Living Donor Kidney Recipients Research Articles

Elevated Incidence of Posttransplant Erythrocytosis After Simultaneous Pancreas Kidney Transplantation

Posttransplant erythrocytosis (PTE) poses a potential risk of thrombosis in kidney transplantation. Clinical observation of our systemically drained simultaneous kidney pancreas transplant (S-SPK) patients showed a higher incidence of PTE and need for phlebotomies. To evaluate the incidence of PTE we analyzed hematocrit (Hct) levels and frequency of phlebotomies in 94 SPK as compared to 174 living donor (LD) recipients and 53 type-I diabetic with kidney transplant only. For study purposes we defined PTE as Hct >50% or the necessity for phlebotomies. Kaplan-Meier plots and Cox proportional hazard models were used to examine the association between the transplant type and PTE. We found an increased incidence of PTE in SPK compared to LD (p < 0.001). In the multivariate model, SPK had a 5-fold risk for the development of PTE (AHR 5.3, 95% CI 1.8, 15.9). The incidence of therapeutic phlebotomy was 13% among SPK patients and 4% in LD kidney recipients; 19 patients altogether. A total of 64 units were phlebotomized (48-SPK and 16-LD). Type I diabetic patients with a kidney transplant showed a 0% incidence of PTE. We observed a greater incidence of PTE and phlebotomies in S-SPK compared to LD with kidney only transplant recipients.

Transplantation of the Type 1 Diabetic Patient

Although simultaneous pancreas-kidney transplantation (SPK) is generally believed to be the treatment of choice in type 1 diabetic patients with kidney failure, there is continuing controversy whether SPK is superior to kidney transplantation alone (KTA), especially when a live donor kidney (LDK) is available. This controversy is highlighted by three recent publications authored by Young et al. (1), Weiss et al. (2), and our group (3). Analyzing data from large registries, all three studies compared kidney graft and patient survival in SPK (all from deceased organ donors) and KTA transplants, whereby the KTA grafts were from deceased (DDK) or living donors (LDK). The three studies are summarized in Table 1( bold ) with respect to data source, treatment modality, length of follow-up, and patient and kidney graft survival. Young et al. and Weiss et al. analyzed U.S. data based on the Organ Procurement and Transplantation Network/United Network for Organ Sharing and the Scientific Registry of Transplant Recipients, respectively. View this table: Table 1. Impact of glycemic control on kidney allograft and patient survival (modified from Morath and Zeier [9]) Young and colleagues found superior kidney graft and patient survival in LDK recipients as compared with SPK recipients after a maximum of 7 years of follow-up. No significant difference was found between deceased donor SPK and DDK patients with respect to kidney graft and patient survival. In contrast, analyzing the international Collaborative Transplant Study (CTS) database, which collects data from 46 countries in five continents, our group found that SPK and LDK yielded clearly superior kidney graft and patient survival as compared with DDK alone. Importantly, in the CTS analysis, patient survival beyond year 10 after transplantation in SPK recipients was significantly better than that of recipients of a LDK without a pancreas graft (hazard ratio = 0.55; P = 0.005), as demonstrated for transplants …

ABO incompatible living donor kidney transplantation: a dream come true. Experience of Hospital Clínic of Barcelona

During the last years the number of patients on waiting list for kidney transplantation has been stable. Living donor kidney transplantation is nowadays a chance to increase the pool of donors. However, there are a group of patients with ABO incompatibility, making impossible the transplant until now. The aim of the present study is to describe the experience of Hospital Clinic Barcelona on ABO incompatible living transplantation. A retrospective- descriptive study was made based on 11 living donor kidney recipients with ABO incompatibility in Hospital Clinic of Barcelona from October'06 to January'09. Selective blood group, antibody removal with specific immunoadsortion, immunoglobulin and anti- CD 20 antibody were made until the immunoglobulin (IgG) and isoaglutinine (IgM) antibody titters were 1/8 or lower. Immunosuppressive protocol was adjusted to particular recipient characteristics. Isoaglutinine titters were set before, during and post desensitization treatment and two weeks after transplant. Immunological, medical and surgical evaluation was the standard in living donor kidney transplant program. Medium age of donors and recipients were 47.8 +/- 12.4 and 44.4 +/- 14.1 years, respectively. 90% of donors were females and 73% of recipients males. Follow-up time was 10.2 +/- 10.2 months. Siblings and spouses were the most frequent relation (n=4, 36.4%, respectively). Chronic glomerulonephritis, adult polycystic kidney disease and Alport syndrome, the most frequent cause of end-stage renal disease. All the patients acquire appropriate isoaglutinine titters pre transplant (< 1/8), requiring 5.54 +/- 2.6 immunoadsorption sessions pretransplant and 2.82 posttransplant. One patient didn t need any immunoadsorption session (incompatibility blood group B) and another patient plasma exchange instead of immunoadsorption for being hypersensitized with positive flow cytometry crossmatch. Posttransplant isoaglutinine titters remained low. Two patients had cellular acute rejection episode (type IA and IB of Banff classification) with good response to corticosteroid treatment. Patient and graft survival were 91% at first year and remain stable during the follow-up. A graft lost by death of patient in relation to haemorrhagic shock developed within the first 72 hours after transplantation. Renal graft function at first year was excellent with serum creatinine of 1.3 +/- 0.8 mg/dl, creatinine clearance of 62.6 ml/min/1.73 m2 and proteinuria of 244.9 mg/U-24h. ABO incompatible living donor kidney transplantation represent an effective and safe alternative in certain patients on waiting list for renal transplant, obtaining excellent results in patient and graft survival, with good renal graft function.

Long-Term Results of ABO-Incompatible Kidney Transplantation With Antigen-Specific Immunoadsorption and Rituximab

ABO-incompatible (ABOi) kidney transplantation has gained a renewed interest during the past years. In 2001, a protocol for ABOi kidney transplantation based on antigen-specific immunoadsorption and rituximab was introduced at our center. In this study long-term graft function using this protocol was assessed. All ABOi kidney recipients with >1-year follow-up (n=15) were compared with all ABO-compatible (ABOc) living donor kidney recipients maintained on the same basic immunosuppression (n=27). Patient and graft survival as well as rejections and calculated glomerular filtration rate were analyzed. Mean follow-up was 3 years. There was no significant difference in patient and graft survival nor in rejection episodes. Mean glomerular filtration rate (79-83 ml/min) was equivalent at 1, 2, and 3 years in both groups. We conclude that ABOi kidney transplantation using antigen-specific immunoadsorption and rituximab is equivalent to standard ABOc living donor kidney transplantation. ABOi transplantation following this protocol does not have a negative impact on graft function long-term.

Superiority of Pediatric En Bloc Renal Allografts Over Living Donor Kidneys: A Long-term Functional Study

Growing waiting list for kidney transplantation in the United States makes it imperative to expand donor pool to use of pediatric kidneys. Because en bloc pediatric kidneys double nephron numbers, it would be interesting to learn how they fare compared to living donor kidneys long term. Retrospective chart review was performed on all 72 pediatric en bloc and 75 live adult donor kidney recipients transplanted between January 1990 and December 2001. Long term graft function was assessed with glomerular filtration rate (GFR) using the abbreviated modification of diet in renal disease (MDRD) formula. Pediatric donor was 16.9 +/- 11.2 months old and weighed 10.7 +/- 3.8 kg. Nine en bloc kidneys thrombosed at a mean of 4.2 days posttransplantation. Proteinuria was detected later posttransplantation in en bloc group (45.6 +/- 33.6 months vs. 23.4 +/- 16.3 months, P = 0.002). Pediatric en bloc recipients had significantly higher GFR up to 8 years posttransplantation. One-year graft survival was significantly better in live donor group (93.3% vs. 81.9%, P = 0.041) but five-year graft survival rates were similar (86.7% vs. 76.3%, P = 0.125). One-year and five-year patient survival rates were similar between en bloc and live donor groups (97.3% vs. 98.6%, P = 0.585 and 94.6% vs. 93.0%, P = 0.688, respectively). Early postoperative graft thrombosis remain a challenge with pediatric en bloc renal transplants, but once the allografts survive early postoperative course, they provide better long-term function than living donor kidney transplants. In order to alleviate burden on waiting list, pediatric en bloc kidneys should be transplanted more often when available.

Clinicopathological evaluation of renal allograft treated with anti‐CD25 monoclonal antibody

Twenty-seven living-donor kidney recipients were treated with the antibody against CD25 as the induction immunosuppressive agent. They did not develop acute rejection within 1 month after transplantation, and mean serum creatinine level at 1 month was 1.0 +/- 0.4 mg/dL. There were no findings of acute rejection or drug-induced nephrotoxicity in protocol biopsies at 1 month following transplantation. After 1 month had passed, acute rejection occurred in three cases. The pathological grade of acute rejection varied from borderline to grade III by Banff classification. The careful inspection is necessary to find out the occurrences of acute rejection more than 2 months after transplantation because immunological situation has been changing around this period.

Long-term survival following simultaneous kidney-pancreas transplantation versus kidney transplantation alone in patients with type 1 diabetes mellitus and renal failure

Background: Pancreas transplantation improves quality of life and prevents the progression of secondary complications of diabetes. Whether these benefits translate into a long-term survival advantage is not entirely clear. Methods: Using the United Network for Organ Sharing database, we analyzed long-term survival in 18,549 patients with type 1 diabetes and renal failure who received a kidney transplant between 1987 and 1996. Patient survival was calculated using the Kaplan-Meier method. Proportional hazards models were used to adjust for effects of differences in recipient and donor variables between simultaneous kidney-pancreas transplants (SKPTs) and kidney-alone transplants. Results: SKPT and living donor kidney recipients had a significant crude survival distribution advantage over cadaver kidney transplant recipients (8-year survival rates: 72% for SKPT recipients, 72% for living donor kidney recipients, and 55% for cadaver kidney recipients). The survival advantage for SKPT recipients over cadaver kidney recipients diminished, but persisted after adjusting for donor and recipient variables and kidney graft function as time-varying covariates. SKPT recipients had a high mortality risk relative to living donor kidney recipients through 18 months posttransplantation (hazards ratio, 2.2; P < 0.001), but had a lower relative risk (hazard ratio, 0.86; P < 0.02) thereafter. In SKPT recipients, maintenance of a functioning pancreas graft was associated with a survival benefit. Conclusion: The long-term survival of SKPT recipients is superior to that of cadaver kidney transplant recipients with type 1 diabetes. There is no difference in survival of SKPT recipients and living donor kidney recipients with type 1 diabetes at up to 8 years' follow-up; the former have a greater early mortality risk and the latter have a greater late mortality risk. Results of this study suggest that successful simultaneous kidney-pancreas transplantation is not only life enhancing, but life saving. Am J Kidney Dis 41:464-470.

Severe acute renal failure after exposure to sirolimus-tacrolimus in two livin donor kidney reciplents

We began a clinical trial in African Americans comparing sirolimus-tacrolimus to standard immunosuppression. We report two African American male living donor kidney recipients who developed acute renal failure after exposure to sirolimus-tacrolimus. Both patients received similar doses of sirolimus and tacrolimus to achieve target levels of 5 to 15 ng/mL and prednisone in tapering doses. Renal function and tacrolimus and sirolimus levels were systematically monitored. Although both kidneys functioned immediately, acute oliguric renal failure developed approximately 2 weeks after transplantation. Transplant kidney biopsy showed acute tubular necrosis in patient 2. Sirolimus-tacrolimus was then stopped in both patients. Both patients required temporary hemodialysis. Renal function returned 2 weeks later and was normal 2 months after transplantation on tacrolimus plus mycophenolate mofetil. Combination sirolimus-tacrolimus may cause nephrotoxicity in some patients by mechanisms that are presently unexplained.

Opportunistic pulmonary infection after renal transplantation

INFECTIOUS complications in kidney transplant recipients are associated with significant morbidity and mortality. The risk of infection is based on two main factors: recent or past exposure to infectious agents, and the patient’s level of immunosuppression. Bacterial infections usually occur in the first month following transplantation, and technical issues related to the procedure can play an important etiologic role. Most febrile illness that occurs in kidney recipients between 1 and 6 months posttransplantation is caused by cytomegalovirus (CMV) and other opportunistic agents. The regimen and level of immunosuppression are important in the pathogenesis of these infectious complications. Kidney recipients whose grafts have come from cadavers tend to develop more frequent and severe infectious complications than living-donor kidney recipients due to the increased level of immunosuppression that is usually needed in the former group. Also, recipients of cadaveric kidneys who receive induction antilymphocyte globulin (ATG) preparations have higher infection rates than those who do not receive this treatment. Further, research has shown that patients who receive azathioprine as their primary immunosuppressive agent have a higher rate of infection than patients on cyclosporine-based regimens. Beyond 6 months, in patients with well-functioning allografts who are on stable maintenance immunosuppression the pattern of infection is similar to that in the general population. Another significant finding is that transplant recipients often develope infection that simultaneously involves several causal agents. This underlines the importance of considering concomitant infection in patients who do not respond to the initial line of treatment. While the incidence of tuberculosis (TB) after kidney transplantation in highly industrialized countries is low, the figure for developing regions is significantly higher. Mycobacterial disease should be considered in any patient with fever of unknown etiology. Most cases of Mycobacterium tuberculosis infection in kidney transplant recipients are due to reactivation of latent TB lesions. Important risk factors for reactivation include nonwhite race, history of active TB, presence of a marked abnormality on a chest radiograph, exposure to a person with a confirmed case of TB, and skin test positivity. In transplant patients, the clinical presentation of tuberculosis may be atypical, and extrapulmonary and miliary tuberculosis is seen more frequently than in the normal population. With regard to fungal infection, in kidney transplant recipients these most commonly present as prolonged fever that does not respond to antibiotic therapy. These infections are associated with very high mortality. The most common fungal infections reported in first series from developing countries were candidiasis, aspergillosis, and cryptococcosis. Several factors influence the development of symptomatic CMV infection after kidney transplantation, but most important are the CMV serologic statuses of the donor and recipient. Symptomatic CMV infection can be primary, can occur due to reactivation of latent infection, or can arise secondary to superinfection. The most severe form is usually observed when a CMV-seronegative recipient receives a graft from a CMV-seropositive donor. Host cell–mediated immunity and the type and level of immunosuppressive therapy influence the development of symptomatic CMV infections. Polyclonal and monoclonal antilymphocyte antibody treatments have the highest CMVpromoting effect, and represent the most important factor in the development of CMV infections after kidney transplantation. Nocardia is a filamentous gram-negative soil organism that can cause pneumonia. This infection also frequently disseminates to the brain and results in abscess formation. The overall mortality associated with nocardiosis in kidney transplant recipients is 25%, but this figure jumps to 44% in patients who have central nervous system involvement.

No detectable microchimerism in long-term tolerant recipients of living-donor kidneys

No detectable microchimerism in long-term tolerant recipients of living-donor kidneys

THE IMPACT OF ACUTE REJECTION EPISODES ON LONG-TERM GRAFT FUNCTION AND OUTCOME IN 1347 PRIMARY RENAL TRANSPLANTS TREATED BY 3 CYCLOSPORINE REGIMENS

To characterize factors of importance for the occurrence of acute rejection as well as study the impact of these episodes on long-term renal survival and function, a total of 819 acute rejection episodes were studied in 951 primary cadaveric donor kidney recipients (CD) and in 396 primary living donor kidney recipients (LD). The patients were treated by three immunosuppressive schedules, namely, CsA given in a high dose, a medium dose, or a low dose. Additionally, all patients received PRED and patients in the low-dose group received AZA. The incidence of acute rejection was higher and occurred earlier after transplantation in the CsA medium dose and low dose groups than in the CsA high dose group (P < 0.05 and P < 0.01, respectively). Although the incidence of first acute rejection was similar in CD and LD patients, 59.1% vs. 60.6%, it was successfully reversed by antirejection treatment in a higher percentage in LD patients. The estimated graft half-life was shorter in patients who had acute rejection episodes than those who did not, 6.6 years vs. 12.5 years in CD patients (P < 0.0001). Renal function at 1-5 years after transplantation was stable, but significantly poorer in CD patients who had experienced acute rejection than in patients who had not, with the mean creatinine clearance rates in the ranges 45-47 vs. 54-60 ml/min in the other groups (P < 0.0001). In a stepwise Cox regression analysis in CD recipients, risk factors for acute rejection were CsA (low dose) treatment schedule, immunization as displayed by presence of panel-reactive antibodies and positive B cell cross-match, young recipient age, disease of diabetes mellitus, and HLA-DR mismatching. In LD recipients, the corresponding risk factors were treatment schedule, young recipient, HLA mismatching, and transplantation from parent to child. Thus, the study has demonstrated some factors of importance for acute rejection episodes in CsA-treated patients as well as showing the detrimental effect of these episodes on long-term graft survival and renal function. These results suggest that a primary aim of future treatment strategies should be to reduce the incidence of these episodes.

The utility of cyclosporine weaning in renal transplantation.

Abrupt conversion of cyclosporine immunosuppression to conventional treatment with azathioprine and prednisone avoids long-term cyclosporine nephrotoxicity, albeit at the cost of a 20% to 40% rejection rate. The authors investigated the benefits and risks of a cyclosporine weaning protocol in 24 cadaveric and 9 live donor kidney recipients treated with a sequential quadruple immunosuppressive protocol. In cadaver kidney recipients, slow tapering of cyclosporine resulted in a 19% (p less than 0.001) improvement in the glomerular filtration rate, as estimated by the inverse ratio of the plasma creatinine concentration. Cadaver kidney recipients were stratified according to graft function (GFR ratio greater than 0.76, less than 0.76) at the of cyclosporine discontinuation. In 12 patients with well-functioning grafts, a 24% improvement was observed, whereas in 12 patients with poor graft function, the gain was limited to 13%. Patients with limited graft function tended to have more acute rejection episodes before cyclosporine weaning (0.92 +/- 0.64 versus 0.42 +/- 0.64, not significant). When the 24 cadaver kidney recipients were stratified according to onset of graft function after transplantation (days to plasma creatinine of 250 mumol/L), need for dialysis, panel reactive antibodies (PRA), and duration of cyclosporine treatment, no significant differences in graft function were observed at the onset or end of cyclosporine weaning. Acute graft rejection before cyclosporine weaning was the only variable associated with a significantly lower estimated glomerular filtration rate ratio at the end of cyclosporine treatment (0.83 +/- 0.11 versus 0.67 +/- 0.16, p less than 0.01). Weaning of cyclosporine was associated with a minimal risk of acute graft rejection. A single patient with stable graft function at the onset of the weaning process experienced an acute but reversible rejection episode 2 months after cyclosporine was discontinued. In summary, gradual weaning of cyclosporine improves graft function, and eliminates the excessive risk of acute graft rejection without the need for additional corticosteroid treatment.

Transplantation in patients with diabetic nephropathy

Detailed results of 12 combined pancreas and kidney transplantations (Comb) were compared with those of two matched diabetic controls per patient--one living donor kidney recipient (LD) and one cadaveric donor kidney recipient (CD--who, though eligible for pancreas transplantation also, preferred kidney transplantation only. Mean follow-up was 22, 23, and 21 months in the three groups. There was no mortality in the LD group, but two CD and one Comb patient died from cardiovascular disease. Two kidneys were lost in both the Comb and the LD group, compared to five in the CD group. Ten major vascular events occurred and three of them were lethal. The only LD case was one below-knee amputation; the other nine were equally distributed in the Comb and CD groups. The time spent in the hospital was shorter for the LD group. Thus, in the short run, LDs confer the best results, whereas in the long term the better metabolic control in the Combs may prove favorable.

Survival Analysis of 1563 Renal Transplants in Brazil: Report of the Brazilian Registry of Renal Transplantation

Little is known about renal transplantation activity in developing countries. The objective of this study was to evaluate patient and graft survival among the different types of renal transplant recipients in Brazil. The study population consisted of 1563 patients receiving renal grafts for the first time between 1 October 1987 and 31 December 1989 in 49 transplant centres in Brazil. Data were prospectively collected through individual patient questionnaires. Of the 1563 transplantations performed, 1051 (67%) were from living donors, 467 (30%) from cadaver donors, and 45 (3%) unspecified. A total of 963 (62%) transplants came from living related donors (10% HLA-identical, 45% HLA-haploidentical and 6% HLA-distinct). Among the transplant recipients, only 7% were more than 55 years old, 5% were younger than 15 and 4% had diabetes mellitus. Blacks accounted for 24% of patients receiving transplants. An immunosuppressive regimen, including cyclosporin was used in 75% of cadaver kidney recipients, in 42% of living donor kidney recipients; and in 43% and 75% of HLA-haploidentical and HLA-distinct living related donor recipients, respectively. At 2 years, patient survival for living donor and cadaver donor transplant recipients was 89% and 80% respectively, and graft survival was 76% and 61% respectively. Patient survival for recipients of HLA-identical, haploidentical, and distinct living related donor kidneys was respectively 94%, 90%, and 81% at 2 years, and graft survival was 90%, 75%, and 65% respectively. Graft survival for recipients of HLA-distinct living related donor and non-related donor kidneys compared to cadaver donor kidneys was not significantly different at 2 years (63% vs 61%, P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Transplantation in patients with diabetic nephropathy: Outcome of combined pancreas and kidney transplantation compared with kidney transplantation only

Abstract. Detailed results of 12 combined pancreas and kidney transplantations (Comb) were compared with those of two matched diabetic controls per patient-one living donor kidney recipient (LD) and one cadaveric donor kidney recipient (CD)-who, though eligible for pancreas transplantation also, preferred kidney transplantation only. Mean follow-up was 22,23, and 21 months in the three groups. There was no mortality in the LD group, but two CD and one Comb patient died from cardiovascular disease. Two kidneys were lost in both the Comb and the LD group, compared to five in the CD group. Ten major vascular events occurred and three of them were lethal. The only LD case was one below-knee amputation; the other nine were equally distributed in the Comb and CD groups. The time spent in the hospital was shorter for the LD group. Thus, in the short run, LDs confer the best results, whereas in the long term the better metabolic control in the Combs may prove favorable.

A four-year experience with donor blood transfusion protocols for living-donor renal transplantation.

Our experience over the last 4 years with HLA-identical, donor-specific transfusion (DST), and Imuran (IM) + DST living-donor transplants in 206 patients is presented. Transplants from 8 completely incompatible sibling donors, 4 distantly related donors, and 7 unrelated donors are included. Except for a slightly higher average serum creatinine, and a markedly reduced rate of donor-specific sensitization in the IM + DST group when compared with the DST group (14% vs. 31%, P less than .005), the results of transplantation using these 3 protocols have been equivalent. Actuarial one-year survival was 97% for patients and 93% for grafts for the combined group of 206 patients. Of the 44 patients who entered the DST or IM + DST protocols but were not transplanted, 31 patients (70%) have subsequently been transplanted, and all 5 recipients of living-donor kidneys and 20 of 26 recipients of cadaveric kidneys (77%) have functioning grafts. Because it optimizes the availability of transplantable living-donor kidneys, gives results equivalent to those obtained with HLA-identical donors and the DST protocol, and is not associated with clinically apparent adverse effects, we now use the IM + DST protocol for all living-donor transplants except those between HLA-identical donor-recipient pairs.