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- Fibrogenesis in Kidney Transplant: Dysfunction Progress BiomarkersPublication . Costa, J S; Alves, R; Sousa, V; Marinho, C; Romãozinho, C; Santos, L; Macário, F; Pratas, J; Prado E Castro, L; Campos, M; Figueiredo, AFibrogenesis markers, such as alpha-actin (AA), CD163 (macrophages), and E-cadherin, have been studied as chronic kidney allograft injury (CAI) predictors, a major cause of allograft failure. OBJECTIVE: Investigate the value of these markers in predicting CAI and initiation of dialysis. MATERIALS AND METHODS: Retrospective analysis of 26 kidney allograft biopsies (from 22 patients with CAI) during 2 years, evaluating intensity and percentage of marked cells on glomeruli and tubulointerstitial compartment. At the time of the biopsy, patients were 45.5 ± 15.8 years and 4.2 years after transplant, and they had a mean glomerular filtration rate (GFR) of 25.8 ± 9.9 mL/min. From an average of 8.5 glomeruli per biopsy, there was ≤25% sclerosis in 17 cases, 26% to 50% in 5, and >50% in 4. Interstitial fibrosis or tubular atrophy affected ≤25% of cortical area in 14 cases, 26% to 50% in 8, and >50% in 2. Twelve patients started dialysis 5.8 ± 4.7 years after transplant, with an average GFR 20.9 mL/min at the time of the biopsy. RESULTS: There was a higher intensity and percentage of CD163-marked cells in the tubulointerstitial compartment in advanced interstitial fibrosis. We found an association between intensity of AA in the tubulointerstitial compartment and initiation of dialysis (P = .003) and a negative correlation between intensity of E-cadherin loss and GFR (r = -0.56, P = .012). CONCLUSIONS: In our study, intensity of tubulointerstitial AA was shown to be a predictor of initiation of dialysis, and E-cadherin loss intensity was associated to CAI progression. However, prospective and larger studies are needed to evaluate the predictive value of these markers.
- Polyomavirus Nephropathy: Ten-Year ExperiencePublication . Costa, JS; Ferreira, E; Leal, R; Bota, N; Romãozinho, C; Sousa, V; Marinho, C; Santos, L; Macário, F; Alves, R; Pratas, J; Campos, M; Figueiredo, ABACKGROUND: Polyomavirus nephropathy (BKVN) is an important cause of chronic allograft dysfunction (CAD). Recipient determinants (male sex, white race, and older age), deceased donation, high-dose immunosuppression, diabetes, delayed graft function (DGF), cytomegalovirus infection, and acute rejection (AR) are risk factors. Reducing immunosuppression is the best strategy in BKVN. The objective of our study was to evaluate CAD progression after therapeutic strategies in BKVN and risk factors for graft loss (GL). METHODS: Retrospective analysis of 23 biopsies, from patients with CAD and histological evidence of BKVN, conducted over a period of 10 years. Glomerular filtration rate was <30 mL/min in 16 patients at the time of the BKVN diagnosis. RESULTS: BKVN was histologically diagnosed in 23 recipients (19 men, 4 women). All patients were white, with age of 51.2 ± 12.1 years (6 patients, age >60 years), and 22 had a deceased donor. Diabetes affected 4 patients, DGF occurred in 3, cytomegalovirus infection in 2, and AR in 15. All patients were medicated with calcineurin inhibitors (CNI) (95.7% tacrolimus) and corticoids, and 16 also received an antimetabolite. One year after antimetabolite reduction/discontinuation and/or CNI reduction/switching and/or antiviral agents, graft function was decreased in 11 patients, increased/stabilized in 10, and unknown in 2. GL occurred in 9 patients. Older age (hazard ratio, 1.76; 95% confidence interval, 0.94-3.28) and DGF (hazard ratio, 2.60; 95% confidence interval, 0.54-12.64) were the main risk factors for GL. The lower GFR at the time of the BKVN diagnosis was associated with an increased risk of initiation of dialysis. CONCLUSIONS: GL occurred in 39.1% of patients with BKVN and DGF; older age and lower GFR at the time of diagnosis were important risk factors. Early diagnosis of BKVN is essential to prevent GL.
- What Can We Do When All Collapses? Fatal Outcome of Collapsing Glomerulopathy and Systemic Lupus Erythematosus With Diffuse Alveolar Hemorrhage: Case ReportPublication . Pinto, H; Leal, R; Rodrigues, L; Santos, L; Romãozinho, C; Macário, F; Alves, R; Pratas, J; Sousa, V; Marinho, C; Prado E Castro, L; Costa, F; Campos, M; Mota, A; Figueiredo, ANTRODUCTION: Collapsing glomerulopathy (CG) is a rare form of glomerular injury. Although commonly associated with human immunodeficiency virus (HIV) infection, it can occur in association with systemic lupus erythematosus (SLE). CASE REPORT: We present the case of a 50-year-old man, with chronic kidney disease secondary to focal and segmental glomerulosclerosis, who received a cadaveric kidney transplant in 2007. There were no relevant intercurrences until May 2015, when he presented with nephrotic range proteinuria (± 4 g/d). A graft biopsy was performed and it did not show any significant pathological changes. In September, he developed a full nephrotic syndrome (proteinuria 19 g/d) and a graft biopsy was repeated. CG features were evident with a rich immunofluorescence. Antinuclear antibodies (ANA) and anti-double-stranded DNA (anti-dsDNA) antibodies were positive; the remaining immunologic study was normal. Viral markers for HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) were negative. The patient was treated with corticosteroid pulses and plasmapheresis (seven treatments). A rapid deterioration of kidney function was seen and he became dialysis dependent. He was discharged with a low-dose immunosuppressive treatment. In October, he was hospitalized with diffuse alveolar hemorrhage (DAH). The auto-immune study was repeated, revealing complement consumption and positive titers of ANA and Anti-dsDNA antibodies. Anti-neutrophil cytoplasmic antibodies (ANCAs) and antiglomerular basement membrane antibody (anti-GBM) were negative. Treatment with intravenous corticosteroids, plasmapheresis, and human immunoglobulin was ineffective and the outcome was fatal. CONCLUSION: This case report highlights the possible association of CG and SLE. To our knowledge, it is the first case of SLE presenting with CG and DAH, with the singularity of occurring in a kidney transplant recipient receiving immunosuppression.
- Surgical Complications in Early Post-transplant Kidney RecipientsPublication . Pinto, H; Leal, R; Rodrigues, L; Santos, L; Romãozinho, C; Macário, F; Alves, R; Bastos, C; Roseiro, A; Costa, F; Campos, M; Mota, A; Figueiredo, ABACKGROUND: The purpose of this study was to determine the incidence of early surgical complications of kidney transplantation in our institution and its association with donor and recipient factors, as well as patient and transplant outcome. METHODS: A retrospective cohort study of all kidney transplants performed during 2015 was made. We evaluated the incidence of surgical complications and the outcome of patients and grafts at a 3-month follow-up interval. RESULTS: During the study period, 141 kidney transplants occurred. Seventeen patients had surgical complications (6 urologic, 6 vascular, and 5 other complications). Five patients lost the graft during the follow-up. Older age was associated with other surgical complications (P = .023), and graft loss was associated with the existence of surgical complications, namely, vascular complications (P <.001). For both surgical complications in general and urologic complications, a statistically significant relationship was found with patient weight (P = .003 and P = .034, respectively). The correlation between body mass index (BMI) and surgical complications was not statistically significant. CONCLUSIONS: Our study reveals that older and heavier patients have a higher risk of surgical complications and that vascular complications are associated with graft loss. A statistically significant relationship was not found between BMI and surgical complications, which could indicate that BMI is not the ideal obesity marker. The incidence of surgical complications found in our study is similar to the literature. The selection of transplant recipients is a difficult task, and the possibility of additional surgical complications in older and overweight patients should be taken into account.
- Early Rehospitalization Post-Kidney Transplant Due to Infectious Complications: Can We Predict the Patients at Risk?Publication . Leal, R; Pinto, H; Galvão, A; Rodrigues, L; Santos, L; Romãozinho, C; Macário, F; Alves, R; Campos, M; Mota, A; Figueiredo, AINTRODUCTION: Rehospitalization early post-kidney transplant is common and has a negative impact in morbidity, graft survival, and health costs. Infection is one the most common causes, and identifying the risk factors for early readmission due to infectious complications may guide a preventive program and improve outcome. The aim of this study was to evaluate the incidence, characterize the population, and identify the risk factors associated with early readmission for infectious complications post-kidney transplantation. METHODS: We performed a retrospective cohort study of all the kidney transplants performed during 2015. The primary outcome was readmission in the first 3 months post-transplant due to infectious causes defined by clinical and laboratory parameters. RESULTS: We evaluated 141 kidney transplants; 71% of subjects were men, with an overall mean age of 50.8 ± 15.4 years. Prior to transplant, 98% of the patients were dialysis dependent and 2% underwent pre-emptive living donor kidney transplant. The global readmission rate was 49%, of which 65% were for infectious complications. The most frequent infection was urinary tract infection (n = 28, 62%) and the most common agent detected by blood and urine cultures was Klebsiella pneumonia (n = 18, 40%). The risk factors significantly associated with readmission were higher body mass index (P = .03), diabetes mellitus (P = .02), older donor (P = .007), and longer cold ischemia time (P = .04). There were 3 graft losses, but none due to infectious complications. CONCLUSION: There was a high incidence of early rehospitalization due to infectious complications, especially urinary tract infections to nosocomial agents. The risk factors identified were similar to other series.
- Nephrotic Range Proteinuria in Renal Transplantation: Clinical and Histologic Correlates in a 10-year Retrospective StudyPublication . Leal, R; Pinto, H; Galvão, A; Santos, L; Romãozinho, C; Macário, F; Alves, R; Pratas, J; Sousa, V; Marinho, C; Prado E Castro, L; Campos, M; Mota, A; Figueiredo, AINTRODUCTION: There is a high incidence of nephrotic proteinuria in renal transplant recipients, which is an accurate predictor of graft loss. Despite this, its histologic correlates and prognostic implications are still not well characterized. We assessed the clinical and histological correlates of kidney transplantation patients with nephrotic range proteinuria. METHODS: We have retrospectively analyzed clinical and histological data from 50 kidney transplantation biopsy specimens from 44 renal transplant recipients with nephrotic range proteinuria between 2006 and 2015. The median follow-up time was 93 months (range, 14 months to 190 months). RESULTS: The mean age of the patients was 45.2 ± 13.7 years and our cohort included 86% recipients of deceased-donor grafts. The maintenance immunosuppressive regimen included calcineurin inhibitors in 68% and mammalian target of rapamycin inhibitors in 32% of patients. The average proteinuria was 6.9 ± 3.8 g/d and 52% of patients presented with nephrotic syndrome. The main histological findings were transplant glomerulopathy (22%), de novo glomerular disease (22%), and recurrence of primary disease (22%). Tubular atrophy and interstitial fibrosis was present in 78% of the biopsy specimens. Thirty-one patients (62%) lost the graft at follow-up. There was no statistically significant difference between the histologic diagnosis nor the proteinuria levels and the outcome of the graft. CONCLUSIONS: The main causes of nephrotic range proteinuria in patients undergoing biopsy were transplant glomerulopathy, recurrence of the underlying disease, and de novo glomerulonephritis. Nephrotic range proteinuria was related to a high rate of graft loss.
- Suppressing inflammation in rheumatoid arthritis: Does patient global assessment blur the target? A practice-based call for a paradigm changePublication . Ferreira, RJ; Duarte, C; Ndosi, M; de Wit, M; Gossec, L; Pereira da Silva, JAIn current management paradigms of Rheumatoid Arthritis (RA), patient global assessment (PGA) is crucial to decide whether a patient has attained remission (target) or needs reinforced therapy. We investigated whether the clinical and psychological determinants of PGA are appropriate to support this important role.