Renal allografts from donors older than 70 years are useful for single transplantation.

Kidney transplantation has been related in elderly recipients to a greater longevity compared with dialysis. Due to the scarcity of donors, transplantation of older patients depends on the acceptance of older donors. We compared the characteristics and evolution of transplants from donors >or=70 years (n = 53) with those from donors >55-<70 years (n = 201). Group D >or=70 included older recipients (65.37 +/- 4.9 vs 55.92 +/- 9.66 years; P = .000) and more women (62.3% vs 45.3%; P = .02), with more peripheral arterial disease (10.9% vs 2.4%; P = .011). No differences in donor characteristics were observed. Induction treatment with thymoglobulin or basiliximab was more common in D >or=70 (81.1% vs 57.3%; P = .006), with no differences in other immunosuppressive drugs. The incidence of delayed graft function (DGF) was similar (P = .82), with a trend to a lower incidence of acute rejection episodes among D>or=70 (11.8% vs 22.5%; P = 0.09). Serum creatinine and proteinuria levels did not differ during follow-up (P > .05). Patients in D >or=70 displayed more episodes of urinary sepsis (19.1% vs 6.4%; P = .008), but no differences were observed in cytomegalovirus (CMV) infection (P = .629), neoplasia (P = .118), ischemic cardiopathy (P = .642), or hospital readmission due to infections (P = .567). Graft survivals at 5 years were 70% and 75% (P = .279) among groups D >or=70 and D>55-<70, respectively, and patient survivals at 5 years were 88% and 88% (P = .63), respectively. In conclusion, our study showed that selected kidneys from donors older than 70 years were followed with excellent graft and patient survivals, permitting older patients on renal replacement therapy to benefit from renal transplantation.

Histological findings of early graft biopsies in old donor renal transplant patients receiving induction therapy.

Since recipients of transplants from elderly donors are exposed to an increased risk of delayed graft function (DGF) and acute rejection episodes, administration of induction treatment represents an alternative to preserve renal mass and improve graft survival. We compared the evolution and histological findings of early graft biopsies among 38 recipients treated with Thymoglobulim (33.6%) versus 75 (66.4%) with basiliximab. No differences were observes in the rate of DGF (P = .39). Forty kidneys were biopsed during the first 2 weeks after transplantation: 9 in the Thymoglobulin group (23.68%) and 31 in the basiliximab group (41.3%). Histological evaluation showed: acute tabular necrosis in 7 (78%) Thymoglobulin patients versus 14 (45%) basiliximab patients, with calcineurin nephrotoxicity in 2 (22%) and 1 (3.2%), respectively. An acute rejection episode was not diagnosed in the Thymoglobulin group, but 13 patients (17.3%) in the basiliximab group experienced this complication (P = .006). Banff classification showed: 6 grade IA (19.4%), 1 grade IB (3.2%), 3 grade IIA (9.7%), 1 grade IIB (3.2%), and 2 grade III (6.5%). Six of these patients required rescue treatment with Thymoglobulin. Serum creatinine and proteinuria levels between the 2 groups were not different (P > .05). There were no differences in cytomegalovirus (CMV) disease (P = .152), admission due to infection (P = .120), or neoplasia (P = .29). Graft and patient survivals at 3 years did not show a difference. The histological findings revealed that low doses of Thymoglobulin were much more effective to prevent renal inflammation and acute rejection episodes than basiliximab among renal transplant recipients, albiet without differences in survival at a mean of 3 years follow-up.

Beginning hemodialysis: do patients with a failed renal transplant start in worse condition?

OBJECTIVE: Predialysis management of patients with kidney transplant failure is a topic of growing interest. Herein we have reviewed a group of patients with a failed kidney transplant who returned to dialysis to compare them with patients with native kidney failure. PATIENTS AND METHODS: We analyzed 25 patients who returned to dialysis after a failed renal transplant (group A) and 38 patients initiating dialysis after native kidney failure (group B). RESULTS: We did not observe significant differences in the glomerular filtration rate (GFR), potassium, calcium, phosphorus, albumin, and hemoglobin levels between the 2 groups at the beginning of dialysis. Erythropoietin resistance index (ERI) was higher in group A. Progression of renal disease in the 2 years before dialysis was faster in group A, with a greater monthly decline in GFR and higher levels of systolic blood pressure. Renal transplant patients needed more evaluations in the 6 months before initiating dialysis: 1.75 +/- 0.97 vs 0.70 +/- 2.61 evaluations/month (P = .000). Also, the number of hospitalizations during the years before and after dialysis initiation was higher among group A. Patient survival after return to dialysis at 1 year was 75% in group A and 97% in group B (log-rank; P = .09). CONCLUSIONS: Patients with a failed kidney allograft initiated dialysis in similar condition to those with native kidney failure. The faster GFR decline may be related to immunosuppressive treatment. Transplant patients needed more frequent evaluations and more hospitalizations before and after dialysis initiation, indicating a higher morbidity rate.

[Diagnosing neoplasia in a kidney transplant unit]. / Diagnóstico de neoplasias en una consulta de trasplante renal.

BACKGROUND AND AIM: Cancer is one of the major causes of death with functioning allograft among renal transplant patients. The increasing age of patients in the waiting list has derived in a higher risk of cancer in this population. The aim of this study was to analyze the incidence of cancer in the waiting list and kidney transplant patients. METHODS: Between November/1996 and November/2007 we assisted 825 patients in the outpatient renal transplant clinic, 467 were transplanted, 120 remained in the waiting list and 238 have been removed from the waiting list or died. RESULTS: During this period, 97 malignancies were diagnosed, 33 of 32 kidney transplant candidates and 64 of 62 renal transplant patients. The comparative analysis between this two groups showed that candidates had higher frequency of solid organ tumours compared with a higher incidence of skin cancer in transplanted patients. Mean time between transplant and cancer diagnosis was 42.6 +/- 32.7 months, 48% of malignancies were diagnosed within the first three years postransplant. When comparing kidney transplant patients with and without cancer diagnosis, the formers were older and had worse patient survival at five years. Allograft survival was similar for both groups. CONCLUSIONS: we want to emphasize the extreme importance of a detailed screening in the renal transplant candidates and transplanted patients due to a higher incidence of malignancies in this population.

Treatment of renal transplant failure.

INTRODUCTION: Among graft failures beyond months, we performed progressive reduction and complete withdrawal of immunosuppressive drugs and steroids over a period of 6 months. PATIENTS AND METHODS: We analyzed the treatment and complications associated with all late allograft failures in 34 patients (8.19%) out of 415 patients transplanted from November 1996 to November 2006. RESULTS: In 21 patients (61.8%), the progressive reduction of immunosuppressive treatment was effective and well tolerated; however, in 13 patients (38.2%) there was rejection of the allograft at 10.74 +/- 8.95 months (0.77-34.80) after the failure. With the reintroduction of these drugs, the rejection was controlled in seven patients, but in the other six we had to embolize the allograft, which had to be repeated in one case. Embolization was well tolerated, but in one case there was migration of one coil to the femoral artery. One patient treated with drug withdrawal experienced emphysematous pyelonephritis after repeated urinary infections, requiring a nephrectomy. Thirteen (38.2%) of the patients with late failures have been admitted for a second transplant; five of them showed HLA sensitization. CONCLUSIONS: Conservative treatment with progressive withdrawal of immunosuppression was effective and well tolerated in two-thirds of the patients with late renal allograft failure, but one-third of the patients rejected the graft and needed allograft embolization. Infection of the graft and HLA sensitization can complicate the course of these patients.

Risk factors and prognosis for proteinuria in renal transplant recipients.

INTRODUCTION: Proteinuria in renal transplant recipients has been recognized as a risk factor of progression of chronic allograft nephropathy and for cardiovascular disease, the main causes of transplant failure. PATIENTS AND METHODS: We analyzed the risk factors for persistent proteinuria (>0.5 g/day) among 337 kidney allograft recipients with a minimum follow-up of 6 months, among a series of 375 transplants performed during a decade, as well as their association with allograft and patient survivals. Patients with proteinuria greater than 0.5 g/d were treated with angiotensin-converting enzyme inhibitors (ACEI) and/or angiotensin-receptor blockers. RESULTS: After a mean follow-up of 53.35 +/- 52.63 months, 68 patients (20.17%) had persistent proteinuria greater than 0.5 g/d. Female patients (P = .012), body mass index (BMI) >25 (P = .008), pretransplant HLA sensitization (P = .039), and delayed graft function (DGF; P = .001) were associated with proteinuria. Induction treatment with antithymocyte globulin (P = .030) and treatment with tacrolimus instead of cyclosporine (P = .046) were associated with an increased risk of proteinuria. Multivariate analysis confirmed the independent value of DGF (RR = 2.23; 95% confidence interval [CI] 1.22 to 4.07; P = .009) and BMI >25 (RR = 1.968; 95% CI 1.05 to 3.68; P = .035) to predict postransplant proteinuria. The mean values of serum creatinine (P = .000) and systolic blood pressure (P < .05) were persistently higher from the early stages after transplantation in the proteinuric group. Graft survival at 5 years was 69% among patients who developed proteinuria and 93% in those without proteinuria (P = .000), with no differences in patient survival (P = .062). CONCLUSION: Proteinuria in renal transplant recipients was related to immunological and nonimmunological factors, some of which, such as hypertension and obesity could be modifiable. Proteinuria in renal transplant recipients predicted a worse allograft survival despite of intensive treatment of hypertension including ACEI/angiotensin-receptor blockers.

Benefits derivated from late steroid withdrawal in renal transplant recipients.

Because corticosteroids have adverse metabolic effects, inducing bone-mineral imbalance and contributing to infections among renal transplant recipients, many withdrawal trials have been attempted to reduce adverse events and improve quality of life. We retrospectively analyzed the safety and efficacy of late steroid withdrawal, after the first posttransplant year, among a selected group of kidney allograft recipients. In 42 low immunological risk allograft recipients, among 382 patients transplanted during a decade, corticosteroids were progressively reduced and completely withdrawn. The evolution of clinical and biochemical parameters after the withdrawal were analyzed. Corticosteroid withdrawal was performed as a mean of 52.16 +/- 28.41 months posttransplant, with subsequent follow-up without steroid treatment of 18.13 +/- 16.11 months. Comparing the most recent evaluation with the data previous to steroid withdrawal, patients showed a significant decreases in diastolic pressure (P = .039), total cholesterol (P = .000), and low-density lipoprotein cholesterol levels (P = .039), but not in triglyceride levels (P = .33). Body weight did not change (P = .77), but increased fasting glucose levels were noted (P = .03), in absence of new diagnosed diabetes mellitus. A significant reduction in cyclosporine Neoral (P = .01) or tacrolimus doses were detected (P = .01). At the last visit, serum creatinine in the whole group remained stable (P = .06). Only five patients showed an increase in serum creatinine more than 20% (from 1.44 +/- 0.41 to 1.94 +/- 0.45 mg/dL P = .04) and proteinuria did not increase (P = .94). No patient was diagnosed with a rejection episodes or required corticosteroid resumption. Graft and patient survivals were 100% at the end of follow-up. In conclusion, our data showed that late corticosteroid withdrawal in renal transplant recipients of low immunological risk is safe and is followed by an improvement in their metabolic profile and in blood pressure.

Calcineurin inhibitor reduction based on maintenance immunosuppression with mycophenolate mofetil in renal transplant patients: POP study.

Since calcineurin inhibitors (CNI) have been introduced, they have become the cornerstone of immunosuppression for renal transplant patients, but their cardiovascular and neurological toxicities, and primarily their renal toxicity, have brought about an increased effort to find combinations of immunosuppressants that are either CNI-free or that use minimum doses of these drugs. The weight of immunosuppression therefore lies with drugs that have a better toxicity profile. The POP observational transverse study including 213 renal transplant patients was designed to study CNI minimization strategies. The mean time of transplant evolution to the time of reduction was 9.9 +/- 11.8 months. The acute rejection rate to the start of reduction was 9.4%. Almost all the patients were undergoing treatment with CNI + mycophenolate mofetil (MMF) + steroids in the immediate posttransplantation period. When reduction was chosen, all patients were undergoing treatment with MMF (mean dose at the start of reduction = 1490.7 +/- 478.0 mg/d). Among the cohort, 66.7% of patients were being treated with tacrolimus (mean C0 levels 13.3 +/- 6.6 ng/mL) and 33.3% with cyclosporine (mean C0 levels 192.2 +/- 94.0 ng/mL; mean C2 levels 1097.5 +/- 457.6). The main reasons for withdrawal were nephrotoxicity (55.9% of the cases), as well as prevention of adverse effects (21.6%). The mean target CNI dose reduction was 41.4% +/- 21.45% in the tacrolimus group and 28.6 +/- 10.0% in the cyclosporine group. In conclusion, CNI toxicity, primarily renal toxicity, makes reduction of these drugs based on the use of full MMF doses an alternative to manage renal transplant patients.

Effect of overweight on kidney transplantation outcome.

INTRODUCTION: Obesity is a prevalent problem in renal transplant recipients that is followed by reduced graft and patient survivals. Because the prevalence of overweight (OW) is increasing in the renal transplant population, we studied the influence of OW on graft and recipient evolution. PATIENTS AND METHODS: We analyzed a series of 337 patients with renal allografts having a mean follow-up of 53.4 +/- 30.6 months. We excluded 39 patients obese at transplantation. We compared the evolution of 134 OW patients (45.5%), and 160 patients (54.4%) with a body mass index <25 (NW group). RESULTS: OW patients were older (P = .000) with a higher prevalence of hypertension (P = .028), left ventricular hypertrophy (P = .014), and dyslipidemia (P = .001). They had received kidneys from older donors (P = .019). OW patients showed a higher incidence of acute tubular necrosis (ATN) (P = .006), without a higher incidence of acute rejection episodes (P = .756). Postransplant diabetes mellitus was more frequent (P = .000), and systolic blood pressure (P < .05), total cholesterol (P < .05), and tryglicerides were higher (P < .05) in the OW group. Serum creatinine at 6 months (P = .007) and proteinuria >0.5 g/24 hours, (P = .023) were higher among the OW group. Graft survival was not different between groups, but patient survival was lower in the OW group (P = .002). A logistic regression analysis showed that the recipient age (RR: 5.243) and the presence of OW (RR: 1.100) were independent prognostic factors for patient death. CONCLUSIONS: OW was a common situation among renal transplant candidates. It was associated with worse cardiovascular and metabolic profiles. OW patients showed worse allograft function and lower patient survival. A major effort must be exerted to avoid excessive weight gain, particularly among those OW at transplantation.

[Seasonal perodicity in vascular access thrombosis for haemodialysis]. / Ritmo estacional en la trombosis del acceso vascular para hemodiálisis.

Different studies have shown that some clinical events, particularly cardiovascular and thrombotic events, show a regularity in its appearance. The aim of our study was to analyse the possible existence of seasonal periodicity in the incidence of the vascular access thrombosis in patients on chronic haemodialysis. Prospectively, we collected information of 164 patients with 250 episodes of vascular access thrombosis referred to our hospital from january 1995 to december 1999. An ANOVA test for comparison of the means, and a time series analysis were performed. During the five year study the consecutive number of thrombosis were 43, 57, 55, 59 and 36. When the different seasons were analysed, the cumulative number of events in summer during the study period were 91, a significant increase compared to spring, autumn, and winter (54, 54, and 51, respectively; p<0.001). Time series analysis confirmed that thrombolic events during summer showed an increased incidence over the mean (p<0.001), and it occurred every year. The same results were obtained when the PTFE grafts were analyzed separetely (july RR 2.62, p=0.002; august, RR 2.37, p=0.04), but not with the arteriovenous fistulae. In conclusion, this study showed a seasonal periodicity of vascular access thrombosis, with a PTFE graft. Although the causes were unknown, these data alert us on the convenience of an increased attention to the vascular access during the summer months in order to prevent its thrombosis.

Transplant renal artery stenosis: association with acute vascular rejection.

BACKGROUND: Transplant renal artery stenosis, the prevalence of which varies from 2% to 12%, is an important cause of hypertension and allograft dysfunction. We sought to determine the clinical characteristics of this disorder, assessing, predisposing factors, establishing treatment options, and examining patient outcomes. PATIENTS AND METHODS: Among 321 renal allograft recipients between November 1996 and December 2004, six patients were identified with this finding. We analyzed their clinical data before and after treatment compared with the 315 recipients face of the disorder. RESULTS: The six patients with the disorder were diagnosed within the first year (2 to 8 months; median 5.5 months). All patients displayed renal dysfunction, peripheral edema, and new-onset or uncontrolled hypertension at presentation. Abnormal Doppler findings were observed in 5 (83.3%) patients. The hemodynamically significant stenosis was successfully treated with percutaneous transluminal angioplasty (PTA) in all six. However, 3 (50%) patients displayed recurrent stenosis requiring a second PTA. The mean serum creatinine level decreased from a pre-PTA value of 4.4 +/- 1.8 mg/dL to a 1-month post-PTA value of 2.2 +/- 0.5 mg/dL (P = .027). Patients had no significant improvement in mean systolic and diastolic pressure. Vascular acute rejection episodes were more frequent among the affected than the control group (3/6; 50% vs 18/315; 5.7%; P < .001). No differences were found in age, sex, donor type, etiology of renal disease, immunosuppression, acute tubular necrosis, acute cellular rejection, cold ischemia time, or HLA matching. CONCLUSION: Transplant renal artery stenosis is a common cause of hypertension and renal allograft dysfunction. Acute vascular rejection is associated with this disorder.

Erythropoietin treatment in the sixth posttransplant month as a prognostic factor for renal allograft survival.

The purpose of this work was to assess the prognostic value of the need for erythropoietin (EPO) treatment at 6 months after transplantation. We retrospectively reviewed the outcomes of 143 consecutive cadaveric kidney transplants performed between January 2000 and April 2004, functioning at 6 months postransplantation. Patients were divided into two groups: group EPO6m (n = 24) received EPO treatment in the sixth month, and a control group (n = 119) did not receive EPO. Renal function deterioration (RFD) was considered to be a sustained decrease in creatinine clearance (CrCl) greater than 20% between the sixth month postransplant and the last visit. Mean follow-up was 38 +/- 16 months. The mean ages of the donor (57 +/- 9 vs 49 +/- 12 years; P = .001) and the recipient (59 +/- 12 vs 47 +/- 17 years; P = .000) were greater in the EPO6m group. Delayed graft function (83% vs 48%; P = .001) was more frequent in the EPO6m group. At 6 months after transplantation the EPO6m group showed lower hemoglobin (11.52 +/- 1.71 vs 13.32 +/- 1.69 g/dL; P = .000), higher serum creatinine (2.31 +/- 0.72 vs 1.65 +/- 0.53 mg/dL; P = .000), lower CrCl (33.53 +/- 10.83 vs 53.6 +/- 17.58 mL/min; P = .000), and similar proteinuria. RFD was more common in the EPO6m group (38% vs 10%; P = .026), with a different pattern of evolution of CrCl (-0.098 +/- 0.176 vs +0.093 +/- 0.396 mL/min/mo, P = .000). Multivariate analysis demonstrated that treatment with EPO at 6 months was the only predictor of RFD (RR 4.46; 1.58 to 12.58; P = .005). The need for EPO at 6 months postransplant was a good predictor of later renal allograft deterioration, more sensitive than serum creatinine or proteinuria.

FTY720 versus MMF with cyclosporine in de novo renal transplantation: a 1-year, randomized controlled trial in Europe and Australasia.

FTY720 is a novel immunomodulator investigated in de novo renal transplantation and other therapeutic areas including multiple sclerosis. This 1-year multicenter, randomized, phase III study in 668 de novo renal transplant patients compared FTY720 2.5 mg plus full-dose cyclosporine (FDC) or FTY720 5.0 mg plus reduced-dose cyclosporine (RDC), with mycophenolate mofetil (MMF) plus FDC. The primary efficacy endpoint was the composite incidence of first treated biopsy-proven acute rejection (BPAR), graft loss, death or premature study discontinuation at month 12. Primary efficacy with FTY720 2.5 mg and MMF (32.4% and 30.2%; p = NS), plus mortality and BPAR incidence, were comparable. Patients receiving FTY720 5.0 mg plus RDC were discontinued from treatment due to increased risk of acute rejection (primary endpoint incidence 47.3%). FTY720 was associated with lower creatinine clearance (month 12: 53.1, 56.0 vs. 65.1 mL/min; p < 0.001) and more macular edema cases (2.2% and 1.3% vs. 0%), whereas cytomegalovirus infections were higher with MMF (6.2% and 10.6% vs. 18.1% p < 0.0001 and p = 0.0139, respectively). FTY720 2.5 mg provided comparable rejection prophylaxis over 12 months versus MMF; however, FTY720 5.0 mg did not support a 50% reduction in cyclosporine exposure. The cause of macular edema cases and lower creatinine clearance with FTY720 in de novo transplantation needs further investigation.

[Chronological aggregation of subcutaneous mycosis in renal transplant recipients]. / Agregación cronológica de cuatro casos de micosis subcutánea invasiva en receptores de trasplante renal.

We present four cases of subcutaneous invasive mycosis in renal transplant recipients that happened in our Unit during a period of eight months. The Microbiology Department did not find any fungi when they studied possible reservoirs and vectors for transmission. We speculate about the reasons of this chronological aggregation. We discuss the treatment that we used for these infections.

[Renal transplantation with positive crossmatch]. / Trasplante renal en presencia de una prueba cruzada positiva.

INTRODUCTION: Lymphocytotoxic antibodies reduce the expectancy of renal transplantation due to the increased risk of a positive crossmatch. MATERIAL AND METHODS: We analyzed the evolution of eight kidney transplants performed in our unit in presence of a positive crossmatch with historical T and/or B lymphocyte positive crossmatches. RESULTS: Mean panel reactivity was 76,6 +/- 25,7% (r: 22-100%), been higher than 75% in six patients. Six patients were recipients of a second or third transplant. Immunosuppression consisted of quadruple therapy including induction with thymoglobuline. Five patients had delayed graft function, and one had primary non-function of the graft. One patient lost her graft due to chronic allograft nephropathy in the second year postransplantation. Six patients maintained a good renal function (serum creatinine 1,2 +/- 0,5 mg/dl, proteinuria 0,20 +/- 0,34 g/day). CONCLUSION: Renal transplantation in presence of a positive cross-match with historical serum and T lymphocytes and/or B lymphocytes, was followed by a satisfactory graft survival.

[Post-transplant diabetes mellitus associated with acute hepatitis C virus infection in a renal transplant recipient]. / Diabetes mellitus postrasplante asociada a hepatitis aguda por virus de la hepatitis C en un receptor de injerto renal.

There are some controversial reports about the pathogenic role of hepatitis C virus infection on diabetes mellitus in renal graft recipients. We report a case of a renal transplanted who developed diabetes mellitus post-transplantation during an acute hepatitis C virus infection. We discuss the multifactorial etiology of post-transplant diabetes mellitus, and the possible interaction between tacrolimus and an acute virus C infection on its pathogenesis.