Carmen Cantarell

Achieving chronic kidney disease treatment targets in renal transplant recipients: results from a cross-sectional study in Spain.

Background. Kidney transplant recipients are considered to have chronic kidney disease (CKD) irrespective of glomerular filtration rate (GFR) or presence or absence of markers of kidney damage. The aim of this work was to investigate the prevalence of CKD-stages and whether the guidelines for general population (Kidney Disease Outcomes Quality Initiative) are routinely followed in kidney transplant in Spain. Patients and Methods. Two thousand one hundred sixty renal transplant recipients followed up at the outpatient clinics in 4 University Hospitals were included. The estimated GFR (eGFR) was calculated according to the abbreviated modification of diet in renal disease equation, and the patients were classified following the Kidney Disease Outcomes Quality Initiative stages. Results. Chronic kidney failure (eGFR <60 mL/min/1.73 m2) was present in 1505 patients (69.7%), 54.4% were 3T-stage (eGFR 30-59); 13.0% were 4T-stage (eGFR 15-30), and 2.3% were 5T-stage. The prevalence of severe anemia increased from 4.1% in 1T-stage to 44% in 5T-stage (P=0.000) as did the percentage of patients on erythropoiesis-stimulating agents from 1.3% to 68% (P=0.000). The intact parathyroid hormone levels increased as graft function declined and 45% of 5T-stage patients had intact parathyroid hormone levels more than 300. Calcium and vitamin D supplements were administered to 50% and 40% of patients, respectively. Hypertension was quite common and increased with the progression of CKD. The mean total cholesterol was 192±39 mg/dL, and the levels did not increase with the decline in graft function. Approximately 60% had suboptimal cholesterol despite 50% being on statins treatment. Conclusions. CKD and their complications were prevalent in renal transplant recipients. The control of some of these complications is far below targets established for nontransplant CKD patients despite a progressive intensification of therapy as graft function declines.

Cysteamine (Cystagon®) adherence in patients with cystinosis in Spain: successful in children and a challenge in adolescents and adults

Background Cysteamine has improved survival and prognosis in cystinosis. Increasing numbers of patients reach adulthood and face new challenges such as compliance that wanes over time. The aim of this study was to evaluate adherence to cysteamine treatment in a group of cystinotic patients in Spain in an attempt to identify potential therapy pitfalls and improve the overall care of affected individuals. Despite the impact of cysteamine on prognosis, there is a paucity of data regarding adherence. Method Thirty-four cystinotic patients (21 male) 38% ≥18 years were enrolled in a voluntary, anonymous survey. Replies were obtained from patients (15/34), mothers (11/34), fathers (4/34) and both parents (4/34). Results Patient age (median and interquartile range) at diagnosis was 1 year (0.57–1), and patient age at Cystagon® initiation was also 1 year (0.8–1.8). Sixteen (47%) were kidney transplant (KTx) recipients; six were retransplanted. Age at first KTx 10 years (8.7–13.7). Patient understanding of multiorgan involvement in cystinosis: 4.1 organs reported; eye 97% and kidney 91%. Cysteamine was given by mother (100%) and father (83%) in <11 year olds, or self-administered (94%) in ≥11 year olds. Four daily doses in 89% versus 56% in <11 year olds or ≥11 year olds, with fixed schedule in 94% versus 50% in <11 or ≥11 year olds and progressive loss of reminders over time. Furthermore, 44% complained of unpleasant smell. Motivation for treatment compliance was 100% versus 40% in <11 versus ≥11 year olds, respectively. Disease impact in patients <18 years is as follows: school (29%), social (14%), ‘feeling different’ (10%); in patients ≥18 years: ‘feeling different’ (62%), professional (39%) and job absenteeism (31%). Referring physician: paediatric nephrologist (94%) and nephrologist (63%) in <11 versus ≥11 year olds. Ophthalmological follow-up: 83% versus 38% in <11 versus ≥11 year olds. Patient opinion of physician expertise: paediatric nephrologist (94%) and nephrologist (44%). New treatment options (65%) and better information (42%) were demanded to improve adherence. Conclusion Treatment with Cystagon is effective in young patients. However, adherence diminishes over time in adolescents and adults despite disease impact. Strategies such as better information on the disease, patient self-care promotion and facilitated transition to adult healthcare services are required to improve compliance and the clinical management of cystinosis.

Histological findings in two renal transplants accomplishing operational tolerance criteria

Operational tolerance is defined as stable renal function in transplants without immunosuppression for at least 1 year. We present histological assessments of two patients with operational tolerance. The first withdrew immunosuppression in 2005 and presents stable renal function (creatinine 1.5 mg/dL) without proteinuria. The biopsy showed mild chronic tubulointerstitial changes without inflammation. The second withdrew immunosuppression in 2009 and maintains stable renal function (creatinine 1.6 mg/dL) with mild proteinuria. Histology showed chronic humoural rejection and Class II anti-human leukocyte antigen antibodies were detected. These cases suggest that a renal biopsy may be useful to rule out subclinical pathology in patients with operational tolerance.

Heterogeneity of induction therapy in Spain: changing patterns according to year, centre, indications and results

Background. The use of induction drugs has increased markedly over the last 15 years in the USA, but there are few data about their use in other countries. Moreover, there are not enough data about when they are indicated and their long-term effects. The aim of our study was to know the rates of use and the drugs used as induction therapy, in which patients they were prescribed and the long-term graft survival effect in Spain. Methods. We conducted a retrospective cohort study with adult patients (4861) receiving a kidney allograft in Spain over four different years (1990, 1994, 1998 and 2002) with a functioning graft at the end of the first post-transplant year. Induction therapy was defined as when the patient received polyclonal antibodies, OKT3 monoclonal antibodies or anti-CD25 monoclonal antibodies. Results. From 1990 to 2002, the use of induction therapy in Spain changed, with a progressive reduction in the use of OKT3 and an increasing use of anti-CD25 antibodies. There were great differences in the rate of induction use from one centre to another, although with a common trend to greater use at each centre. Induction therapy was mainly prescribed in patients with a higher rejection risk (higher panel reactive antibody (PRA) titres and mismatches and re-transplants) and in older and diabetic recipients. Lastly, patients who were treated with induction therapy had significant higher allograft survival than those who did not (P value = 0.035). Conclusions. The use of induction therapy in Spain has changed, with an increasing use of monoclonal antibodies in recent years. Induction therapy has a protective role in long-term graft survival.

Apolipoprotein A-Ib as Biomarker of FSGS Recurrence After Kidney Transplantation: Diagnostic Performance in a Prospective Cohort and Assessment of its Prognostic Value

Grupo Español de actualización en Transplante (GREAT). Background Recurrence of idiopathic FSGS is a serious complication after kidney transplantation. Currently, there are no accurate means to diagnose the relapses or to detect the patients at risk. In a previous study we detected Apolipoprotein A-Ib (ApoA-Ib) specifically in urine of kidney transplanted patients that showed recurrence of FSGS. In the present work we aim to confirm the diagnostic performance of ApoA-Ib to detect FSGS recurrence and assess its possible prognostic value. Methods Between January 2013 and December 2015 a urine sample was obtained in three groups of kidney transplant patients treated at the nephrology department of 16 major Spanish hospitals: FSGS patients that relapsed after kidney transplantation (FSGS-R), FSGS patients that did not show recurrence after kidney transplantation (FSGS-NR) and non-FSGS kidney transplanted patients (No-FSGS). ApoA-Ib was determined in the urine of these patients by immunodetection. To assess the ApoA-Ib predictive ability of detecting patients at risk of relapse, 33 patients with idiopatic FSGS were included before transplantation. Thirteen of them were transplanted and followed up to 1 year after transplantation. In these patients ApoA-Ib was periodically determined. Results In the FSGS-R group 14 out of 15 (93.3 %) were positive for apoA-Ib whereas only 2 out of 22 (9.1 %) in the FSGS-NR group and 3 out of 24 (12.5 %) in the No-FSGS group tested positive for ApoA-Ib (P value < 0.001). ApoA-Ib sensitivity and specificity to detect FSGS recurrence were 94.1% and 90.9% to discriminate non-relapsing FSGS patients or 94.1% and 87.5% to discriminate transplanted patients without FSGS as the primary disease. These results were consistent with the obtained in our previous cohort of FSGS patients. The presence of ApoA-Ib in urine was only related to FSGS recurrence and was independent of proteinuria levels or renal function. ApoA-Ib was present in 37.9 % of the FSGS patients before transplantation which is similar to the FSGS recurrence incidence after transplantation (30-50 %). Four of the 13 followed patients showed FSGS recurrence. ApoA-Ib predated FSGS relapse in 4 out of 5 recurrence episodes observed in 4 patients, while in 9 patients who did not relapse ApoA-Ib was negative in 37 out of 38 samples. Conclusions ApoA-Ib has the potential to be a good complementary diagnostic biomarker of FSGS relapses after transplantation, providing a confident exclusion of relapse even in the presence of high proteinuria. It has also a potential to detect patients at risk of relapse, even before transplantation, which should be further evaluated in a larger cohort. The authors thank Oreto Prat, Estefanía Lozano and Anna Caraben for their technical assistance. Grupo Español de Actualización en Trasplante (GREAT, Spanish Group for New Projects in Transplantation): Carme Cantarell (Hospital Vall d’Hebron, Barcelona), Lluis Guirado (Fundació Puigvert, Barcelona), Francisco Gonzalez Roncero (Hospital Virgen del Rocio, Sevilla), Juan C. Ruiz San Millan (Hospital Marqués de Valdecilla, Santander) Carlos Jiménez (Hospital Universitario La Paz, Madrid), Isabel Beneyto (Hospital La Fe, Valencia), Sofia Zárraga (Hospital de Cruces, Barakaldo), Javier Paul (Hospital Miguel Servet, Zaragoza), Vicenç Torregrosa (Hospital Clínic, Barcelona), Ricardo Lauzurica (Hospital Germans Trias i Pujol, Badalona), Angel Alonso (Hospital de A Coruña, A Coruña), Carmen Díaz (Hospital Central de Asturias, Oviedo), Ana Fernández (Hospital Ramón y Cajal, Madrid), Auxiliadora Mazuecos (Hospital Puerta del Mar, Cadiz), Domingo Hernández (Hospital Carlos Haya, Malaga), Alberto Rodriguez (Hospital Reina Sofia, Cordoba), Antonio Osuna (Hospital Virgen de las Nieves, Granada), Antonio Franco (Hospital General, Alicante), Luisa Jimeno (Hospital Virgen de la Arrixaca, Murcia), Marta Crespo (Hospital del Mar, Barcelona).

Hepatitis C Virus Infection in Kidney Transplant Recipients: Final Results from a Spanish Multicenter Study

Grupo Español De Actualizacion En Trasplante. Background HCV is a relevant negative prognosis factor for graft and transplant recipient survival.New direct-acting antivirals(DAA)allow us to solve this problem in an effective way.It is crucial to know their real impact in our daily practice. Methods Observational,retrospective and prospective study.We analyze treatment results with DAA,in kidney transplant(KT)recipients from 15 hospitals,regarding effectiveness,tolerance and impact on immunosuppression and renal function-proteinuria in a short-medium term. Results Until November 2017,226 KT recipients were included (9combined liver- kidney transplants).69.7%male; average age 54.2±9yo;KT length 11.4±10years. More than 50%showed stage 3-4 chronic kidney disease. Immunosuppressive therapies: tacrolimus(70%) or cyclosporine (18%) with MMF(76%). Predominant genotype was 1b(68.1%), 1a(13.8%),3(7.8 %), 4(6%) and 2(4.3%);51% had grade 3-4 of fibrosis, 17% portal hypertension. The main DAA used was sofosbuvir(91%)combined with ledipasvir(55%), simeprevir(14%)or daclatasvir(13%);in 9 cases(7%)the combination of paritaprevir-ritonavir-ombitasvir-dasabuvir(3D)was employed;18% were treated with Ribavirin as coadjuvant. Side effects were limited,23.5 %,and without relevance, except for anemia caused by Ribavirin.2 patients interrupted the treatment, due to neurotoxicity caused by the interaction between 3D and tacrolimus and anemia caused by Ribavirin (both had virological response).All the patients that completed the treatment (213)are alive and show virological response in 98% of cases and with SVR-12.Liver function analysis improved: 74%normal vs 21% before the treatment (p<0.001). Renal function did not change significantly. Tacrolimus level at the end was lower with respect to the beginning (6.6 vs 7.3 ng/ml, p=0.03), in spite of a slight increase in the dose (3.5 vs 2.6 mg/day p=0.01). Conclusions DAA are highly effective in KT patients, with good tolerance,making it possible to solve the problem and having a good chance to improve the prognosis in our patients.The use of DAA in these patients requires special control and coordination with hepatologists, especially when 3D or Ribavirin is used.