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F Moreso

Publications and source records attributed to F Moreso.

At least 19 recordsLinked to original sources

Immunosuppression for dual kidney transplantation with marginal organs: the old is better yet.

Immunosuppressive protocols in dual kidney transplantation (DKT) are based on calcineurin inhibitors (CNI). We wonder whether a CNI-free immunosuppression can improve outcome in older patients receiving a DKT with marginal donor organs. Thirty-six were treated with CsA, MMF and prednisone (CsA group) and 42 with rATG, SRL, MMF and prednisone (SRL group). Incidence of delayed graft function and acute rejection was 44% and 11% in the CsA group, and 40% and 8% in the SRL group. CMV infection incidence was low in both protocols. Three-year patient survival was 89% in the CsA and 76% in the SRL group. One- and 3-year graft survival after censoring for dead with a functioning allograft was 94.2% and 94% in CsA and 95% and 90% in SRL, respectively. Renal function was similar in both groups whereas proteinuria was higher in the SRL group. Uninephrectomy due to graft thrombosis or urinary-related complications was numerically higher in the SRL (21%) than in the CsA group (8%) (p = 0.13) and it was associated with renal failure and proteinuria. In DKT, a new induction immunosuppressive protocol based on rATG, SRL, MMF and prednisone does not offer any advantage in comparison to the old CsA, MMF and prednisone.

Calcineurin Inhibitors↗

Subclinical rejection impairs glomerular adaptation after renal transplantation.

After transplantation, glomerular volumes increases and large glomerular volume at 4 months is associated with better renal function. The aim is to characterize glomerular adaptation after the fourth month in two serial protocol biopsies and its relationship with subclinical rejection and chronic allograft nephropathy (CAN). Mean glomerular volume (Vg) was estimated according to the Weibel and Gomez method in a 4-month and 1-year serial protocol biopsies in 61 stable grafts. Glomerular enlargement (deltaVg) was calculated as the Vg difference between both biopsies. Banff schema was used to evaluate renal biopsies. Vg increased from 4.4+/-2.4 to 5.7+/-2.6 x 10(6) microm3 (P<0.001). Mean deltaVg was 1.0 x 10(6) microm3. Patients with deltaVg<1 were considered as patients with impaired glomerular enlargement (n=29). Impaired glomerular enlargement was associated with increased acute index score in the 4-month (1.83+/-1.56 vs 1.06+/-1.48; P<0.05) and 1-year protocol biopsies (1.52+/-1.59 vs 0.62+/-1.07; P<0.05). Impaired glomerular enlargement was also associated with increased progression of chronic lesions between the 4-month and 1-year biopsy in the glomerular (0.17+/-0.38 vs 0.55+/-0.63; P<0.01), tubular (0.38+/-0.56 vs 0.83+/-0.85; P<0.01), and interstitial compartment (0.41+/-0.57 vs 0.90+/-0.86; P<0.01). The proportion of sclerotic glomeruli between both biopsies increased in patients with impaired glomerular enlargement (1.5+/-3.9 to 5.3+/-10.1, P<0.05) while it did not modify in patients with glomerular enlargement (2.1+/-7.3 vs 2.6+/-4.5; P=NS). During the first year, glomeruli enlarge but this adaptation mechanism is impaired in patients with subclinical rejection. Moreover, impaired glomerular enlargement is associated with progression of CAN.

Acute Disease↗

Subclinical rejection associated with chronic allograft nephropathy in protocol biopsies as a risk factor for late graft loss.

Chronic allograft nephropathy (CAN) in protocol biopsies is associated with graft loss while the association between subclinical rejection (SCR) and outcome has yielded contradictory results. We analyze the predictive value of SCR and/or CAN in protocol biopsies on death-censored graft survival. Since 1988, a protocol biopsy was done during the first 6 months in stable grafts with serum creatinine <300 micromol/L and proteinuria <1 g/day. Biopsies were evaluated according to Banff criteria. Borderline changes and acute rejection were grouped as SCR. CAN was defined as presence of interstitial fibrosis and tubular atrophy. Mean follow-up was 91 +/- 46 months. Sufficient tissue was obtained in 435 transplants. Biopsies were classified as normal (n = 186), SCR (n = 74), CAN (n = 110) and SCR with CAN (n = 65). Presence of SCR with CAN was associated with old donors, percentage of panel reactive antibodies and presence of acute rejection before protocol biopsy. Cox regression analysis showed that SCR with CAN (relative risk [RR]: 1.86, 95% confidence interval [CI]: 1.11-3.12; p = 0.02) and hepatitis C virus (RR: 2.27, 95% CI: 1.38-3.75; p = 0.01) were independent predictors of graft survival. In protocol biopsies, the detrimental effect of interstitial fibrosis/tubular atrophy on long-term graft survival is modulated by SCR.

Adolescent↗

Therapy with plasmapheresis and intravenous immunoglobulin for acute humoral rejection in kidney transplantation.

BACKGROUND: Acute humoral rejection (AHR) is characterized by acute graft dysfunction associated with de novo production of donor-specific alloantibodies (DSA) and C4d deposition in peritubular capillaries of the renal allograft. It has been reported the combination of plasmapheresis (PP) and intravenous gamma globulin (IVIG) as effective rescue therapy for established AHR. METHODS: Between 1999 and 2004, seven kidney allografts recipients suffered from AHR diagnosed by severe rejection and C4d staining in peritubular capillaries. All patients had a negative cross-match before renal transplantation. RESULTS: All patients were treated with daily sessions of PP and in four cases IVIG was added after the last PP session. Tacrolimus and mycophenolate mofetil were employed as maintenance immunosuppressive regimen. In one case, rituximab was added to PP and IVIG owing to refractory humoral rejection. At 1 year, patient survival was 100%, allograft survival was 70%, and the mean serum creatinine was 201 micromol/L. CONCLUSIONS: AHR is a severe form of rejection associated with a poor prognosis, but its early diagnosis and treatment with PP and IVIG allows reversal of AHR reaching a 70% graft survival at 1 year.

Acute Disease↗

Long-term effect of hepatitis C virus chronic infection on patient and renal graft survival.

BACKGROUND: Hepatitis C virus (HCV) infection increases morbimortality in renal transplantation. The immune response against the HVC is not predictable in a great proportion of patients developing into chronic liver disease, glomerulonephritis, or both. PATIENTS: We analyzed the impact of posttransplant chronic hepatitis development on patient and graft survival in 200 HCV-positive/HBsAg-negative renal allograft recipients transplanted between 1981 and 2003. RESULTS: Ninety-eight patients developed chronic ALT elevation (ALT+), while 102 did not (ALT-). There was no difference in acute rejection episodes (ARE), acute tubular necrosis, donor and recipient age, gender, HLA mismatches, and number of previous renal transplants. Development of ALT+ was associated with a worse patient survival (90% vs 65% at 15 years of follow-up, P = .007; RR = 3.8, CI = 1.4-10.1), an effect that was independent of other variables as time on dialysis and age. The main causes of death among ALT+ were chronic liver disease (52%), cardiovascular (26%), and infection (13%), whereas in ALT- they were cardiovascular (33%), cancer (33%), and chronic liver disease (16%). Conversely, graft survival (censoring for patient death with a functioning graft) was higher among ALT+ (50% vs 35% at 15 years of follow-up, P = .04; RR = 1.5, CI = 1.19-2.22). Causes of graft loss in ALT- patients were chronic allograft nephropathy (CAN, 53%), glomerulonephritis (GN, 18%), acute rejection episode (AR, 22%), and death (5%), whereas among ALT+ they were CAN (36%), GN (31%), ARE (10%), and death (21%; P = .01). By multivariate analysis, ALT- (RR = 1.6, CI = 1.07-2.55, P = .02) and de novo GN (RR = 2, CI = 1.29-3.09, P = .002) were associated with worse renal allograft survival. CONCLUSION: Our results suggested that a better immune response against the HCV lead to greater patient survival but poorer graft survival.

Adult↗

Arterial elasticity measurement in renal transplant patients under anticalcineurin immunosuppression.

INTRODUCTION: Calcineurin inhibitors may be associated with decreased arterial elasticity and increased vascular risk. We measured pulse wave velocity (PWV) in large or small arteries as an index of elasticity. The aim of our study was to determine aortic and radial arterial elasticity in 30 stable kidney transplant patients treated with calcineurin inhibitor immunosuppression. PATIENTS AND METHODS: In stable kidney transplant patients we determined the usual biochemical parameters as well as lipid profiles, 24-hour blood pressure (BP) monitoring (CBPM) using a chronobiological program (Garapa), and PWV with a HDI-PWV CR-2000 monitor. RESULTS: Sixteen patients received cyclosporine (CsA, G-1) and 14 tacrolimus (G-2) immunosuppression. There were no baseline differences regarding age (G-1: 56 +/- 12 years, G-2: 56 +/- 14 years), renal transplant follow-up (G-1: 7 +/- 3 years, G-2: 7.5 +/- 3 years), Systolic BP, pulse pressure or plasma creatinine (G-1: 163 +/- 35 umol/L, G-2: 173 +/- 26 umol/L). Patients in the G-1 showed higher diastolic BP (79 +/- 11 vs 74 +/- 8 mm Hg), greater proteinuria (1.26 +/- 0.4 vs 0.6 +/- 0.2 g/d, P < .05), total cholesterol (5.51 +/- 1.2 mmol/L) and low-density lipoprotein (3.08 +/- 0.3 vs 2.99 +/- 0.3 mmol/L, P = NS). Aortic arterial elasticity was decreased in G-1 patients (10.4 +/- 6 vs 14.3 +/- 2 mL/mm Hg x10, P < .05) as well as that in the radial artery (G-1: 5.52 +/- 1 vs 5.57 +/- 1.2 mL/mm Hg x100, P = NS). Almost 100% of the patients presented normal diurnal BP with high nocturnal BP in a nondipper pattern in both groups. CONCLUSION: Calcineurin immunosuppression may contribute to arterial stiffness in kidney transplant patients. No differences between CsA or tacrolimus were observed in our study. CBPM and PWV are useful tools to evaluate subclinical atherosclerosis in renal transplant patients.

Adult↗

Glomerular size in early protocol biopsies is associated with graft outcome.

Long-term consequences of glomerular enlargement after transplantation are not well understood. The aim is to evaluate the relationship between glomerular volume (Vg) estimated in protocol biopsies, graft function and graft survival. Vg and Banff chronic damage score were evaluated in protocol biopsies at 4 months. Creatinine clearance (CrCl) was estimated by the Cockroft-Gault formula. Vg estimated in 144 patients was 4.8 +/- 2.0 x 10(6)mu(3). It was associated with donor age (r = 0.23, p < 0.01), recipient body mass index (r = 0.17, p = 0.04), delayed graft function (Vg = 5.9 +/- 2.3 vs. 4.6 +/- 1.9 x 10(6)mu(3), p < 0.01) and CrCl (r = 0.17, p = 0.04). The best cutoff of Vg, Banff chronic damage score and CrCl was determined by Cox regression analysis, being 5.0 x 10(6)mu(3) for Vg (relative risk (RR): 2.4, 95% confidence interval (CI): 1.03-5.6), >2 for chronic damage score (RR: 3.4, 95% CI: 1.03-8.9) and 60 mL/min for CrCl (RR: 3.5, 95% CI: 1.04-11.9). These variables were independent predictors of death-censored graft survival. According to Vg and CrCl, four groups of patients were defined. Patients with small glomeruli and high CrCl had a 95% graft survival while patients with large glomeruli and low CrCl had a 45% graft survival at 15 years (p < 0.01). Large glomerular volume, high Banff chronic score and poor early renal function in stable grafts are independently associated with death-censored graft survival.

Adolescent↗

Preservation of renal function during maintenance therapy with cyclosporine.

During the last 20 years the management of cyclosporine (CsA) has improved due to the introduction of microemulsion technology, C2 monitoring, and combination with other new immunosuppressants. All these modifications have reduced the incidence of biopsy-proven acute rejection episodes to approximately 10%. However despite the wide experience, there are unanswered questions regarding CsA monitoring after the first year. Available clinical and histological data suggest that the therapeutic range to avoid nephrotoxicity or underimmunosuppression during the maintenance period is rather narrow. Furthermore, the combination of CsA with new immunosuppressants may modify the target CsA levels. Although the utility of C2 levels during the first year has been well characterized, there are few data on its utility for maintenance therapy, particularly the therapeutic range for C2 levels in patients receiving different immunosuppressive combinations. Since serum creatinine does not precisely reflect the progression of chronic allograft nephropathy, the efficacy of C2 monitoring during the maintenance period must be assessed not only by means of evaluation of renal function, but also histologic assessment using protocol biopsies.

Biopsy↗

Histologic findings in protocol biopsies performed in stable renal allografts under different immunosuppressive schedules.

Protocol biopsies performed in stable renal allografts show different degrees of acute and chronic lesions. Histologic findings in protocol biopsies have been related to graft outcome. We evaluated histologic lesions observed in protocol biopsies performed in patients under different immunosuppression therapies. From June 1988 a protocol biopsy was performed at approximately 4 months in patients who fulfilled the following criteria: serum creatinine <300 micromol/L; stable renal function; and proteinuria <1 g/d. Histologic lesions were graded according to 1997 Banff criteria. For the present study we considered the following groups according to immunosuppressive schedule: (i) induction therapy with polyclonal or monoclonal antilymphocytic antibodies associated with cyclosporine and prednisone (n=201); (ii) cyclosporine, mycophenolate mofetil, and prednisone (n=127); and (iii) tacrolimus, mycophenolate mofetil, and prednisone (n=51). On protocol biopsy patients treated with tacrolimus displayed a lower acute score (0.61+/-1.01 vs 1.24+/-1.23 in group I, 1.28+/-1.41 in group II; P<.0001) and a higher proportion of normal biopsies (57.1% vs 41.9% in group I, 45.1% in group II; P=.016). A similar proportion of chronic lesions (chronic score of group I: 1.30+/-1.56; group II: 1.34+/-1.80; group III: 1.51+/-0.95; P=NS) was observed in the three groups. Protocol biopsies displayed fewer acute lesions in patients treated with tacrolimus. This result suggests that the efficacy of new immunosuppression schedules can be evaluated using the protocol biopsy as a surrogate marker of graft outcome.

Adult↗

Doxazosin GITS trough to peak ratio and 24-hour blood pressure monitoring in the management of hypertension in renal transplant patients.

UNLABELLED: We have studied 20 patients, 10 male, 10 female, mean age 52.5+/-10.9 years, who received a cadaver kidney transplant between June 1996 and January 1999. The patients presented with mild or moderate high BP and were treated on a maintained immunosuppression with an anti-calcineurin agent and steroids, associated or not to mycophenolate-mofetil. At baseline, a 24-hour ambulatory BP monitoring was performed. General biochemical parameters were determined and doxazosin GITS (Gastro-Intestinal Therapeutic System) in a single dose of 4 mg/d was started. Doxazosin GITS was titrated four weeks after up to 8 mg/d if the BP was greater than 140/90 mm Hg. At week 12, biochemical analysis were repeated as well as the 24-hour BP monitoring and the T/P ratio was calculated. RESULTS: The patients were divided in responders, T/P index >50%, n=10 or not-responders, T/P index <50%, n=10 patients). No differences in systolic BP (SBP), diastolic BP(DBP), plasma creatinine or proteinuria were seen at base-line. DBP was lower in responders than in non-responders (P=ns). Doxazosin doses were 5.5+/-3 mg/d vs 5.8+/-3 and T/P ratio 0.70+/-0.13 vs 0.17+/-0.14, (P=.001). There were no variations in pl. t. cholesterol, triglycerides, glucose or uric acid. CONCLUSIONS: Treatment was safe and efficient, not increasing metabolic adverse effects. Doxazosin GITS is a safe agent which can reduce cardiovascular risk. In our patients, the good T/P ratio has been associated with a best diastolic BP control. This good profile should be taken into account for 24-hour BP control in hypertensive renal transplant patients.

Antihypertensive Agents↗

Serial protocol biopsies to quantify the progression of chronic transplant nephropathy in stable renal allografts.

AIM: To evaluate the utility of intimal thickness and interstitial width as a primary efficacy variable in the design of clinical trials aimed to modify the natural history of chronic allograft nephropathy. METHODS: A donor and a 4-month protocol biopsy were evaluated in 40 stable grafts according to the Banff schema. In 27 patients, a second protocol biopsy was done at 1 yr. Arterial intimal volume fraction (Vvintima/artery) and cortical interstitial volume fraction (Vvinterstitium/cortex) were estimated with a point counting technique. RESULTS: Chronic Banff scores increased during follow-up, while acute scores reached its peak at 4 months. Vvintima/artery and Vvinterstitium/cortex significantly increased at 4 months, but not at 1 yr. Vvintima/artery at 4 months correlated with donor Vvintima/artery (r = 0.57, p < 0.001), histocompatibility (r = 0.38, p = 0.01) and serum cholesterol (r = 0.31, p = 0.047). Vvinterstitium/cortex at 4 months correlated with recipient body surface area (r = 0.44, p = 0.004) and delayed graft function (p = 0.016). Power calculations showed that Vvintima/artery and Vvinterstitium/cortex allow an important reduction in minimum sample size of a hypothetical trial aimed to prevent chronic allograft nephropathy. CONCLUSIONS: Intimal thickening and interstitial widening progresses rapidly during the first 4 months after transplantation and slowly thereafter. These parameters can be considered as a primary efficacy variable in trials aimed to prevent chronic allograft nephropathy.

Adolescent↗

Practice variations in the evaluation of adult candidates for cadaveric kidney transplantation: a survey of the European Transplant Centers.

BACKGROUND: This survey was conducted to investigate similarities and differences in the diagnostic evaluation of adult candidates for cadaveric renal transplantation and the criteria for acceptance to the cadaveric renal transplant waiting-list in the European transplant centers. METHODS: A questionnaire listing 45 diagnostic procedures (consultations of 9 specialties, 18 imaging techniques and 18 laboratory investigations), 45 medical conditions constituting possible reasons for exclusion from renal transplantation, and 10 properties characterizing the responding transplant center was sent to 214 European transplant centers. RESULTS: A completed questionnaire was returned by 154 of 214 centers (72%). Significant disagreement (P<0.001) exists about the necessity of 28 of the 45 surveyed diagnostic procedures and about the acceptability of transplant candidates for 15 of the 45 surveyed medical conditions. The influence of center characteristics on the observed practice variations was examined by multinomial logistic regression (factors: Center size, waiting-list pressure, responsibility for organizing the diagnostic work-up, status of transplant center, responsibility for decision about acceptance of candidates and geographic location of center): In 13 of 28 controversial diagnostic procedures, geographic location of the centers turned out to be the only significant determining factor (P<0.001), whereas the dissent about medical conditions is not influenced significantly by the analyzed factors. CONCLUSION: The detected significant practice variations in the evaluation of renal transplant candidates may either indicate where scientific evidence is missing and more clinical research is needed or where the existing evidence has not been adequately disseminated and convincing guidelines should be established.

Adult↗

Protocol renal allograft biopsies and the design of clinical trials aimed to prevent or treat chronic allograft nephropathy.

BACKGROUND: The minimum sample size to perform a clinical trial aimed to modify the natural history of chronic allograft nephropathy (CAN) is very large. Since the presence of chronic tubulointerstitial damage in renal protocol biopsy specimens is an independent predictor of late outcome, we evaluated whether protocol biopsies could facilitate the design of trials aimed to prevent or treat CAN. METHODS: Two hundred eighty-two protocol biopsy specimens were obtained 3 months after transplantation in 280 patients with serum creatinine levels <300 micromol/L, proteinuria <1000 mg/day, and stable function. The specimens were evaluated according to the Banff criteria. RESULTS: Graft survival depended on the presence of CAN and renal transplant vasculopathy (RTV). Thus, biopsy specimens were classified as: (a) no CAN (n=174); (b) CAN without RTV (n=87); and (c) CAN with RTV (n=21). Graft survival at 10 years was 95%, 82%, and 41%, respectively (P=0.001). Total serum cholesterol before transplantation was 4.5+/-1.1, 4.6+/-1.1, and 5.3+/-1.6 mmol/L, respectively (P=0.009) and it was the only predictor of RTV. Power analysis (beta=20%, alpha=5%) was done to evaluate whether protocol biopsies can facilitate the design of clinical trials aimed either to prevent or treat CAN. We showed that the most feasible approach would be to use the presence of CAN as the primary efficacy end point in a prevention trial. To demonstrate a 50% reduction in the incidence of CAN at 3 months, 570 patients would be required. CONCLUSIONS: Protocol biopsies may allow a reduction of sample size and especially the time of follow-up in a trial aimed to prevent CAN.

Biopsy↗

Different diagnostic approaches to adult candidates for cadaveric kidney transplantation in Europe.

We investigated which diagnostic procedures are mandatory for all transplant candidates irrespective of their individual situation in European transplant centres, how homogeneously these are applied and what centre characteristics determine differences in the diagnostic approach. A questionnaire was sent to European renal transplant centres asking which of 45 listed diagnostic procedures are mandatory for every transplant candidate. The 154 participating centres require 15.6 +/- 5.6 (4-33) mandatory tests, with significantly less mandatory diagnostics in centres in the UK (8.5 +/- 3.9) and Scandinavia (9.8 +/- 2.3). Geographic location is the single significant factor in multifactorial analysis of possibly related factors. Detailed analysis revealed 16 tests that are required significantly less often in the north of Europe. There are significant differences in the evaluation of renal transplant candidates across Europe. In some parts of Europe transplant candidates are either investigated more discriminately or less comprehensively than in other regions.

Adult↗