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  • Estimating glomerular filtration rate in kidney transplantation: Still searching for the best marker
    Publication . Santos, J.; Martins, L.
    Kidney transplantation is the treatment of choice for end-stage renal disease. The evaluation of graft function is mandatory in the management of renal transplant recipients. Glomerular filtration rate (GFR), is generally considered the best index of graft function and also a predictor of graft and patient survival. However GFR measurement using inulin clearance, the gold standard for its measurement and exogenous markers such as radiolabeled isotopes ((51)Cr EDTA, (99m)Tc DTPA or (125)I Iothalamate) and non-radioactive contrast agents (Iothalamate or Iohexol), is laborious as well as expensive, being rarely used in clinical practice. Therefore, endogenous markers, such as serum creatinine or cystatin C, are used to estimate kidney function, and equations using these markers adjusted to other variables, mainly demographic, are an attempt to improve accuracy in estimation of GFR (eGFR). Nevertheless, there is some concern about the inability of the available eGFR equations to accurately identify changes in GFR, in kidney transplant recipients. This article will review and discuss the performance and limitations of these endogenous markers and their equations as estimators of GFR in the kidney transplant recipients, and their ability in predicting significant clinical outcomes.
  • Overhydration prevalence in peritoneal dialysis - A 2 year longitudinal analysis
    Publication . Aguiar, P.; Santos, O.; Teixeira, L.; Silva, F.; Azevedo, P.; Vidinha, J.; Ferrer, F.; Carvalho, M.; Cabrita, A.; Rodrigues, A.
    Hypervolemia is a major concern in dialysis patients, and is associated with increased cardiovascular risk and death. Cross sectional analysis have previously demonstrated that peritoneal dialysis (PD) patients are not more overhydrated when compared to haemodialysiś ones. This study was designed to evaluate longitudinal trends in hydration status and corporal composition in a PD population.
  • Membranoproliferative glomerulonephritis and x-linked agammaglobulinemia: an uncommon association
    Publication . Lavrador, V.; Correia, F.; Sampaio, R.; Candido, C.; Sameiro-Faria, M.; Marques, L.; Mota, C.
    Introduction. X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by agammaglobulinemia requiring replacement treatment with immunoglobulin. The association of XLA and membranoproliferative glomerulonephritis (MPGN) is unexpected and, to our knowledge, only one case was previously published. Case Report. The authors report the case of a 10-year-old boy with family history and prenatal diagnosis of XLA, treated from birth with intravenous immunoglobulin replacement therapy. He presented with pneumonia, macroscopic hematuria, nephrotic proteinuria, hypoalbuminemia, and hypercholesterolemia with normal renal function and serum complement levels. Renal histology showed immune complex mediated MPGN. He was started on high dose prednisolone and ramipril and switched to weekly subcutaneous immunoglobulin. After a 4-month treatment, hematuria and proteinuria significantly improved and prednisolone was gradually tapered without relapse. Conclusion. The pathogenic process underlying MPGN development in this patient is unknown but residual humoral immunity might play an important role. Thus, this case highlights the risk of autoimmune disorders among patients with XLA
  • Hepatocyte growth factor signalizes peritoneal membrane failure in peritoneal dialysis
    Publication . Bernardo, A.; Oliveira, J.; Santos, O.; Carvalho, M.; Cabrita, A.; Rodrigues, A.
    BACKGROUND: Hepatocyte growth factor (HGF) counteracts peritoneal fibrosis in animal models and in-vitro studies, but no study explored effluent HGF in peritoneal dialysis (PD) patients with ultrafiltration failure (UFF). Our aim was to assess the relationship between effluent HGF with UF profile, free water transport (FWT) and small-solute transport. METHODS: We performed 4-hour, 3.86% PET with additional UF measurement at 60 minutes in 68 PD patients. MTACcreatinine, FWT, small-pore ultrafiltration, and effluent HGF were quantified. RESULTS: Effluent HGF negatively correlated with UF (r=-0.80, p=0.009) and FWT (r=-0.69, p=0.04). Patients with UFF had higher dialysate HGF (103 pg/mL vs 77 pg/mL, p=0.018) and, although not statistically significant, those with FWT compromise had also higher dialysate HGF compared with subgroup of UFF without FWT compromise (104 pg/mL vs 88 pg/mL, p=0.08). FWT≤45% without clinical UFF was documented in some patients who also had increased effluent HGF. CONCLUSIONS: Dialysate HGF concentration is significantly higher among patients with UFF, specially, if FWT is impaired, being a sign of peritoneal membrane deterioration.
  • Posttransplant allosensitization in low immunological risk kidney and kidney-pancreas graft recipients.
    Publication . Malheiro, J.; Tafulo, S.; Dias, L.; Martins, La Salete; Fonseca, Isabel; Almeida, M.; Pedroso, S.; Freitas, F.; Beirão, I.; Castro-Henriques, A.; Cabrita, A.
    INTRODUCTION: Posttransplantation allosensitization prevalence and effect on kidney grafts outcomes remain unsettled. METHODS: Between 2007 and 2012, 408 patients received a primary kidney graft (with 68 patients also receiving a pancreas graft) after a negative cytotoxic crossmatch. All patients had a pretransplant negative anti-HLA screening and 0% panel reactive antibodies. We analyzed retrospectively the results of anti-HLA antibodies screening by Luminex assay, performed between 6 and 24 months after transplant, and searched for the risk factors for antibody positivity and its impact on kidney graft outcomes. RESULTS: Anti-HLA antibodies prevalence at 6 months was 17.4%. Previous steroid-insensitive acute rejection was the only risk factor for both anti-HLA classes detected antibodies. Antithymocyte globulin induction was also a risk factor for anti-HLA-I antibodies. Antibody positivity status was associated with reduced graft function at 12 months and graft survival at 5 years (91.5% versus 96.4%, P = 0.03). In multivariable Cox analysis, delayed graft function (HR = 6.1, P < 0.01), HLA mismatches >3 (HR = 10.2, P = 0.03), and antibody positivity for anti-HLA class II (HR = 5.1, P = 0.04) or class I/II (HR = 13.8, P < 0.01) were independent predictors of graft loss. CONCLUSIONS: Allosensitization against HLA class II ± I after transplant was associated with adverse kidney graft outcomes. A screening protocol seems advisable within the first year in low immunological risk patients.
  • Potential cardiovascular risk protection of bilirubin in end-stage renal disease patients under hemodialysis
    Publication . Sameiro-Faria, M.; Kohlova, M.; Ribeiro, S.; Rocha-Pereira, P.; Teixeira, L.; Nascimento, H.; Reis, F.; Miranda, V.; Bronze-da-Rocha, E.; Quintanilha, A.; Belo, L.; Costa, E.; Santos-Silva, A.
    We evaluated the potential cardiovascular risk protection of bilirubin in hemodialysis (HD) patients. An enlarged set of studies were evaluated in 191 HD patients, including hematological study, lipid profile, iron metabolism, nutritional, inflammatory markers, and dialysis adequacy. The TA duplication screening in the UDP-glucuronosyltransferase 1 A1 (UGT1A1) promoter region was also performed. The UGT1A1 genotype frequencies in HD patients were 49.2%, 42.4%, and 8.4% for 6/6, 6/7, and 7/7 genotypes, respectively. Although no difference was found in UGT1A1 genotype distribution between the three tertiles of bilirubin, significant differences were found with increasing bilirubin levels, namely, a decrease in platelet, leukocyte, and lymphocyte counts, transferrin, oxidized low-density lipoprotein (ox-LDL), ox-LDL/low-density lipoprotein cholesterol ratio, apolipoprotein (Apo) A, Apo B, and interleukin-6 serum levels and a significant increased concentration of hemoglobin, hematocrit, erythrocyte count, iron, transferrin saturation, Apo A/Apo B ratio, adiponectin, and paraoxonase 1 serum levels. After adjustment for age these results remained significant. Our data suggest that higher bilirubin levels are associated with beneficial effects in HD patients, by improving lipid profile and reducing the inflammatory grade, which might contribute to increase in iron availability. These results suggest a potential cardiovascular risk protection of bilirubin in HD patients
  • Effect of Aging in the Perception of Health-Related Quality of Life in End-Stage Renal Disease Patients under Online-Hemodiafiltration
    Publication . Moura, A.; Madureira, J.; Alija, P.; Fernandes, J.; Oliveira, J.; Lopez, M.; Filgueiras, M.; Amado, L.; Sameiro-Faria, M.; Miranda, V.; Santos-Silva, A.; Costa, E.
    This work aimed to evaluate how aging could influence patients’ perception of health quality of life (HRQOL), as well as, the effect of aging on dialysis adequacy and in hematological, iron status, inflammatory and nutritional markers. In this transversal study were enrolled 305 ESRD patients under Online-hemodiafiltration (OL-HDF) (59.67% males; 64.9 ± 14.3 years old). Data about comorbidities, hematological data, iron status, dialysis adequacy, nutritional and inflammatory markers were collected from patient’s records. Moreover, HRQOL score, by using the Kidney Disease Quality of Life-Short Form (KDQOL-SF), was assessed. Analyzing the results according to quartiles of age, significant differences were found for some parameters evaluated by the KDQOL-SF instrument, namely for work status, physical functioning and role-physical, which decreased with increasing age. We also found a higher proportion of diabetic patients, a decrease in creatinine, iron, albumin serum levels, transferrin saturation and nPCR, with increasing age. Moreover, significant negative correlations were found between age and mean cell hemoglobin concentration, iron, transferrin saturation, albumin, nPCR, work status, physical functioning and role-physical. In conclusion, our results showed that aging is associated with a decreased work status, physical functioning and role-physical, with a decreased dialysis adequacy, iron availability and nutritional status, and with an increased proportion of diabetic patients and of patients using central venous catheter, as the vascular access. The knowledge of these changes associated with aging, which have impact in the quality of life of the patients, could be useful in their management.
  • Urinary ATP may be a dynamic biomarker of detrusor overactivity in women with overactive bladder syndrome
    Publication . Silva-Ramos, M.; Silva, I.; Oliveira, O.; Ferreira, S.; Reis, M.; Oliveira, J.; Correia-de-Sá, P.
    Background Nowadays, there is a considerable bulk of evidence showing that ATP has a prominent role in the regulation of human urinary bladder function and in the pathophysiology of detrusor overactivity. ATP mediates nonadrenergic-noncholinergic detrusor contractions in overactive bladders. In vitro studies have demonstrated that uroepithelial cells and cholinergic nerves from overactive human bladder samples (OAB) release more ATP than controls. Here, we compared the urinary ATP concentration in samples collected non-invasively from OAB women with detrusor overactivity and age-matched controls. Methods Patients with neurologic diseases, history of malignancy, urinary tract infections or renal impairment (creatinine clearance <70 ml/min) were excluded. All patients completed a 3-day voiding diary, a 24 h urine collection and blood sampling to evaluate creatinine clearance. Urine samples collected during voluntary voids were immediately freeze-preserved for ATP determination by the luciferin-luciferase bioluminescence assay; for comparison purposes, samples were also tested for urinary nerve growth factor (NGF) by ELISA. Results The urinary content of ATP, but not of NGF, normalized to patients’ urine creatinine levels (ATP/Cr) or urinary volume (ATP.Vol) were significantly (P<0.05) higher in OAB women with detrusor overactivity (n = 34) than in healthy controls (n = 30). Significant differences between the two groups were still observed by boosting urinary ATP/Cr content after water intake, but these were not detected for NGF/Cr. In OAB patients, urinary ATP/Cr levels correlated inversely with mean voided volumes determined in a 3-day voiding diary. Conclusion A high area under the receiver operator characteristics (ROC) curve (0.741; 95% CI 0.62–0.86; P<0.001) is consistent with urinary ATP/Cr being a highly sensitive dynamic biomarker for assessing detrusor overactivity in women with OAB syndrome.
  • Estimating Kidney Function in the Critically Ill Patients
    Publication . Seller-Pérez, G.; Herrera-Gutiérrez, M.; Maynar-Moliner, J.; Sánchez-Izquierdo-Riera, J.; Marinho, A.; do Pico, J.
    Glomerular filtration rate (GFR) is an accepted measure for assessment of kidney function. For the critically ill patient, creatinine clearance is the method of reference for the estimation of the GFR, although this is often not measured but estimated by equations (i.e., Cockroft-Gault or MDRD) not well suited for the critically ill patient. Functional evaluation of the kidney rests in serum creatinine (Crs) that is subjected to multiple external factors, especially relevant overhydration and loss of muscle mass. The laboratory method used introduces variations in Crs, an important fact considering that small increases in Crs have serious repercussion on the prognosis of patients. Efforts directed to stratify the risk of acute kidney injury (AKI) have crystallized in the RIFLE or AKIN systems, based in sequential changes in Crs or urine flow. These systems have provided a common definition of AKI and, due to their sensitivity, have meant a considerable advantage for the clinical practice but, on the other side, have introduced an uncertainty in clinical research because of potentially overestimating AKI incidence. Another significant drawback is the unavoidable period of time needed before a patient is classified, and this is perhaps the problem to be overcome in the near future.
  • Acute Kidney Injury in the Critically Ill Patient
    Publication . Herrera-Gutiérrez, M.; Seller-Pérez, G.; Maynar-Moliner, J.; Sánchez-Izquierdo-Riera, J.; Marinho, A.; Do pico, J.