Preclinical Assessment of Autologous Tolerogenic Dendritic Cells From End-stage Renal Disease Patients.

BACKGROUND: Kidney transplantation is the therapeutic of choice for patients with kidney failure. While immunosuppressive drugs can control graft rejection, their use is associated with increased infections and cancer, and they do not effectively control chronic graft rejection. Cell therapy is an attractive strategy to minimize the use of pharmacological drugs. METHODS: We recently developed a protocol to generate human monocyte-derived autologous tolerogenic dendritic cells (ATDCs) from healthy volunteers. Herein, we transferred the ATDC manufacturing protocol to a Good Manufacturing Practice (GMP)-compliant facility. Furthermore, we compared the phenotype and in vitro functions of ATDCs generated from patients with end-stage renal disease to those generated from healthy volunteers. RESULTS: We describe the critical steps for GMP-compliant production of ATDCs and define the quality criteria required to allow release of the cell products. Furthermore, we showed that ATDCs generated from healthy volunteers and patients with kidney failure display the same tolerogenic profile based on their phenotype, resistance to maturation, and ability to modulate T-cell responses. CONCLUSIONS: Together, these results allowed us to define the production process and the quality criteria for the release of ATDCs before their administration in patients receiving a kidney transplant.

Warm red blood cell autoantibodies and clinical diagnoses in patients with or without autoimmune hemolysis.

OBJECTIVES: Red blood cell autoantibodies (RBC autoAbs) of IgG class are found in the majority of patients with warm autoimmune hemolytic anemia (wAIHA) but sometimes also during the pretransfusion testing of patients with different diagnoses but without hemolysis. The aim of the study was to identify the main differences between these two groups of patients according to age, gender, subclass and titer of IgG RBC autoAbs and diagnosis. MATERIAL AND METHODS: In the 9-year retrospective study, data were collected from records of 291 patients with IgG RBC autoAbs detected by gel technique, from which 111 with wAIHA. RESULTS: More than 85% of patients in both groups were over 40 years old, with male to female ratio 1:1.9 in wAIHA vs 1:1.3 in patients without hemolysis (P=0.0916). The main characteristics of patients with wAIHA vs patients without hemolysis were: IgG only 38% vs 70%, IgG+Complement 62% vs 30%, total IgG1 79% vs 55%, IgG1+IgG3 35% vs 11%, titer of 100 for IgG1+IgG3 17% vs 3% (P<0.0001), respectively, while titer of 100 for IgG1 18% vs 9% (P=0.0241). The underlying diagnosis in wAIHA vs patients without hemolysis: hematologic disorders 41% vs 22% (P=0.0006), autoimmune disorders 12% vs 13% (P=0.8033), solid tumors 5% vs 14% (P=0.0154) and surgery procedures 6% vs 26% (P<0.0001). CONCLUSION: We observed more wAIHA patients with high titer of IgG1 and high prevalence of IgG1+IgG3 and consider that patients without hemolysis having identical results might be interesting to find out how they are protected from damage by RBC autoAbs.

Kidney biopsy-based management of maintenance immunosuppression is safe and may ameliorate flare rate in lupus nephritis.

The optimal duration of maintenance immunosuppressive therapy for patients with lupus nephritis who have achieved clinical remission has not been established. Furthermore, clinical and histologic remissions are often discordant. We postulated that continuing therapy for patients with persistent histologic activity on kidney biopsies done during maintenance and discontinuing therapy only for patients without histologic activity would minimize subsequent lupus nephritis flares. To test this, a cohort of 75 prospectively-followed patients with proliferative lupus nephritis was managed using kidney biopsies performed during maintenance therapy. These patients had been on immunosuppression for at least 42 months, had responded, and had maintained their clinical response for at least 12 months before the kidney biopsy was repeated. Maintenance therapy was withdrawn if the biopsy showed an activity index of zero, but was continued if the biopsy showed an activity index of one or more. A lupus nephritis flare developed in seven patients during the average 50 months from the third biopsy and the final clinic visit for a flare rate of 1.5/year; significantly less than reported flare rates. Baseline clinical parameters (serum creatinine, proteinuria) and serologic parameters (complement C3, C4 and anti-dsDNA) did not predict an activity index of zero on the third biopsy or who would have a lupus nephritis flare. No patients developed end-stage kidney disease. Four patients developed de novo chronic kidney disease. There were no serious adverse events related to biopsy. Thus, at an experienced center, biopsy-informed management of maintenance immunosuppression is safe and may improve the lupus nephritis flare rate compared to conventional clinical management.

Assessment of variation in B-cell receptor heavy chain repertoire in patients with end-stage renal disease by high-throughput sequencing.

Background/Aims: End-stage renal disease (ESRD), characterized by progressive loss of rental function during the disease course, has been reported to be correlated with immune dysregulation. To date, a majority of previous studies on immune response to ESRD have been focused on the T-cell response. This prospective study was to assess the B-cell receptor (BCR) heavy chain repertoire in ESRD patients.Materials and methods: A total of 10 ESRD patients and six healthy controls were prospectively enrolled in this study. BCR immunoglobulin heavy chain (IGH) repertoire in the peripheral blood from ESRD patients and healthy individuals were analyzed by means of next generation sequencing (NGS) in combination with multiplex PCR, Illumina sequencing, and the international ImMunoGeneTics database (IMGT).Results: Abnormal BCR complementary-determining region 3 (CDR3) sequences were identified in relation to ESRD. We also found that the degree of the B-cell clonal expansion in the ESRD group was significantly greater than that in the control group (p < .05), whereas the distributions of BCR CDR3, V, D, J, and V-J gene segments were comparable between the ESRD and control groups. T-test for analysis of the distribution ratio of the V, D, J, and V-J genes revealed five up-regulated genes and nine down-regulated genes associated with ESRD, and there were significant differences between the ESRD and control groups (p < .05).Conclusions: We have provided a successful approach to analyzing peripheral B-cell repertoire in ESRD patients, and the results suggest a direct correlation between the BCR repertoire and ESRD. The ESRD-specific BCR CDR3 sequences may hold promise for potentially therapeutic benefit.

Managing highly sensitized renal transplant candidates in the era of kidney paired donation and the new kidney allocation system: Is there still a role for desensitization?

Kidney paired donation (KPD) and the new kidney allocation system (KAS) in the United States have led to improved transplantation rates for highly sensitized candidates. We aimed to assess the potential need for other approaches to improve the transplantation rate of highly sensitized candidates such as desensitization. Using the UNOS STAR file, we analyzed transplant rates in a prevalent active waiting-list cohort as of June 1, 2016, followed for 1 year. The overall transplantation rate was 18.9% (11 129/58769). However, only 9.7% (213/2204) of candidates with a calculated panel reactive antibody ≥99.9% received a transplant, and highly sensitized candidates were less likely to receive a living donor transplant. Among candidates with a CPRA ≥ 99.5% (ie. 100%), only 2.5% of transplants were from living donors (13 total, 7 from KPD). Nearly 4 years after KAS (6/30/2018), 1791 actively wait-listed candidates had a CPRA of ≥99.9% and 34.6% (620/1791) of these had ≥5 years of waiting time. Thus, despite KPD and KAS, many sensitized candidates have not been transplanted even with prolonged waiting time. We conclude that candidates with a CPRA ≥ 99.9% and sensitized candidates with an incompatible living donor and prolonged waiting time may benefit from desensitization to improve their ability to receive a transplant.

Outcomes, complications, and economic impact of ABO-incompatible living kidney transplantation: A single-center Japanese cohort study.

ABO-incompatible kidney transplantation (ABO-ILKT) has been reported to have a higher rate of early complications and higher medical costs than ABO-compatible kidney transplantation (ABO-CLKT). We aimed to compare the clinical outcomes, complications, and medical costs between ABO-ILKTs and ABO-CLKTs at 2 years post-transplantation. We included 65 ABO-ILKTs and 94 ABO-CLKTs in this retrospective analysis. The patient survival, graft survival, rejection incidence, and graft function were similar between ABO-CLKT and ABO-ILKT. The hospitalization costs for ABO-CLKT and ABO-ILKT were 26 544 ± 4168 USD and 34 906 ± 18 732 USD, respectively (P = 0.0001). Total 2-year medical costs were 77 117 ± 15 609 USD and 85 325 ± 33 997 USD for ABO-CLKT and ABO-ILKT, respectively, indicating that the medical costs of ABO-ILKT recipients were non-significantly higher than those of ABO-CLKT recipients at 2 years post-transplantation (P = 0.0866). ABO-ILKT and ABO-CLKT recipients showed similar infectious adverse events and complications. In conclusion, medical cost at 2 years post-transplantation, including transplant hospitalization cost, and the frequency of early complications were not significantly higher in the ABO-ILKT group than in the ABO-CLKT group. ABO-ILKT is an acceptable treatment for patients with ESRD and is comparable to ABO-CLKT not only in terms of outcomes but also in terms of medical cost.

Is immunoglobulin A nephropathy different in different ethnic populations?

Immunoglobulin A nephropathy (IgAN) is one of the commonest global patterns of primary glomerulonephritis and remains a leading cause of chronic kidney disease and end-stage renal disease. The sole diagnostic criterion of IgAN remains the presence of dominant mesangial immunoglobulin A deposits on kidney biopsy. Beyond this defining feature, there is significant heterogeneity in the epidemiology, clinical presentation, renal progression and long-term outcomes of IgAN in different ethnic populations. Mirroring this heterogeneity in clinical phenotypes, there is also marked ethnic variation in the extent of histopathological lesions observed on kidney biopsy, which may partly explain the well-documented differences in response to immunomodulatory agents reported in different regions of the world. In parallel, disparities have been identified in genetic association studies and key pathogenic pathways in different ethnic populations. Understanding the basis for these differences in IgAN has important implications for both clinical care and future research. In this review, we will examine the impact of ethnicity on the epidemiology, clinical presentation and outcomes, pathogenesis and genetic associations in IgAN.

Would hemodialysis patients benefit from a Staphylococcus aureus vaccine?

Staphylococcus aureus bloodstream infection can have potentially catastrophic consequences for patients on hemodialysis. Consequently, an effective vaccine to prevent S aureus infection would have a significant influence on morbidity and mortality in this group. To date, however, efforts to develop a vaccine have been unsuccessful. Previous antibody-inducing vaccine candidates did not prevent or attenuate S aureus infection in clinical trials. Recent advances have helped to elucidate the role of specific T-cell subsets, notably T-helper cell 1 and T-helper cell 17, in the immune response to S aureus. These cells are essential for coordinating an effective phagocytic response via cytokine production, indirectly leading to destruction of the organism. It is now widely accepted that next-generation S aureus vaccines must also induce effective T-cell-mediated immunity. However, there remains a gap in our knowledge: how will an S aureus vaccine drive these responses in those patients most at risk? Given that patients on hemodialysis are an immunocompromised population, in particular with specific T-cell defects, including defects in T-helper cell subsets, this is likely to affect their ability to respond to an S aureus vaccine. We urgently need a better understanding of T-cell-mediated immunity in this cohort if an efficacious vaccine is ever to be realized for these patients.

Targeting Immunity in End-Stage Renal Disease.

BACKGROUND: Despite the stable incidence of end-stage renal disease (ESRD), it continues to be associated with an unacceptably high cardiovascular risk. SUMMARY: ESRD is characterized by enhanced oxidative stress and severe inflammation, which boost cardiovascular risk, thus increasing cardiovascular-associated mortality rate. While substantial effort has been made in the technological innovation of dialytic techniques, few significant advances have been made to reduce inflammation in patients with ESRD. Indeed, this contrasts with the extensive scientific breakthroughs made in the basic field of science in targeting inflammation. There is thus a pressing need for clinical trials to test the effect of reducing inflammation in patients with ESRD. Here, we will revisit the negative effect of ESRD on inflammation and explore the impact of enhanced inflammation on cardiovascular outcomes and survival in patients with ESRD. Finally, we will discuss the need for clinical trials that target inflammation in ESRD, as well as weigh potential disadvantages and offer novel innovative approaches. Key Message: We will try to understand why the issue of inflammation has not been successfully addressed thus far in patients with ESRD, while at the same time weighing the potential disadvantages and offering novel innovative approaches for targeting inflammation in patients with ESRD.

De Novo Donor-Specific Human Leukocyte Antigen Antibody Screening in Kidney Transplant Recipients After the First Year Posttransplantation: A Medical Decision Analysis.

Screening for de novo donor-specific antibodies (dnDSA) in stable kidney transplant recipients is routine practice in some centers. Patients with DSA are at increased risk of graft loss and early intervention may improve outcomes. However, the costs and benefits of dnDSA surveillance are unknown. A medical decision analysis to examine a screening strategy was developed for kidney transplant recipients who had stable graft function and were DSA negative 1 year posttransplant. In the base case, a modest 25% reduction in graft loss in dnDSA-positive patients treated with increased immunosuppression resulted in 0.04618 quality-adjusted years (QALYs) gained. However, benefits from reduced graft loss were eliminated if there was a small increased risk of death from added therapy. The incremental cost effectiveness was marginal at approximately $120 000-250 000 per QALY, but could be more or less favorable depending on several key variables such as efficacy of treatment, screening costs, incidence rate of subclinical dnDSA, and patient survival. Screening performed the best in patients with lower mortality rates and higher baseline incidence rates of dnDSA. Further study is warranted to gather the necessary high-quality evidence to justify screening.

2013 Banff Criteria for Chronic Active Antibody-Mediated Rejection: Assessment in a Real-Life Setting.

Significant changes in the criteria for chronic active antibody-mediated rejection (CAABMR) were made in the Banff 2013 classification. These modifications expanded the number of patients diagnosed with CAABMR, with undetermined clinical significance. We compared the 2007 and 2013 criteria for the composite end point of death-censored graft failure or doubling of serum creatinine in 123 patients meeting the criterion related to the morphologic evidence of chronic tissue injury. In all, 18% and 36% of the patients met the 2007 and 2013 criteria, respectively. For the criterion related to antibody interaction with endothelium, only 25% were positive based on the 2007 definition compared with 82% using the 2013 definition. Cox modeling revealed that a 2013 but not a 2007 diagnosis was associated with the composite end point (adjusted hazard ratio 2.5 [95% confidence interval (CI) 1.2-5.2] vs. 1.6 [95% CI 0.7-3.8], respectively). The 2013 criterion based on both the C4d score and the glomerulitis plus peritubular capillaritis score (g+ptc) was more strongly associated with the end point than the 2007 criterion based only on C4d; however, when dissected by component, only the C4d component was significant. The association with clinical outcomes improved with the 2013 criteria. This is related to the new C4d threshold but not to the g+ptc ≥2 component.

Risk assessment of tuberculosis in immunocompromised patients. A TBNET study.

RATIONALE: In the absence of active tuberculosis, a positive tuberculin skin test (TST) or interferon-γ release assay (IGRA) result defines latent infection with Mycobacterium tuberculosis, although test results may vary depending on immunodeficiency. OBJECTIVES: This study compared the performance of TST and IGRAs in five different groups of immunocompromised patients, and evaluated their ability to identify those at risk for development of tuberculosis. METHODS: Immunocompromised patients with HIV infection, chronic renal failure, rheumatoid arthritis, solid-organ or stem-cell transplantation, and healthy control subjects were evaluated head-to-head by the TST, QuantiFERON-TB-Gold in-tube test (ELISA), and T-SPOT.TB test (enzyme-linked immunospot) at 17 centers in 11 European countries. Development of tuberculosis was assessed during follow-up. MEASUREMENTS AND MAIN RESULTS: Frequencies of positive test results varied from 8.7 to 15.9% in HIV infection (n = 768), 25.3 to 30.6% in chronic renal failure (n = 270), 25.0% to 37.2% in rheumatoid arthritis (n = 199), 9.0 to 20.0% in solid-organ transplant recipients (n = 197), 0% to 5.8% in stem-cell transplant recipients (n = 103), and 11.2 to 15.2% in immunocompetent control subjects (n = 211). Eleven patients (10 with HIV infection and one solid-organ transplant recipient) developed tuberculosis during a median follow-up of 1.8 (interquartile range, 0.2-3.0) years. Six of the 11 patients had a negative or indeterminate test result in all three tests at the time of screening. Tuberculosis incidence was generally low, but higher in HIV-infected individuals with a positive TST (3.25 cases per 100 person-years) than with a positive ELISA (1.31 cases per 100 person-years) or enzyme-linked immunospot result (1.78 cases per 100 person-years). No cases of tuberculosis occurred in patients who received preventive chemotherapy. CONCLUSIONS: Among immunocompromised patients evaluated in this study, progression toward tuberculosis was highest in HIV-infected individuals and was poorly predicted by TST or IGRAs. Clinical trial registered with www.clinicaltrials.gov (NCT 00707317).

Assessment of immune status in relation to vitamin D levels in children on regular hemodialysis.

The two most common causes of death in patients with chronic kidney disease (CKD) are cardiovascular diseases and infections, and both have been linked to impaired vitamin D levels and dysregulated immune response. The aim of this work is to study the relation between vitamin D levels in children with end-stage renal disease (ESRD) on regular hemodialysis (HD) and their immune status. This case-control study was conducted at the Nephrology Unit, Department of Pediatrics, the Zagazig University Hospital, from April 2010 to August 2010. We studied 27 children with ESRD on regular HD (group-A) whose mean age was 8 ± 1.3 years; there were 15 males and 12 females. The study patients were divided into two groups depending on the degree of vitamin D deficiency; group-A1 had 12 patients, all of whom had vitamin D deficiency defined as serum concentration of 25-hydroxy vitamin D3 [25(OH) D3] of 15-30 ng/mL. Group-A2 had 15 patients with more severe vitamin D deficiency (<15 ng/mL). Twenty healthy age- and sex-matched children served as the control group (group-B); their mean age was 7.8 ± 1.6 years and they included 12 males and eight females. All subjects underwent thorough history taking, clinical examination and the following investigations: complete blood count, lymphocyte count, blood urea, serum creatinine, total serum calcium, ionized calcium, serum phosphorus, plasma 25(OH)D3, intact para-thormone (iPTH), serum interleukin-10 (IL-10) and soluble IL-2 receptor (SIL-2R). We found that the vitamin D level was significantly lower in the patient group (group-A) than in the control-group (group-B). The IL-10 level was significantly lower in group-A than in group-B, and the SIL-2R level was significantly higher in group-A than in group-B. We found a significant positive correlation between serum 25(OH)D3 levels and serum IL-10, while there was a negative correlation between 25(OH)D3 levels and SIL-2R; this correlation was not significant. Our findings suggest that 25(OH)D3 levels affect the immune state in patients through their effect on both limbs of immunity, the anti-inflammatory and the pro-inflammatory, but the effect was higher on the anti-inflammatory IL-10. We conclude that the serum levels of vitamin D are lower in children with ESRD than in age-matched controls, and that it is significantly positively related to the anti-inflammatory IL-10 and negatively related to the pro-inflammatory SIL-2R. Further studies are required to throw more light on the role of vitamin D supplementation in children with ESRD in maintaining immune balance.

Disparities in periodontitis prevalence among chronic kidney disease patients.

Because of adverse effects of uremia in the innate and adaptive immune systems, we hypothesized that chronic kidney disease (CKD) patients would have higher prevalence of moderate periodontitis compared with individuals without CKD. We examined this hypothesis using the NHANES III dataset, including 12,081 adults stratified by Race-Ethnicity. We followed the American Academy of Periodontology/Centers for Disease Control and Prevention definition for moderate periodontitis. Estimated glomerular filtration rate (GFR) was calculated based on calibrated serum creatinine levels according to the Modification of Diet in Renal Disease Study formula. Analyses incorporated NHANES sampling weights. Overall, 14.6% of individuals with CKD were classified as having moderate periodontitis, compared with 8.7% in the non-CKD group (p = 0.001). A significant dose-response association (p = 0.001) was observed between prevalence of moderate periodontitis and CKD stages among non-Hispanic Blacks and Mexican-Americans, but not so for non-Hispanic Whites. Prevalence of periodontitis among participants with CKD was substantially higher among non-Hispanic Blacks (38.9%) and Mexican-Americans (37.3%) compared with non-Hispanic Whites (12.9%). Multivariate logistic regression models showed that Mexican-Americans and non-Hispanic Blacks with CKD were approximately 30% to 60% more likely to have moderate periodontitis compared with those without CKD, after adjustment for diabetes status and other potential confounders.

Assessment of an Interferon-gamma release assay for the diagnosis of latent tuberculosis infection in haemodialysis patient.

BACKGROUND: The accurate diagnosis of latent tuberculosis infection (LTBI) in haemodialysis patients remains elusive. Impaired immune function associated with chronic kidney failure causes a high number of anergic tuberculin skin tests (TST). Interferon-gamma (INF-gamma) release assays (IGRAs) measuring the INF-gamma secretion of tuberculosis specific T-cells have several advantages over the TST but their significance in dialysis patients is currently uncertain. METHODS: This study examines the test-performances of the QuantiFERON Gold InTube (QFT-GIT) in a cohort of 39 haemodialysis (HD) patients and 52 healthy individuals. RESULTS: INF-gamma secretion in HD patients was significantly lower than in healthy controls, however, mitogen-anergic QFT-GIT results were only found in 2.5% of HD-patients. INF-gamma secretion was independent of duration of HD treatment, dialysis quality and nutritional status. The QFT-GIT showed a closer association with TB risk factors as a proxy for past exposure to TB than the TST. CONCLUSIONS: We conclude that the QFT-GIT is a valid alternative to the TST. Together with the survey of TB risk factors, it may help to diagnose LTBI more accurately in HD-patients.

The use of alternative anti-coagulation strategies for a nocturnal home hemodialysis patient with heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a potentially catastrophic hyercoagulable state. The prevalence of HIT in individuals doing nocturnal home hemodialysis (NHD) is unknown and the appropriate treatment protocol has yet to be determined. The objective is to describe the clinical course and treatment plan ofa patient who developed HIT while undergoing NHD. A 49-year-old man with a past history of end stage renal disease (ESRD) of unknown etiology was initiated on NHD in February 2005. His clinical and biochemical parameters improved after conversion to NHD. However, excessive bleeding at the vascular access sites complicated his treatments. Clinical investigations revealed development of HIT Alternative therapeutic strategies were attempted to enable our patient to continue NHD: unfractionated heparin, citrated regional anticoagulation, Danaparoid, and Argatroban. In conclusion, NHD patients with HIT pose a specific clinical challenge. We speculate that the augmented exposure of heparin coupled with a primed autoimmune response may be responsible for the development of HIT in our patient. Further research is required to elucidate the appropriate clinical monitoring and treatment strategy for this patient.

[Assessment of the usefulness of the presence of antithyroid peroxidase antibodies (TPOAb) in patients with end-stage renal failure treated with hemodialysis]. / Ocena przydatnosci obecnosci przeciwcial przeciw tyreoperoksydazie (TPOAb) u chorych ze schylkowa niewydolnosca nerek (SNN) leczonych hemodializami (HD).

Due to a high frequency of autoimmune diseases in patients with ESRF we observed for 4 years 8 patients treated with HD with high level of TPOAb and 8 patients without TPOAb. Aim of the study was to estimate the role of TPOAb as a prognostic factor of hypothyreosis. We observed in a 4-years follow-up significant increase of TSH (p<0.05) in patients with high TPOAb level. fT3 and fT4 did't change in this time. In the group without TPOAb we observed significant (p<0.01) decrease of fT3 probably due to the disturbances in T4 to T3 conversion. Our results don't permit us to draw a final conclusions but induce us to further observation of hypothyreosis development in patients with ESRF.

The variability and accurate assessment of microinflammation in haemodialysis patients.

BACKGROUND: Systemic microinflammation is correlated with atherosclerosis. It needs a reliable assessment. This study explores the temporal variations of three inflammatory indexes [C-reactive protein (CRP), serum amyloid A (SAA) and interleukin-6 (IL-6)] in a period free of clinical events and tests the reliability of their multiple measurements for the assessment of microinflammation in haemodialysis (HD) patients, a population at high risk of atherosclerotic cardiovascular disease. METHODS: For 4 months, serum CRP, SAA and IL-6 were measured in 29 HD patients during the weeks they were free of inflammatory clinical events (> or =12 measurements for each index in every patient). The components of the variance as well as the reliability of two to five measurements for each index, aimed at assessing microinflammation precisely, were computed. RESULTS: The median (interquartile range) of CRP was 2.3 (0.9-4.9) mg/l, of SAA 3.7 (2.1-9.3) mg/l and of IL-6 4.4 (2.2-7.7) pg/ml. Patients were approximately equally distributed between three groups of low, intermediate and high variability for each index. The contribution of intraindividual (biological) variation to the total of variance was 71.3%, 69.3% and 86.7% for CRP, SAA and IL-6, respectively (higher than in all other similar studies in healthy populations). Using two measurements, the estimated reliability was 57-68% for CRP in two-thirds of the patients (comparable with that found in healthy subjects) and 57% for SAA and IL-6 in only one-third of the patients. Increasing the number of measurements up to five did not change the reliability. CONCLUSIONS: Individual factors significantly influence the levels of inflammatory indexes in HD patients in periods free of inflammatory clinical events. The mean of two weekly CRP measurements, but not of SAA or IL-6, seems to assess microinflammation in most patients with a sufficient reliability.

[Clinical results of the various replacement therapies for chronic renal failure: haemodialysis and renal transplantation]. / Risultati clinici delle diverse terapie sostitutive dell'insufficienza renale cronica: emodialisi e trapianto renale.

Results from recent studies have demonstrated that kidney-transplanted patients have better expectation and quality of life than dialysis patients on a waiting list for kidney transplant. Moreover, the scientific literature has conclusively shown that the survival of the patient and of the kidney graft are better in patients who received a kidney from a living donor, than in patients who received a cadaveric kidney. The main factors that may have a negative influence on the kidney transplant are: the recipient's age, diabetes mellitus, smoking and the time spent on dialysis before the transplant. The shortage of cadaveric kidneys and the small number of living kidney transplant are the main obstacles to a more widespread use of kidney transplantation. Kidney transplant from living donors needs to be implemented because it represents the best treatment for patients with kidney failure and it can decrease or even avoid the need for dialysis before kidney transplantation.