dl). Death censored allograft survival was not significantly different among patients without AR and with low SCr(6mo) (group 1, n=376), patients without AR but with an elevated SCr(6mo) (group 2, n=117), and patients with AR but low SCr(6mo) (group 3, n=185). In contrast, graft survival was significantly worse in patients with AR and an elevated SCr(6mo) (group 4, n=165) compared with patients in the other three groups (Cox, P<0.0001). The elevated SCr(6mo) in group 4 patients was not necessarily the consequence of AR, as 32% of patients in group 4 had a SCr at 10 days after transplantation (SCr(10d)), before they had AR, that was equal to or higher than the SCr(6mo). Based on this observation we investigated the implications of the SCr(10d) concentration for graft prognosis. The SCr(10d) correlated weakly with graft survival (Cox, P=0.05). However, an elevated SCr(10d) correlated with other potential risk factors for graft survival including: Older donors (P<0.0001), male recipients (P<0.0001), and heavier recipients (P<0.0001, all by multivariate regression); and posttransplant factors such as, increasing numbers of AR (P<0.0001), higher posttransplant blood pressure (P<0.0001), and lower doses of cyclosporine (P<0.0001, all by multivariate regression). In conclusion, graft dysfunction predicts poor graft survival only when associated with AR. Similarly, AR predicts a poor renal allograft survival only when associated with graft dysfunction. The SCr(10d) is an indicator of risk factors from both the donor and recipient, and an elevated SCr(10d) predicts a higher risk of acquiring additional risk factors early after transplantation.

Clinical and economic impact of flow cytometry crossmatching in primary cadaveric kidney and simultaneous pancreas-kidney transplant recipients.

We retrospectively compared the clinical and financial impact of a final cross-match by T cell flow cytometry (FXM) versus conventional complement-dependent cytotoxicity (CXM) in consecutive primary cadaveric kidney (K) and primary simultaneous cadaveric pancreas-kidney (SPK) transplant recipients. Mean follow-up was 14 months for both the K (range, 5-22 months) and SPK (range, 5-22 months) recipients. There were no instances of a positive CXM result if the FXM result was negative. However, 18 of the 102 (18%) K recipients and 11 of the 66 (17%) SPK recipients were FXM positive, CXM negative, but no grafts lost to hyperacute rejection in this group. In addition, patient survival, graft survival, incidence of acute rejection, and kidney and pancreas function (immediate and late) were not different in the FXM-positive versus the FXM-negative groups. Charges for the CXM and FXM methods were compared over a 6-month period. During that period, the FXM charges averaged $583 less per recipient than the CXM charges (58% reduction in charges), and the time required to perform the FXM method was 50% of that required for the CXM method. These results demonstrate that a clinical pathway for primary transplantation that utilizes the FXM rather than the CXM final cross-match is clinically safe, with no adverse effect on posttransplant outcome, reduces organ preservation time by shortening the waiting period for the final cross-match results, and significantly reduces the tissue typing charges. However, about 9% of all primary K and SPK recipients will be FXM positive, CXM negative on final cross-match and will be unnecessarily denied a transplant. In this study, we describe a method to identify these patients so that they can be tested by traditional CXM to avoid being denied access to donor organs.

Function and survival of renal allografts from the same donor transplanted into kidney-only or kidney-pancreas recipients.

BACKGROUND: The aim of this study was to assess whether kidney-pancreas transplantation (KPT) compromises the prognosis of kidney transplantation (KT). METHODS: This study included 368 paired recipients who received grafts from the same donor (184 KPT/184 KT), i.e., renal grafts with the same pretransplant functional and pathologic characteristics. RESULTS: KPT recipients (KPR) were significantly younger and included fewer African-Americans (22% vs. 6%, P=0.0005) than recipients of kidney alone (KR). During year 1 after transplant surgery, KPR were re-admitted more often than KR (4.2+/-2 vs. 2.8+/-2, P < 0.0001). The number of acute rejections (AR) and the serum creatinine were not significantly different in KR and KPR up to 3 years after transplant. After 44+/-29 months, 13% of KR and 17% of KPR died (NS), and 17% of KR and 16% of KPR lost their kidneys (NS). In KPR, reduced renal graft survival did not correlate with AR (P=0.44), but it correlated with: older donors, younger recipients, elevated serum creatinine at 6 months, pancreas loss, and the number of episodes of acute graft dysfunction evaluated by biopsy (multivariate analysis). By Cox, graft and patient survival were not significantly different in KR and KPR. However, the patient survival of KPR < 40 years of age was lower than that of KR (P=0.02). Renal biopsies (n=165) in 40 paired recipients showed no significant differences in AR, interstitial fibrosis, or vascular pathology. CONCLUSIONS: Renal graft function, structure, and survival are not different in KPR and KR, but the correlates of renal graft survival are different in these two groups of recipients.

Increased incidence of gastrointestinal surgical complications in renal transplant recipients with polycystic kidney disease.

BACKGROUND: We had the impression that, although our renal transplant recipients with polycystic kidney disease (PKD) had excellent long-term renal graft function, they had an increased incidence of postoperative gastrointestinal (GI) complications. METHODS: Over a 10-year period (1987 through 1996), 1467 renal transplants were performed in 1417 patients; 145 of these transplants involved PKD recipients. In the PKD group, 18 patients (12.4%) developed a posttransplant complication necessitating GI surgery (PKD-GI), an incidence twice that in the non-PKD recipients (73 patients or 6.2%, non-PKD-GI). RESULTS: PKD and non-PKD recipients displayed no significant difference in mortality. The PKD patients had better long-term renal graft survival than the non-PKD patients (P=0.08). There was no difference in mortality (P>0.6) or renal graft survival (P>0.6) between the PKD-GI and PKD-non-GI groups. The PKD-GI group had no increased mortality over the non-PKD-GI patients (P>0.6), despite a higher incidence of GI surgical complications in the PKD group versus the non-PKD group (overall: 12.4 vs. 6.2%, P<0.01; within 90 days of transplant: 7.6 vs. 3.3%, P<0.02) and a greater propensity for small and large bowel complications (overall: 9.0 vs. 2.6%; P< 0.001; less than 90 days: 6.9 vs. 2.0%, P<0.002). The PKD-GI recipients tended toward less long-term graft loss than their non-PKD-GI counterparts (11.1 vs. 27.4%; P=.22). The PKD-GI recipients suffered no acute rejection episodes within 90 days after their GI operation versus 11 of 73 non-PKD-GI recipients (O vs. 15.1%; P=0.075). CONCLUSIONS: PKD recipients of renal grafts should be watched closely early after transplant because of their increased risk of GI complications. These complications resulted in no increase in mortality or graft loss compared to non-PKD recipients with GI complications despite the PKD group's higher incidence of bowel perforation and increased age at time of transplant.

Obese living kidney donors: short-term results and possible implications.

BACKGROUND: Living kidney donation has increased recently as the shortage of cadaveric organs continues. This increase has occurred in part, due to expanded donor criteria, including obese patients. This is a potential concern because obesity is associated with surgical complications, possibly death, and chronic medical problems. To address this concern, we examined the outcome of a large group of obese (ObD) and nonobese living kidney donors (NObD). METHODS: A total of 107 obese (body mass index> or =27 kg/m2) and 116 nonobese (body mass index<27 kg/m2) living kidney donors donating at a single institution between 1990 and 1996 were studied. Surgical complications, operative duration, and hospital length of stay were assessed. Preoperative blood pressure, serum creatinine, creatinine clearance, protein excretion, fasting glucose, and hemoglobin A1C were measured and first degree relatives with diabetes were identified. RESULTS: Overall complications were significantly more common in ObD, 16.8 vs. 3.4% (P=0.0012). The majority of complications in the entire cohort, 56%, were wound related and were significantly more common in ObD (P=0.016). There was no significant increase in nonwound-related infections, bleeding, or cardiopulmonary events. There were no deaths or major complications. Operative time was significantly longer in ObD 151+/-30 vs. 141+/-29 min (P<0.05) but hospital duration was no different. Predonation, blood pressure in ObD was significantly higher, (P<0.05) and they more often had a family history of diabetes, 46 vs. 30% (P<0.05) than nonobese donors. Renal function, proteinuria, fasting glucose, or hemoglobin A1C were no different. CONCLUSION: With prudent selection, the use of obese living kidney donors appears safe in the short term. They experience more minor complications, usually wound related, and slightly longer operations. Given a higher baseline blood pressure and family history of diabetes, the long-term effect on the remaining solitary kidney in ObD needs to be examined.

Pathologic classification of chronic allograft nephropathy: pathogenic and prognostic implications.

BACKGROUND: After transplantation renal allografts frequently develop interstitial fibrosis and tubular atrophy, and these pathologic changes are the hallmarks of chronic allograft nephropathy (CN). However, the diagnosis of CN has no specific pathogenic implications. In this study we sought to determined whether a subclassification of CN according to vascular pathology correlates with posttransplant events, particularly acute rejection, and graft survival. METHODS: A total of 419 patients with moderate to severe CN were subdivided into: (1) transplant arteriopathy (TA, n=233, 56%); (2) arteriolar hyalinosis (AH, n=89, 21%); and (3) no characteristic vascular pathology (IFb, n=97, 23%). RESULTS: Patients with AH differed significantly from patients with TA or IFb in the following parameters: (1) AH was diagnosed later after transplantation (P=0.001); (2) fewer patients with AH had acute rejection (AR) before the diagnosis of CN (P<0.0001). For example, 44% of AH and 75% of TA had AR before CN; (3) patients with AH also had fewer AR episodes than the other two groups (P<0.0001); finally, (4) graft survival was better in patients with AH than in patients with TA (P=0.01 by chi2, P=0.001 by Cox). In contrast, there were no significant differences between patients with TA and IFb. By multivariate analysis the survival of grafts with CN correlated with: (1) serum creatinine at diagnosis (P<0.0001), (2) recipient's weight (P=0.004); (3) presence of FGS or level of proteinuria (P=0.03); and (4) the occurrence of AR after the diagnosis of CN (P<0.0001). Regarding the latter, AR were more common (P=0.007) and more numerous (P=0.005) in patients with TA or IFb than in AH. CONCLUSIONS: CN can be classified according to vascular pathology in the majority of cases, and this classification correlates with graft survival. Although some forms of CN are closely associated with the occurrence of AR others are not. This study also uncovered several variables that correlate with the survival of grafts with CN.

Clinical implications of the diagnosis of renal allograft infarction by percutaneous biopsy.

BACKGROUND: Herein we investigated the relationships between acute rejection (AR), infection, and renal allograft infarcts, particularly those infarcts that occur beyond the immediate posttransplant period and that affect functioning grafts. METHODS: Infarcts (n=59) were classified as: (1) early (EI; <2 months after transplant; n=32); or (2) late (LI; >2 months; n=27). Controls included patients with severe AR but without infarction (n=84). RESULTS: There were not significant differences in donor or recipient characteristics between infarcts and controls. At diagnosis, patients with infarcts were more likely to be infected (30%) than controls (14%, P=0.01); 15% of infarcts and 1% of controls had disseminated cytomegalovirus (P=0.04). Infarct and AR coexisted in the biopsy specimens of 66% of patients with EI and 62% of patients with LI, but the AR severity ranged from borderline to severe. Furthermore, 30% of patients with EI/LI had a history of severe AR. Graft survival was 47% in patients with EI, 22% in patients with LI (NS), and 71% in controls (P<0.0001, chi-square and Cox regression). Correlates of better graft survival in infarcts included: older recipient (P=0.03); smaller area of infarction in the biopsy specimen (P=0.04); and use of anti-AR therapy (P=0.03). Therapy was effective in patients with EI (treated, 71% survival; untreated, 29%, P=0.02) but not in patients with LI (25% vs. 23%). CONCLUSIONS: Allograft infarcts are associated with AR in 64% of patients, but the AR may be mild. Infarcts are associated with infections. Graft survival is worse in patients with infarcts than in patients with severe AR, consequently these two pathologic diagnoses should not be considered as a single entity.