Josefina Santos

Impact Assessment in Living Kidney Donation: Psychosocial Aspects in the Donor

BACKGROUND Living donor kidney transplantation has a positive influence on graft survival and recipient quality of life (QoL). We assessed the psychosocial impact of donation to the donor. METHODS Before and after the procedure 32 living kidney donors (mean age 41 years) completed the Zung Self-Rating Anxiety and Depression Scales; a Sociodemographic, Short-Form 36 Health Survey (SF-36), and a Donation Perceptions Questionnaire. RESULTS Living kidney donors were siblings (62.5%), parents (34.4%), or a daughter (3.1%). Transplantation was not successful in two cases: one recipient death and one graft failure. No significant changes were observed in donor QoL except for the SF-36 social functioning subscale that showed significant improvement after donation (P = .038). A reduction in depression symptom frequency was verified after donation (from 65.6% to 46.9%). There was an almost significant decrease in depression scores (P = .077), which was in fact was significant when one considered only successful transplants (P = .021). There was no significant variation in anxiety scores among donors. Time since transplantation was inversely correlated with overall anxiety (r = .443, P = .011), and with somatic anxiety subscales (r = .357, P = .045). For most donors, the decision to donate was easy and spontaneous. Nearly all donors would donate again and strongly encourage others to donate. CONCLUSIONS Except for the social functioning scale that improved, no significant changes were observed in QoL of living kidney donors after the procedure. Depression scores significantly decreased after donation, but anxiety scores remained stable. Donors, who were mostly siblings, showed positive perceptions about donation, did not regret their decision, and strongly recommend it to others.

Metformin in patients with chronic kidney disease: strengths and weaknesses.

A wide array of benefits has been attributed to metformin. These include attenuation of abnormal glucose metabolism (diabetes treatment and prevention), weight neutrality or weight loss, improvement in the pathophysiologic components of metabolic syndrome (insulin resistance, subclinical inflammation, and endothelial dysfunction), lipid-lowering properties, cardiovascular protection, and antineoplastic potential. Metformin itself is not a nephrotoxic drug. Initially appointed as the safest hypoglycemic agent in chronic kidney disease, its use has been limited in these patients because of the perceived risk of lactic acidosis. A fear perpetuated by numerous case reports in which it is implicated. Current guidelines stipulate that it must be used with caution in estimated glomerular filtration rates (eGFRs) of less than 60 mL/minute and not at all in eGFRs of less than 30 mL/minute. Identified risk factors for metformin-associated lactic acidosis include acute kidney injury, hypoxemia, sepsis, alcohol abuse, liver failure, myocardial infarction, and shock. Treatment may include supportive care and dialysis techniques. On the other hand, it is likely that the use of metformin would be beneficial in many with chronic kidney disease according to the advantages associated with attenuation of metabolic syndrome and cardiovascular protection. The reality of severe metformin-induced lactic acidosis in the absence of chronic renal impairment raises the question of limitation of its use in these patients.

Oxidative stress in kidney transplantation: malondialdehyde is an early predictive marker of graft dysfunction.

Background Oxidative stress is one of the most important components of the ischemia-reperfusion process after kidney transplantation (KTx) and increases with graft dysfunction. Methods This prospective study was conducted on 40 consecutive KTx recipients to evaluate time-dependent changes in oxidative stress-related parameters within the first week after KTx and to assess their performance in predicting delayed graft function (DGF=dialysis requirement during initial posttransplant week) and graft function at 1 year. Blood samples were collected before (day 0) and after KTx (days 1, 2, 4, and 7). Total antioxidant capacity, plasma levels of malondialdehyde (MDA), and activities of glutathione peroxidase, glutathione reductase and superoxide dismutase were measured. Multivariable linear mixed and linear regression models, receiver-operating characteristic (ROC), and areas under ROC curves (AUC-ROC) were used. Results At all time points after KTx, mean MDA levels were significantly higher in patients developing DGF (n=18). Shortly after KTx (8–12 hr), MDA values were higher in DGF recipients (on average, +0.16 &mgr;mol/L) and increased further on following day, contrasting with prompt functioning recipients. Day 1 MDA levels accurately predicted DGF (AUC-ROC=0.90), with a performance higher than SCr (AUC-ROC=0.73) and similar to cystatin C (AUC-ROC=0.91). Multivariable analysis revealed that MDA levels on day 7 represented an independent predictor of 1-year graft function. Antioxidant enzyme activities were not significantly changed during the study period and were not predictors of 1-year graft function. Conclusions Increased MDA levels on day 1 after KTx might be an early prognostic indicator of DGF, and levels on day 7 might represent a useful predictor of 1-year graft function.

Estimating glomerular filtration rate in kidney transplantation: Still searching for the best marker.

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.

Neutrophil Gelatinase-Associated Lipocalin in Kidney Transplantation Is an Early Marker of Graft Dysfunction and Is Associated with One-Year Renal Function

Urinary neutrophil gelatinase-associated lipocalin (uNGAL) has been suggested as potential early marker of delayed graft function (DGF) following kidney transplantation (KTx). We conducted a prospective study in 40 consecutive KTx recipients to evaluate serial changes of uNGAL within the first week after KTx and assess its performance in predicting DGF (dialysis requirement during initial posttransplant week) and graft function throughout first year. Urine samples were collected on post-KTx days 0, 1, 2, 4, and 7. Linear mixed and multivariable regression models, receiver-operating characteristic (ROC), and areas under ROC curves were used. At all-time points, mean uNGAL levels were significantly higher in patients developing DGF (n = 18). Shortly after KTx (3–6 h), uNGAL values were higher in DGF recipients (on average +242 ng/mL, considering mean dialysis time of 4.1 years) and rose further in following days, contrasting with prompt function recipients. Day-1 uNGAL levels accurately predicted DGF (AUC-ROC = 0.93), with a performance higher than serum creatinine (AUC-ROC = 0.76), and similar to cystatin C (AUC-ROC = 0.95). Multivariable analyses revealed that uNGAL levels at days 4 and 7 were strongly associated with one-year serum creatinine. Urinary NGAL is an early marker of graft injury and is independently associated with dialysis requirement within one week after KTx and one-year graft function.

Long-term peritoneal dialysis experience in Portugal

Peritoneal dialysis (PD) penetration varies widely. Since the beginning of this therapy, indications have changed and outcomes have improved. In Portugal, PD still remains clearly underutilized. The results of a 20 year PD programme were evaluated: 312 cumulative patients, 48±16 years, 27% >60 years old, 27% diabetic, 59% with prior hemodialysis (HD). The main reason for admission was vascular access failure (48.7%). Admission due to patient preference has increased significantly between first and second decades of the programme (33% vs 47% (P<0.001)); 98 patients (31.4%) were treated with automated PD but this prescription increased to 43% of the active patients. A total of 376 Tenckhoff catheters were surgically implanted, recently by the Popovich-Moncrief technique (77 catheters): the cumulative survival was 82%, 64% and 50% at 1, 3 and 5 years, respectively. A better catheter survival was found in the last decade (85.7%, 69.6%, 54.8% versus 77.3%, 55.5%, 40.2%, at 1, 3 and 5 years, respectively (P=0.007). The patient and technique cumulative survivals were 91, 74, 55% and 85, 67, 41%, at 1, 3, and 5 years, respectively. The main drop-out was to hemodialysis (35.8%), followed by death (23.7%), and transplantation (21.5%). Peritonitis and access-related infections caused 35% of the transfer to HD. Cardiovascular events caused 58% of deaths. The median PD retention was 35.5 months. The rate of peritonitis has decreased to one episode /30 patient months. Hospital admission has also decreased to 4.8 days/patient year. This is a first report on long-term PD experience in Portugal. It has been an effective modality of renal replacement therapy, reflected by the growing patient preference in our PD programme. Experience, knowledge and new technical solutions have improved the outcomes.

Leptin and Adiponectin During the First Week After Kidney Transplantation: Biomarkers of Graft Dysfunction?

CONTEXT AND OBJECTIVE Based on evidence that leptin and adiponectin are removed from circulation primarily by the kidney, we designed a study to examine the longitudinal changes of these adipokines during the first week after kidney transplantation (KTx) and to test the hypothesis that higher levels of leptin and/or adiponectin could be early biomarkers of delayed graft function (DGF=dialysis requirement during the first post-transplant week) and acute rejection. STUDY DESIGN Repeated-measures prospective study. MATERIAL AND METHODS Forty consecutive adult patients with end-stage renal disease who were undergoing KTx. Leptin and adiponectin were measured in blood samples that were collected before (day-0) and after KTx (days-1, 2, 4 and 7). Linear mixed-models, receiver operating characteristic and area under curve (AUC-ROC) were used. RESULTS At post-transplant day-1, leptinemia and adiponectinemia declined 43% and 47%, respectively. At all times studied after KTx, the median leptin levels were significantly higher in patients developing DGF (n=18), but not adiponectin levels. Shortly after KTx (day-1), leptin values were significantly higher in DGF recipients in contrast to patients with promptly functioning kidneys, approximately two times higher when controlling for gender and BMI. The leptin reduction rate between pre-tranplant and one-day after KTx moderately predicted DGF (AUC=0.73). On day-1, serum leptin predicted DGF (AUC-ROC=0.76) with a performance slightly better than serum creatinine (AUC-ROC=0.72), even after correcting for BMI (AUC-ROC=0.73). Separating this analysis by gender showed that the performance of leptin in predicting DGF for male gender (AUC-ROC=0.86) improved. CONCLUSIONS Kidney graft function is an independent determinant of leptin levels, but not of adiponectin. Leptin levels at day-1 slightly outperformed serum creatinine in predicting the occurrence of DGF, and more accurately in male gender. No significant association was detected with acute rejection.

Diagnosis and Treatment of Acute Humoral Kidney Allograft Rejection

Acute humoral rejection (AHR) is a severe form of rejection associated with poor graft survival. Prompt diagnosis and rapid institution of therapy are crucial to improve the prognosis. A therapeutic approach based on plasmapheresis, intravenous imunoglobulin, and rituximab seems to be effective in refractory cases. Herein we have described our experience with 11 patients with biopsy-proven AHR who were treated between January 2005 and June 2008. Seven of these patients had panel reactive antibodies titers more than 50%. The diagnosis was based on Banff 2001 criteria; treatment consisted of a combination of plasmapheresis and intravenous immunoglobulin. Four refractory cases were also treated with a single dose of rituximab. One graft was lost due to thrombosis. All other patients recovered graft function with an average creatinine level of 1.6 mg/dL at 8.6 +/- 2.7 months of follow-up.

Characterization of End-Stage Renal Disease After Liver Transplantation in Transthyretin Amyloidosis (ATTR V30M)

Transthyretin (TTR) amyloidosis, an autosomal-dominant disease, is characterized by peripheral and autonomic neuropathy--familial amyloidotic polyneuropathy (FAP). End-stage renal disease (ESRD) occurs at 10 years after the onset of neuropathy. Orthotopic liver transplantation (OLT) is the usual treatment of choice. We evaluated FAP patients, ATTR V30M, before and after OLT who started dialysis within 3 months after surgery. The 11 patients had an age at the onset of neuropathy of 31.9 ± 6.3 years with a mean evolution of disease to OLT of 4.54 ± 2.5 years. The glomerular filtration rate was <60 mL/min in 2 patients, 2 displayed nephrotic range proteinuria, and 3 had microalbuminuria. Elective pacemaker implantation was necessary in 8 subjects. Post-OLT 3 patients developed proteinuria, 2 of whom showed increasing nephrotic syndrome. Dysautonomia worsened leading to bladder catheterization in 6. In patients with previous normal renal function and proteinuria <3 g/d, the evolution of neuropathy to the first dialysis was 14.6 ± 4.2 years versus 7.5 ± 1.1 among the other subjects. Overall, dialysis was implemented at 7.4 ± 4.9 years after surgery. There was no liver graft dysfunction. The heart evaluation post-OLT showed the following: 3 patients with de novo dysrhythmias requiring pacemaker implantation and 3 with N-terminal pro-natriuretic peptide levels >10,000 pg/mL. Death occurred in 4 subjects at an average of 26 months after initiation of dialysis. Concerning ESRD, there was no clear benefit of transplantation in the early stages. Patients with normal renal function and lower levels of proteinuria showed slower progression to ESRD, irrespective of their duration of neuropathy.

Characterization of the fast neutron irradiation facility of the Portuguese Research Reactor after core conversion

The fast neutron irradiation facility of the Portuguese Research Reactor was characterized after the reduction in uranium enrichment and rearrangement of the core configuration. In this work we report on the determination of the hardness parameter and the 1MeV equivalent neutron flux along the facility, in the new irradiation conditions, following ASTM E722 standard.