Prolonged‐release tacrolimus was developed to provide a more convenient once‐daily dosing that could improve patient adherence. We conducted a multicenter, prospective, observational, 12‐month study ...to describe the efficacy, safety and patient preference of conversion from tacrolimus twice‐daily to once‐daily formulation in stable kidney transplant recipients in routine clinical practice. Conversion was made on a 1 mg: 1 mg basis (1 mg: 1.1 mg in patients with trough levels <6 ng/mL). The study included 1832 patients (mean age (±SD): 50.0 ± 13.4 years; 62.7% male). After conversion, a modest reduction in tacrolimus trough levels, necessitating an increase in daily dose, was observed (mean changes at 12 months of –9.1% and +1.24%, respectively; p < 0.0001). Mean glomerular filtration rate did not change significantly (56.5 ± 19.7 mL/min at conversion vs. 55.7 ± 20.6 mL/min at 12 months). Proteinuria, blood pressure, lipid, hepatic and glucose parameters remained stable. Eight patients (0.4%) had acute rejection and 34 patients (1.85%) discontinued treatment. Almost all patients (99.4%) preferred the once‐daily formulation, because of less frequent dosing (66%) and improved adherence (34%). In conclusion, at similar doses to twice‐daily tacrolimus, once‐daily formulation provided stable renal function, a low acute rejection rate, and good tolerability in stable kidney transplant recipients in the routine clinical practice setting.
This study of 1832 renal transplant patients reports that conversion from twice‐daily tacrolimus to the once‐daily prolonged‐release formulation in a routine clinical practice setting results in stable renal function and a low acute rejection rate with a good tolerability profile.
Recurrence of idiopathic focal segmental glomerulosclerosis (FSGS) following kidney transplantation occurs in a large percentage of patients. Accurate prediction of recurrence and elucidation of its ...pathogenesis are major therapeutic goals. To detect differential proteins related to FSGS recurrence, proteomic analysis was performed on plasma and urine samples from 35 transplanted idiopathic FSGS patients, divided into relapsing and nonrelapsing. Several proteins were detected increased in urine of relapsing FSGS patients, including a high molecular weight form of apolipoprotein A‐I, named ApoA‐Ib, found exclusively in relapsing patients. This finding was verified by Western blot individually in the 35 patients and validated in an independent group of 40 patients with relapsing or nonrelapsing FSGS, plus two additional groups: FSGS‐unrelated patients showing different proteinuria levels (n = 30), and familial FSGS transplanted patients (n = 14). In the total of 119 patients studied, the ApoA‐Ib form was detected in 13 of the 14 relapsing FSGS patients, and in one of the 61 nonrelapsing patients. Only one of the 30 patients with FSGS‐unrelated proteinuria tested positive for ApoA‐Ib, and was not detected in familial patients. Urinary ApoA‐Ib is associated with relapses in idiopathic FSGS and warrants additional investigation to determine its usefulness as biomarker of relapse following transplantation.
This study finds a modified form of apolipoprotein A‐I, named Apo A‐Ib, associated to focal segmental glomerulosclerosis (FSGS) relapses after transplantation; Apo A‐Ib is present in the urine of relapsing idiopathic FSGS patients, while absent in non‐relapsing FSGS, in familiar FSGS and in patients with FSGS‐unrelated proteinuria.
Abstract Background There are few reports about the clinical course and prognosis of monoclonal gammopathy of undetermined significance (MGUS) in long-term immunosuppressed patients. Our aim was to ...study the association and evolution of MGUS and renal transplantation. Methods Subjects submitted to renal transplantation between 1996 and 2011 who presented MGUS before or after immunosuppressive treatment was established were selected. Results Patients (N = 587) underwent kidney transplantation in our center during the selected period. MGUS was detected in 17 (2.9%) patients (10 men and 7 women with a mean age of 69.9 ± 10.07 years), with a median follow-up of 6 years. All patients had a functioning graft. Nine had MGUS before transplantation. One patient had multiple myeloma, and 8 remained stable. Eight patients had development of MGUS after transplantation. Six patients remained stable, 1 showed no MGUS, and 1 displayed an increased monoclonal component in further controls. Conclusions In our study, renal transplantation is not a risk factor for the development of malignant processes in patients with MGUS before transplantation. There is a group of patients who tend to have MGUS after transplantation; nevertheless, they had a benign evolution during a 6-year follow-up.
The high incidence of new‐onset diabetes mellitus after transplantation (NODAT) suggests the need to find new factors to explain the pathogenesis. Our objectives were (1) to confirm that low levels ...of pre‐transplant adiponectin are an independent risk factor for the development of NODAT in a larger transplanted population; (2) to analyze whether adiponectin is a better predictor of NODAT than other inflammatory markers (C‐reactive protein (CRP), interleukin‐6 (IL‐6), tumor necrosis factor‐alpha (TNF‐α) and pregnancy‐associated plasma protein A (PAPP‐A)) and (3) to assess the relationship between obesity, inflammatory markers and NODAT. One hundred ninety‐nine non‐diabetic patients (128 men; age: 53 ± 11 years; body mass index (BMI) 24.98 ± 3.76 kg/m2) were included. Pre‐transplant plasma glucose, insulin, adiponectin, CRP, TNF‐α, IL‐6 and PAPP‐A were measured. Forty‐five patients developed NODAT. Patients with NODAT had a greater BMI (p = 0.005). Adiponectin was lower (p < 0.001) and CRP higher (p = 0.032) in patients with NODAT. Multivariate logistic regression and Cox analysis showed that the calcineurin inhibitor used, pre‐transplant BMI and adiponectin were predictors of NODAT. ROC analysis showed that an adiponectin concentration of 11.4 μg/mL had a significant negative prediction for NODAT risk (sensitivity: 81% and specificity: 70%). Of the inflammatory markers studied, adiponectin proved to be an independent predictor of NODAT.
This analysis of non‐diabetic kidney transplant recipients found that serum adiponectin levels were an independent predictor of new onset diabetes after transplantation, with high levels associated with reduced risk.
Abstract Cholesterol-crystal embolization (CE) usually presents as an acute or subacute multisystemic disease. When affecting native kidneys prognosis is poor, often leading to chronic kidney ...disease. Presentation in renal allografts is a rare condition although probably underdiagnosed. If renal CE originates from the recipient, allograft survival is usually good, whereas if the donor is the origin, graft dysfunction and subsequent graft loss are common. Associated risk factors are common to native and transplanted kidneys. We report 2 renal graft recipients of different cadaveric donors, both male and 68 years old, diagnosed with CE in renal grafts at 19 and 72 months after transplantation, respectively. They presented previous risk factors for CE, including severe atherosclerosis. They presented insidious and asymptomatic impairment of renal function initially. Renal graft biopsy specimens showed CE in the interlobular arteries. Potential triggers for CE were suspended and high doses of steroids were started. However, progressive decline in renal function and requirement of chronic dialysis occurred within the first year after diagnosis in both cases. Herein we discuss the causal or incidental role of CE in the graft failure of these cases, highlighting the serious outcome despite the recipient origin of the CE and the initiation of treatment.
Abstract Introduction Nodular arteriolar hyalinosis (NAH) is a typical, although not specific, histological finding of calcineurin inhibitor toxicity (CNIT). The objective of our study was to assess ...the reason why some patients showing strong NAH in renal graft biopsies who underwent calcineurin inhibitor (CNI) withdrawal presented very poor outcome whereas others improved graft function. Material and Methods We performed 207 renal graft biopsies between January 2011 and May 2014 due to clinical criteria. In 13 patients CNI withdrawal was performed, and the major histopathological finding was severe NAH. The results after this action were analyzed. Results We selected 2 groups: good outcome and poor outcome. Eight patients showed good results including stabilization or improvement of graft function. Five patients presented poor results requiring chronic hemodialysis. C4d staining was negative in all biopsy specimens, and peritubular capillaritis was not observed. To identify potential prognostic markers we retrospectively reviewed biopsy samples looking for minor or nonspecific features, especially inflammation scores both global and on fibrotic areas as per Banff classification. Mean serum creatinine level at time of biopsy and mean arteriolar hyalinosis score did not show significant differences between both groups. In contrast, the poor results group presented a higher mean global inflammation score compared with the good results patients. Conclusions NAH is not a risk factor for poor renal graft outcome by itself. Other histopathologic findings, usually considered as secondary markers, like the inflammation score, should be considered before deciding CNI withdrawal.
Abstract Background Post-transplant recurrent glomerulonephritis (RGN) is the third cause of graft failure in the first year after renal transplantation (RT). The purpose of this study was to analyze ...the incidence of RGN, clinical presentation, and clinical evolution of transplanted renal graft in patients who underwent RT at our center. Methods We studied patients with glomerulonephritis (GN) who underwent RT (2007 to 2013).We analyzed sex, age, time in dialysis, type of GN, type of RT, time to post-transplant RGN, kidney function at the time of diagnosis of RGN, and renal graft evolution. Renal biopsy samples were processed in the anatomic pathology laboratory. Results Three hundred sixteen patients received kidney transplantation during this time period. In 83 cases, the reason for transplantation was primary GN. Of these 83 patients, 15 (18%) had RGN confirmed by renal biopsy. Data for these 15 patients include sex: 73.3% men, 26.7% women; mean age: 42.2 (29–73) years; type of RT: 80% cadaveric donor (CD) versus 20% living donor (LD); type of GN: 18.4% immunoglobulin (Ig)A nephropathy, 35.7% membranous GN, 10.53% type I membrano-proliferative GN (MPGN I), and 16.6% focal segmental glomerular sclerosis (FSGS). The mean time to post-transplant RGN was 2 years (1 month to 16 years). Patients who received an LD transplant had a shorter time to post-transplant RGN than those who had a CD transplant. One patient with FSGS and one with MPGN I had a time to post-transplant RGN of less than 1 year. In the evolution of renal function, 33.3% of patients had graft failure. Conclusions The incidence of RGN was lower (18%) than that published in the literature. Membranous nephropathy was the most frequent cause of post-transplant RGN. Patients who underwent LD transplantation and those with IgA nephropathy had a shorter interval of time to post-transplant RGN than patients with FSGS and MPGN I.
Abstract Background Some lesions not included in the Banff classification, such as inflammation in the scarred areas and total inflammation, have been described to have prognostic value in the ...evaluation of graft biopsies. Our aim was to reassess kidney graft biopsies and study the impact of histopathologic lesions, both those graded in the Banff classification and those related to inflammation, on the graft function and evolution. Methods We selected 20 biopsies exhibiting chronic pathology without a specific phenotype, and we reevaluated them with the use of a modified Banff score. Results We found statistically significant association between the presence of total inflammation ( P = .048; P = .038), the presence of inflammation in scared area ( P = .037; P = .018), and creatinine at the time of renal biopsy and 1 year after the renal biopsy, respectively. Conclusions Our results suggest that the presence of both inflammation in the scarred areas and total inflammation are related to renal function at the time of the biopsy and to renal function 1 year after the biopsy.
Abstract Hepatitis C (HC) is a very relevant negative prognosis factor for graft and transplant recipient survival. New direct-acting antivirals (DAAs) allow us to solve this problem in an effective ...way. It is crucial to understand their real impact in our daily practice. We analyzed treatment results with DAA, free of interferon, in kidney transplant recipients (KTRs) from 15 Spanish hospitals (Grupo Español de Actualización en Trasplante), regarding effectiveness, tolerance, and impact on immunosuppression, renal function-proteinuria, and diabetes. One hundred nineteen KTRs were included (9 combined liver-kidney transplants). The main DAA used was sofobusvir (91%) combined with ledipasvir (55%), simeprevir (14%), or daclatasvir (13%); in 9 cases (7%), a paritaprevir-ritonavir-ombitasvir-dasabuvir combination (3D) was used; Ribavirin was used as a coadjuvant in 18%. Side effects were limited (23.5%) and without relevance in general, except in 7 patients for whom we needed to interrupt the treatment due to neurotoxicity (1) caused by drug interaction (3D and tacrolimus) or anemia (3) by Ribavirin or others. Ninety-four patients had completed the treatment when data were analyzed: virological response was seen in 97.8% % of cases. Liver function analysis improved: 84% normal versus 21% before starting the treatment ( P < .001). Renal function and proteinuria did not change. Tacrolimus level at the end of DAA-treatment was significantly lower with respect to the beginning (5.8 ± 2.1 ng/mL vs. 7.4 ± 1.8 ng/mL, P = .03), despite a slight increase in the dose (2.6 mg/d vs. 2.3 mg/d, P = .17). DAA are highly effective in the treatment of hepatitis C in KTRs with good tolerance in general, making it possible to solve the problem and have a good chance to improve the prognosis in our transplantation patients. The use of these therapies in KTRs requires special control and coordination with digestive professionals, especially if 3D or Ribavirin is used.
Summary
Background Skin cancer is the most common malignancy occurring in kidney transplant recipients (KTRs).
Objectives Our purpose was to investigate, prospectively, the cumulative incidence of ...cancerous and precancerous skin lesions as well as their risk factors in a close follow‐up population of KTRs from a Mediterranean area of Spain.
Patients and methods One hundred and seventy‐four consecutive KTRs were examined at the moment of transplant and then at 6‐month intervals. The cumulative incidence of skin cancer was computed. To analyse the role of potential risk factors (age at transplantation, cause of renal failure, duration of pretransplant dialysis, type of immunosuppressive regimen, sun‐reactive skin type and history of occupational sun exposure), the Cox regression method was used.
Results After a median follow‐up of 72 months (range, 12–140), 39 patients (25·3%) developed 142 tumours 84 basal cell carcinoma (BCC) and 58 squamous cell carcinoma (SCC). The BCC/SCC ratio was 1·4 : 1. The cumulative incidence for skin cancer was 13% after 3 years of graft survival, increasing to 27·5% at 6 years and 48% at 10 years. Only age at the time of transplantation and occupational sun exposure had statistical significance as risk factors (P < 0·001).
Conclusions Our study confirms the high incidence of non‐melanoma skin cancer among KTRs in a Mediterranean population with occupational sun exposure and the patient's age at the time of transplantation being the main risk factors. We believe that all organ transplant programs should provide educational information about protecting oneself from the sun as well as include follow‐up visits by dermatologists in order to facilitate early diagnosis and treatment of skin cancer.
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