Characteristics, management and outcomes of atypical haemolytic uraemic syndrome in kidney transplant patients: a retrospective national study.

BACKGROUND: Kidney transplantation (KTx) is a strong trigger for the development of either recurrent or de novo atypical haemolytic uraemic syndrome (aHUS). According to previous studies, eculizumab (ECU) is effective for prophylaxis and for treatment of recurrence. METHODS: We evaluated the experiences of Spanish patients with recurrent and de novo aHUS associated with KTx, treated or not treated with ECU. In the de novo group, we classified patients as having early de novo (during the first month) or late de novo aHUS (subsequent onset). RESULTS: We analysed 36 cases of aHUS associated with KTx. All of the 14 patients with pre-KTx diagnosis of aHUS were considered to have high or moderate risk of recurrence. Despite receiving grafts from suboptimal donors, prophylactic ECU was effective for avoiding recurrence. The drug was stopped only in two cases with low-moderate risk of recurrence and was maintained in high-risk patients with no single relapse. There were 22 de novo aHUS cases and 16 belonged to the early de novo group. The median time of onset in the late group was 3.4 years. The early group had a better response to ECU than the late group, probably due to earlier diagnosis and use of the drug. No genetic pathogenic variant was detected in de novo aHUS cases, suggesting a secondary profile of the disease. ECU was stopped in all de novo patients with no relapses. ECU was well tolerated in all cases. CONCLUSIONS: Both groups (pre-aHUS and de novo) presented different clinical profiles, management approaches and outcomes. One should consider aHUS regardless of time after KTx. Genetic studies are crucial to stratify risks of relapse and to determine necessary lengths of treatment. We suggest short ECU treatment for de novo cases without pathogenic mutation and that ECU treatment be considered pre-emptively for patients with moderate or high risk of recurrence.

Inflammation, Senescence and MicroRNAs in Chronic Kidney Disease.

BACKGROUND: Patients with chronic kidney disease (CKD) show a chronic microinflammatory state that promotes premature aging of the vascular system. Currently, there is a growth interest in the search of novel biomarkers related to vascular aging to identify CKD patients at risk to develop cardiovascular complications. METHODS: Forty-five CKD patients were divided into three groups according to CKD-stages [predialysis (CKD4-5), hemodialysis (HD) and kidney transplantation (KT)]. In all these patients, we evaluated the quantitative changes in microRNAs (miRNAs), CD14+C16++ monocytes number, and microvesicles (MV) concentration [both total MV, and monocytes derived MV (CD14+Annexin V+CD16+)]. To understand the molecular mechanism involved in senescence and osteogenic transdifferentation of vascular smooth muscle cells (VSMC), these cells were stimulated with MV isolated from THP-1 monocytes treated with uremic toxins (txMV). RESULTS: A miRNA array was used to investigate serum miRNAs profile in CKD patients. Reduced expression levels of miRNAs-126-3p, -191-5p and -223-3p were observed in CKD4-5 and HD patients as compared to KT. This down-regulation disappeared after KT, even when lower glomerular filtration rates (eGFR) persisted. Moreover, HD patients had higher percentage of proinflammatory monocytes (CD14+CD16++) and MV derived of proinflammatory monocytes (CD14+Annexin V+CD16+) than the other groups. In vitro studies showed increased expression of osteogenic markers (BMP2 and miRNA-223-3p), expression of cyclin D1, ß-galactosidase activity and VSMC size in those cells treated with txMV. CONCLUSION: CKD patients present a specific circulating miRNAs expression profile associated with the microinflammatory state. Furthermore, microvesicles generated by monocytes treated with uremic toxins induce early senescence and osteogenic markers (BMP2 and miRNA-223-3p) in VSMC.

Hemoglobin variability in nondialysis chronic kidney disease: examining the association with mortality.

BACKGROUND AND OBJECTIVES: Anemia and hemoglobin (Hb) variability are associated with mortality in hemodialysis patients who are on erythropoiesis-stimulating agents (ESA). Our aim was to describe the degree of Hb variability present in nondialysis patients with chronic kidney disease (CKD), including those who were not receiving ESA, and to investigate the association between Hb variability and mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Hb variability was determined using 6 mo of "baseline" data between January 1, 2003, and October 31, 2005. A variety of definitions for Hb variability were examined to ensure consistency and robustness. RESULTS: A total of 6165 patients from 22 centers in seven countries were followed for a mean of 34.0 +/- 15.8 mo; 49% were prescribed an ESA. There was increased Hb variability with ESA use; the residual SD of Hb was 4.9 +/- 4.4 g/L in patients who were not receiving an ESA, compared with 6.8 +/- 4.8 g/L. Hb variability was associated with a small but significantly increased risk for death per g/L residual SD, irrespective of ESA use. Multivariate linear regression model explained only 11% of the total variance of Hb variability. CONCLUSIONS: Hb variability is increased in patients who have CKD and are receiving ESA and is associated with an increased risk for death (even in those who are not receiving ESAs). This analysis cannot determine whether Hb variability causally affects mortality. Thus, the concept of targeting Hb variability with specific agents needs to be examined within the context of factors that affect both Hb variability and mortality.

Cytometric bead array (CBA) for the measurement of cytokines in urine and plasma of patients undergoing renal rejection.

Renal rejection is associated with an active immune response regulated by cytokines and in which immunocompetent cells are involved. Previous studies have measured high levels of cytokines in the urine and plasma in various renal dysfunction states. However, some methods used to measured cytokines hinder their use as a diagnostic tool in renal rejection. In this report, cytokine levels were determined in the plasma and urine of kidney transplant patients, with renal rejection and without it, using a cytometric bead array (CBA) technique. Concentrations of six human cytokines (IL-2, IL-4, IL-5, IL-10, TNF-alpha and INF-gamma) were established. Results show that patients who develop renal rejection presented high levels of IL-10 and IFN-gamma cytokines in plasma and urine compared to patients without renal rejection. The CBA technique displayed greater sensitivity in the determination of cytokines in urine than the conventional ELISA technique. Finally, when standard cytokines in plasma and in urine were compared, it was observed that, in plasma, levels of IL-4, IL-5, IL-10, TNF-alpha and IFN-gamma were detected, whereas in urine the levels detected were of IL-4, IL-5, IL-10 and IFN-gamma. These results indicate that the CBA assay is a sensitive method to measure cytokines in urine. In kidney transplant patients undergoing acute renal rejection, the presence of cytokines in urine reflects renal damage and could be a useful method in the diagnosis of renal rejection.

Marked reduction in the prevalence of hepatitis C virus infection in hemodialysis patients: causes and consequences.

BACKGROUND: The prevalence of hepatitis C virus (HCV) infection in hemodialysis (HD) patients has decreased significantly in the course of the past decade in most HD units. The objective of this study is to analyze the causes of this reduction and obtain additional information for the near future that could be of use for health services planning. METHODS: All patients who underwent HD in the Province of Cordoba, Spain, between January 1992 and December 2002 were studied. We analyzed annual exclusions from the HD program of HCV-positive patients (deaths and kidney transplantations) and inclusions (predialysis patients, patients with chronic graft rejection, and HD patients with acute HCV infection). The trend in the time series of measurements was calculated by means of exponential smoothing with 2 parameters. RESULTS: In December 1992, the prevalence of antibody to HCV (anti-HCV) was 24% (N = 54), whereas by December 2002, it had decreased to 9.2% (N = 35). Of 657 predialysis patients included in the maintenance HD program, 2.8% (n = 19) were positive for anti-HCV. Annual mean incidence of acute HCV infection was 0.5%, and the median was 0.32%. Mean crude annual mortality rates were 12.2% for anti-HCV-positive patients versus 9.9% for anti-HCV-negative patients. The trend in this time series suggests that by 2006, the prevalence of anti-HCV in HD patients will be approximately 2.5%. CONCLUSION: Causes implicated in the reduction in prevalence of HCV infection in HD patients are a greater mortality rate, stabilization of the incidence of acute HCV infection, and a low percentage of HCV infection in predialysis patients. By the end of 2006, the rate of HCV infection in HD patients will be very close to that of the predialysis population.