Risk factors for Pneumocystis pneumonia after the first 6 months following renal transplantation.

Pneumocystis pneumonia (PCP) incidence was decreased in renal transplant thanks to prophylaxis, recommended during the first months after transplantation. However, many late PCP cases are observed after the first 6 months and recommendations to maintain or reintroduce prophylaxis are lacking. The objective of the study was to identify risk factors to guide the individual prescription of prophylaxis, 6 months after transplantation. Thirty-three late PCP cases were identified between 1995 and 2012 in Lille Hospital, France, and were compared to 72 randomized controls transplant recipients. In univariate analysis, age of donor (>48 years), retransplantation, a decrease glomerular filtration rate (≤45 mL/min), induction therapy mediated by anti-thymocyte globulin (ATG), steroid maintenance, high calcineurin inhibitors (CNI) doses (tacrolimus ≥0.5 mg/kg/day and cyclosporine ≥2.1 mg/kg/day), and cytomegalovirus (CMV) infection were significantly associated with PCP. In multivariate analysis, ATG (hazard ratio [HR]: 2.4 [1.1-5.4]), steroid therapy (HR: 3.1 [1.20-7.84], CNI (HR: 2.9 [1.28-6.38], and CMV (HR: 6.1 [2.74-16.33] remained associated with late PCP. In conclusion, we confirm that intensive immunosuppressive regimen and CMV infection are critical risk factors for late PCP and should be taken into account to decide on maintenance or reintroduction of a prophylactic treatment.

Cost-effectiveness of home telemonitoring in chronic kidney disease patients at different stages by a pragmatic randomized controlled trial (eNephro): rationale and study design.

BACKGROUND: Home telemonitoring has developed considerably over recent years in chronic diseases in order to improve communication between healthcare professionals and patients and to promote early detection of deteriorating health status. In the nephrology setting, home telemonitoring has been evaluated in home dialysis patients but data are scarce concerning chronic kidney disease (CKD) patients before and after renal replacement therapy. The eNephro study is designed to assess the cost effectiveness, clinical/biological impact, and patient perception of a home telemonitoring for CKD patients. Our purpose is to present the rationale, design and organisational aspects of this study. METHODS: eNephro is a pragmatic randomised controlled trial, comparing home telemonitoring versus usual care in three populations of CKD patients: stage 3B/4 (n = 320); stage 5D CKD on dialysis (n = 260); stage 5 T CKD treated with transplantation (n= 260). Five hospitals and three not-for-profit providers managing self-care dialysis situated in three administrative regions in France are participating. The trial began in December 2015, with a scheduled 12-month inclusion period and 12 months follow-up. Outcomes include clinical and biological data (e.g. blood pressure, haemoglobin) collected from patient records, perceived health status (e.g. health related quality of life) collected from self-administered questionnaires, and health expenditure data retrieved from the French health insurance database (SNIIRAM) using a probabilistic matching procedure. DISCUSSION: The hypothesis is that home telemonitoring enables better control of clinical and biological parameters as well as improved perceived health status. This better control should limit emergency consultations and hospitalisations leading to decreased healthcare expenditure, compensating for the financial investment due to the telemedicine system. TRIAL REGISTRATION: This study has been registered at ClinicalTrials.gov under NCT02082093 (date of registration: February 14, 2014).

Collapsing glomerulopathy is common in the setting of thrombotic microangiopathy of the native kidney.

Thrombotic microangiopathy (TMA) is a poorly recognized cause of collapsing glomerulopathy. The frequency and significance of collapsing glomerulopathy associated with renal TMA have not been specifically studied in native kidney biopsy specimens. Here we retrospectively documented clinicopathologic features of 53 patients with histologically proven TMA in the native kidney, with special emphasis on changes due to focal segmental glomerulosclerosis (FSGS). Histological TMA was related to hypertensive nephropathy in 21 patients, genetic complement abnormalities in 9, drugs in 7, and to other causes in 16 patients. Almost half (26 patients) presented with arteriolar, 6 with glomerular, and 21 with mixed TMA. Using the Columbia classification system for the 53 patients with histological TMA, 33 had concurrent FSGS lesions with collapsing glomerulopathy the dominant variant in 19 patients (58% of the FSGS cases), not otherwise specified in 9 patients, cellular in 3, and perihilar or tip lesions in 1 patient each. The presence of FSGS was associated with a poor renal prognosis, with no prognostic difference between collapsing glomerulopathy and other FSGS variants. Thus, collapsing glomerulopathy is frequently found in native kidney biopsies with TMA, suggesting that endothelial injury may play an important role in the pathophysiology of FSGS.

Renal Cortical Necrosis in Postpartum Hemorrhage: A Case Series.

BACKGROUND: Pregnancy-related renal cortical necrosis may lead to end-stage renal disease. Although this obstetric complication had virtually disappeared in high-income countries, we have noted new cases in France over the past few years, all following postpartum hemorrhage. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We retrospectively identified 18 patients from 5 French nephrology departments who developed renal cortical necrosis following postpartum hemorrhage in 2009 to 2013. OUTCOMES: Obstetric and renal features, therapeutic measures, and kidney disease outcome were studied. RESULTS: All patients had a severe postpartum hemorrhage (mean blood loss, 2.6±1.1 [SD] L). Hemodynamic instability and disseminated intravascular coagulation were reported in 5 and 11 patients, respectively. All developed rapid onset of acute kidney injury and required hemodialysis. Diagnosis of renal cortical necrosis was performed 4 to 33 days following delivery. At 6 months postpartum, 8 patients remained dialysis dependent and none recovered normal kidney function. The length of exposure to tranexamic acid treatment was significantly more prolonged in women whose estimated glomerular filtration rate remained <15mL/min/1.73m(2) (7.1±4.8 vs 2.9±2.4 hours; P=0.03). LIMITATIONS: Retrospective study; small sample size. CONCLUSIONS: In the setting of gravid endothelium, the conjunction of disseminated intravascular coagulation with the life-saving use of procoagulant and antifibrinolytic agents (recently implemented in France in a postpartum hemorrhage treatment algorithm) may give rise to a risk for uncontrolled clotting in the renal cortex and hence irreversible partial or diffuse cortical necrosis.

Long-term outcome after early cyclosporine withdrawal in kidney transplantation: ten years after.

BACKGROUND: Despite long-term side effects, calcineurin inhibitors (CNI) remain a cornerstone of immunosuppression in renal transplantation. Few trials assessed the long-term outcome after early CNI withdrawal. METHODS: This intention-to-treat study assessed the 10-year outcome of 108 patients randomly converted from a cyclosporine (CsA)-mycophenolate mofetil (MMF)-prednisone regimen to a dual therapy (CsA-prednisone or MMF-prednisone) at 3 months postgraft. RESULTS: At 10 years, 3.7% in the CsA group and 35.2% in the MMF group remained on the protocol regimen (P<.001). eGFR was higher in the MMF group (64.4±21 vs 49.7±14.7 mL/min/1.73 m², P<.001), although acute rejection (12 vs 4 in the CsA group, P=.03) and Class II DSA incidences were increased. CNI-related toxicity (P=.019) and moderate-to-severe IF/TA (P=.004) were higher in the CsA group. Ten-year graft and patient survivals were not different. In multivariate analysis, acute rejection remained the strongest predictor of graft loss (HR=11.64, 95% CI [5.05-26.79], P<.0001). CONCLUSIONS: MMF withdrawal largely failed due to CNI toxicity, while CsA withdrawal led to increased graft failure due to uncontrolled acute rejection without increasing graft survival. From this study, it remains unclear which patients could benefit from limiting CNI exposure.

Long-term reproducibility of diurnal intraocular pressure patterns in patients with glaucoma.

PURPOSE: To evaluate the long-term reproducibility of diurnal intraocular pressure (IOP) patterns in patients with primary open-angle glaucoma (POAG). DESIGN: Database study. PARTICIPANTS: Ninety-two patients with POAG. METHODS: We reviewed the records of patients with POAG who underwent 4 diurnal IOP curve measurements 6 months apart with Goldmann applanation tonometry recorded in the sitting position at 9 am, 10 am, 11 am, noon, 2 pm, 3 pm, 4 pm, and 5 pm. MAIN OUTCOME MEASURES: Intervisit agreement of IOP by time point and of diurnal IOP curve parameters (mean, standard deviation, range, maximum, maximum hour, minimum, and minimum hour) was assessed using intraclass correlation coefficients (ICCs). Analyses were performed in all eyes and separately in eyes with and without hypotensive medications, and in eyes naïve and non-naïve of filtering surgery. RESULTS: Between-visit agreement of IOP values at each time point was generally poor, with ICCs ranging from 0.26 to 0.77 in all patients (1 of 8 time points with ICC >0.75), from -0.07 to 0.60 in patients without hypotensive medications (zero time points with ICC >0.75), from 0.29 to 0.80 in patients with hypotensive medications (3 time points with ICCs >0.75), from 0.21 to 0.68 in filtering surgery-naïve patients (zero time points with ICC >0.75), and from 0.21 to 0.87 in patients with previous filtering surgeries (5 time points with ICCs >0.75). The predictive value of the first diurnal IOP curve to estimate the risk of IOP fluctuations during the 3 subsequent curves was limited (only 6.4% of the patients with an IOP range ≥30% of the mean IOP on the first curve presented similar fluctuations on the 3 subsequent curves; 77.1% of the patients who did not have an IOP range ≥30% of the mean IOP on the first curve had an IOP range ≥30% of the mean IOP on at least 1 of the 3 subsequent curves). CONCLUSIONS: Patients with POAG do not manifest a reproducible diurnal IOP pattern from month to month. A single diurnal IOP curve in patients with POAG poorly characterizes IOP fluctuations and has limited value in clinical practice.

A prevalent C3 mutation in aHUS patients causes a direct C3 convertase gain of function.

Atypical hemolytic uremic syndrome (aHUS) is a rare renal thrombotic microangiopathy commonly associated with rare genetic variants in complement system genes, unique to each patient/family. Here, we report 14 sporadic aHUS patients carrying the same mutation, R139W, in the complement C3 gene. The clinical presentation was with a rapid progression to end-stage renal disease (6 of 14) and an unusually high frequency of cardiac (8 of 14) and/or neurologic (5 of 14) events. Although resting glomerular endothelial cells (GEnCs) remained unaffected by R139W-C3 sera, the incubation of those sera with GEnC preactivated with pro-inflammatory stimuli led to increased C3 deposition, C5a release, and procoagulant tissue-factor expression. This functional consequence of R139W-C3 resulted from the formation of a hyperactive C3 convertase. Mutant C3 showed an increased affinity for factor B and a reduced binding to membrane cofactor protein (MCP; CD46), but a normal regulation by factor H (FH). In addition, the frequency of at-risk FH and MCP haplotypes was significantly higher in the R139W-aHUS patients, compared with normal donors or to healthy carriers. These genetic background differences could explain the R139W-aHUS incomplete penetrance. These results demonstrate that this C3 mutation, especially when associated with an at-risk FH and/or MCP haplotypes, becomes pathogenic following an inflammatory endothelium-damaging event.

Osteomalacia induced by vitamin D deficiency in hemodialysis patients: the crucial role of vitamin D correction.

Vitamin D deficiency/insufficiency is significantly prevalent in chronic kidney disease. Data in the literature are however scarce about the effects of this deficiency on bone metabolism in hemodialysis (HD) patients. Moreover, it is still debated whether low vitamin D levels should be normalized in HD patients. In this paper, we report two cases showing the deleterious consequences of vitamin D deficiency in HD patients which is characterised by hypophosphatemia, hypocalcemia and osteomalacia (OM) leading to bone fractures. As vitamin D repletion is an easy way to treat OM, this report underlines the importance of monitoring and correction of vitamin D deficiency in this population.

Giant osteoclasts in patients under bisphosphonates.

BACKGROUND: Bisphosphonates have been widely used for treatment of high bone resorption states. It lowers bone turnover by inhibiting osteoclasts bone resorption with various mechanisms of actions: inhibition of osteoclast formation and attachment to the bone surface, induction of metabolic injury, alteration of vesicle trafficking and induction of osteoclast apoptosis. Bone biopsies studies from patients under bisphosphonates have shown that some resorption parameters are decreased as expected but the number of osteoclasts seems not to be necessarily decreased. The description of osteoclasts morphology from patients treated with bisphosphonates has rarely been reported in the literature. CASE PRESENTATION: We describe in this paper two patients treated with bisphosphonates from whom iliac crest bone biopsies have shown large, multinucleated and apoptotic osteoclasts that were not associated with bone resorption activities. The characteristics of these osteoclasts are described and the literature reviewed. CONCLUSION: The appropriate recognition of these giant osteoclasts in bone tissues from patients treated with bisphosphonates is of primary importance for bone pathologists and should not be interpreted as signs of increased bone resorption as seen in hyperparathyroidism, bone cancer or Paget's disease of bone.

UMOD polymorphism rs12917707 is not associated with severe or stable IgA nephropathy in a large Caucasian cohort.

BACKGROUND: Genetic factors are suspected in the pathogenesis of IgA nephropathy, as well as in the course of IgA nephropathy progression towards end stage renal failure. UMOD polymorphism rs12917707 is known to associate with end stage renal failure of mixed aetiologies. METHODS: We tested a large cohort of Caucasian patients for association of rs12917707 with IgA nephropathy showing a benign, stable course and with IgA nephropathy that progressed toward end stage renal failure. RESULTS: No association was observed between either groups, and a non-significant trend was observed for more severe IgA nephropathy with the allele reported to protect against end stage renal failure of mixed aetiologies. CONCLUSION: We conclude that UMOD is unlikely to play a role in IgA nephropathy pathogenesis nor progression to end stage renal failure, and suggest that UMOD effects are restricted to some causes of renal disease, e.g. diabetes or hypertension.

Crohn's disease and nontropical endomyocardial fibrosis.

The pathogenesis of endomyocardial fibrosis (EMF) is poorly understood. EMF may result from autoimmune scarring of the endocardium. Clinically, EMF presents as a restrictive cardiomyopathy. EMF is commonly reported in tropical countries. In Western countries, EMF is associated with hypereosinophilia and reported as Loeffler endocarditis. We report a Caucasian patient with Crohn's disease and EMF, and discuss a possible linkage between the two conditions.

Renal involvement in MELAS syndrome - a series of 5 cases and review of the literature.

Renal dysfunction is increasingly recognized as a potential clinical feature of mitochondrial cytopathies such as mitochondrial encephalomyopathy, lacticacidosis and stroke-like episodes (MELAS) syndrome. Five cases of MELAS syndrome with renal involvement from 4 unrelated families are presented in this case series. Three of the 5 patients had a history of maternally-inherited diabetes and/or deafness. Focal and segmental glomerulosclerosis and arteriolar hyaline thickening were the most striking findings on renal biopsy. In addition to clinical presentation with the typical symptoms of MELAS syndrome, genetic testing in these patients identified the A3243G point mutation in the tRNALeu gene of the mitochondrial DNA (mtDNA). The diagnosis of MELAS syndrome was thus considered to be unequivocal. The incidence of kidney disease in MELAS syndrome may be underestimated although a study is required to investigate this hypothesis. As the A3243G mtDNA mutation leads to a progressive adult-onset form of focal segmental glomerulosclerosis (FSGS), screening for the MELAS A3243G mtDNA mutation should therefore be performed especially in patients with maternally-inherited diabetes or hearing loss presenting with FSGS.

The role of Thymoglobulin induction in kidney transplantation: an update.

The rabbit antithymocyte globulin Thymoglobulin first became available over 25 yr ago and is the most widely used lymphocyte-depleting preparation in solid organ transplantation. Thymoglobulin targets a wide range of T-cell surface antigens as well as natural killer-cell antigens, B-cell antigens, plasma cell antigens, adhesion molecules and chemokine receptors, resulting in profound, long-lasting T-cell depletion. Randomized studies have established the anti-rejection efficacy of Thymoglobulin in kidney transplantation. Experimental and clinical data suggest that Thymoglobulin administration may ameliorate ischemia reperfusion injury, thus reducing the incidence of delayed graft function (DGF). Studies have demonstrated the benefit of using Thymoglobulin to facilitate immunosuppression minimization, both for corticosteroid and calcineurin inhibitor (CNI) withdrawal or avoidance, with potential improvement in cardiovascular and renal outcomes. The optimal cumulative dose for Thymoglobulin induction is 6-7.5 mg/kg, with vigilant short- and long-term monitoring of hematological status. Induction with Thymoglobulin is now indicated in immunologically high-risk patients, in those at increased risk of DGF and to maintain efficacy in low-risk transplant recipients receiving steroid or CNI minimization or avoidance regimens. We suggest that in future trials Thymoglobulin be tested with costimulation signal blockers and other immunosuppressants with the objective of establishing operational tolerance.

Three-year outcome of isolated glomerulitis on 3-month protocol biopsies of donor HLA antibody negative patients.

Transplant glomerulitis (TG) can lead to the diagnosis of acute humoral rejection when associated with C4d. Recent data have shown that, in patients with donor-specific antibodies, TG is a sign of humoral rejection, even in the absence of C4d. However, the clinical significance of isolated TG, i.e. TG without C4d deposition or morphological evidence of rejection, has not been specifically studied in protocol biopsies of recipients without donor-specific antibodies. We compared 20 isolated TG-patients with 44 selected recipients without TG or any rejection-associated change. The two groups had similar baseline characteristics. After a 3 year follow-up, renal function, acute rejection rate, and development of HLA antibodies were not significantly different between the two groups. Isolated TG had no deleterious consequences on the 3 year graft outcome. Eleven patients of the glomerulitis-group had another allograft biopsy during follow-up: glomerular lesions returned to normal in six patients whereas the persistence of glomerulitis or features consistent with chronic transplant glomerulopathy were noticed in the remaining five patients. Four of these five patients had pretransplant non-donor specific HLA antibodies. In conclusion, although isolated TG had no impact on allograft function at 3 year, histological outcome could be related to patient sensitization.

Maturity onset diabetes of the young: clinical characteristics and outcome after kidney and pancreas transplantation in MODY3 and RCAD patients: a single center experience.

The diabetes and renal phenotype of patients with maturity-onset diabetes of the young (MODY) on a transplantation waiting list is not known; neither is their outcome after pancreas (PT) and/or kidney transplantation (KT). Between 2002 and 2009, we screened 50 of 150 patients referred for kidney and pancreas transplantation to the Kremlin-Bicêtre center for HNF1B and HNF1A mutations if one or more of the following criteria was present (i) an atypical history of diabetes (ii) diabetes with at least one affected parent or two affected relatives, (iii) an absence of auto-antibodies at diagnosis (iv) a persistent secretion of fasting C peptide (v) a personal or a family history of renal cysts or dysplasia. Their phenotype and their outcome were analyzed. Four HNF1A (MODY3) and eight HNF1B mutations [renal cysts and diabetes (RCAD)] were identified. All MODY3 patients had diabetic nephropathy, but only 50% of RCAD patients. Four patients underwent a kidney and pancreas transplantation and two a kidney transplant alone. After 4.1 ± 1.1 years of follow-up, 83% of patients still have a functioning kidney and 75% a functioning pancreas. PT can be proposed with good results for MODY3 and RCAD patients.

Epithelial-to-mesenchymal transition predicts cyclosporine nephrotoxicity in renal transplant recipients.

Maintenance immunosuppression with cyclosporine A (CsA) can cause nephrotoxicity in renal transplant recipients. Identifying patients at increased risk for CsA nephrotoxicity may allow interventions to prolong graft survival. Here, we studied the effect of early CsA withdrawal or maintenance among 96 kidney recipients at risk for interstitial fibrosis and tubular atrophy (IF/TA) on the basis of tubular expression of vimentin and ß-catenin in a protocol biopsy performed 3 months after transplant. In this retrospective analysis of biopsies collected during a randomized trial of early withdrawal of CsA or mycophenolate mofetil, the semiquantitative score of early phenotypic changes suggestive of epithelial-to-mesenchymal transition (EMT) progressed with time among those maintained on a CsA-containing regimen. EMT-positive grafts displayed a significantly higher IF/TA score and greater progression of the IF/TA score at 12 months (P=0.001 and 0.008, respectively). EMT-positive grafts exposed to CsA also had a greater decrease in estimated GFR compared with EMT-negative grafts exposed to CsA and EMT-positive grafts withdrawn from CsA exposure. Multivariable analysis revealed that the presence of EMT was an independent risk factor for a 10% decline in graft function up to 4 years posttransplant (odds ratio 4.49; 95% confidence interval 1.02 to 19.9). Collectively, these data demonstrate that changes consistent with EMT are strong prognostic biomarkers in renal transplant recipients exposed to CsA.

CYP3A5 and ABCB1 polymorphisms in donor and recipient: impact on Tacrolimus dose requirements and clinical outcome after renal transplantation.

BACKGROUND: The effect of potentially relevant genetic polymorphisms, CYP3A5 6986A>G and ABCB1 3435C>T, on Tacrolimus pharmacokinetics and graft clinical outcome was investigated in donor and recipient DNA samples from 209 kidney transplant patients. METHODOLOGY/PRINCIPAL FINDINGS: The mean follow-up was 21.8 ± 9 months. The Tacrolimus dose, trough blood concentrations (C0) and C0/dose ratio were only statistically correlated with the recipient CYP3A5 genotype. CYP3A5 and ABCB1 genotypes appeared to have no influence on the incidence of Biopsy Proven Acute Rejection and Delayed Graft Function. Renal function was not affected by CYP3A5 and ABCB1 genotypes. Histological evaluation of biopsies revealed also no significant association between Tacrolimus toxicity features and donor or recipient CYP3A5 and ABCB1 polymorphisms. Tacrolimus sparing appeared to be independent of CYP3A5 and ABCB1 genotypes. CONCLUSIONS/SIGNIFICANCE: Recipient CYP3A5 6986A>G polymorphism explains part of the interindividual variability of the pharmacokinetics of Tacrolimus. The clinical outcome at 2-year follow-up does not appear to be related to the donor or recipient CYP3A5 6986A>G and/or ABCB1 3435C>T polymorphisms.

Daclizumab versus antithymocyte globulin in high-immunological-risk renal transplant recipients.

Nondepleting anti-CD25 monoclonal antibodies (daclizumab) and depleting polyclonal antithymocyte globulin (Thymoglobulin) both prevent acute rejection, but these therapies have not been directly compared in a high-risk, HLA-sensitized renal transplant population. We randomly assigned 227 patients, who were about to receive a kidney graft from a deceased donor, to either Thymoglobulin or daclizumab if they met one of the following risk factors: current panel reactive antibodies (PRA) >30%; peak PRA >50%; loss of a first kidney graft from rejection within 2 yr of transplantation; or two or three previous grafts. Maintenance immunosuppression comprised tacrolimus, mycophenolate mofetil, and steroids. Compared with the daclizumab group, patients treated with Thymoglobulin had a lower incidence of both biopsy-proven acute rejection (15.0% versus 27.2%; P = 0.016) and steroid-resistant rejection (2.7% versus 14.9%; P = 0.002) at one year. One-year graft and patient survival rates were similar between the two groups. In a comparison of rejectors and nonrejectors, overall graft survival was significantly higher in the rejection-free group (87.2% versus 75.0%; P = 0.037). In conclusion, among high-immunological-risk renal transplant recipients, Thymoglobulin is superior to daclizumab for the prevention of biopsy-proven acute rejection, but there is no significant benefit to one-year graft or patient survival.

TCF7L2 polymorphism associates with new-onset diabetes after transplantation.

New-onset diabetes after transplantation (NODAT) is a serious and frequent complication in transplant recipients. Whether NODAT shares the same susceptibility genes as type 2 diabetes is unknown. In this multicenter study, we genotyped 1076 white patients without diabetes at transplantation for 11 polymorphisms that associate with type 2 diabetes. We defined NODAT as a fasting plasma glucose > or =126 mg/dl on at least two occasions or de novo hypoglycemic therapy. We compared clinical and genetic factors between patients who developed NODAT within 6 mo of transplantation (n = 118; incidence 11%) and patients without diabetes (n = 958). In multivariate analysis, NODAT significantly associated with the following characteristics: TCF7L2 polymorphism (odds ratio [OR] 1.60 per each T allele; P = 0.002), age (OR 1.03 per year; P < 0.001), body mass index at transplantation (OR 1.09 per unit; P < 0.001), tacrolimus use (OR 2.26; P < 0.001), and the occurrence of a corticoid-treated acute rejection episode (OR 2.78; P < 0.001). In summary, our data show that the TCF7L2 rs7903146 polymorphism, a known risk factor for type 2 diabetes in the general population, also associates with NODAT.

The prognostic impact of cirrhosis on patients receiving maintenance haemodialysis.

BACKGROUND: Further study is needed on the prognostic impact of cirrhosis on haemodialysis patients. AIM: To evaluate cirrhosis' impact according to severity on survival and to provide therapeutic guidelines for haemodialysis cirrhotic patients. METHODS: Patients with end-stage renal failure treated with haemodialysis were included retrospectively from 01/01/2000 to 31/12/2004 and prospectively from 01/01/2005 to 31/12/2014 in our French Region. Clinical data, presence of cirrhosis and its severity were recorded at the beginning of haemodialysis. The primary endpoint was 2-year survival. RESULTS: Seven thousand three hundred and fifty-four patients (96%) without cirrhosis and 304 patients (4%) with cirrhosis were included. Two-year survival in noncirrhotic patients was higher than in cirrhotic patients (71.7% vs 54.4%, P < 0.0001). Patients with decompensated cirrhosis had a worse 2-year outcome (44.1%) as compared to compensated cirrhotic (62.8%, P = 0.002) and noncirrhotic patients (71.7%, P < 0.0001). Compensated and decompensated cirrhosis were independent predictive factors of 2-year mortality. In sensitivity analysis restricted to cirrhotic patients, 2-year survival of Child-Pugh A patients was higher than in Child-Pugh B and C patients (65.5% vs 27.7% vs 0%, P < 0.0001). Development of predictive models based either on severity scores (MELD and Child-Pugh) and extrahepatic comorbidities allowed correct classification of around 70% of patients in terms of mortality and may help to better stratify mortality risk in this population. CONCLUSIONS: Cirrhosis is independently associated with mortality in haemodialysis patients. Patients with severe cirrhosis have a poor 2-year outcome. Severity of cirrhosis and presence of extrahepatic comorbidities should be considered when deciding to initiate renal replacement therapy.