Browsing by Author "Malheiro, J."
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- Acute tubulointersticial nephritis with uveitis: A report of two casesPublication . Silva, F.; Correia, S.; Castro, A.; Moreira, C.; Santos, S.; Malheiro, J.; Santos, J.; Martins, L.; Cabrita, A.Tubulointersticial nephritis and uveitis syndrome is an idiopathic and rare cause of acute kidney injury that should not overlooked, because it usually requires specific therapeutic interventions. We report two distinct cases: a young and an elder female. Both cases presented with unspecific constitutional symptoms but had different onset of renal and ocular involvement. Both were treated with topical and systemic corticoids and although there was a good initial response in both cases, an early relapse after steroids taper was observed in the younger patient and a persistent renal dysfunction in the older one. A high clinical suspicion and understanding of this disease is necessary for an adequate management and treatment of these patients. Recent data associates a worse renal prognosis when the disease appears in advanced age. In both of our cases the outcome was good but we had a short follow-up. The histological presentation of this disease in our older patient was similar to that reported in the literature, with a high percentage of fibrosis and chronicity of renal tissue that can contribute to the higher grade of renal dysfunction in this type of patients.
- Clinical implications of anti-HLA antibodies testing in kidney transplantationPublication . Malheiro, J.; Tafulo, S.Alloantibodies against donor human leukocyte antigens (HLA), termed as donor‑specific antibodies (DSA), are one of the most important factors for both early and late kidney allograft dysfunction. In the past, these antibodies were mainly detected through cell‑based crossmatch tests. Recently, new techniques such as solid phase immunoassays (SPI) have revealed these antibodies in patient sera with a high degree of detail, previously unimaginable. They have allowed us to accurately determine recipients’ allosensitization status, improve pre‑transplant risk assessment with a potential donor and post‑transplant alloimmune monitoring. However, the high sensitivity of these new assays has also created areas of uncertainty about their clinical impact. In the pre‑transplant setting, the presence of preformed DSA has been associated with an increased risk of antibody‑mediated rejection (AMR) and subsequent allograft loss. Nevertheless, several studies have shown that not all DSA are deleterious. Hence, understanding the clinical correlations of DSA characteristics, namely strength, HLA class, complement‑fixing ability or IgG subclasses, is paramount for an adequate stratification of the immunological risk at transplant. Furthermore, given that the number of allosensitized patients on waiting lists is increasing, the added information from these new SPI is essential to improve their chance of being transplanted with an admissible immunological risk. After transplantation, the appearance of de novo DSA (dnDSA) has also been associated with a deleterious effect on kidney allograft survival. Moreover, it has been acknowledged that a majority of late allograft failures are caused by alloantibody‑driven injury. The current challenges, in this setting, are determining cost‑effective DSA screening protocols and understanding which patients could benefit from specific interventions. Furthermore, although therapeutic strategies to control antibody‑induced damage remain limited, the longitudinal surveillance of dnDSA emergence and the clinical correlations of their characteristics will play a crucial role in the improvement of late kidney allograft survival.
- Fgf-23 and vascular calcification in a peritoneal dialysis population with residual renal functionPublication . Santos, S.; Carlos Oliveira, José; Barra, T.; Campos, A.; carvalho, M.; Malheiro, J.; Fonseca, Isabel; Cabrita, A.; Adragão, T.; Rodrigues, AnabelaIntroduction and Aims: Fibroblast growth factor 23 (FGF-23) induces phosphaturia. Its clinical impact is beyond mineral bone disease in chronic kidney disease (CKD), being coupled with vascular calcification and mortality. Residual renal function (RRF) is associated with significant capacity to excrete phosphate in peri- toneal dialysis (PD). Besides testing whether FGF-23 is still related with glomerular filtration rate (GFR) and phosphate excretion in this late stage of CKD (5d), we aimed to explore its link with vascular calcification.Subjects and Methods: FGF-23 (C terminal) was measured in forty prevalent PD patients with RRF, aged 61.5 (51.0-67.0) years old, in renal replacement therapy (RRT) for 43.5 (23-80.0) months; 36.6% were female, 19.5% had diabetes mellitus and 37.5% were under automated PD regimen; 80% were on PD first, and only 20% had previous RRT. Relevant variables including dietary phosphate (P) intake, CKD-bone laboratory parameters, serum 25-hydroxyvitamin D, magnesium (Mg) levels, GFR, urinary phosphate, fractional excretion of phosphorus (FEP), albumin, proBNP and Adragão vascular calcification score were explored. Results: Median levels (25-75% range) of serum variables were: FGF-23 1997 (1623-2149) RU/mL, Mg 0.94 (0.8-1.0) mmol/L, 25-hydroxyvitamin D 30 (18-47) nmol/L, calcium 2.2 (2.0-2.37) mmol/L, phosphorus 1.69 (1.30-1.90) mmol/L, PTH 429 (309-626) pg/mL. FGF-23 correlated positively with serum phosphate (r = 0.39, p = 0.013) and negatively with urine volume (r = -0.48, p = 0.001), phosphaturia (r = -0.594, p < 0.0001) and GFR (r =-0.61,p < 0.0001). However, FGF-23 was not significantly correlated with age, total time of RRT, dietary P, FEP, Mg, nor 25-hydroxyvitamin D. High FGF-23 group had higher FEP. GFR was the single inde- pendent predictor of increased FGF-23. On the other hand, neither FGF-23 nor low FEP/FGF-23 ratio were significantly associated with the vascular calcification score. Only albumin (lower), magnesium (lower) and proBNP (higher) levels significantly differed in calcified versus non-calcified patients (all with p < 0.05). Conclusions: In our population, FGF-23 was not associated with vascular calcification. GFR was the single independent predictor of increased FGF-23 in patients with diuresis. Increment of FGF-23 in PD patients signalizes an active endocrine phosphaturic process compensating renal function loss, as expressed by higher fractional excretion of phosphorus. It alerts for dietetic and therapy optimization. However, its link with vascular calcification still lacks validation.
- Impact of pre-transplant anti-MICA sensitization in graft rejection and survivalPublication . Costa, R.; Malheiro, J.; Tafulo, S.; Santos, C.; Almeida, M.; Pedroso, S.; Martins, L.; Dias, L.; Castro-Henriques, A.Background: Evidence supporting deleterious effect of preformed major histocompatibility class I chain-related A (MICA) antibodies in rejection incidence and graft survival is still unclear. Methods: Retrospective analysis of 554 kidney transplanted patients. Comparison between positive or negative for MICA antibodies patients was performed to characterize sensitizing triggers. Further classification according to pre-transplant flow cytometry-recorded anti–MICA and/or anti-human leukocyte antigen (HLA) antibodies was made to determine first year rejection incidence and graft survival. Multivariate analysis was applied to determine predictors for acute rejection. Results: Pre-formed anti-MICA antibodies were detected in 41 patients (7.4%). HLA sensitization, blood transfusions and pregnancies were frequently found in anti-MICA+ patients but only pre-formed anti-HLA class I antibodies showed independent association (OR 2.67, p= 0.02). Comparing to MICA-/HLA–, MICA-/HLA+ group presented significantly lower first year rejection-free survival (78.6% vs. 89.3%, p< 0.01), mostly occurred in the first six months, while no difference was found in MICA+/HLA– (88.9% vs. 89.3%, p= ns). MICA-/HLA+ showed independent impact in rejection (OR 2.09, p= 0.03), while no evidence was found in MICA+/HLA- (OR 1.08, p= ns). At 4 years, MICA-/HLA+ group presented lower graft survival (85.8% vs. 95.3%, p= 0.03). Again, no difference was found in MICA+/HLA- group (95.1% vs. 95.3%, p= ns). Conclusion: Our results do not support HLA-independent deleterious pathogenic role of pre-formed MICA antibodies on first year rejection incidence and graft survival.
- Impact of preformed donor-specific antibodies against HLA class I on kidney graft outcomes: Comparative analysis of exclusively anti-Cw vs anti-A and/or -B antibodiesPublication . Santos, S.; Malheiro, J.; Tafulo, S.; Dias, L.; Carmo, R.; Sampaio, S.; Costa, M.; Campos, A.; Pedroso, S.; Almeida, M.; Martins, L.; Henriques, C.; Cabrita, A.AIM: To analyze the clinical impact of preformed antiHLA-Cw vs antiHLA-A and/or -B donor-specific antibodies (DSA) in kidney transplantation. METHODS: Retrospective study, comparing 12 patients transplanted with DSA exclusively antiHLA-Cw with 23 patients with preformed DSA antiHLA-A and/or B. RESULTS: One year after transplantation there were no differences in terms of acute rejection between the two groups (3 and 6 cases, respectively in the DSA-Cw and the DSA-A-B groups; P = 1). At one year, eGFR was not significantly different between groups (median 59 mL/min in DSA-Cw group, compared to median 51 mL/min in DSA-A-B group, P = 0.192). Moreover, kidney graft survival was similar between groups at 5-years (100% in DSA-Cw group vs 91% in DSA-A-B group, P = 0.528). The sole independent predictor of antibody mediated rejection (AMR) incidence was DSA strength (HR = 1.07 per 1000 increase in MFI, P = 0.034). AMR was associated with shortened graft survival at 5-years, with 75% and 100% grafts surviving in patients with or without AMR, respectively (Log-rank P = 0.005). CONCLUSION: Our data indicate that DSA-Cw are associated with an identical risk of AMR and impact on graft function in comparison with "classical" class I DSA.
- Implications for patients waiting for a kidney transplant of using the calculated panel reactive antibody (cPRA)Publication . Magriço, R.; Malheiro, J.; Tafulo, S.; Pedroso, S.; Almeida, M.; Martins, L.; Dias, L.; Castro-Henriques, A.; Cabrita, A.Introduction: Kidney transplant improves survival even in highly‑sensitized (HS) patients. To overcome their disadvantage in accessing transplantation, those with high Complement Dependent Cytotoxic PRA (CDC‑PRA) receive additional points during allocation. Whether this strategy reaches all HS patients and how long they wait for a transplant is largely undetermined. Methods: Patients on our unit’s active wait‑list for kidney transplantation in the year 2014 were analyzed. CDC‑PRA and calculated PRA (cPRA) were recorded. To obtain cPRA, antibodies in the last serum available specific for HLA‑A, ‑B or –DR with an intensity > 1000 MFI were considered. Results: The cPRA values in the population (N=551) were 0% (N=312), 1‑79% (N=118) and ≥ 80% (22%; N=121). Among these groups, the proportion of women (29.5, 55.9 and 61.2%, P<0.001), prior sensitizing events (43.3, 80.5 and 96.7%, P<0.001) and time on dialysis (median of 3.9, 4.1 and 6.0 years, P<0.001) increased with cPRA, respectively. In most of those with a cPRA ≥ 80%, the CDC‑PRA raised no suspicion of HS status (median 0%, P25‑75 0‑8%) and only 35 (28.9%) or 12 patients (9.9%) had a CDC‑PRA in the peak serum higher than 50 or 80%, respectively (cut‑offs needed to obtain additional points during allocation). HS patients by cPRA corresponded to 71% vs 15% of patients waiting for ≥ or <8 years, respectively (P<0.001). Even after exclusion of patients with a CDC‑PRA above 50%, this disproportionate representation remained (58% versus 13%, P<0.001). Conclusion: HS patients as measured by cPRA remained longer on the wait‑list, both in the primary analysis and when excluding those with a CDC‑PRA> 50%. Moreover, only 30% of HS by cPRA patients received the extra points designed to improve their transplantability. We consider that both CDC‑PRA and cPRA should be taken into account when defining HS status.
- Membranoproliferative glomerulonephritis associated with type II cryoglobulinaemia in a renal transplant patient with hepatitis CPublication . Bento, C.; Malheiro, J.; Almeida, M.; Martins, L.; Dias, L.; Vizcaíno, J.; Castro-Henriques, A.The most common HCV-related nephropathy is membranoproliferative glomerulonephritis (MPGN), usually in the context of cryoglobulinaemia. The treatment of this entity is not consensual and represents a challenge to clinicians. We report a case of membranoproliferative glomerulonephritis associated with cryoglobulinaemia type II in a 46-year-old Caucasian male recipient of a deceased kidney transplant in 2010. His baseline serum creatinine (SCr) was 1.1 mg/dl. After three years post-transplantation, he presented with nephritic syndrome in association with renal function impairment (SCr – 2.1 mg/dl). The laboratory tests revealed positive rheumatoid factor, hypocomplementaemia and a positive cryocrit with type II cryoglobulinaemia. Antinuclear autoantibodies and anti-double stranded DNA antibodies were negative. Despite the presence of anti-HCV antibodies, the viral load remained undetectable. The allograft biopsy showed lesions compatible with membranoproliferative glomerulonephritis, with staining in the immunofluorescence for granular IgM and C3 and no C4d. He was treated with methylprednisolone pulses followed by oral prednisolone in association with rituximab. Two months after the last dose of rituximab, the SCr improved to 1.27 mg/dl, the proteinuria decreased and serum C3 levels normalized. Cryogloglobulins and rheumatoid factor became negative and HCV RNA remained undetectable. The patient was lost for follow-up. In our case, the treatment with rituximab resulted in a favourable outcome, although a longer follow-up period may be needed to evaluate the clinical response, since other studies reported high relapse rates.
- Mesalazine induced tubulointersticial nephritisPublication . Campos, A.; Santos, S.; Santos, J.; Malheiro, J.; Lobato, L.; Vizcaíno, J.; Cabrita, A.Inflammatory bowel disease and its various treatments may affect the kidney in several ways tubulointersticial nephritis is a rare but serious complication of longer-term mesalazine use. There are few cases reported in the literature. We report the first two cases of mesalazine-induced tubulointersticial nephritis, recently diagnosed in our department. The first one refers to a patient with ulcerous colitis and the second one to a patient with Crohn’s disease. Then the authors present a review of literature about the renal involvement in the inflammatory bowel disease. New cases of mesalazine nephrotoxicity should be reported to allow more accurate incidence estimation of this serious adverse effect. Routine monitoring of renal function is simple, inexpensive and allows an early diagnosis of this complication
- Monoclonal gammopathy of renal significance: Diagnostic workupPublication . Correia, S.; Santos, S.; Malheiro, J.; Cabrita, A.; Martins, L.; Santos, J.The clinical spectrum of diseases associated with monoclonal gammopathies is wide and they are most commonly the consequence of renal deposition of monoclonal immunoglobulin or its components. The differential diagnosis is difficult and renal biopsy is essential. To distinguish many of these pathologies is necessary to use techniques that are not always available, even in tertiary central hospitals. This review will discuss the clinical presentation, pathologic features, treatment, prognosis and common diagnostic difficulties of these entities.
- Pancreas-Kidney Transplantation and the Evolution ofPublication . Martins, L.; Malheiro, J.; Henriques, A.C.; Dias, L.; Dores, J.; Oliveira, F.; Seca, R.; Almeida, R.; Sarmento, A.M.; Cabrita, A.; Teixeira, M.ABSTRACT The recurrence or persistence of pancreatic autoantibodies after pancreas-kidney trans- plantation (PKT) is an intriguing finding. We prospectively analyzed 77 PKTs, searching for risk factors for the expression of these autoimmune markers and their impact on pancreas graft function. Among the 77 PKTs, 24.7% had HLA matches, 20.8% displayed delayed graft function, and 14.3% had acute rejection episodes. Immunosuppression included antithymocyte globulin (ATG)tacrolimus, mycophenolate mofetil (MMF)and steroids. Sixty-five patients had both grafts functioning as follow-up of more than months. In 11 patients anti–glutamic acid decarboxylase (GAD) positivity persists (8) or has recurred (3)of whom show increasing titers. Two patients maintain positive islet cell antibodies (ICA) and anti-GAD antibodies. The patients positive for ICA included who were negative before PKT and who remain positive. The “positive” group (22 patients with positive ICA and/or anti-GAD) did not differ from the global group of 65 functioning PKT in terms of acute rejection episodes, HLA match, and steroid withdrawal. Among the positive patients, there were with borderline glucose levels; however, among the entire “positive” group, the mean fasting glucose, HbA1c, and C-peptide measurements were not significantly different, when compared with the other 65 PKTs. In conclusion, pancreatic autoantibodies may be persistently positive or recur after PKT, despite appropriate immunosuppression. Its impact on long-term pancreas graft survival is unknown. We could not identify risk factors for their expression. An extended follow-up with monitoring and search for other risk factors may be necessary to increase our knowledge in this field.