Histopathological evaluation of pretransplant donor biopsies in expanded criteria donors with high kidney donor profile index: a retrospective observational cohort study.

There is no consensus on the allocation of renal transplants from expanded criteria donors (ECD). The Kidney Donor Profile Index (KDPI) is used without the need for pretransplant donor biopsies (PTDB). We explored whether PTDB based on Remuzzi Score (RS) allows identification of those marginal kidneys in the highest calculated KDPI risk group (>91%) that appropriate for single transplantation. A retrospective study was conducted of 485 consecutive kidneys procured from a single center and transplanted if the RS was ≤4. We compared 5-year kidney and patients survival between KDPI groups and between RS <4 or =4 in the highest KDPI group. The median KDPI (interquartile range) was 71 (66-76) for KDPI <80% (n = 77), 86 (81-90) for KDPI 81-90% (n = 82), and 97 (94-100) for KDPI >91% (n = 205). Patient survival at 5 years was 85.7%, 85.3%, and 76.09% (P = 0.058) and death-censored graft survival was 84.4%, 86.5%, 73.6% (P = 0.015), respectively for each KDPI group. In >91% calculated KDPI group, there were no differences in graft survival depending on the RS (<4 vs. =4) (P = 0.714). The implementation of PTDB based on RS used for allocation of organs with the highest KDPI range could support to the acceptance of suitable organs for single transplantation with good patient and graft survival rate.

Pre-implantation analysis of kidney biopsies from expanded criteria donors: testing the accuracy of frozen section technique and the adequacy of their assessment by on-call pathologists.

Pre-implantation renal biopsies of expanded criteria donors are one of the criteria used for allocation decisions, but there are concerns about the impact of the interobserver variability and the technique to be used. The aim was (i) to compare the original report performed by on-call pathologists using frozen sections (FS) to a retrospective analysis carried out by a trained pathologist using the same frozen section, and (ii) to compare the same FS to subsequently obtained paraffin sections (PS) by the same pathologist. A total of 92 biopsies, 78 from transplanted and 14 from nontransplanted cases, were analyzed. Agreement between observers using the same FS was weaker than the correlation between FS and PS in all the examined parameters (Kendall's Tau b for the Remuzzi score 0.104 vs. 0.306). According to the Remuzzi score, the revised FS analysis would have resulted in a higher rate of organ discard (n = 19) than PS (n = 14) and the original report (n = 6). However, kidneys that would have been discarded according to the retrospective analysis showed adequate outcomes in terms of graft survival and function. Accordingly, the impact of interobserver and technique-related variability can be minimized by the use of a relatively low threshold (RS ≤ 4) for organ acceptance.

An mTOR-inhibitor-based protocol and calcineurin inhibitor (CNI)-free treatment in kidney transplant recipients from donors after cardiac death: good renal function, but high incidence of conversion to CNI.

Donor after cardiac death (DCD) grafts have excellent survival despite the high incidence of delayed graft function (DGF). We assessed the feasibility of a mammalian target of rapamycin inhibitor (mTOR-I) protocol in uncontrolled DCD kidney transplantation and compared it with brain-dead donor (DBD) transplantation under calcineurin inhibitor (CNI) treatment. This retrospective study (2002-2011) included 109 Maastricht category II DCD patients and 218 standard-criteria DBD as controls. Immunosuppression consisted of polyclonal antibody induction, mycophenolate mofetil, prednisone, and mTOR-I (starting on day 6) in the DCD group and tacrolimus in the DBD group. DGF occurred in 72.5% of the DCD group vs. 26.1% of the DBD group (P = 0.001). Patient survival at 1 year was 99.1% vs. 95.9% (P = 0.112), and graft survival was 89% vs. 92.2% (P = 0.253). Patient survival at 5 years was 85.3% vs. 90.1% (P = 0.340) and graft survival was 85.5% vs. 78.8% (P = 0.166). During the first year, 46.8% (n = 51) of DCD patients were converted to CNI therapy. Serum creatinine at 1 year was 1.5(1.26-2) mg/dl vs. 1.4(1.16-1.8) mg/dl (P = 0.078). At 1 year, the acute rejection rate was 7.3% vs. 12.5% (P = 0.766). mTOR-I-based therapy was not associated with inferior graft function or higher rejection rates than standard CNI therapy. DCD kidney transplantation with an mTOR-I-based protocol is feasible but is associated with a high conversion rate to CNI-based therapy.

Clinical management of calcific uremic arteriolopathy before and after therapeutic inclusion of bisphosphonates.

BACKGROUND AND OBJECTIVES: Calcific uremic arteriolopathy (CUA) is a life-threatening condition almost exclusively affecting patients with end-stage renal failure. Several therapies have been employed to treat this disease with irregular results. METHODS: Comparison of a prospective case series with a historical cohort. Group I: 12 patients with CUA diagnosed before 2002 (5 men, 6 on dialysis and 6 with functioning allografts) treated with standard treatment. Group II: 11 patients with CUA diagnosed between 2002 and 2010 (4 men, 6 on dialysis and 5 with functioning allografts) treated with standard treatment and bisphosphonates for 6 months. The diagnosis was made by clinical suspicion and a confirmatory biopsy in both groups. Ten patients had a previous history of high calcium-phosphorus product, 9 had a history of high parathyroid hormone (> 800 pg/ml) levels, 13 had a history of high cumulative steroids and 9 patients were under dicoumarin treatment. Two patients were obese and 5 had diabetes mellitus. RESULTS: In Group I, 58.7% required amputation of the affected limb, 3 patients recovered and 2 died. In all patients of Group II the progression of the skin lesions decreased between 2 and 4 weeks after the start of bisphosphonate therapy with no changes in blood levels of calcium and phosphate. The improvement in pain and lesions was faster in the patients receiving endovenous bisphosphonates. Renal function remained stable in transplant recipients. No adverse effects were observed. CONCLUSIONS: Bisphosphonates could constitute an alternative to treat CUA in addition to standard therapy.

Kidney transplant from a living monozygotic twin donor with no maintenance immunosuppression.

UNLABELLED: From a theoretical point of view, an alloimmune response can not take place, still some type of standard immunosuppression is used in about 60% of patients receiving kidney grafts from their monozygotic twins. We aimed at assessing clinical response in patients receiving renal grafts from a living monozygotic twin donor when no immunosuppressive therapy is used. METHODS: This is a retrospective observational study of patients receiving kidney grafts from their monozygotic twins from 1969 to 2013. The following data were recorded: age, renal graft recipient's primary disease, renal function, renal survival and overall survival. Immunosuppressive therapy included a single intraoperative dose of methylprednisolone 500 mg and no maintenance immunosuppression. RESULTS: Five patients with kidney grafts from their monozygotic twins were dentified in our centre. Mean age at transplantation was 33 years (27-39). One-year overall survival and graft survival were 100%. Mean creatinine level was 0.96 ± 0.2 one year after transplantation, and 1.2 ± 0.37 mg/dl at most recent follow-up. Two patients died with a functional graft more than 15 years after kidney transplantation (causes were melanoma and cardiovascular event respectively). Follow-up was lost in a patient one year after transplantation. Two patients are alive with a functioning graft at 18 months and 42.5 years after transplantation respectively. CONCLUSION: Kidney transplantation from a living monozygotic twin is associated to outstanding clinical outcomes. Immunossuppresive therapy to suppress alloimmune response in probably unnecessary 11 zygosity has been confirmed.

Monthly ibandronate versus weekly risedronate treatment for low bone mineral density in stable renal transplant patients.

INTRODUCTION: Bisphosphonates may aid in treating and preventing bone loss promoted by chronic immunosuppressive treatment and secondary hyperparathyroidism in renal transplant (RT) patients. However, the effectiveness of bisphosphonates is compromised by poor patient compliance. The objective of the study was to compare the effects of once monthly ibandronate with those of weekly risedronate administration on bone mineral density (BMD) and renal function in RT patients. PATIENTS AND METHODS: Sixty-nine patients were prospectively recruited who were at least 12 months post-RT and were treated with either oral ibandronate 150 mg monthly (n=35) or oral risedronate 35 mg weekly (n=34). At baseline and 1 year, creatinine, calcium, alkaline phosphatase, and i-parathyroid hormone were measured, and BMD was determined by dual-energy X-ray absorptiometry. RESULTS: Group I consisted of 35 patients (28 women) treated with ibandronate who were of a mean age of 63±12 years. Group II consisted of 34 patients (30 women) treated with risedronate who were of a mean age of 64±10 years. Lumbar BMD was as follows: baseline T-score (group I vs. group II) of -1.7±0.8 versus -1.9±0.8 (P=NS); and annual T-score of -1.3±0.6 versus -1.4±0.8 (P=NS). After 1 year, lumbar BMD improved to reveal a T-score of -1.3±0.6 in the ibandronate group (P<0.01) and -1.4±0.8 in the risedronate group (P<0.01). Femoral BMD was as follows: baseline T-score (group I vs. group II) of -2.1±0.7 versus -2.2±0.6 (P=NS); and annual T-score of -1.8±0.9 versus -1.8±0.8 (P=NS). Cortical bone also improved in both groups, but results were not statistically significant. No changes in renal function and no adverse effects were observed. CONCLUSION: In RT patients with low BMD, no difference in effects on BMD, renal function, or adverse effects were observed between monthly oral ibandronate and weekly oral risedronate administration.

DXA variations and fractures after simultaneous pancreas-renal transplantation: results of a long-term follow-up.

Simultaneous pancreas-kidney transplant (SPKT) has been associated with an increased risk of fracture. We prospectively evaluated the long-term effects of SPKT on bone mineral density (BMD) and fracture risk. During 1998 to 1999, 29 participants were consecutively monitored, and 18 completed the 10-year follow-up. Laboratory blood parameters, lumbar-dorsal radiography, and DEXA were determined at baseline, 1 year, and 10 years. The medical record was reviewed for peripheral fragility fractures. The BMD revealed no changes between baseline and 1 or 10 years after SPKT. Lumbar-dorsal radiography showed 0% asymptomatic vertebral fractures at baseline and after 1 year with 16.7% at 10 years. Vertebral asymptomatic fractures were correlated with acute rejection episodes (P = 0.025). During the first year, no nonvertebral fractures were identified. At the end of the follow-up, 5 nonvertebral fractures in 4 patients were reported. Dorsal and lumbar spine fractures correlated with lumbar spine t score (r = -0.591, P =0.022) and peripheral fractures with femoral neck t score (r = -0.633, P = 0.013). Patients with SPKT did not show long-term significant loss of BMD. The incidence of vertebral fractures was low and related to steroid treatment; the incidence of peripheral fractures was higher and independent of clinical or biochemical parameters.

Long-term mycophenolate monotherapy in human leukocyte antigen (HLA)-identical living-donor kidney transplantation.

UNLABELLED: Although recipients of a first HLA-identical living-donor kidney transplant seem to need less immunosuppression, there are no guideline recommendations for these patients, and few prospective trials are available. METHODS: We analyzed all PRA-negative patients who received a first kidney transplant from an HLA-identical living donor. The patients received no antibody induction. An intraoperative bolus of 500 mg of methylprednisolone was administered. Then, steroid therapy was withdrawn within one week. Tacrolimus and mycophenolate treatment were started 3 days before transplantation with tacrolimus target levels of 4 to 8 ng/mL. In the absence of rejection, tacrolimus was withdrawn between 3 and 12 months post-transplant to reach mycophenolate mofetil monotherapy of 2 g/day or equivalent. RESULTS: Six patients were treated with the above protocol. At last follow-up, graft and patient survival were 100%. MDRD glomerular filtration rates were 54, 60, and 62 mL/min at 3 months, 12 months and last follow-up, respectively. None of the patients developed PRA post-transplant. One episode of acute rejection Banff IA occurred 9 years after transplantation due to non-adherence with good outcome after treatment. The mean number of concomitant drugs given with mycophenolate was 2.6. Four patients needed antihypertensive drugs. CONCLUSION: Steroid-free de novo treatment and calcineurin-inhibitor weaning with mycophenolate monotherapy is feasible in first HLA-identical kidney transplantation from a living sibling.

Trasplante renal de donante vivo entre gemelos monocigotos sin inmunosupresión de mantenimiento / Kidney transplant from a living monozygotic twin donor with no maintenance immunosuppression

Los pacientes trasplantados de riñón de gemelo monocigótico reciben en un 60% de los casos algún tipo de inmunosupresión estándar a pesar de la imposibilidad teórica para generar una respuesta aloinmune. El objetivo de este estudio es evaluar la respuesta clínica de los receptores renales de donante vivo de gemelo monocigoto sin tratamiento inmunosupresor. Método: Estudio observacional retrospectivo entre 1969 y 2013 de pacientes trasplantados renales de donante vivo entre gemelos monocigotos. Se ha recogido edad y enfermedad primaria del receptor, función renal, supervivencia renal y global. El protocolo inmunosupresor consistía en la administración de una dosis única intraoperatoria de 500mg de metilprednisolona sin otra inmunosupresión de mantenimiento. Resultados: Se identificó a 5 receptores renales de gemelos idénticos en nuestro centro. Edad media en el momento del trasplante 33 años (27-39). La supervivencia a un año de los pacientes y el injerto fue del 100%. La creatinina media al año fue de 0,96±0,2 y al último seguimiento de 1,2±0,37mg/dl. Dos pacientes fallecieron con injerto funcional más de 15 años después del trasplante (uno debido a melanoma y otro debido a un evento cardiovascular). Se perdió el seguimiento de un paciente al año del trasplante. Los 2 pacientes restantes están vivos 18 meses y 42,5 años después del trasplante, respectivamente, con injerto funcionante. Conclusión: El trasplante renal entre gemelos monocigotos ofrece excelentes resultados clínicos. Probablemente el tratamiento inmunosupresor para inhibir la respuesta aloinmune es innecesario en estos casos cuando se haya comprobado la cigosidad (AU)

From a theoretical point of view, an alloimmune response can not take place, still some type of standard immunosuppression is used in about 60% of patients receiving kidney grafts from their monozygotic twins. We aimed at assessing clinical response in patients receiving renal grafts from a living monozygotic twin donor when no immunosuppressive therapy is used. Methods: This is a retrospective observational study of patients receiving kidney grafts from their monozygotic twins from 1969 to 2013. The following data were recorded: age, renal graft recipient's primary disease, renal function, renal survival and overall survival. Immunosuppressive therapy included a single intraoperative dose of methylprednisolone 500mg and no maintenance immunosuppression. Results: Five patients with kidney grafts from their monozygotic twins were dentified in our centre. Mean age at transplantation was 33 years (27-39). One-year overall survival and graft survival were 100%. Mean creatinine level was 0.96±0.2 one year after transplantation, and 1.2±0.37mg/dl at most recent follow-up. Two patients died with a functional graft more than 15 years after kidney transplantation (causes were melanoma and cardiovascular event respectively). Follow-up was lost in a patient one year after transplantation. Two patients are alive with a functioning graft at 18 months and 42.5 years after transplantation respectively. Conclusion: Kidney transplantation from a living monozygotic twin is associated to outstanding clinical outcomes. Immunossuppresive therapy to suppress alloimmune response in probably unnecessary 11 zygosity has been confirmed (AU)