J.M. Morales

Renal Allograft Function and Cardiovascular Risk in Recipients of Kidney Transplantation After Successful Pregnancy

Successful pregnancy is one of the better indicators of quality of life for women who are of child-bearing age with restored fertility after kidney transplantation. Our objective was to evaluate whether pregnancy represented a risk factor for worsening of renal function or for cardiovascular disease among renal transplant recipients. From 1976 to 2007, we followed 30 successful pregnancies in 27 renal recipients in our hospital; three women had two twin gestations. We compared this population with 27 women with renal transplants who were not pregnant. They were of similar ages at transplantation (pregnant 31.1 +/- 5.4 years vs not pregnant 31.3 +/- 5.4 years, P = NS) and similar evolution time between kidney transplantation and pregnancy (51.5 +/- 36 months vs 47.2 +/- 41 months respective; P = NS). There were no acute rejection episodes or graft losses. Renal function measured by serum creatinine and MDRD4 at the end of pregnancy was lower among the pregnant compared with the control group: mainly, 1.1 +/- 0.2 mg/dL versus 0.9 +/- 0.2 mg/dL (P = .05), and 66 +/- 20 mL/min/1.73 m(2) versus 80 +/- 26 mL/min/1.73 m(2) (P = .03). At 1 and 10 years, renal function was similar among the groups. Ten pregnant women developed preeclampsia (37%) and three, gestational diabetes mellitus (11%). There was one major cardiovascular event (4%; acute myocardial infarction) among the pregnant group, whereas there were two in the control group (7.4%; stroke and severe hypertensive retinopathy). One death occurred in each group secondary to cardiovascular complications. Our results showed that successful pregnancy after renal transplantation did not represent a long-term risk factor to worsen renal function and or produce severe cardiovascular complications. Therefore, pregnancy should be promoted. for young women with renal transplants that show excellent function.

Everolimus-based immunosuppression therapy for BK virus nephropathy.

BACKGROUNDnMammalian target of rapamycin inhibitors (mTOR-i) have been proposed as possible immunosuppressants of choice in BK virus nephropathy (BKN) because of their antiviral capacity. On this basis, in 2007, our Service proposed a conversion to everolimus (EVE)-based therapy from calcineurin inhibitors with an anti-calcineurin-free therapy protocol in those patients diagnosed of BKN.nnnMETHODSnA prospective, single-center case series study was performed. Fifteen cases of BKN were diagnosed from 2007 to the end of 2010. According to our protocol, immunosuppressant treatment was modified in 9 of these patients with suspension of mycophenolate and conversion from tacrolimus to EVE.nnnRESULTSnThe renal function achieved by our patients after the transplantation was excellent. Mean serum creatinine (sCr) achieved was 1.16 ± 0.2 mg/dL. Evolution of the renal function after BKN diagnosis and conversion to mTOR-i was positive in all the patients. sCr on diagnosis was 1.85 ± 0.22 mg/dL, sCr at the point in time of conversion to EVE was 2 ± 0.21 mg/dL, and final sCr of the follow-up was 1.6 ± 0.39 mg/dL (P = .05). BK viremia became negative in 5 of our patients and decreased more than 95% in the remaining 4. None of the patients had an acute rejection episode after the change of immunosuppressant.nnnCONCLUSIONSnConversion to mTOR-i-based therapy could provide an added benefit in BKN and could be an effective strategy for the decrease of the viremia and increase of graft survival in selected patients.

Addition of Spironolactone to Dual Blockade of Renin Angiotensin System Dramatically Reduces Severe Proteinuria in Renal Transplant Patients: An Uncontrolled Pilot Study at 6 Months

Experimental and clinical data strongly suggest that aldosterone may contribute to proteinuria and progressive renal disease. In fact, an aldosterone antagonist seems to be effective for controlling proteinuria in native kidneys. However, there is little information about this approach in renal transplant patients, a population in whom the presence and amount of proteinuria represent risk factors for graft loss, cardiovascular disease, and death. The aim of our study was to evaluate whether addition of an aldosterone antagonist, spironolactone, provided an additional antiproteinuric effect to the angiotensin-converting enzyme inhibitor (ACEI) and angiotensin type I receptor antagonists (ARB). We evaluated the effects on severe proteinuria (4.4±1.4 g/d) at 6 months after prescription of spironolactone (25 mg/d) among 11 renal transplant patients with serum creatinine values less than 3 mg/dL who were under treatment with an ACEI plus an ARB. Patients were examined in the renal transplant outpatient clinic every week for the first month and twice a month thereafter. Nine patients showed a more than 50% (mean=81.5%) reduction in proteinuria not only early, but also sustained at 6 months (4.4±1.4 to 2.3±1.1 g/d) with a mild, nonsignificant deterioration in renal function (serum creatinine 1.6±0.32 to 1.7±0.54 mg/dL). This study showed that spironolactone decreased severe proteinuria among patients treated with an ACEI plus an ARB. This therapy is not recommended for patients with glomerular filtration rates below 40 mL/min. Therefore, it is suggested that using triple blockade of RAS is feasible in selected renal transplant patients to reduce proteinuria, although caution is required to avoid severe hyperkalemia.

Results of a Living Donor Kidney Promotion Program

BACKGROUNDnLiving kidney donor transplantation, a treatment option for end-stage kidney failure, may achieve better results than cadaveric donor transplantation. Although its significant use in some countries is due to the scarcity of cadaveric donors, it is also useful because it reduces waiting time for young recipients and avoids dialysis when performed before starting renal replacement therapy. Due to the high rate of cadaveric donation in Spain, there has only been a limited increase in the number of living donor kidney transplantations.nnnMETHODSnIn February 2004, we initiated a program to promote living kidney donation (LKD) through an information plan that was transmitted to the patients by dialysis nephrologists and chronic kidney failure outpatient clinics.nnnRESULTSnFrom February 2004 to March 2010, we evaluated 109 donor and recipient pairs: parent to child (n=48 cases; 44%), spouses (n=32 cases; 29.3%), siblings (n=27; 24.7%), and uncle and nephew (n=2; 1.8%). The mean donor age (49±9 years) was significantly higher than the 39±13 years of the recipients (P<.01). In 45 cases (41.3%), the procedure led to of living kidney donor transplantation but in 58 (53.2%), a transplantation was not performed due to recipient problems (n=53) or donor problems (n=5). In 6 cases (5.5%), the evaluation is still pending. With the initiation of this project, it has been possible to significantly increase the rate of living kidney donor transplantation in our hospital from 0.8% (March to January 2004: 16/1964) to 4.2% (February 2004 to March 2010: 43/1022 transplants; P<.01).nnnCONCLUSIONnA policy of active information together with adequate studies of the potential donor and recipient significantly increased the number of living kidney donor transplantations. The profitability of the study procedure was 50%. The most frequent cause of noncompletion of the procedure was recipient-related problems.

Extended-Release Tacrolimus Therapy in De Novo Kidney Transplant Recipients: Single-Center Experience

BACKGROUNDnAvailable data for extended-release tacrolimus (Tac) except in clinical trials are limited.nnnOBJECTIVEnTo describe our initial experience with once-daily Tac in combination with corticosteroids and mycophenolate mofetil therapy in patients undergoing de novo renal transplantation.nnnPATIENTS AND METHODSnIn this retrospective, observational, single-center study, data were obtained for 49 adult recipients treated with extended-release Tac and 30 patients treated with standard-release Tac (control group). Mean (SD) follow-up in the 2 groups was 3.5 (2.5) months and 4.0 (2.6) months, respectively. The primary characteristics were comparable between the groups.nnnRESULTSnThe acute rejection rate in the extended-release group was 10%, and 13% in the standard-release group. Patient and graft survival rates were 98% and 96% vs 100% and 90%, respectively. Renal function in the 2 groups was comparable: serum creatinine concentration 1.3 (0.2) mg/dL vs 1.45 (0.4) mg/dL. At day 14 posttransplantation, Tac doses were 0.17 mg/kg/d vs 0.14 mg/kg/d, and blood concentrations were 9.0 ng/mL vs 14.0 ng/mL. In recipients older than 60 years, lower dosages of Tac resulted in blood concentrations similar to those in younger patients, with less variation in dosage.nnnCONCLUSIONSnShort-term experience with extended-release Tac therapy in de novo renal recipients confirms its efficacy and safety. Adjusting blood concentrations in the immediate posttransplantation period is less difficult with extended-release Tac compared with the twice-daily formulation.

Everolimus Represents an Advance in Immunosuppression for Patients Who Have Developed Cancer After Renal Transplantation

Renal transplantation provides the best quality of life for the patients with chronic end-stage renal failure. However, the immunosuppression necessary for graft survival may give rise to infectious complications, an increased risk of cardiovascular and neoplastic diseases, all of which can shorten the patients survival. The objective of this study was to evaluate the efficacy and safety of the proliferation signal inhibitor immunosuppressant drugs everolimus among patients who develop neoplasms after renal transplantation. This retrospective study included 25 patients (mean age -56.5 +/- 14.1 years) who were diagnosed with posttransplant neoplastic disease and immunosuppressed with calcineurin inhibitors (CNIs). Treatment was initiated with everolimus with or without CNIs. During the follow-up, the renal function (initial serum creatinine 1.4 mg/dL vs final serum creatinine 1.3 mg/dL) and proteinuria levels (initial 0.3 g/d vs final 0.4 g/d) remained stable. There was a low percentage of patients with relapse of their tumor. One patient had a relapse of bladder cancer with tumor progression at 3 years; another patient with melanoma developed lymph node invasion. There were neither acute rejection episodes nor cardiovascular complications. The results suggested that tumor relapse was low. The results suggested that immunosuppression with everolimus combined with low doses of CNIs or in single-drug therapy is safe immunosuppression for patients who develop posttransplant malignant diseases.

Monotherapy Rapamycin in Renal Transplant Recipients With Lymphoma Successfully Treated With Rituximab

Posttransplantation B-lymphoproliferative (PTBL) disease is a severe complication of organ transplantation, which requires reduction of immunosuppressive treatment. The use of the anti-CD20 monoclonal antibody, Rituximab, improves the survival of these patients. In this setting, maintenance immunosuppressive therapy may represent a challenge. The mammalian target of rapamycin (m-TOR) inhibitor Rapamycin has antiproliferative effects that makes it a safe, efficient option to avoid graft rejection and reduce the malignancy risk. We studied 6 renal recipients (4 men and 2 women) of overall mean age of 50.66 +/- 15.89 years who were diagnosed with lymphoma at a mean time of graft function of 137.0 +/- 68.00 months. All of the patients were Epstein-Barr-negative. Four received a combination of Rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), and 2 received Rituximab only. In all cases complete remission persisted during follow-up of 21.83 +/- 8.34 months. The immunosuppressive treatment was switched to the m-TOR inhibitor Rapamycin at therapeutic trough blood levels of 5-8 ng/dL. The mean time of Rapamycin treatment was 15.5 +/- 8.96 months. Notably, we observed neither acute rejection nor relapse episodes. Renal function remained stable with no significant proteinuria. The serum creatinine level before switching to Rapamycin was 1.06 +/- 0.16 mg/dL and 0.9 +/- 0.14 mg/dL 12 months later. However, 1 patient had to stop Rapamycin treatment due to pneumonitis. Our study suggests that immunosuppressant monotherapy with Rapamycin is safe and efficient for renal recipients who develop lymphoma because of its antitumor effects without nephrotoxicity.

Experimental Design and Analysis of a Gyroelastic Beam

Gyroscopic systems and their properties have been extensively studied as Angular Momentum Devices (AMD), Control Moment Gyros (CMG) or Gyroscopes for various applications such as structure control, stability or energy storage. However, most of the works that have been done are theoretical and do not present experimental implementation. In this work we performed an experimental study of a gyroscope beam system (gyroelastic beam) focused systems on the deflection of cantilever beams or the control of flexural stresses. We first used a simple two-degree of freedom model to better understand the terms governing the design, construction and experimental evaluation of gyroelastic beam systems. We then performed experimental tests at different velocities of the gyroscopic actuator and measured the deflection of the system. The results showed that it is possible to have control of the deflection and the bending forces for this type of configurations which can be exported to helicopter blades or wind turbine blades.