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- Reducing Tacrolimus Levels to Improve Cognitive Function in Kidney Transplant Recipients.Publication . Bigotte Vieira, Miguel
- Biochemical Clusters as Substitutes of Bone Biopsies in Kidney Transplant Patients.Publication . Ferreira, Ana Carina; Mendes, Marco; Silva, Cecília; Cotovio, Patrícia; Aires, Inês; Navarro, David; Caeiro, Fernando; Salvador, Rute; Correia, Bruna; Cabral, Guadalupe; Nolasco, Fernando; Ferreira, AníbalBone and mineral metabolism abnormalities are frequent in kidney transplant recipients and have been associated with cardiovascular morbidity. The primary aim of this study was to analyse the association between routine clinically available biochemical evaluation, non-routine histomorphometric bone evaluation, and vascular disease in kidney transplanted patients. A cross-sectional analysis was performed on 69 patients, 1-year after kidney transplantation. Laboratory analysis, radiography of hands and pelvis, bone biopsy, bone densitometry, and coronary CT were performed. One-year post-transplantation, nearly one-third of the patients presented with hypercalcemia, 16% had hypophosphatemia, 39.3% had iPTH levels > 150 pg/mL, 20.3% had BALP levels > 40 U/L, and 26.1% had hypovitaminosis D. Evaluation of extraosseous calcifications revealed low Adragão and Agatston scores. We divided patients into three clusters, according to laboratory results routinely used in clinical practice: hypercalcemia and hyperparathyroidism (Cluster1); hypercalcemia and high BALP levels (Cluster2); hypophosphatemia and vitamin D deficiency (Cluster 3). Patients in clusters 1 and 2 had higher cortical porosity (p = 0.001) and osteoid measurements, although there was no difference in the presence of abnormal mineralization, or low volume. Patients in cluster 2 had a higher BFR/BS (half of the patients in cluster 2 had high bone turnover), and most patients in cluster 1 had low or normal bone turnover. Cluster 3 has no differences in volume, or turnover, but 60% of the patients presented with pre-osteomalacia. All three clusters were associated with high vascular calcifications scores. Vascular calcifications scores were not related to higher bone mineral density. Instead, an association was found between a higher Adragão score and the presence of osteoporosis at the femoral neck (p = 0.008). In conclusion, inferring bone TMV by daily clinical biochemical analysis can be misleading, and bone biopsy is important for assessing both bone turnover and mineralization after kidney transplantation, although hypophosphatemia combined with vitamin D deficiency is associated with abnormal mineralization. The presence of hypercalcemia with high levels of PTH or high levels of BALP, or hypophosphatemia and vitamin D deficiency should remind us to screen vascular calcification status of patients.Clinical Research: ClinicalTrials.gov ID NCT02751099.
- Individualizing Treatment for CMV with UL97 del597-599 Mutation: Beyond Unusual Response to a Lower Ganciclovir Dose IncreasePublication . Piedade, Ana; Vidal, Helena; Simões, Pilar; Bigotte Vieira, Miguel; Chasqueira, Maria Jesus; Caeiro, Fernando; Aires, Inês; Paixão, Paulo; Jorge, CristinaHuman cytomegalovirus (CMV) infection is the most prevalent infection affecting organ transplant recipients, and it is a cause of morbidity and mortality in patients undergoing kidney transplantation. The introduction of ganciclovir (GCV) for both prophylaxis and treatment has vastly improved patient outcomes. GCV resistance can be caused by mutations in the UL97 phosphotransferase gene or the UL54 polymerase gene. It occurs in 1 to 2% of kidney transplant recipients with CMV infection or disease. Antiviral resistance should be considered when increased viral loads and disease progression are observed despite the administration of adequate antiviral therapy. The degree of resistance varies depending on the type of mutation present. We report a patient with resistance to GCV due to a UL97 del597-599 mutation who, despite typically requiring an 8-fold increase in GCV dose, showed a significant decrease in viral load with just a double dose increase. However, the patient’s overall clinical course remained complicated. Due to severe leukopenia, maribavir had to be started, with a good response. Nevertheless, he ultimately died due to indirect CMV-related complications. This case also highlights the complexity of transplant patients, who present multiple challenges ranging from infections to therapy management.
- Calcium Polystyrene Sulfonate-Induced Colitis: Advanced Characterization of Crystal Nature With Infrared Spectroscopy.Publication . Vidal, Helena; Salgado, Vilma; Alves, Patrícia; Fonseca, Nuno Moreira; Frochot, Vincent; Ferreira, Aníbal; OxfordClassical potassium binders are used in the treatment of hyperkalemia and are widely associated with gastrointestinal side effects, with crystal colonic injury being rare but potentially fatal. In this report, we describe the case of an 82-year-old male with hyperkalemia and calcium polystyrene sulfonate crystal-associated colonic necrosis. Traditionally, this diagnosis has relied on the examination of crystal morphology and polarization through microscopy. Our study enhances crystal identification by incorporating an analysis of the physical characteristics of the crystals using infrared spectroscopy. This is the first description, to our knowledge, of the calcium polystyrene sulfonate infrared spectrum.
- Major Determinants of Primary Non Function From Kidney Donation After Maastricht II Circulatory Death: a Single Center ExperiencePublication . Gaspar, A; Gama, M; Nobre de Jesus, G; Querido, S; Damas, J; Oliveira, J; Neves, M; Santana, A; Ribeiro, JMPurpose: Organ shortage greatly limits treatment of patients with end-stage chronic kidney. Maastricht type 2 donation after circulatory death (DCD) has been shown to have similar results in long term outcomes in kidney transplantation, when compared with brain dead donation. Our main goal was to assess Maastricht type 2 DCD and evaluate factors that impact on early graft function. Methods: A retrospective study was conducted in an ECMO Referral Centre. All patients who received a kidney transplant from Maastricht type 2 DCD were included in study. Early graft function and short term outcomes were assessed. Results: From October 2017 to December 2022, 47 renal grafts were collected from 24 uDCD donors. Median warm ischemia time was 106 min (94-115), cannulation time was 10 min (8; 20) and duration of extracorporeal reperfusion (ANOR) was 180 min (126-214). Regarding early graft function, 25% had immediate graft function, 63.6% had delayed graft function and 11.4% had primary non-function (PNF). There was a correlation between cannulation time (p = 0.006) and ANOR with PNF (p = 0.016). Conclusions: Cannulation time and ANOR were the main factors that correlated with PNF. Better understanding of underlying mechanisms should be sought in future studies to reduce the incidence of PNF.
- A New Onset of Nephrotic Proteinuria in Sjogren DiseasePublication . Furtado, T; Abrantes, C; Valério, P; Soares, E; Góis, M; Natário, A
- Kidney Disease in Ankylosing Spondylitis: a Case Series and Review of the LiteraturePublication . Cunha Rodrigues, A; Cristóvão Marques, J; Reis, M; Góis, M; Sousa, H; Nolasco, FBackground: Kidney disease is a rare manifestation of ankylosing spondylitis (AS) and its pathological alterations remain poorly described. The aim of this study was to investigate the clinical presentation and pathological alterations on kidney biopsy of AS patients and review and discuss the current literature on the issue. Methods: We retrospectively studied the clinical presentation and kidney pathological alterations of 15 Caucasian AS patients submitted to kidney biopsy between October 1985 and March 2021. Results: Patients were predominantly male (66.7%) with median age at the time of kideney biopsy of 47 years [IQR 34 - 62]. Median serum creatinine at presentation was 1.3 mg/dL [IQR 0.9 - 3] and most patients also had either proteinuria (85.7%) and/or hematuria (42.8%). The most common indication for kidney biopsy was nephrotic syndrome (33.3%), followed by acute or rapidly progressive kidney injury (20%) and chronic kidney disease of unknown etiology (20%). Chronic interstitial nephritis (CIN) (n=3) and AA amyloidosis (n=3) were the most common diagnosis. Others included IgA nephropathy (IgAN) (n=2), focal segmental glomerulosclerosis (n=2), membranous nephropathy (n=1), and immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN)(n=1). Conclusions: We present one of the largest series of biopsy-proven kidney disease in Caucasian AS patients. We found a lower prevalence of IgAN than previously reported in Asian cohorts. We found a higher prevalence of CIN and a lower prevalence of AA amyloidosis than that described in previous series of Caucasian patients. We also present the first case of AS-associated IC-MPGN.
- New Onset Nephrotic - Range Proteinuria in a Patient with Chronic Kidney Disease - Not Always What it SeemsPublication . Cardoso Fernandes, S; Góis, M; Viana, H; Ferreira, ACLight chain deposition disease (LCDD) is a rare condition that is characterized by the deposition of monoclonal immunoglobulin light chains in glomerular and tubular basement membranes. We report the case of a 72-yearold male with long-standing and stable chronic kidney disease (CKD) presumably due to hypertension and lithiasis who presented with new-onset nephrotic range proteinuria, anemia and rapidly worsening renal function that eventually led to end-stage renal disease (ESRD) requiring dialysis. Radiologic and laboratory workup found enlarged kidneys in the ultrasound and increased kappa/ lambda ratio (KLR) suggestive of a plasma cell dyscrasia. The patient underwent bone marrow biopsy, confirming the diagnosis of kappa light chains multiple myeloma (MM). Since exclusion of amyloidosis was essential for determining therapeutic strategies, a kidney biopsy was performed, showing deposition of Periodic acid-Schiff (PAS) positive and silver-negative material in the glomeruli, tubular basement membrane, vessels and interstitium and kappa light chain restriction in the immunofluorescence staining. A diagnosis of kappa LCDD secondary to MM was made, and the patient received a Bortezomib-based regimen directed to the plasma cell disorder.
- Improvement of Mineral and Bone Disorders After Renal TransplantationPublication . Ferreira, AC; Mendes, M; Silva, C; Cotovio, P; Aires, I; Navarro, D; Caeiro, F; Ramos, R; Salvador, R; Correia, B; Cabral, G; Nolasco, F; Ferreira, ABackground: Posttransplant mineral and bone diseases are causes of fractures, and their association with cardiovascular events is being studied. Methods: We analyzed the evolution of biochemical, histological, and imaging parameters pre- and 1 y post-renal transplantation in 69 patients and correlated mineral and bone findings with coronary calcifications. At inclusion and after 12 mo, clinical data and echocardiographic findings were recorded, and laboratory evaluations, radiography of the pelvis and hands, and bone biopsy were performed. Noncontrast cardiac computed tomography was performed during the second evaluation. Results: Serum levels of fibroblast growth factor 23 and sclerostin decreased in all patients, parathyroid hormone levels decreased in 89.8% of patients, bone alkaline phosphatase levels decreased in 68.1% of patients, and alpha-Klotho levels increased in 65.2% of patients. More than half of the patients presented with renal osteodystrophy at both biopsies, but histological findings improved: a significant transition from high to normal or low turnover and no significant differences in volume, mineralization defect, or cortical porosity at the 2 evaluations. Alpha-Klotho, sclerostin, and bone alkaline phosphatase shifts affect bone changes. Neither echocardiographic findings nor vascular calcification scores differed between the 2 points. Both the pretransplant period (dialysis vintage, sclerostin, and low bone volume at baseline) and the maintenance of abnormalities in the posttransplant period (high turnover posttransplant) were the most reliable predictors of the severity of the coronary calcification percentile. Conclusions: Renal transplantation improved bone and mineral abnormalities. The pretransplant period determines the severity of calcification.
- Mineral and Bone Metabolism Markers and Mortality in Diabetic Patients on HaemodialysisPublication . Martín-Carro, B; Navarro-González, JF; Ortiz, A; Zoccali, C; Floege, J; Ferreira, MA; Gorriz-Teruel, JL; Carrillo-López, N; Panizo, S; Locatelli, F; Ketteler, M; London, GM; Naves-Díaz, M; Alonso-Montes, C; Cannata-Andía, JB; Fernández-Martín, JLBackground: Diabetic patients on haemodialysis have a higher risk of mortality than non-diabetic patients. The aim of this COSMOS (Current management of secondary hyperparathyroidism: a multicentre observational study) analysis was to assess whether bone and mineral laboratory values [calcium, phosphorus and parathyroid hormone (PTH)] contribute to this risk. Methods: COSMOS is a multicentre, open-cohort, 3-year prospective study, which includes 6797 patients from 227 randomly selected dialysis centres in 20 European countries. The association between mortality and calcium, phosphate or PTH was assessed using Cox proportional hazard regression models using both penalized splines smoothing and categorization according to KDIGO guidelines. The effect modification of the association between the relative risk of mortality and serum calcium, phosphate or PTH by diabetes was assessed. Results: There was a statistically significant effect modification of the association between the relative risk of mortality and serum PTH by diabetes (P = .011). The slope of the curve of the association between increasing values of PTH and relative risk of mortality was steeper for diabetic compared with non-diabetic patients, mainly for high levels of PTH. In addition, high serum PTH (>9 times the normal values) was significantly associated with a higher relative risk of mortality in diabetic patients but not in non-diabetic patients [1.53 (95% confidence interval 1.07-2.19) and 1.17 (95% confidence interval 0.91-1.52)]. No significant effect modification of the association between the relative risk of mortality and serum calcium or phosphate by diabetes was found (P = .2 and P = .059, respectively). Conclusion: The results show a different association of PTH with the relative risk of mortality in diabetic and non-diabetic patients. These findings could have relevant implications for the diagnosis and treatment of chronic kidney disease-mineral and bone disorders.