Management of immunosuppressive therapy in kidney transplant recipients with COVID-19. A multicentre national study derived from the Spanish Society of Nephrology COVID registry.

INTRODUCTION: SARS CoV2 infection has had a major impact on renal transplant patients with a high mortality in the first months of the pandemic. Intentional reduction of immunosuppressive therapy has been postulated as one of the cornerstone in the management of the infection in the absence of targeted antiviral treatment. This has been modified according to the patient`s clinical situation and its effect on renal function or anti-HLA antibodies in the medium term has not been evaluated. OBJECTIVES: Evaluate the management of immunosuppressive therapy made during SARS-CoV2 infection, as well as renal function and anti-HLA antibodies in kidney transplant patients 6 months after COVID19 diagnosis. MATERIAL AND METHODS: Retrospective, national multicentre, retrospective study (30 centres) of kidney transplant recipients with COVID19 from 01/02/20 to 31/12/20. Clinical variables were collected from medical records and included in an anonymised database. SPSS statistical software was used for data analysis. RESULTS: renal transplant recipients with COVID19 were included (62.6% male), with a mean age of 57.5 years. The predominant immunosuppressive treatment prior to COVID19 was triple therapy with prednisone, tacrolimus and mycophenolic acid (54.6%) followed by m-TOR inhibitor regimens (18.6%). After diagnosis of infection, mycophenolic acid was discontinued in 73.8% of patients, m-TOR inhibitor in 41.4%, tacrolimus in 10.5% and cyclosporin A in 10%. In turn, 26.9% received dexamethasone and 50.9% were started on or had their baseline prednisone dose increased. Mean creatinine before diagnosis of COVID19, at diagnosis and at 6 months was: 1.7 ±â€¯0.8, 2.1 ±â€¯1.2 and 1.8 ±â€¯1 mg/dl respectively (p < 0.001). 56.9% of the patients (N = 350) were monitored for anti-HLA antibodies. 94% (N = 329) had no anti-HLA changes, while 6% (N = 21) had positive anti-HLA antibodies. Among the patients with donor-specific antibodies post-COVID19 (N = 9), 7 patients (3.1%) had one immunosuppressant discontinued (5 patients had mycophenolic acid and 2 had tacrolimus), 1 patient had both immunosuppressants discontinued (3.4%) and 1 patient had no change in immunosuppression (1.1%), these differences were not significant. CONCLUSIONS: The management of immunosuppressive therapy after diagnosis of COVID19 was primarily based on discontinuation of mycophenolic acid with very discrete reductions or discontinuations of calcineurin inhibitors. This immunosuppression management did not influence renal function or changes in anti-HLA antibodies 6 months after diagnosis.

Outcome of Kidney Transplants from Viremic and Non-Viremic Hepatitis C Virus Positive Donors into Negative Recipients: Results of the Spanish Registry.

Historically, donor infection with hepatitis-C virus (HCV) has been a barrier to kidney transplantation. However, in recent years, it has been reported that HCV positive kidney donors transplanted into HCV negative recipients offer acceptable mid-term results. However, acceptance of HCV donors, especially viremic, has not broadened in the clinical practice. This is an observational, multicenter, retrospective study including kidney transplants from HCV positive donors into negative recipients reported to the Spanish group from 2013 to 2021. Recipients from viremic donors received peri-transplant treatment with direct antiviral agents (DAA) for 8-12 weeks. We included 75 recipients from 44 HCV non-viremic donors and 41 from 25 HCV viremic donors. Primary non function, delayed graft function, acute rejection rate, renal function at the end of follow up, and patient and graft survival were not different between groups. Viral replication was not detected in recipients from non-viremic donors. Recipient treatment with DAA started pre-transplant avoids (n = 21) or attenuates (n = 5) viral replication but leads to non-different outcomes to post-transplant treatment with DAA (n = 15). HCV seroconversion was more frequent in recipients from viremic donors (73% vs. 16%, p < 0.001). One recipient of a viremic donor died due to hepatocellular carcinoma at 38 months. Donor HCV viremia seems not to be a risk factor for kidney transplant recipients receiving peri-transplant DAA, but continuous surveillance should be advised.

Recurrence of immune complex and complement-mediated membranoproliferative glomerulonephritis in kidney transplantation.

INTRODUCTION: Membranoproliferative glomerulonephritis (MPGN) represents a histologic pattern of glomerular injury that may be due to several aetiologies. Few studies have comprehensively analysed the recurrence of MPGN according to the current classification system. METHODS: We collected a multicentre, retrospective cohort of 220 kidney graft recipients with biopsy-proven native kidney disease due to MPGN between 1981 and 2021 in 11 hospitals. Demographic, clinical and histologic parameters of prognostic interest were collected. The main outcomes were time to kidney failure, time to recurrence of MPGN and disease remission after recurrence. RESULTS: The study group included 34 complement-mediated and 186 immune complex-mediated MPGN. A total of 81 patients (37%) reached kidney failure in a median follow-up of 79 months. The main predictors of this event were the development of rejection episodes and disease recurrence. In all, 54 patients (25%) had a disease recurrence in a median of 16 months after kidney transplantation. The incidence of recurrence was higher in patients with dysproteinaemia (67%) and complement-mediated MPGN (62%). In the multivariable model, complement-mediated MPGN emerged as a predictor of recurrence. A total of 33 patients reached kidney failure after recurrence. The main determinants of no remission were early time to recurrence (<15 months), estimated glomerular filtration rate <30 mL/min/1.73 m2 and serum albumin <3.5 g/dL at the time of recurrence. CONCLUSIONS: One-fourth of the patients with native kidney disease due to MPGN developed clinical recurrence in the allograft, especially in cases with complement-mediated disease or in those associated with dysproteinaemia. The kidney outcomes of disease recurrence with currently available therapies are heterogeneous and thus more effective and individualized therapies are needed.

[Management of immunosuppressive therapy in kidney transplant recipients with COVID19. A multicentre national study derived form the S.E.N. COVID registry.] / Manejo de la inmunosupresión en pacientes trasplantados de riñón con COVID19. Estudio multicéntrico nacional derivado del registro COVID de la S.E.N.

INTRODUCTION: SARS CoV2 infection has had a major impact on renal transplant patients with a high mortality in the first months of the pandemic. Intentional reduction of immunosuppressive therapy has been postulated as one of the cornerstone in the management of the infection in the absence of targeted antiviral treatment. This has been modified according to the patient`s clinical situation and its effect on renal function or anti-HLA antibodies in the medium term has not been evaluated. OBJECTIVES: Evaluate the management of immunosuppressive therapy made during SARS-CoV2 infection, as well as renal function and anti-HLA antibodies in kidney transplant patients 6 months after COVID19 diagnosis. MATERIAL AND METHODS: Retrospective, national multicentre, retrospective study (30 centres) of kidney transplant recipients with COVID19 from 01/02/20 to 31/12/20. Clinical variables were collected from medical records and included in an anonymised database. SPSS statistical software was used for data analysis. RESULTS: 615 renal transplant recipients with COVID19 were included (62.6% male), with a mean age of 57.5 years.The predominant immunosuppressive treatment prior to COVID19 was triple therapy with prednisone, tacrolimus and mycophenolic acid (54.6%) followed by m-TOR inhibitor regimens (18.6%). After diagnosis of infection, mycophenolic acid was discontinued in 73.8% of patients, m-TOR inhibitor in 41.4%, tacrolimus in 10.5% and cyclosporin A in 10%. In turn, 26.9% received dexamethasone and 50.9% were started on or had their baseline prednisone dose increased.Mean creatinine before diagnosis of COVID19, at diagnosis and at 6 months was: 1.7±0.8, 2.1±1.2 and 1.8±1 mg/dl respectively (p<0.001).56.9% of the patients (N=350) were monitored for anti-HLA antibodies. 94% (N=329) had no anti-HLA changes, while 6% (N=21) had positive anti-HLA antibodies. Among the patients with donor-specific antibodies post-COVID19 (N=9), 7 patients (3.1%) had one immunosuppressant discontinued (5 patients had mycophenolic acid and 2 had tacrolimus), 1 patient had both immunosuppressants discontinued (3.4%) and 1 patient had no change in immunosuppression (1.1%), these differences were not significant. CONCLUSIONS: The management of immunosuppressive therapy after diagnosis of COVID19 was primarily based on discontinuation of mycophenolic acid with very discrete reductions or discontinuations of calcineurin inhibitors. This immunosuppression management did not influence renal function or changes in anti-HLA antibodies 6 months after diagnosis.

Breakthrough Infections Following mRNA SARS-CoV-2 Vaccination in Kidney Transplant Recipients.

BACKGROUND: The clinical effectiveness of coronavirus disease 2019 (COVID-19) vaccination in kidney transplant (KT) recipients is lower than in the general population. METHODS: From April to October 2021, 481 KT recipients with COVID-19, included in the Spanish Society of Nephrology COVID-19 Registry, were analyzed. Data regarding vaccination status and vaccine type were collected, and outcomes of unvaccinated or partially vaccinated patients (n = 130) were compared with fully vaccinated patients (n = 351). RESULTS: Clinical picture was similar and survival analysis showed no differences between groups: 21.7% of fully vaccinated patients and 20.8% of unvaccinated or partially vaccinated died (P = 0.776). In multivariable analysis, age and pneumonia were independent risk factors for death, whereas vaccination status was not related to mortality. These results remained similar when we excluded patients with partial vaccination, as well as when we analyzed exclusively hospitalized patients. Patients vaccinated with mRNA-1273 (n = 213) showed a significantly lower mortality than those who received the BNT162b2 vaccine (n = 121) (hazard ratio: 0.52; 95% confidence interval, 0.31-0.85; P = 0.010). CONCLUSIONS: COVID-19 severity in KT patients has remained high and has not improved despite receiving 2 doses of the mRNA vaccine. The mRNA-1273 vaccine shows higher clinical effectiveness than BNT162b2 in KT recipients with breakthrough infections. Confirmation of these data will require further research taking into account the new variants and the administration of successive vaccine doses.

Use and Safety of Remdesivir in Kidney Transplant Recipients With COVID-19.

INTRODUCTION: Remdesivir has demonstrated antiviral activity against coronavirus, shortening the time to recovery in adults hospitalized with moderate/severe COVID-19. Severe adverse events such as acute kidney injury have been reported. Scant data are available on the use and safety of remdesivir in kidney transplant recipients. METHODS: We present a multicenter cohort study of 51 kidney transplant recipients with COVID-19 treated with remdesivir. Outcomes and safety were assessed. RESULTS: Mean age at diagnosis was 60 years, with a median time since kidney transplant of 4.5 years. Mean time since admission to remdesivir was 2 days. Twenty-eight patients (54.9%) required mechanical ventilation (19 noninvasive). Mortality was 18.9% and markedly higher if aged ≥65 years (45% vs. 3.2% in younger patients). Acute kidney injury was present in 27.7% of patients, but was diagnosed in 50% before treatment. No patients required remdesivir discontinuation because of adverse events. We did not find significant hepatoxicity or systemic symptoms resulting from the drug. CONCLUSION: In our cohort of kidney transplant recipients, remdesivir was well tolerated and safe in renal and hepatic toxicity, but randomized trials are needed to assess its efficacy.

COVID-19 in transplant recipients: The Spanish experience.

We report the nationwide experience with solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients diagnosed with coronavirus disease 2019 (COVID-19) in Spain until 13 July 2020. We compiled information for 778 (423 kidney, 113 HSCT, 110 liver, 69 heart, 54 lung, 8 pancreas, 1 multivisceral) recipients. Median age at diagnosis was 61 years (interquartile range [IQR]: 52-70), and 66% were male. The incidence of COVID-19 in SOT recipients was two-fold higher compared to the Spanish general population. The median interval from transplantation was 59 months (IQR: 18-131). Infection was hospital-acquired in 13% of cases. No donor-derived COVID-19 was suspected. Most patients (89%) were admitted to the hospital. Therapies included hydroxychloroquine (84%), azithromycin (53%), protease inhibitors (37%), and interferon-ß (5%), whereas immunomodulation was based on corticosteroids (41%) and tocilizumab (21%). Adjustment of immunosuppression was performed in 85% of patients. At the time of analysis, complete follow-up was available from 652 patients. Acute respiratory distress syndrome occurred in 35% of patients. Ultimately, 174 (27%) patients died. In univariate analysis, risk factors for death were lung transplantation (odds ratio [OR]: 2.5; 95% CI: 1.4-4.6), age >60 years (OR: 3.7; 95% CI: 2.5-5.5), and hospital-acquired COVID-19 (OR: 3.0; 95% CI: 1.9-4.9).

The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy.

A cyclical corticosteroid-cyclophosphamide regimen is recommended for patients with primary membranous nephropathy at high risk of progression. We hypothesized that sequential therapy with tacrolimus and rituximab is superior to cyclical alternating treatment with corticosteroids and cyclophosphamide in inducing persistent remission in these patients. This was tested in a randomized, open-label controlled trial of 86 patients with primary membranous nephropathy and persistent nephrotic syndrome after six-months observation and assigned 43 each to receive six-month cyclical treatment with corticosteroid and cyclophosphamide or sequential treatment with tacrolimus (full-dose for six months and tapering for another three months) and rituximab (one gram at month six). The primary outcome was complete or partial remission of nephrotic syndrome at 24 months. This composite outcome occurred in 36 patients (83.7%) in the corticosteroid-cyclophosphamide group and in 25 patients (58.1%) in the tacrolimus-rituximab group (relative risk 1.44; 95% confidence interval 1.08 to 1.92). Complete remission at 24 months occurred in 26 patients (60%) in the corticosteroid-cyclophosphamide group and in 11 patients (26%) in the tacrolimus-rituximab group (2.36; 1.34 to 4.16). Anti-PLA2R titers showed a significant decrease in both groups but the proportion of anti-PLA2R-positive patients who achieved immunological response (depletion of anti-PLA2R antibodies) was significantly higher at three and six months in the corticosteroid-cyclophosphamide group (77% and 92%, respectively), as compared to the tacrolimus-rituximab group (45% and 70%, respectively). Relapses occurred in one patient in the corticosteroid-cyclophosphamide group, and three patients in the tacrolimus-rituximab group. Serious adverse events were similar in both groups. Thus, treatment with corticosteroid-cyclophosphamide induced remission in a significantly greater number of patients with primary membranous nephropathy than tacrolimus-rituximab.

Use of tocilizumab in kidney transplant recipients with COVID-19.

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin-6 (IL-6) release. The IL-6-receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID-19) . In this pandemic, kidney transplant (KT) recipients are a high-risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID-19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL-6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D-dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C-reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004-1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID-19 but randomized trials are needed.

Duration of Treatment with Corticosteroids and Recovery of Kidney Function in Acute Interstitial Nephritis.

BACKGROUND AND OBJECTIVES: Drug-induced acute interstitial nephritis represents an emerging cause of acute kidney disease, especially among polymedicated elderly patients. Although corticosteroids are frequently used, controversy exists about the timing of initiation, efficacy, safety, and duration of treatment. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective study of 182 patients with biopsy-proven drug-induced acute interstitial nephritis from 13 Spanish centers. Exposure was defined as the length of corticosteroid treatment. The main outcome was the level of serum creatinine at month 6, with respect to baseline values. RESULTS: The most common offending agents were nonsteroidal anti-inflammatory drugs (27%). In 30% of patients, the offending drug could not be identified. The median time to suspected drug withdrawal was 11 days (interquartile range, 5-22). All patients presented with acute kidney disease and were treated with corticosteroids. The mean initial dose of prednisone was 0.8±0.2 mg/kg per day. High-dose corticosteroid treatment was maintained for 2 weeks (interquartile range, 1-4). After 6 months, the mean recovered GFR was 34±26 ml/min per 1.73 m2 and ten patients required maintenance dialysis. Use of high-dose corticosteroids for 3 weeks or treatment duration >8 weeks were not associated with better recovery of kidney function. In the multivariable analysis, delayed onset of steroid treatment (odds ratio, 1.02; 95% confidence interval, 1.0 to 1.04) and the presence of interstitial fibrosis of >50% on the kidney biopsy specimen (odds ratio, 8.7; 95% confidence interval, 2.7 to 27.4) were both associated with serum creatinine level at month 6 of >75%, with respect to baseline values. CONCLUSIONS: High-dose corticosteroid treatment for 3 weeks or prolonged treatment for >8 weeks were not associated with greater kidney function recovery in drug-induced acute interstitial nephritis. A delay in the initiation of corticosteroids resulted in worse recovery of kidney function.

Arteriovenous fistulae after renal biopsy: diagnosis and outcomes using Doppler ultrasound assessment.

BACKGROUND: Percutaneous renal biopsy (PRB) is an important technique providing relevant information to guide diagnosis and treatment in renal disease. As an invasive procedure it has complications. Most studies up to date have analysed complications related to bleeding. We report the largest single-center experience on routine Doppler ultrasound (US) assessment post PRB, showing incidence and natural history of arteriovenous fistulae (AVF) post PRB. METHODS: We retrospectively analysed 327 consecutive adult PRB performed at Ramon Cajal University Hospital between January 2011 and December 2014. All biopsies were done under real-time US guidance by a trained nephrologist. Routine Doppler mapping and kidney US was done within 24 h post biopsy regardless of symptoms. Comorbidities, full blood count, clotting, bleeding time and blood pressure were recorded at the time of biopsy. Post biopsy protocol included vitals and urine void checked visually for haematuria. Logistic regression was used to investigate links between AVF, needle size, correcting for potential confounding variables. RESULTS: 46,5% were kidney transplants and 53,5% were native biopsies. Diagnostic material was obtained in 90,5% (142 grafts and 154 native). Forty-seven AVF's (14.37%) were identified with routine kidney Doppler mapping, 95% asymptomatic (n = 45), 28 in grafts (18.4%) and 17 natives (9.7%) (p-value 0.7). Both groups were comparable in terms of comorbidities, passes, cylinders or biopsy yield (p-value NS). 80% were <1 cm in size and 46.6% closed spontaneously in less than 30 days (range 3-151). Larger AVF's (1-2 cm) took a mean of 52 days to closure (range 13-151). Needle size was not statistically significant factor for AVF (p-value 0.71). CONCLUSIONS: Contrary to historical data published, AVF's are a common complication post PRB that can be easily missed. Routine US Doppler mapping performed by trained staff is a cost-effective, non-invasive tool to diagnose and follow up AVF's, helping to assess management.

Anti-neutrophil cytoplasmic antibody-associated vasculitis with renal involvement: Analysis of 89 cases. / Vasculitis asociada a anticuerpos contra el citoplasma de neutrófilo con afectación renal: análisis de 89 casos.

INTRODUCTION: The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with renal involvement are associated with high morbi-mortality. In this study we analyse if the prognosis of these diseases have improved in recent years, and which factors influence the outcomes. MATERIAL AND METHODS: Retrospective single-centre observational study, which included all patients diagnosed with microscopic polyangiitis and granulomatosis with polyangiitis with renal involvement in the last 25 years. Demographic, clinical and biochemical parameters of prognostic interest were recorded. The differences between four chronological periods were analysed, along with the determinants of a poor outcome (death or end-stage renal disease). RESULTS: Eighty-nine patients were included (mean age 64±15 years). Sixty-four patients (72%) had microscopic polyangiitis and 25 (28%) granulomatosis with polyangiitis. During the study period, 37 (42%) patients died. Through Cox regression analysis, the best determinants of mortality were the initial glomerular filtration rate (HR 0.911; P=.003), Charlson comorbidity index (HR 1.513; P<.0001) and tobacco smoking (HR 1.816; P=.003). 35% developed end-stage renal disease, and the best determinants (by competing-risk regression) were: initial glomerular filtration rate (sub-hazard ratio [SHR]: 0.791; P<.0001), proteinuria (SHR: 1.313; P<.0001), and smoking status (SHR: 1.848; P=.023). No differences were found in patients' mortality or renal survival between the different study periods. CONCLUSIONS: Prognosis of anti-neutrophil cytoplasm antibodies vasculitis with renal involvement treated with conventional immunosuppressive therapy remains unsatisfactory, and continues to have increased long-term complications and mortality.

Vasculitis asociada a anticuerpos contra el citoplasma de neutrófilo con afectación renal: análisis de 89 casos / Anti-neutrophil cytoplasmic antibody-associated vasculitis with renal involvement: Analysis of 89 cases

Introducción: Las vasculitis con anticuerpos contra el citoplasma de neutrófilo con afectación renal se asocian con una elevada morbimortalidad. En este estudio se analiza si el pronóstico de estas vasculitis ha mejorado en los últimos años, y cuáles son los factores que condicionan su evolución. Material y métodos: Estudio retrospectivo de observación que incluyó a pacientes con poliangitis microscópica y granulomatosis con poliangitis con afectación renal diagnosticados en nuestro hospital durante los últimos 25 años. Se recogieron los parámetros demográficos, clínicos y bioquímicos de interés pronóstico, y se analizaron las diferencias según 4 períodos cronológicos, así como los determinantes de una peor evolución (muerte o insuficiencia renal terminal). Resultados: Se incluyeron 89 pacientes (edad media 64 ± 15 años). Sesenta y cuatro pacientes (72%) presentaban poliangitis microscópica y 25 (28%) granulomatosis con poliangitis. Durante el período de estudio, 37 (42%) pacientes fallecieron. Mediante análisis de regresión de Cox, los determinantes de mortalidad fueron el filtrado glomerular basal (HR 0,911; p = 0,003), índice de Charlson (HR 1,513; p < 0,0001) y exposición al tabaco (HR 1,816; p = 0,003). El 35% desarrolló insuficiencia renal terminal. Los mejores determinantes de este acontecimiento (en competencia de riesgo por muerte) fueron: filtrado glomerular basal (sub-hazard ratio [SHR]: 0,791; p < 0,0001), proteinuria (SHR: 1,313; p < 0,0001), y hábito tabaco (SHR: 1,848; p = 0,023). No se observaron diferencias en la supervivencia total o renal en los diferentes períodos estudiados. Conclusiones: El pronóstico de las vasculitis con anticuerpos contra el citoplasma de neutrófilo con afectación renal y tratamiento inmunosupresor convencional sigue siendo desfavorable, asociándose con numerosas complicaciones y elevada mortalidad (AU)

Introduction: The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with renal involvement are associated with high morbi-mortality. In this study we analyse if the prognosis of these diseases have improved in recent years, and which factors influence the outcomes. Material and methods: Retrospective single-centre observational study, which included all patients diagnosed with microscopic polyangiitis and granulomatosis with polyangiitis with renal involvement in the last 25 years. Demographic, clinical and biochemical parameters of prognostic interest were recorded. The differences between four chronological periods were analysed, along with the determinants of a poor outcome (death or end-stage renal disease). Results: Eighty-nine patients were included (mean age 64 ± 15 years). Sixty-four patients (72%) had microscopic polyangiitis and 25 (28%) granulomatosis with polyangiitis.During the study period, 37 (42%) patients died. Through Cox regression analysis, the best determinants of mortality were the initial glomerular filtration rate (HR 0.911; P = .003), Charlson comorbidity index (HR 1.513; P < .0001) and tobacco smoking (HR 1.816; P = .003). 35% developed end-stage renal disease, and the best determinants (by competing-risk regression) were: initial glomerular filtration rate (sub-hazard ratio [SHR]: 0.791; P < .0001), proteinuria (SHR: 1.313; P < .0001), and smoking status (SHR: 1.848; P = .023). No differences were found in patients’ mortality or renal survival between the different study periods. Conclusions: Prognosis of anti-neutrophil cytoplasm antibodies vasculitis with renal involvement treated with conventional immunosuppressive therapy remains unsatisfactory, and continues to have increased long-term complications and mortality (AU)

Bone fractures and lumbar mineral density after renal transplantation. A long-term cross-sectional study.

BACKGROUND: The purpose of this work was to investigate the association of vertebral and peripheral fractures 10 yr after grafting with bone metabolic markers and body mass density (BMD). PATIENTS AND METHODS: One hundred thirty-eight recipients with stable graft function were included in a cross-sectional study. Graft function, biochemical mineral metabolism markers and body mass density (DEXA) were measured. Vertebral fractures were assessed by a semiquantitative analysis of lateral spine X-ray exam. RESULTS: At the time of the study, intact parathyroid hormone levels were 127.5 ± 78.4 pg/mL and serum calcidiol 20.4 ± 9.3 ng/mL. DEXA showed osteopenia in 47% and osteoporosis in 23% at lumbar spine, 51% and 14% at femoral neck, and 53% and 8% at trochanter. Eighty-five recipients presented vertebral fractures, 69 mild and 16 moderate/severe fractures. In the multivariate analysis, vertebral fractures were associated with older age (p = 0.010), length of follow-up (p = 0.022) and trochanter T-score (p = 0.038). Twenty-three patients presented peripheral fractures and 19 of them also had vertebral fractures. Patients with peripheral fractures were younger, mostly women and had lower BMD. CONCLUSIONS: Vertebral fractures were associated with lower BMD at trochanter. Most fractures were mild and were several times more frequent than in general population. Their clinical significance needs to be determined.

The impact of darbepoetin alfa in early post-transplant anaemia management: retrospective exploratory study.

BACKGROUND AND OBJECTIVES: The use of darbepoetin alfa in the first week of post-renal transplant (RT). METHODS: Retrospective observational study carried out in four hospitals, which included all adult patients that underwent RT for 9 months with haemoglobin data during the first 6 months of post-transplant (n=129). Darbepoetin alfa was administered in accordance with the clinical practice. RESULTS: Darbepoetin alfa was administered in the first week to 60 individuals (46.5%), who had a mean baseline Hb (± standard deviation) of 12.7 g/dl ± 1.6g/dl. Anaemia incidence (Hb<11 g/dl) during the first month was higher in patients who did not receive darbepoetin alfa (40.6% vs. 25.0% in patients treated with darbepoetin alfa, P=.045). No anaemia incidence differences were observed during months +2 to +6. There was a tendency towards transfusion decrease in patients who received darbepoetin alfa (13.3% vs. 20.3%, P=.295). Renal recovery time was similar but in the subgroup which received grafts from donors with asystole there was a tendency towards a faster recovery with darbepoetin alfa (15.1 ± 7.7 vs. 20.1 ± 8.8 days, P=.157). The creatinine clearance rate at 3 and 6 months was similar. Fourteen patients (10.9%) suffered from cardiovascular events with no relation to darbepoetin alfa (P=.772). CONCLUSIONS: Administering darbepoetin alfa in the first week following renal transplant reduces anaemia incidence during the first month without increase cardiovascular events.

Impacto de darbepoetina alfa en el manejo de la anemia precoz postrasplante renal: estudio retrospectivo exploratorio / The impact of darbepoietin alfa in early post-transplant anaemia management: retrospective exploratory study

Antecedentes y objetivos: Se ha evaluado el uso de darbepoetina alfa en la primera semana postrasplante renal (TR). Métodos: Estudio observacional, retrospectivo, realizado en cuatro hospitales, que incluyó todos los pacientes adultos que fueron sometidos a TR durante un período de 9 meses con los datos de hemoglobina (Hb) durante los primeros 6 meses postrasplante (n = 129). Darbepoetina alfa fue administrada de acuerdo con la práctica clínica. Resultados: Se administró darbepoetina alfa en la primera semana a 60 individuos (46,5 %), los cuales presentaban una Hb media (± desviación estándar) basal de 12,7 ± 1,6 g/dl. La incidencia de anemia (Hb < 11 g/dl) durante el primer mes fue superior en los pacientes que no recibieron darbepoetina alfa (40,6 % vs. 25,0 % en los pacientes tratados, p = 0,045). No se observaron diferencias en la incidencia de la anemia entre los meses +2 a +6. Hubo una tendencia hacia la disminución de transfusiones en los pacientes que recibieron darbepoetina alfa (13,3 % vs. 20,3 %, p = 0,295). El tiempo de recuperación renal fue similar, pero, en el subgrupo que recibió injertos procedentes de donantes en asistolia, hubo una tendencia hacia una recuperación más rápida con darbepoetina alfa (15,1 ± 7,7 vs. 20,1 ± 8,8 días, p = 0,157). El aclaramiento de creatinina a los 3 y 6 meses fue similar. Catorce pacientes (10,9 %) sufrieron un evento cardiovascular, sin relación con darbepoetina alfa (p = 0,772). Conclusiones: La administración de la darbepoetina alfa en la primera semana tras el trasplante renal reduce la incidencia de anemia durante el primer mes, sin aumentar los eventos cardiovasculare (AU)

Background and objectives: The use of darbepoetin alfa in the first week of post-renal transplant (RT). Methods: Retrospective observational study carried out in four hospitals, which included all adult patients that underwent RT for 9 months with haemoglobin data during the first 6 months of post-transplant (n=129). Darbepoetin alfa was administered in accordance with the clinical practice. Results: Darbepoetin alfa was administered in the first week to 60 individuals (46.5%), who had a mean baseline Hb (±standard deviation) of 12.7g/dl±1.6g/dl. Anaemia incidence (Hb<11g/dl) during the first month was higher in patients who did not receive darbepoetin alfa (40.6% vs. 25.0% in patients treated with darbepoetin alfa, P=.045). No anaemia incidence differences were observed during months +2 to +6. There was a tendency towards transfusion decrease in patients who received darbepoetin alfa (13.3% vs. 20.3%, P=.295). Renal recovery time was similar but in the subgroup which received grafts from donors with asystole there was a tendency towards a faster recovery with darbepoetin alfa (15.1±7.7 vs. 20.1±8.8 days, P=.157). The creatinine clearance rate at 3 and 6 months was similar. Fourteen patients (10.9%) suffered from cardiovascular events with no relation to darbepoetin alfa (P=.772). Conclusions: Administering darbepoetin alfa in the first week following renal transplant reduces anaemia incidence during the first month without increase cardiovascular events (AU)

Are low levels of 25-hydroxyvitamin D a risk factor for cardiovascular diseases or malignancies in renal transplantation?

BACKGROUND: Observational studies in healthy people suggest an inverse relationship between 25-hydroxy-vitamin D (25(OH)D levels) and cardiovascular diseases and malignancies. We performed an observational prospective study in renal transplant recipients to investigate the effects of vitamin D deficiency on cardiovascular and malignancy risks. METHODS: From 389 renal transplant recipients, 331 with a functioning graft at 12 months were included in the study. Mineral metabolism parameters were measured at 1, 3, 4 and 12 months. Information regarding the cardiovascular events and malignancies were collected from an electronic database. RESULTS: According to the 1-year mean of 25(OH)D levels, 75 recipients (22.7%) had a normal vitamin D status, 161 (48.6%) had insufficiency and 95 (28.7%) had deficiency in vitamin D levels. During the follow-up, 80 recipients presented at least one cardiovascular event. The total cardiovascular diseases included: 27 patients with coronary diseases, 25 with cardiac failure, 18 with arrhythmia, 11 with acute cerebrovascular events and 19 with peripheral vascular disease. Cardiovascular events were not associated with 25(OH)D levels or vitamin D status, and the 10-year cumulative incidence was 29.3% for normal vitamin D status and 31.6% for insufficiency and 51.9% for deficiency (P = 0.216). Furthermore, Cox univariate analysis showed no association between cardiovascular events and vitamin D levels or vitamin D status. In addition, 53 recipients presented at least one malignancy: 33 non-melanoma skin malignancies and 20 non-skin malignancies (5 prostate, 3 kidney and urinary tract, 2 colon, 2 lung, 2 lymphoma, 2 breast and 4 from other locations). The cumulative incidence of malignancies was 21.3% for normal vitamin D status, 22.7% for insufficiency and 16.7% for deficiency (P = 0.818). CONCLUSIONS: Our data suggested that low vitamin D levels were not associated with an increased risk of cardiovascular diseases or malignancies. However, due to the small number of patients and events, the results should not be considered as definitive. Additional studies with a higher number of patients are required to elucidate the true impact of vitamin D status on cardiovascular and malignancy risks.

Very early steroid withdrawal or complete avoidance for kidney transplant recipients: a systematic review.

BACKGROUND: The safety and efficacy of early steroid withdrawal or avoidance in patients receiving a kidney transplant (KT) are controversial. METHODS: We performed a systematic review and a meta-analysis of the randomized controlled studies about steroid avoidance or withdrawal after a few days in patients receiving a KT and treated with antibody induction and cyclosporine (CsA) or tacrolimus (Tac) plus mycophenolate mofetil (MMF) (nine available studies and 1934 participants). RESULTS: Death and graft loss (including or excluding death with function) were similar in steroid avoidance and control patients, with no differences between CsA and Tac studies. After steroid avoidance, acute rejection was more frequent than conventional steroid use in CsA trials [risk ratios (RR) 1.59, 95% confidence intervals (95% CI) 1.01-2.49] but not when Tac was used (RR 1.06, 95% CI 0.79-1.42). Steroid avoidance was associated with less frequent new-onset diabetes mellitus, but this decrease was only evident with CsA (RR 0.54, 95% CI 0.30-0.98), whereas this difference was not significant analysing Tac studies (RR 0.75, 95% CI 0.32-1.77). Despite this trend, the corresponding interaction tests were not statistically significant (P = 0.140 and P = 0.535, for acute rejection and new-onset diabetes mellitus, respectively). Serum creatinine, creatinine clearance, mean blood pressure, serum cholesterol and serum triglycerides were similar in both groups. CONCLUSIONS: Steroid avoidance or early withdrawal within the first 2 weeks is safe in KT recipients receiving induction with anti-interleukin-2 receptor antibodies or thymoglobulin and a drug regimen based on calcineurin inhibitor and MMF. However, the real benefits remain unclear.

A retrospective study on outcome of microscopic polyangiitis in chronic renal replacement therapy.

BACKGROUND: Pauci-immune vasculitis is a heterogeneous disorder with an unfavourable prognosis. Renal involvement is frequently observed in antineutrophil cytoplasm autoantibody (ANCA)-associated small-vessel vasculitis and is an important cause of end-stage renal disease (ESRD). Renal replacement therapy (RRT) is frequently required. Although better prognosis under dialysis is well known, the long-term follow-up of pauci-immune renal vasculitis with RRT is rarely reported. METHODS: We described 24 patients with pauci-immune vasculitis and requirement of dialysis who were admitted in our institutions from January 1989 to December 2008. Mean age was 65 ± 12 years at the beginning of dialysis. There were 12 males and 12 females. Patients with Wegener's granulomatosis, Churg-Strauss syndrome or evidence of anti-glomerular basement membrane were excluded. The study group was formed by patients with a diagnosis of necrotizing extracapillary glomerulonephritis and microscopic polyangiitis. RESULTS: The distribution according to ANCAs was 14 p-ANCA (58%), 5 c-ANCA (21%) and 5 ANCA-negative (21%) pauci-immune renal vasculitis. Pulmonary renal syndrome (PRS) was observed in 10 patients at the onset of vasculitis. Corticosteroids and daily cyclophosphamide were administered to 18 patients, and one patient had intravenous cyclophosphamide. Five patients received isolated corticosteroid therapy. Early reduction in cyclophosphamide dosage was required in five patients due to leucopaenia. Mean follow-up after first dialysis was 89 ± 66 months (range 2-208). Twenty patients were included in haemodialysis (HD), and four patients were included in peritoneal dialysis (PD). At the end of the study, nine patients had received a cadaveric kidney transplant (KT). Relapses rate after the onset of dialysis was 0.03 episode/patient/year. PRS-associated relapses after beginning dialysis were observed in four patients. Main therapy in relapses was also corticosteroids and cyclophosphamide. Survival rates for year 1, 2 and 5 was 91%, 91% and 85%, respectively. Overall mortality at the end of the study was 31.8%. Five patients died in the PRS group, but only one death was associated with progressive pulmonary fibrosis. Higher mortality was observed in PRS vasculitis present at the onset of RRT (50% vs 16.7%, P = NS). Better outcome in patients who received a renal transplantation was observed (88.8% vs 53.8%, P = NS). Conclusions. Despite a low number of patients in this series, pauci-immune vasculitis prognosis under dialysis seems equal to other causes of chronic kidney disease. This study observed a low rate of relapses after beginning dialysis. Poor prognosis is related to severe complications at the beginning of RRT. Today, kidney transplantation is an important therapeutic option for these patients.