Supplemented ERA-EDTA Registry data evaluated the frequency of dialysis, kidney transplantation, and comprehensive conservative management for patients with kidney failure in Europe.

The aims of this study were to determine the frequency of dialysis and kidney transplantation and to estimate the regularity of comprehensive conservative management (CCM) for patients with kidney failure in Europe. This study uses data from the ERA-EDTA Registry. Additionally, our study included supplemental data from Armenia, Germany, Hungary, Ireland, Kosovo, Luxembourg, Malta, Moldova, Montenegro, Slovenia and additional data from Israel, Italy, Slovakia using other information sources. Through an online survey, responding nephrologists estimated the frequency of CCM (i.e. planned holistic care instead of kidney replacement therapy) in 33 countries. In 2016, the overall incidence of replacement therapy for kidney failure was 132 per million population (pmp), varying from 29 (Ukraine) to 251 pmp (Greece). On 31 December 2016, the overall prevalence of kidney replacement therapy was 985 pmp, ranging from 188 (Ukraine) to 1906 pmp (Portugal). The prevalence of peritoneal dialysis (114 pmp) and home hemodialysis (28 pmp) was highest in Cyprus and Denmark respectively. The kidney transplantation rate was nearly zero in some countries and highest in Spain (64 pmp). In 28 countries with five or more responding nephrologists, the median percentage of candidates for kidney replacement therapy who were offered CCM in 2018 varied between none (Slovakia and Slovenia) and 20% (Finland) whereas the median prevalence of CCM varied between none (Slovenia) and 15% (Hungary). Thus, the substantial differences across Europe in the frequency of kidney replacement therapy and CCM indicate the need for improvement in access to various treatment options for patients with kidney failure.

Severe and malignant hypertension are common in primary atypical hemolytic uremic syndrome.

Malignant hypertension is listed among the causes of secondary thrombotic microangiopathy, but pathogenic mutations in complement genes have been reported in patients with hypertension-induced thrombotic microangiopathy. Here we investigated the frequency and severity of hypertension in 55 patients with primary atypical hemolytic uremic syndrome (aHUS). A genetic analysis was performed in all patients, and funduscopic examination was performed in all the patients with Grades 2 and 3 hypertension. A cohort of 110 patients with malignant hypertension caused by diseases other than aHUS served as control. Thirty-six patients with aHUS presented Grade 2 or Grade 3 hypertension and funduscopic examination showed malignant hypertension in 19. Genetic abnormalities in complement were found in 19 patients (37% among patients with malignant hypertension). Plasmapheresis was performed in 46 patients and 26 received eculizumab. Renal and hematological responses were significantly lower after plasmapheresis (24%) than after eculizumab (81%). Renal survival was significantly higher in patients treated with eculizumab (85% at one, three and five years) compared to patients who did not receive this treatment (54%, 46% and 41%), respectively. Response to eculizumab was independent of hypertension severity and the presence of complement genetic abnormalities. Among patients with malignant hypertension caused by other diseases the prevalence of thrombotic microangiopathy was very low (5%). Thus, severe and malignant hypertension are common among patients with aHUS and eculizumab treatment leads to a higher renal survival when compared to plasmapheresis. However, thrombotic microangiopathy is uncommon among patients presenting with malignant hypertension caused by diseases other than aHUS.

Effectiveness of mycophenolate mofetil in C3 glomerulonephritis.

C3 glomerulonephritis is a clinicopathologic entity defined by the presence of isolated or dominant deposits of C3 on immunofluorescence. To explore the effect of immunosuppression on C3 glomerulonephritis, we studied a series of 60 patients in whom a complete registry of treatments was available over a median follow-up of 47 months. Twenty patients had not received immunosuppressive treatments. In the remaining 40 patients, 22 had been treated with corticosteroids plus mycophenolate mofetil while 18 were treated with other immunosuppressive regimens (corticosteroids alone or corticosteroids plus cyclophosphamide). The number of patients developing end-stage renal disease was significantly lower among treated compared with untreated patients (3 vs. 7 patients, respectively). No patient in the corticosteroids plus mycophenolate mofetil group doubled serum creatinine nor developed end-stage renal disease, as compared with 7 (significant) and 3 (not significant), respectively, in patients treated with other immunosuppressive regimens. Renal survival (100, 80, and 72% at 5 years) and the number of patients achieving clinical remission (86, 50, and 25%) were significantly higher in patients treated with corticosteroids plus mycophenolate mofetil as compared with patients treated with other immunosuppressive regimens and untreated patients, respectively. Thus, immunosuppressive treatments, particularly corticosteroids plus mycophenolate mofetil, can be beneficial in C3 glomerulonephritis.

Mycophenolate in refractory and relapsing lupus nephritis.

BACKGROUND: Mycophenolate (MF) is effective as induction and maintenance treatment in patients with lupus nephritis (LN). This study evaluates the efficacy and safety of MF in patients with refractory and relapsing LN. METHODS: Data were retrospectively obtained for 85 patients (35 refractory and 50 relapsing) from 11 nephrology departments in Spain. The primary endpoints were the incidence and cumulative number of renal responses and relapses and their relationship with baseline clinical and analytical data. The secondary endpoint was the appearance of side effects. RESULTS: The main clinical and analytical variables were similar both in refractory and relapsing LN. Most of the patients had received cyclophosphamide, and all of them switched to MF. 74 patients (87%) achieved a response (69% partial, 31% complete). Age at starting MF, gender, pathological classification, body mass index, blood pressure, baseline renal function, and proteinuria were not associated with achieving response. After stopping MF, 3 of 19 patients (15.7%) relapsed, all at 6 months of follow-up. No differences were found between clinical and analytical variables and number of relapses. Side effects were unremarkable, except for 1 patient, who died of thrombocytopenia and ovarian hemorrhage. CONCLUSIONS: Switching to MF from other immunosuppressive treatments is effective and safe in refractory and relapsing LN.

Spontaneous remission of nephrotic syndrome in membranous nephropathy with chronic renal impairment.

BACKGROUND: Spontaneous remission (SR) of nephrotic syndrome, in the absence of immunosuppressive treatment, is relatively common among patients with idiopathic membranous nephropathy (IMN) and normal renal function. However, it has not been reported in patients with chronic renal impairment. METHODS: All patients with IMN who had developed SR in the presence of chronic renal insufficiency were identified among the nephrology departments that belong to the Spanish Group for the Study of Glomerular Diseases (GLOSEN). Their characteristics and outcome after SR were studied. RESULTS: Eleven patients were identified. All of them showed renal insufficiency and nephrotic syndrome at the time of renal biopsy. Serum creatinine (Scr) continued to increase in the following months, reaching a peak value of 2.6 ± 1.5 mg/dL (range 1.7-6.5). Angiotensin converting enzyme inhibitors or spironolactone were prescribed in 10/11 patients at renal biopsy or shortly after it. Nephrotic proteinuria persisted during the first months of follow-up, but it started to spontaneously decrease 12 ± 7 months (2-30 months) after renal biopsy. Finally, complete (nine patients) or partial (two patients) remission of nephrotic syndrome was observed. Coinciding with proteinuria remission, renal function tended to improve. Nephrotic syndrome relapsed in two patients, accompanied by a rapid deterioration of renal function. In the remaining nine patients, remission persisted throughout a follow-up of 146 ± 64 months. Mean Scr at the last visit was 1.9 ± 0.9 mg/dL and proteinuria 0.2 g/24 h. CONCLUSION: SR of nephrotic syndrome can also be observed in membranous nephropathy patients exhibiting chronic renal impairment.

Spontaneous remission of nephrotic syndrome in idiopathic membranous nephropathy.

Spontaneous remission is a well known characteristic of idiopathic membranous nephropathy, but contemporary studies describing predictors of remission and long-term outcomes are lacking. We conducted a retrospective, multicenter cohort study of 328 patients with nephrotic syndrome resulting from idiopathic membranous nephropathy that initially received conservative therapy. Spontaneous remission occurred in 104 (32%) patients: proteinuria progressively declined after diagnosis until remission of disease at 14.7 +/- 11.4 months. Although spontaneous remission was more frequent with lower levels of baseline proteinuria, it also frequently occurred in patients with massive proteinuria: 26% among those with baseline proteinuria 8 to 12 g/24 h and 22% among those with proteinuria >12 g/24 h. Baseline serum creatinine and proteinuria, treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists, and a >50% decline of proteinuria from baseline during the first year of follow-up were significant independent predictors for spontaneous remission. Only six patients (5.7%) experienced a relapse of nephrotic syndrome. The incidence of death and ESRD were significantly lower among patients with spontaneous remission. In conclusion, spontaneous remission is common among patients with nephrotic syndrome resulting from membranous nephropathy and carries a favorable long-term outcome with a low incidence of relapse. A decrease in proteinuria >50% from baseline during the first year predicts spontaneous remission.

A search for cyclophilin-A gene variants in cyclosporine A-treated renal transplanted patients.

BACKGROUND: The cyclophilin A (CypA)-cyclosporine (CsA) complex promotes immune response. The variation at the CypA gene could explain CsA-pharmacokinetics and clinical outcomes among CsA-treated patients. METHODS: The study included 290 kidney transplanted patients (65% male; mean age 51 +/- 15 yr), treated with CsA. The five CypA- exons and the promoter region were analysed through single-strand conformation analysis, denaturing high performance liquid chromatography, and direct sequencing. The effect of a promoter polymorphism (-11 G/C) on gene expression was analysed in cell-cultures. RESULTS: We found two polymorphisms in the promoter (-11 G/C) and exon 1 (+36 G/A). Genotype frequencies did not differ between patients according to their pharmacokinetics status. In vitro studies showed that -11 G/C affected gene expression. The -11 G allele was significantly associated with clinical nephrotoxicity (p = 0.006). The strongest predictors for nephrotoxicity were a donor age > or =55 yr, and the promoter GG + GC genotypes. CONCLUSIONS: Our work suggests that a CypA-promoter polymorphism (-11 G/C) could be associated with clinical nephrotoxicity. Replication of this study in other populations is necessary to define the role of CypA-variants in the main clinical outcomes among CsA-treated kidney-transplanted patients.

Quality of life of patients with chronic renal allograft rejection and anemia.

BACKGROUND: The treatment with recombinant human erythropoietin (rHuEPO) of anemia associated with renal insufficiency (RI) improves the health-related quality of life (HRQOL) of those patients. The objective of this study was to evaluate the HRQOL of patients with chronic allograft nephropathy (CAN) and anemia associated to RI, and the effect of rHuEPO treatment on the HRQOL. METHODS: This prospective study consisted of 17 kidney transplant patients with RI caused by CAN and anemia who received rHuEPO. The hemoglobin (Hb) target was 12 g/dL. Serum Hb, hematocrit (Hct) and creatinine clearance (CrCl) were collected. HRQOL was evaluated with the Kidney Disease Quality of Life Short-Form 36 (SF-36) questionnaire at the start, at the 3rd and 6th month and at the end of the follow-up. SF-36 scores (eight scales, physical component summary (PCS) and mental component summary (MCS) were standardized by age and gender using the Spanish population norms. The "effect size" was also calculated for each score. RESULTS: Hb and Hct statistically improved from the start to the 3rd month and to the end of the study (p<0.01). Although the CrCl remained stable during most of the follow-up, it worsened (p=0.002) around the 13th month. SF-36 scores at the beginning were worse than that of the general population. Three SF-36 scales statistically improved; role-physical, vitality and mental health. The effect size was moderate for pain (0.41), role-emotional (0.39) and MCS (0.42); and large for role-physical (0.65), vitality (0.81) and mental health (0.74). CONCLUSIONS: The poor HRQOL of patients with CAN and anemia improves with rHuEPO treatment, the effect size varying from moderate to large.

Relationship between functional ability in older people, immune system status, and intensity of response to CMV.

Shorter survival in the elderly has been associated with deterioration of the immune system and also with functional disability. To analyze the relationship between functional and immune impairment in older individuals, we studied 100 elderly who lived in a nursing home, were age matched, and grouped according to their functional status. We characterized cell subpopulations by flow cytometry, quantified TREC by RT-PCR, and measured the T-cell proliferation and activation response (IFN-γ by ELISPOT, CD69) against anti-CD3 and CMV. Specific antibody titers against influenza virus and CMV were determined by ELISA. Individuals with worse functional status had significantly higher levels of NK cells and fewer B cells. These poorly functioning elders also had a significantly lower proportion of CD4+ T cells, increased CD8+ T cells, and a decreased CD4/CD8 ratio. TREC levels in CD4+ T cells were significantly lower in individuals with a high disability. Lower TREC levels correlated with a lower frequency of naïve T-cell subpopulations (CD45RA+CCR7+) and higher percentages of effector cells (CD45RA-CCR7-). The functionally impaired group had lower anti-CD3 responses, but gradually increased responses against CMV. Similarly, the higher CMV titers were found in elderly with worse functional status. On the contrary, the functional response in vivo, and the titer of antibodies generated after vaccination against influenza virus, was higher in individuals with better performance status. In summary, we concluded that the functional decline of elderly individuals was clearly associated with the aging of their immune system, and the intensity of the response to CMV.

NKG2D expression in CD4+ T lymphocytes as a marker of senescence in the aged immune system.

Human aging is characterized by changes in the immune system which have a profound impact on the T-cell compartment. These changes are more frequently found in CD8+ T cells, and there are not well-defined markers of differentiation in the CD4+ subset. Typical features of cell immunosenescence are characteristics of pathologies in which the aberrant expression of NKG2D in CD4+ T cells has been described. To evaluate a possible age-related expression of NKG2D in CD4+ T cells, we compared their percentage in peripheral blood from 100 elderly and 50 young adults. The median percentage of CD4+ NKG2D+ in elders was 5.3% (interquartile range (IR): 8.74%) versus 1.4% (IR: 1.7%) in young subjects (p < 0.3 × 10(-10)). CD28 expression distinguished two subsets of CD4+ NKG2D+ cells with distinct functional properties and differentiation status. CD28+ cells showed an immature phenotype associated with high frequencies of CD45RA and CD31. However, most of the NKG2D+ cells belonged to the CD28(null) compartment and shared their phenotypical properties. NKG2D+ cells represented a more advanced stage of maturation and exhibited greater response to CMV (5.3 ± 3.1% versus 3.4 ± 2%, p = 0.037), higher production of IFN-γ (40.56 ± 13.7% versus 24 ± 8.8%, p = 0.015), lower activation threshold and reduced TREC content. Moreover, the frequency of the CD4+ NKG2D+ subset was clearly related to the status of the T cells. Higher frequencies of the NKG2D+ subset were accompanied with a gradual decrease of NAIVE and central memory cells, but also with a higher level of more differentiated subsets of CD4+ T cells. In conclusion, CD4+ NKG2D+ represent a subset of highly differentiated T cells which characterizes the senescence of the immune system.

Identification of epitopes and immunodominant regions on the MICA protein defined by alloantibodies from kidney transplant patients.

BACKGROUND: Several reports showed a contribution of anti-MICA (major histocompatibility complex class I chain-related molecule A) antibodies (Abs) to the development of acute and chronic rejection. Identification of the epitopes to which the Abs bind may help to determine immunoreactive regions essential for the major histocompatibility complex compatibility between donor and recipients, leading to the best outcome of the transplant. METHODS: Sera from 284 kidney transplant patients were screened for anti-MICA Abs by Luminex assay. MICA allele typing of the recipients was determined. The epitopes of MICA were mapped by screening a synthesized library of overlapping peptides from the extracellular domains of the protein against the sera from kidney transplant patients with anti-MICA Abs. RESULTS: Antibodies against MICA were detected in 50 of 284 patients (17.6%) and correlated with the development of acute rejection. Nine antigenic regions were immunoreactive with anti-MICA Abs in the sera samples. Four of these continuous epitopes mapped to polymorphic amino acids (aa). Five antigenic regions were shared epitopes found in all the MICA alleles. The polymorphic residues, 173 (E/K), 175 (S/G), and 181 (R/T), had determined allele-specific epitopes (reactivity patterns 1 and 2). In contrast, the aa 208Y and 213T were implicated in the cross-reactivity among alleles. CONCLUSIONS: The presence of anti-MICA Abs could be an important marker for diagnosis because of their contribution to the outcome of the graft, regardless of presence of anti-HLA Abs. Additionally, the identification of epitopes revealed the in vivo antigens of the transplant and is spurring the development of new matching strategies to reduce the incidence of acute and chronic rejection.

CD127(low) expression in CD4+CD25(high) T cells as immune biomarker of renal function in transplant patients.

BACKGROUND: Noninvasive tests measuring cellular immunity could help predict immunologic risk and subsequent allograft dysfunction in transplant patients. CD25 is a promising marker of activation. Recent descriptions of CD127 expression as a discriminating factor between regulatory and activated T cells suggest its potential utility. METHODS: Expression of CD127 in CD4+CD25 T cells was analyzed by flow cytometry in peripheral blood from 62 renal transplanted patients and 30 healthy controls. Forty patients presented stable graft function and 22 suffered renal failure. RESULTS: Renal transplant patients showed higher levels of CD127(high) and a lower frequency of CD127(low) than healthy controls (0.63% vs. 0.29% [P<0.001] and 1.4% vs. 2.4% [P<0.001], respectively). However, high frequencies of not only CD127(high) but also CD127(low) showed a significant correlation with serum creatinine levels (P=0.012 and P=0.003, respectively). Allogenic stimulation in vitro increased the frequency of CD127(low) subset in a dose dependent manner. Furthermore, in patients with a high frequency of CD127(low) subset, this consisted mostly of FoxP3 negative cells, discarding their regulatory origin. Median frequency of CD127(low), but not CD127(high), cells showed significant differences between patients with stable function and with renal failure (P<0.005), with 16.7% and 53.1% of individuals above the median CD127(low) value (1.4%), respectively. CONCLUSION: Quantification of CD127(low) subset through staining of CD4+ T cells with the combined markers CD127/CD25/CD45RO has been demonstrated to be a significant tool for monitoring the outcome course of renal transplant patients.

The timely construction of arteriovenous fistulae: a key to reducing morbidity and mortality and to improving cost management.

BACKGROUND: Some investigators have shown that the initial placement of a catheter or graft, instead of the timely construction of an arteriovenous fistula (AVF), late referral to nephrology services and unplanned dialysis increase morbidity and mortality in chronic haemodialysis (CHD) patients. Furthermore, a delay in providing an adequate AVF entails significant increases in treatment-related costs. This study was limited to the analysis of the effects of the lack of an adequate vascular access for CHD on morbidity and mortality. METHODS: According to the vascular access they had in the first 3 months of CHD treatment 96 patients were divided into three groups (VA group): Group 1 (G1), having an adequate AVF in the first 3 months; Group 2 (G2), starting with a catheter but finishing with an AVF; and Group 3 (G3) starting and finishing with a catheter. Time-dependent Cox regression analysis was performed to identify variables associated with survival, and the standardized mortality index (SMI) was calculated. Finally, we studied cost-effectiveness. RESULTS: Time-dependent Cox regression and logistic regression analyses showed the statistically significant variable to be the VA group. To ensure that mortality was comparable between VA groups, eliminating age bias, the findings were adjusted applying SMI. G1 patients appear to have a lesser risk of death (relative risk, 0.39) than G2 and G3 patients, as do G2 relative to G3 patients. Also, after adjustment with SMI, patients over 65 years, presumably at greater risk of death, have a lower mortality than the

Documento básico da 1ª CNCTS / Basic document of 1st National Conference of Science and Technology in Health

Contém idéias e propostas originadas de texto preliminar elaborado em julho de 1994, enriquecidas com contribuições geradas de discussões institucionais e conferências estaduais de ciência e tecnologia em saúde, constituindo-se em subsídios para a I Conferência Nacional de Ciência e Tecnologia em Saúde