Hemodialysis vascular graft as a focus of persistent Q fever.

Vascular access infection is a frequent complication in hemodialysis patients. We report the second case worldwide of a prosthetic hemodialysis vascular graft infection by Coxiella burnetii, with intense hypermetabolism on PET-CT, Q fever serology consistent with persistent infection, and positive C. burnetii DNA in the blood and removed vascular graft.

Indole 3-acetic acid, indoxyl sulfate and paracresyl-sulfate do not influence anemia parameters in hemodialysis patients.

BACKGROUND: The main reason for anemia in renal failure patients is the insufficient erythropoietin production by the kidneys. Beside erythropoietin deficiency, in vitro studies have incriminated uremic toxins in the pathophysiology of anemia but clinical data are sparse. In order to assess if indole 3-acetic acid (IAA), indoxyl sulfate (IS), and paracresyl sulfate (PCS) -three protein bound uremic toxins- are clinically implicated in end-stage renal disease anemia we studied the correlation between IAA, IS and PCS plasmatic concentrations with hemoglobin and Erythropoietin Stimulating Agents (ESA) use in hemodialysis patients. METHODS: Between June and July 2014, we conducted an observational cross sectional study in two hemodialysis center. Three statistical approaches were conducted. First, we compared patients treated with ESA and those not treated. Second, we performed linear regression models between IAA, IS, and PCS plasma concentrations and hemoglobin, the ESA dose over hemoglobin ratio (ESA/Hemoglobin) or the ESA resistance index (ERI). Third, we used a polytomous logistic regression model to compare groups of patients with no/low/high ESA dose and low/high hemoglobin statuses. RESULTS: Overall, 240 patients were included in the study. Mean age ± SD was 67.6 ± 16.0 years, 55.4% were men and 42.5% had diabetes mellitus. When compared with ESA treated patients, patients with no ESA had higher hemoglobin (mean 11.4 ± 1.1 versus 10.6 ± 1.2 g/dL; p <0.001), higher transferrin saturation (TSAT, 31.1 ± 16.3% versus 23.1 ± 11.5%; p < 0.001), less frequently an IV iron prescription (52.1 versus 65.7%, p = 0.04) and were more frequently treated with hemodiafiltration (53.5 versus 36.7%). In univariate analysis, IAA, IS or PCS plasma concentrations did not differ between the two groups. In the linear model, IAA plasma concentration was not associated with hemoglobin, but was negatively associated with ESA/Hb (p = 0.02; R = 0.18) and with the ERI (p = 0.03; R = 0.17). IS was associated with none of the three anemia parameters. PCS was positively associated with hemoglobin (p = 0.03; R = 0.14), but negatively with ESA/Hb (p = 0.03; R = 0.17) and the ERI (p = 0.02; R = 0.19). In multivariate analysis, the association of IAA concentration with ESA/Hb or ERI was not statistically significant, neither was the association of PCS with ESA/Hb or ERI. Identically, in the subgroup of 76 patients with no inflammation (CRP <5 mg/L) and no iron deficiency (TSAT >20%) linear regression between IAA, IS or PCS and any anemia parameter did not reach significance. In the third model, univariate analysis showed no intergroup significant differences for IAA and IS. Regarding PCS, the Low Hb/High ESA group had lower concentrations. However, when we compared PCS with the other significant characteristics of the five groups to the Low Hb/high ESA (our reference group), the polytomous logistic regression model didn't show any significant difference for PCS. CONCLUSIONS: In our study, using three different statistical models, we were unable to show any correlation between IAA, IS and PCS plasmatic concentrations and any anemia parameter in hemodialysis patients. Indolic uremic toxins and PCS have no or a very low effect on anemia parameters.

Undercorrection of hypernatremia is frequent and associated with mortality.

BACKGROUND: About 1% of patients admitted to the Emergency Department (ED) have hypernatremia, a condition associated with a mortality rate of 20 to 60%. Management recommendations originate from intensive care unit studies, in which patients and medical diseases differ from those in ED. METHODS: We retrospectively studied clinical characteristics, treatments, and outcomes of severely hypernatremic patients in the ED and risk factors associated with death occurrence during hospitalization. RESULTS: During 2010, 85 cases of severe hypernatremia ≥ 150 mmol/l were admitted to ED. Hypernatremia occurred in frail patients: mean age 79.7 years, 55% institutionalized, 28% with dementia.Twenty four percent of patients died during hospitalization. Male gender and low mean blood pressure (MBP) were independently associated with death, as well as slow natremia correction speed, but not the severity of hyperosmolarity at admission. Infusion solute was inappropriate for 45% of patients with MBP <70 mmHg who received hypotonic solutes and 22% of patients with MBP ≥ 70 mmHg who received isotonic solutes or were not perfused. CONCLUSIONS: This is the first study assessing outcome of hypernatremic patients in the ED according to the treatment provided. It appears that not only a too quick, but also a too slow correction speed is associated with an increased risk of death regardless of initial natremia. Medical management of hypernatremic patients must be improved regarding evaluation and treatment.

Chronic hepatitis E virus infection is specifically associated with an interferon-related transcriptional program.

BACKGROUND: Hepatitis E virus (HEV) is a new causative agent of chronic hepatitis in solid organ transplant recipients. Clinical studies suggest that the occurrence and persistence of chronic HEV infection are related to the immunological status of patients. METHODS: We used whole-genome microarray and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to compare the transcriptional profiles of whole blood from 8 kidney transplant recipients with chronic HEV infection and 8 matched kidney transplant recipients without HEV infection. RESULTS: We found that 30 genes in HEV-infected patients were upregulated, compared with those in control patients, as determined by microarray analysis. In contrast, no genes were downregulated. The 30 upregulated genes included 25 interferon-stimulated genes. Increased expression of the genes that encode IFIT1, IFI44L, RSAD2, EPSTI1, and ISG15 was confirmed by qRT-PCR. Interestingly, the expression levels of these genes were associated with the persistence of HEV infection. CONCLUSIONS: Increased expression of interferon-stimulated genes may favor the persistence of an HEV infection. Whether the expression of interferon-stimulated genes is a marker of ongoing viremia or independent prognostic marker of HEV clearance needs further investigations. CLINICAL TRIALS REGISTRATION: NCT01090232.

Infection with hepatitis E virus in kidney transplant recipients in southeastern France.

Hepatitis E virus (HEV) is an emerging cause of acute hepatitis in Europe, particularly in southern France, and HEV is a new causative agent of chronic hepatitis and cirrhosis in immunocompromised patients. However, the data regarding HEV infection after kidney transplantation are still scarce with respect to the clinical issues that have been raised, and no study has specifically focused on kidney transplant recipients. This study described the clinical features and outcomes of HEV infections in a cohort of kidney transplant recipients living in southeastern France. The epidemiological, clinical, and virological characteristics of HEV infections diagnosed by PCR over a 53-month period were retrospectively analyzed in a cohort of 1,350 kidney transplant recipients monitored at the Marseille University Hospital. Sixteen HEV infections were diagnosed, all of which were autochthonous and involved genotype 3 viruses (HEV-3). Chronic infections occurred in 80% of these patients and resolved in half of the cases after a median time of 39 months. The rate of HEV clearance was 54% after a decrease in the dose of immunosuppressants. One patient developed liver cirrhosis 14 months after infection and experienced acute rejection after a decrease in the dose of immunosuppressants. Autochthonous HEV-3 infections in kidney transplant recipients progress to chronicity in most cases and might be complicated by early liver cirrhosis. Chronic HEV infection can resolve following the reduction of immunosuppressive therapy, but ribavirin may be required if reduction of the immunosuppressant dose is not associated with HEV clearance or is inappropriate for the patient management.

Systematic Comparison of Uremic Toxin Removal Using Different Hemodialysis Modes: A Single-Center Crossover Prospective Observational Study.

Many hypotheses could explain the mortality decrease observed using hemodiafiltration, such as reduction of intradialytic hypotension and more efficient toxin removal. We led a systematic analysis of representative uremic toxin removal with hemodialysis (HD), online postdilution hemodiafiltration (postHDF) and online predilution hemodiafiltration (preHDF), in a single-center crossover and prospective observational study. The primary outcome was the reduction ratio of uremic toxins of the three categories defined by the Eutox group. Twenty-six patients were treated by those three techniques of extra renal epuration. Mean Kt/Vurea was not different between the treatment methods. Mean reduction ratio of beta2microglobulin was significantly higher for both HDF treatments than for HD (p < 0.001). Myoglobin, kappa, and lambda free light chain reduction ratio was significantly different between the modes: 37.75 ± 11.95%, 45.31 ± 11% and 61.22 ± 10.56%/57.21 ± 12.5%, 63.53 ± 7.93%, and 68.40 ± 11.79%/29.12 ± 8.44%, 34.73 ± 9.01%, and 45.55 ± 12.31% HD, preHDF, and postHDF, respectively (p < 0.001). Mean protein-bound solutes reduction ratio was not different between the different treatments except for PCS with a higher reduction ratio during HDF treatments. Mean albumin loss was always less than 2 g. HDF improved removal of middle molecules but had no effect on indoles concentration without any difference between synthetic dialysis membranes.

Evolution of Anelloviridae strains distribution in serial blood and biopsy samples from a renal transplant patient.

A few studies investigated the natural history of viruses belonging to the family Anelloviridae in transplant patient. The case of a 64-year-old kidney transplant recipient is described. Molecular analysis of serial blood samples collected before and after transplant was performed during a period of 510 days. Two kidney biopsies were also analyzed. All blood samples tested positive for Anelloviridae DNA, with the identification of sequences belonging to the three taxonomic genera identified in humans. Sequences distribution during the follow-up was multimodal. A sequence nearly identical to one present in the blood before transplant was further characterized in one biopsy sample.

Membranoproliferative glomerulonephritis and mixed cryoglobulinemia after hepatitis C virus infection secondary to glomerular NS3 viral antigen deposits.

BACKGROUND: We report on 3 cases of membranoproliferative glomerulonephritis associated with mixed cryoglobulin in patients with hepatitis C virus (HCV) antibodies but a negative blood viral load. These cases explore the pathogenesis of the renal disease. METHODS: We searched for occult HCV infection in peripheral blood mononuclear cells, cryoprecipitate, bone marrow cells, and glomeruli using ultrasensitive PCR assays and immunohistochemistry. We also looked for infraclinical B cell lymphoma by computed tomodensitometry, bone marrow aspiration and biopsy, and lymphocyte typing. RESULTS: By PCR assays, we did not evidence occult hepatitis C infection in peripheral blood mononuclear cells, bone marrow cells, or cryoprecipitates. In the only patient with available kidney specimen, we evidenced HCV-NS3 antigen in glomeruli. HCV-associated lymphoma was excluded, but mild polyclonal B lymphocytosis was present in the 3 patients. Remission occurred spontaneously in 1 patient, and in another patient it occurred after rituximab treatment. The third patient was lost to follow-up. CONCLUSIONS: In patients with hepatitis C-negative viral load, membranoproliferative glomerulonephritis could be induced by the persistence of HCV antigen in the kidney but not in hematopoietic cells. Nonlymphomatous B cell proliferation may also be induced by chronic viral stimulation.

Comparative safety and efficiency of five percutaneous kidney biopsy approaches of native kidneys: a multicenter study.

BACKGROUND: Renal biopsy (RB) is necessary for the diagnosis, prognosis, and therapy guidance of native kidney diseases. Few studies have compared outcomes of RB procedures. We retrospectively compared the safety and efficiency of five biopsy procedures. METHODS: The number of glomeruli on light microscopy (LM) and on immunofluorescence (IF) and serious adverse events following RB performed in five nephrology units (C1-C5) were collected. C1 performed ultrasound (US) assessment before RB and used a 14-gauge core-cutting needle biopsy gun, C2 US guidance and a 14-gauge needle, C3 tomodensitometry guidance and a 14-gauge needle, C4 US guidance and a 16-gauge needle, and C5 tomodensitometry guidance and a 16-gauge needle. RESULTS: RB was performed in 943 adults between January 2006 and July 2010. Serious adverse events occurred in 1.5% of biopsies. The complication rate was not different between nephrology units. The mean number of glomeruli on biopsy was 14.2 ± 8.6 with LM and 4.4 ± 3.3 on IF. It was different according to the nephrology unit for LM (p = 0.01) and for IF (p < 0.001). The number of failed biopsies was influenced by the nephrology unit and radiological guidance technique, favoring real-time US guidance. Failed biopsies using US or tomodensitometry assessment before RB was certainly due to kidney imprecise localization since it was often non-renal tissue sampling. At least 10 glomeruli were found in 69% of biopsies on LM. This rate varied according to the nephrology unit (p = 0.004) and was higher when 14-gauge needles were used in comparison with 16-gauge needles. CONCLUSION: RB is safe regardless of the technical procedure, but radiological guidance and needle size influence the efficiency of biopsies.

Parvovirus 4 in French in-patients: a study of hemodialysis and lung transplant cohorts.

The epidemiology and the clinical implication of human parvovirus 4 (PARV4) in human populations is still under evaluation. The distribution of PARV4 DNA was determined in cohorts of French hemodialysis and lung transplant patients. Plasma samples (n=289) were tested for PARV4 by real-time PCR assay (ORF2), and amplification products selected at random were sequenced. Analysis of available serological and biological markers was also undertaken. Fifty-seven samples out of 185 (30.8%) were positive for PARV4 DNA in the cohort of hemodialysis patients. A higher prevalence of the virus was identified in patients with markers of HBV infection. PARV4 was also identified in 14 out of 104 samples (13.5%) from lung transplant recipients, with no clear-cut association with available clinical markers. Point mutations located on the zone of real-time detection were identified for some amplification products. This study describes the detection of PARV4 in the blood of hemodialysis and lung transplanted patients with significant difference in prevalence in these two cohorts. Further studies will be needed in order to understand better both the potential implication in host health and the natural history of this virus.

High Resolution Melt analysis for mutation screening in PKD1 and PKD2.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder. It is characterized by focal development and progressive enlargement of renal cysts leading to end-stage renal disease. PKD1 and PKD2 have been implicated in ADPKD pathogenesis but genetic features and the size of PKD1 make genetic diagnosis tedious. METHODS: We aim to prove that high resolution melt analysis (HRM), a recent technique in molecular biology, can facilitate molecular diagnosis of ADPKD. We screened for mutations in PKD1 and PKD2 with HRM in 37 unrelated patients with ADPKD. RESULTS: We identified 440 sequence variants in the 37 patients. One hundred and thirty eight were different. We found 28 pathogenic mutations (25 in PKD1 and 3 in PKD2 ) within 28 different patients, which is a diagnosis rate of 75% consistent with literature mean direct sequencing diagnosis rate. We describe 52 new sequence variants in PKD1 and two in PKD2. CONCLUSION: HRM analysis is a sensitive and specific method for molecular diagnosis of ADPKD. HRM analysis is also costless and time sparing. Thus, this method is efficient and might be used for mutation pre-screening in ADPKD genes.

Diagnostic performance of pulmonary ultrasonography and a clinical score for the evaluation of fluid overload in haemodialysis patients.

INTRODUCTION: There is no feasible benchmark in daily routine to estimate the hydration status of haemodialysis patients, which is essential to their management. OBJECTIVE: We performed a study in haemodialysis patients to assess the diagnostic performance of pulmonary ultrasound and clinical examination for the evaluation of fluid overload using transthoracic echocardiography as a gold standard. METHODS: Thirty-one patients receiving chronic haemodialysis patients were included. Evaluation of hydration status was assessed weekly before haemodialysis sessions using clinical and Echo Comet Score from pulmonary ultrasound and transthoracic echocardiography (reference method). RESULTS: Five patients had a transthoracic echocardiography overload. Compared with transthoracic echocardiography, the diagnostic performance of the clinical overload score has a sensitivity of 100%, a specificity of 77%, a positive predictive value of 50% and a negative predictive value of 100% with a κ of 0.79. Only orthopnoea (P=0.008), jugular turgor (P=0.005) and hepatic-jugular reflux (P=0.008) were significantly associated with transthoracic echocardiography overload diagnosis. The diagnostic performance of Echo Comet Score by pulmonary ultrasound has a sensitivity of 80%, a specificity of 58%, a positive predictive value of 26% and a negative predictive value of 94%. Ten patients (32.3%) had an increase of extravascular pulmonary water without evidence of transthoracic echocardiography or clinical overload. CONCLUSIONS: Our clinical score has a convincing diagnostic performance compared to transthoracic echocardiography and could be easily used in daily clinical routine to adjust dry weight. The evaluation of the overload using pulmonary ultrasound seems poorly correlated with the overload evaluated by transthoracic echocardiography. Extravascular pulmonary water undetected by clinical examination and transthoracic echocardiography remains a parameter that requires further investigation.

Nanobacteria are mineralo fetuin complexes.

"Nanobacteria" are nanometer-scale spherical and ovoid particles which have spurred one of the biggest controversies in modern microbiology. Their biological nature has been severely challenged by both geologists and microbiologists, with opinions ranging from considering them crystal structures to new life forms. Although the nature of these autonomously replicating particles is still under debate, their role in several calcification-related diseases has been reported. In order to gain better insights on this calciferous agent, we performed a large-scale project, including the analysis of "nanobacteria" susceptibility to physical and chemical compounds as well as the comprehensive nucleotide, biochemical, proteomic, and antigenic analysis of these particles. Our results definitively ruled out the existence of "nanobacteria" as living organisms and pointed out the paradoxical role of fetuin (an anti-mineralization protein) in the formation of these self-propagating mineral complexes which we propose to call "nanons." The presence of fetuin within renal calculi was also evidenced, suggesting its role as a hydroxyapatite nucleating factor.

Osseous metaplasia in a kidney allograft.

Osseous metaplasia is defined by the presence of heterotopic normal bone tissue in a soft tissue. The bone matrix is associated with osteoblasts, osteoclasts, adipocytes and haematopoietic stem cells. Osseous metaplasia pathophysiology is not well known, but many factors have been incriminated including chronic inflammation and chronic ischaemia. We describe the second case of osseous metaplasia in a kidney allograft. Numerous factors might favour its development including factors linked to transplantation failure environment.

Myocardial infarction is a complication of factor H-associated atypical HUS.

Cardiac complications are frequently seen in thrombotic thrombocytopaenic purpura related to ADAMTS13 deficiency. We describe the case of a 43-year-old woman who was diagnosed with an atypical haemolytic-uraemic syndrome (aHUS) associated with a pathogenic mutation in the factor H gene (C623S). After 15 days of treatment, she suffered a sudden cardiac arrest and died despite intensive resuscitation attempts. She showed only one cardiovascular risk factor, hypercholesterolaemia. Her sudden death was secondary to cardiac infarction related to a coronary thrombotic microangiopathy. This is the first case of aHUS related to a mutation in the factor H gene associated with cardiac microangiopathy. This case emphasizes the need to screen for cardiac complication during the treatment of aHUS.

Population pharmacokinetics analysis of mycophenolic acid in adult kidney transplant patients with chronic graft dysfunction.

The aim of this study is to develop a population pharmacokinetic model for total and free mycophenolic acid (MPA) in adult kidney transplant patients with chronic graft dysfunction to understand the contribution of potentially relevant covariates to the inter- and the intraindividual variability of MPA in these patients. Twenty patients received mycophenolate mofetil orally up to 1 g twice daily were enrolled in this prospective pharmacokinetic study. Two hundred twenty-nine total and 257 free concentration-time points were determined using reversed-phase high-performance liquid chromatography/ultraviolet at 21 days and 6 months after initiation of mycophenolate mofetil therapy. Data were analyzed using nonlinear mixed effects modeling. A two-compartment model, with zero-order input and first-order elimination from the central compartment, which combined total and free concentration, was selected. Intersubject variability (ISV) was estimated on the clearance, central volume of distribution, and intercompartmental clearance. Only body weight (WT, kg), occasion, and albumin concentration (mg/L) were kept as covariates in the final model. The population pharmacokinetic parameters were: clearance, 0.27 x WT (L/h) on Day 21 and 0.233 x WT (L/h) at 6 months (ISV, 51%; interoccasion variability, 47%); central distribution volume, 47.6 L (ISV, 31%); intercompartmental clearance, 33.1 L/h (ISV, 128%); peripheral distribution volume, 724 L; duration of infusion, 0.64 (hours), and binding capacity, 0.0012 L/mg. The multiple regression analysis between free and total MPA concentration led to the following model: free MPA concentration (mg/L) = 0.31 + 0.02 total MPA concentration (mg/L) - 0.007 albumin (g/L). The large inter- and intravariability of MPA raises questions about the value of the use of therapeutic monitoring and limited sampling strategies as currently practiced. Moreover, none of the data presented here could justify measurement of free concentration for therapeutic drug monitoring.

Pharmacodynamics of unfractionated heparin during and after a hemodialysis session.

BACKGROUND: Anti-Xa activity is used as a clinical guide to anticoagulation with heparin, but heparin dosing regimens for hemodialysis were established before anti-Xa assays were developed; thus, the optimal regimen for heparin dosing was not determined. The aim is to confirm the interesting characteristics of unfractionated heparin pharmacokinetics for hemodialysis anticoagulation, provide insight into the hemorrhagic risk of hemodialysis patients, and determine the dose of unfractionated heparin and its adequate mode of administration. STUDY DESIGN: Cross-sectional study of the pharmacokinetics of unfractionated heparin performed during and after a 4-hour midweek hemodialysis session. SETTING & PARTICIPANTS: 35 long-term hemodialysis patients at the Sainte-Marguerite Unit of the Marseille University Hospital, Marseille, France. PREDICTOR: Hemodialysis anticoagulation with continuous unfractionated heparin infusion at a dose of 50 IU/kg/session (25 IU/kg/h during the first hour, 12.5 IU/kg during the second and third hours, and stop during the last hour). OUTCOME & MEASUREMENTS: Anti-Xa activity was monitored during the 10 hours after the beginning of the hemodialysis session. Levels of 0.3 to 0.7 IU/mL are considered sufficient for anticoagulation. Pharmacokinetics was determined by using a population approach (nonlinear mixed-effects modeling). The final model and corresponding parameter values (including interindividual and residual variability) were used to simulate 1,000 replicates. RESULTS: No case of clotting was recorded. A pharmacokinetic model with 1 compartment and first-order elimination best fitted the data. Terminal half-life was 54 minutes. Median anti-Xa activities were 0.55 IU/mL at peak, 0.25 IU/mL at end of the 4-hour session, and less than 0.1 IU/mL at 90 minutes after the session. We simulated a continuous infusion of the dose of 50 IU/kg for 1, 2, 3, and 4 hours. Peak values were 1.1, 0.8, 0.6, and 0.5 IU/mL, respectively. Values at the end of the session were 0.12, 0.18, 0.3, and 0.5 IU/mL, respectively. Values became less than 0.1 IU/mL at 15, 60, 105, and 120 minutes after the session, respectively. LIMITATIONS: Interindividual variability in unfractionated heparin pharmacokinetics. CONCLUSIONS: Unfractionated heparin administered by means of a 3-hour continuous infusion for hemodialysis anticoagulation provided an efficient and safe effect that quickly disappeared after the end of the session.

Mycophenolate mofetil monotherapy in membranous nephropathy: a 1-year randomized controlled trial.

BACKGROUND: Treatment of patients with membranous glomerulonephritis (MGN) is controversial because of the lack of clear benefit of the immunosuppressive regimens on patient or renal survival. The objective of this study is to evaluate the efficacy and safety of mycophenolate mofetil (MMF) for patients with MGN. STUDY DESIGN: 1-year prospective, randomized, and controlled clinical trial. SETTING & PARTICIPANTS: 36 patients with biopsy-proven idiopathic MGN and nephrotic syndrome. INTERVENTION: 19 patients received MMF (2 g/d) for 12 months and 17 patients were in the control group. All patients had the same conservative treatment based on renin-angiotensin blockers, statins, low-salt and low-protein diet, and diuretics in case of edema. OUTCOMES & MEASUREMENTS: End points were the mean proteinuria over creatinuria ratio in mg/g throughout the study and numbers of complete and partial remissions at 1 year (month 12). Data were analyzed on an intention-to-treat analysis. RESULTS: Mean proteinuria over creatinuria ratio was stable in both groups throughout the study (P = 0.1). Mean proteinuria over creatinuria ratio was 4,690 +/- 2,212 mg/g in the MMF group and 6,548 +/- 4,601 mg/g in the control group (95% confidence interval of the difference, -619 to +4,247; P = 0.1). Remission was complete in 3 patients (1 in the MMF group, 2 in the control group; P = 0.5) and partial in 11 patients (6 in the MMF group, 5 in the control group; P = 0.9). The probability of complete or partial remission did not differ between the 2 groups after 12 months (relative risk, 0.92; 95% confidence interval, 0.48 to 1.75; P = 0.7). Kidney function was stable in the 2 groups according to estimated glomerular filtration rate and serum creatinine level. LIMITATIONS: The small number of patients and short follow-up prevent generalizations. CONCLUSIONS: A 12-month regimen of MMF did not decrease mean proteinuria over creatinuria ratio or increase partial and complete remissions. Serious adverse effects were observed in 4 patients (20%) receiving MMF.

Natural killer cell alterations correlate with loss of renal function and dialysis duration in uraemic patients.

BACKGROUND: Natural killer (NK) cells provide a first line of immune defence towards infections and tumours, and participate in atherosclerosis and pregnancy diseases, of which there is a higher incidence in uraemic patients. Still, their relative contribution to the immunodeficient state associated with renal failure is poorly documented. METHODS: A multivariate and comparative analysis of lymphocyte subsets in haemodialysed (HD) and undialysed (UD) uraemic patients in comparison to healthy donors (HC) is provided in this article. NK-mediated cytotoxicity, degranulation and interferon secretion were compared in HD and HC. RESULTS: Evaluation of NK cells in 210 HD patients concluded with a decrease in NK cell counts in comparison to HC. Multivariate analysis associated lowered NK cell counts in UD patients with decreased renal clearance and higher NK counts HD with male gender and age. The 32% NK cell count decrease observed in sex- and age-matched groups (n = 88) was associated with B- and CD8(+)T-lymphocyte defects. NK cell functions were similar in subgroups of HD and HC matched for NK cell counts. Longer dialysis duration was associated with improved NK cytototoxic activity. While the expression of receptors modulating NK cytotoxicity were not modified, expression of the activation markers CD69 and NKp44, CD94 and chemokine receptors CX3CR1 and CXCR4 was altered in HD. CONCLUSIONS: This study is the first to associate decrease in renal function with selective fading of NK cell number and identify haemodialysis duration as a factor influencing NK cell function. It further shows that lower cell counts rather than intrinsic NK cell dysfunction per se characterize immune disorders in HD.