Apolipoprotein A-Ib as a biomarker of focal segmental glomerulosclerosis recurrence after kidney transplantation: diagnostic performance and assessment of its prognostic value - a multi-centre cohort study.

Recurrence of idiopathic focal segmental glomerulosclerosis (FSGS) is a serious complication after kidney transplantation. FSGS relapse is suspected by a sudden increase in proteinuria but there is not an accurate noninvasive diagnostic tool to confirm this entity or to detect patients at risk. We aimed to validate the diagnostic performance of ApoA-Ib to detect FSGS relapses by measuring urinary ApoA-Ib in a retrospective cohort of 61 kidney transplanted patients (37 FSGS and 24 non-FSGS). In addition, to assess the ApoA-Ib predictive ability, ApoA-Ib was measured periodically in a prospective cohort of 13 idiopathic FSGS patients who were followed during 1 year after transplantation. ApoA-Ib had a sensitivity of 93.3% and a specificity of 90.9% to diagnose FSGS relapses, with a high negative predictive value (95.2%), confirming our previous results. In the prospective cohort, ApoA-Ib predated the recurrence in four of five episodes observed. In the nonrelapsing group (n = 9), ApoA-Ib was negative in 37 of 38 samples. ApoA-Ib has the potential to be a good diagnostic biomarker of FSGS relapses, providing a confident criterion to exclude false positives even in the presence of high proteinuria. It has also the potential to detect patients at risk of relapse, even before transplantation.

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.

Cirrhosis, liver transplantation and HIV infection are risk factors associated with hepatitis E virus infection.

BACKGROUND: Acute and chronic hepatitis E have been associated with high mortality and development of cirrhosis, particularly in solid-organ recipients and patients infected by human immunodeficiency virus. However, data regarding the epidemiology of hepatitis E in special populations is still limited. AIMS: Investigate seroprevalence and possible factors associated with HEV infection in a large cohort of immunosuppressed patients. METHODS: Cross-sectional study testing IgG anti-HEV in serum samples from 1373 consecutive individuals: 332 liver-transplant, 296 kidney-transplant, 6 dual organ recipients, 301 non-transplanted patients with chronic liver disease, 238 HIV-infected patients and 200 healthy controls. RESULTS: IgG anti-HEV was detected in 3.5% controls, 3.7% kidney recipients, 7.4% liver transplant without cirrhosis and 32.1% patients who developed post-transplant cirrhosis (p<0.01). In patients with chronic liver disease, IgG anti-HEV was also statistically higher in those with liver cirrhosis (2% vs 17.5%, p<0.01). HIV-infected patients showed an IgG anti-HEV rate of 9.2%, higher than those patients without HIV infection (p<0.03). Multivariate analysis showed that the factors independently associated with anti-HEV detection were liver cirrhosis, liver transplantation and HIV infection (OR: 7.6, 3.1 and 2.4). HCV infection was a protective factor for HEV infection (OR: 0.4). CONCLUSIONS: HEV seroprevalence was high in liver transplant recipients, particularly those with liver cirrhosis. The difference in anti-HEV prevalence between Liver and Kidney transplanted cases suggests an association with advanced liver disease. Further research is needed to ascertain whether cirrhosis is a predisposing factor for HEV infection or whether HEV infection may play a role in the pathogeneses of cirrhosis.

Late evolution of kidney transplants in elderly donors and recipients receiving initial immunosuppressant treatment with daclizumab, mycophenolate mofetil, and delayed introduction of tacrolimus.

BACKGROUND: Organ transplants in elderly recipients have increased over the past few years. This situation poses specific problems both in terms of organs and recipients; therefore, immunosuppressant regimens must be adapted accordingly. A previous study demonstrated good initial results in kidney transplant cases in which older donors and recipients (average ages of 64.4 years and 61.3 years) had received initial immunosuppressant therapy with daclizumab and mycophenolate mofetil as well as delayed introduction of reduced-dose tacrolimus. In this study we reviewed the long-term results in the same group of patients. METHODS: An observational, retrospective multi-centre study carried out at a national level to determine survival rates and renal function in 126 patients included in the initial study (127 patients who survived the first year with a functioning graft, 123 treated according to protocol). We gathered data from the 2nd to the 6th year for 120, 118, 113, 102 and 62 patients, respectively. The evolution of renal function, relevant clinical data, and safety profiles were also analysed. RESULTS: After five years, most patients continued with the initial immunosuppressant regimen: 92% tacrolimus and 80% mycophenolate mofetil; 48% had abandoned steroids and proliferation signal inhibitors had been introduced in 3%. Patient and graft survival (adjusted for patient death) after five years was 93.1% and 93.8%, respectively. The main cause of death was neoplasia (in 7 out of 10 cases) whilst graft loss was mainly due to death with a functioning graft. The other causes of death were 2 acute myocardial infarctions and a gastrointestinal haemorrhage. Renal function was moderately but significantly reduced with the passing of time (P<.001): average creatinine levels in the overall group of patients rose from 1.60 ± 0.50mg/dl after the 1st year to 1.63 ± 0.70 mg/dl at the end of study. MDRD dropped from 46.28 ± 15.64 ml/min after the 1st year to 45.69 ± 15.44 ml/min at the end of study (P<.01). Only two acute rejections were observed after the 1st year. There were 19 cardiovascular events registered in 12 patients. CONCLUSIONS: The regimen used in our study was useful and appropriate for elderly donor-recipient pairs as demonstrated by the good long-term survival results, continued optimum renal function, and acceptable safety profile.

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.

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 m) 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.