A regimen with caplacizumab, immunosuppression, and plasma exchange prevents unfavorable outcomes in immune-mediated TTP.

The anti-von Willebrand factor nanobody caplacizumab was licensed for adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) based on prospective controlled trials. However, few data are available on postmarketing surveillance. We treated 90 iTTP patients with a compassionate frontline triplet regimen associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab. Outcomes were compared with 180 historical patients treated with the standard frontline treatment (TPE and corticosteroids, with rituximab as salvage therapy). The primary outcome was a composite of refractoriness and death within 30 days since diagnosis. Key secondary outcomes were exacerbations, time to platelet count recovery, the number of TPE, and the volume of plasma required to achieve durable remission. The percentage of patients in the triplet regimen with the composite primary outcome was 2.2% vs 12.2% in historical patients (P = .01). One elderly patient in the triplet regimen died of pulmonary embolism. Patients from this cohort experienced less exacerbations (3.4% vs 44%, P < .01); they recovered durable platelet count 1.8 times faster than historical patients (95% confidence interval, 1.41-2.36; P < .01), with fewer TPE sessions and lower plasma volumes (P < .01 both). The number of days in hospital was 41% lower in the triplet regimen than in the historical cohort (13 vs 22 days; P < .01). Caplacizumab-related adverse events occurred in 46 patients (51%), including 13 major or clinically relevant nonmajor hemorrhagic events. Associating caplacizumab to TPE and immunosuppression, by addressing the 3 processes of iTTP pathophysiology, prevents unfavorable outcomes and alleviates the burden of care.

Laboratory diagnosis of heparin-induced thrombocytopenia: A retrospective experience.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a severe complication of heparin therapy associated with thrombosis that requires a quick diagnosis. Therefore, laboratory assays must provide an accurate and swift answer. This work aims to evaluate the performances of an ELISA assay, especially when combined with 4T risk score, and a functional assay. METHODS: Data were collected for 894 patients treated by heparin who underwent anticoagulant switch because of HIT suspicion and were examined by a multidisciplinary expert team who confirmed or ruled out HIT diagnosis. All patients were tested for anti-PF4 IgG with Asserachrom HPIA IgG (ELISA), and 307 were tested with a platelet aggregation test done on platelet-rich plasma (PRP-PAT). The 4T risk score was available for 607 of them. RESULTS: HIT was diagnosed in 232 patients. 4T risk score had a 94.2% negative predictive value (NPV) for risk scores ≤3 and 77.3% for risk scores ≤5. The sensitivity of ELISA was 90.9%, its specificity 79.0%, and its NPV 96.1%. When combined with 4T risk score, its NPV reached 100% and 97% for risk scores ≤3 and ≤5, respectively. PRP-PAT sensitivity was 70.4%, and its specificity was 92.3%. Combination of ELISA and PRP-PAT had a 0.7% false-negative rate. CONCLUSION: This study shows that ELISA can rule out HIT with an excellent NPV, especially when combined with the 4T risk score. Nonetheless, it has low specificity; hence, it needs to be associated with a functional assay.

Dialysis dose and mortality in haemodialysis: is higher better?

BACKGROUND: The effect of dialysis dose on mortality remains unsettled. Current guidelines recommend targeting a single-pool Kt/V (spKt/V) at 1.20-1.40 per thrice-weekly dialysis session. However, the optimal dialysis dose remains mostly disputed. METHODS: In a nationwide registry of all incident patients receiving thrice-weekly haemodialysis, 32 283 patients had available data on dialysis dose, estimated by Kt/V and its variants epuration volume per session (Kt) and Kt indexed to body surface area (Kt/A). Survival was analysed with a multivariate Cox model and a concurrent risk model accounting for renal transplantation. A predictive model of Kt in the upper quartile was developed. RESULTS: Regardless of the indicator, a higher dose of dialysis was consistently associated with better survival. The survival differential of Kt was the most discriminating, but marginally, compared with the survival differential according to Kt/V and Kt/A. Patient survival was higher in the upper quartile of Kt (>69 L/session) then deteriorated as the Kt decreased, with a difference in survival between the upper and lower quartile of 23.6% at 5 years. Survival differences across Kt distribution were similar after accounting for kidney transplantation as a competing risk. Predictive factors for Kt in the upper quartile were arteriovenous fistula versus catheters and graft, haemodiafiltration versus haemodialysis, scheduled dialysis start versus emergency start, long weekly dialysis duration and spKt/V measurement versus double-pool equilibrated Kt/V. CONCLUSIONS: Our data confirm the existence of a relationship between dialysis dose and survival that persisted despite correcting for known confounders. A model for predicting a high dose of dialysis is proposed with practical relevance.

Impact of first-wave COronaVIrus disease 2019 infection in patients on haemoDIALysis in Alsace: the observational COVIDIAL study.

BACKGROUND: There are only scarce data regarding the presentation, incidence, severity and outcomes of coronavirus disease 2019 (COVID-19) in patients undergoing long-term haemodialysis (HD). A prospective observational study was conducted in eight HD facilities in Alsace, France, to identify clinical characteristics of HD patients with COVID-19 and to assess the determinants of the risk of death. METHODS: All HD patients tested positive for COVID-19 from 5 March to 28 April 2020 were included. Collected data included patient characteristics, clinical features at diagnosis, laboratory data, treatments and outcomes. RESULTS: Among 1346 HD patients, 123 tested positive for COVID-19. Patients had a median age of 77 years (interquartile range 66-83), with a high number of comorbidities (3.2 ± 1.6 per patient). Symptoms were compatible in 63% of patients. Asthenia (77%), diarrhoea (34%) and anorexia (32%) were frequent at diagnosis. The delay between the onset of symptoms and diagnosis, death or complete recovery was 2 (0-5), 7 (4-11) and 32 (26.5-35) days, respectively. Treatment, including lopinavir/ritonavir, hydroxychloroquine and corticosteroids, was administered in 23% of patients. The median C-reactive protein (CRP) and lymphocyte count at diagnosis was 55 mg/L (IQR 25-106) and 690 Ly/µL (IQR 450-960), respectively. The case fatality rate was 24% and determinants associated with the risk of death were body temperature {hazard ratio [HR] 1.96 [95% confidence interval (CI) 1.11-3.44]; P = 0.02} and CRP at diagnosis [HR 1.01 (95% CI 1.005-1.017); P < 0.0001]. CONCLUSIONS: HD patients were found to be at high risk of developing COVID-19 and exhibited a high rate of mortality. While patients presented severe forms of the disease, they often displayed atypical symptoms, with the CRP level being highly associated with the risk of death.

Metabolic syndrome in haemodialysis patients: prevalence, determinants and association to cardiovascular outcomes.

BACKGROUND: In the general population, metabolic syndrome (MetS) is predictive of major adverse cardiovascular events (MACE). Waist circumference (WC), a component of the MetS criteria, is linked to visceral obesity, which in turn is associated with MACE. However, in haemodialysis (HD) patients, the association between MetS, WC and MACE is unclear. METHODS: In a cross-sectional study of 1000 HD patients, we evaluated the prevalence and characterised the clinical predictors of MetS. The relationship between MetS and its components, alone or in combination, and MACE (coronary diseases, peripheral arteriopathy, stroke or cardiac failure), was studied using receiver operating characteristics (ROC) curves and logistic regression. RESULTS: A total of 753 patients were included between October 2011 and April 2013. The prevalence of MetS was 68.5%. Waist circumference (> 88 cm in women, 102 cm in men) was the best predictor of MetS (sensitivity 80.2; specificity 82.3; AUC 0.80; p <  0.05). In multivariate analysis, MetS was associated with MACE (OR: 1.85; 95CI 1.24-2.75; p <  0.01), but not WC alone. There was a stronger association between the combination of abdominal obesity, hypertriglyceridaemia and low high-density lipoprotein cholesterol with MACE after exclusion of impaired fasting glucose and hypertension. CONCLUSIONS: MetS is frequent and significantly associated with MACE in our haemodialysis cohort and probably in other European dialysis populations as well. In HD patients, a new simplified definition could be proposed in keeping with the concept of the "hypertriglyceridaemic waist".

Survival advantage of planned haemodialysis over peritoneal dialysis: a cohort study.

Background: Previous studies comparing the outcomes in haemodialysis (HD) with those in peritoneal dialysis (PD) have yielded conflicting results. Methods: The aim of the study was to compare the survival of planned HD versus PD patients in a cohort of adult incident patients who started renal replacement therapy (RRT) between 2006 and 2008 in the nationwide REIN registry (Réseau Epidémiologie et Information en Néphrologie). Patients who started RRT in emergency or stopped RRT within 2 months were excluded. Adjusted Cox models, propensity score matching and marginal structural models (MSMs) were used to compensate for the lack of randomization and provide causal inference from longitudinal data with time-dependent treatments and confounders including transplant censorship, modality change over time and time-varying covariates. Results: Among a total of 13 767 dialysis patients, 13% were on PD at initiation of RRT and 87% were on HD. The median survival times were 53.5 months or 4.45 years and 38.6 months or 3.21 years for patients starting on HD and PD, respectively. Regardless of the model used, there was a consistent advantage in terms of survival for HD patients: hazard ratio (HR) 0.76 [95% confidence interval (95% CI) 0.69-0.84] with the Cox model using propensity score; HR 0.67 (95% CI 0.62-0.73) in the Cox model with censorship for each treatment change; and HR 0.82 (95% CI 0.69-0.97) with MSMs. However, MSMs tended to reduce the survival gap between PD and HD patients. Conclusion: This large cohort study using various statistical methods to minimize the bias appears to demonstrate a better survival in planned HD than in PD.

Clinical and genetic heterogeneity in familial steroid-sensitive nephrotic syndrome.

BACKGROUND: Familial steroid-sensitive nephrotic syndrome (SSNS) is a rare condition. The disease pathophysiology remains elusive. However, bi-allelic mutations in the EMP2 gene were identified, and specific variations in HLA-DQA1 were linked to a high risk of developing the disease. METHODS: Clinical data were analyzed in 59 SSNS families. EMP2 gene was sequenced in families with a potential autosomal recessive (AR) inheritance. Exome sequencing was performed in a subset of 13 families with potential AR inheritance. Two variations in HLA-DQA1 were genotyped in the whole cohort. RESULTS: Transmission was compatible with an AR (n = 33) or autosomal dominant (AD, n = 26) inheritance, assuming that familial SSNS is a monogenic trait. Clinical features did not differ between AR and AD groups. All patients, including primary (n = 7) and secondary steroid resistant nephrotic syndrone (SRNS), (n = 13) were sensitive to additional immunosuppressive therapy. Both HLA-DQA1 variations were found to be highly linked to the disease (OR = 4.34 and OR = 4.89; p < 0.001). Exome sequencing did not reveal any pathogenic mutation, neither did EMP2 sequencing. CONCLUSIONS: Taken together, these results highlight the clinical and genetic heterogeneity in familial SSNS. Clinical findings sustain an immune origin in all patients, whatever the initial steroid-sensitivity. The absence of a variant shared by two families and the HLA-DQA1 variation enrichments suggest a complex mode of inheritance.

Epitope Spreading of Autoantibody Response to PLA2R Associates with Poor Prognosis in Membranous Nephropathy.

The phospholipase A2 receptor (PLA2R1) is the major autoantigen in idiopathic membranous nephropathy. However, the value of anti-PLA2R1 antibody titers in predicting patient outcomes is unknown. Here, we screened serum samples from 50 patients positive for PLA2R1 for immunoreactivity against a series of PLA2R1 deletion mutants covering the extracellular domains. We identified reactive epitopes in the cysteine-rich (CysR), C-type lectin domain 1 (CTLD1), and C-type lectin domain 7 (CTLD7) domains and confirmed the reactivity with soluble forms of each domain. We then used ELISAs to stratify 69 patients positive for PLA2R1 by serum reactivity to one or more of these domains: CysR (n=23), CysRC1 (n=14), and CysRC1C7 (n=32). Median ELISA titers measured using the full-length PLA2R1 antigens were not statistically different between subgroups. Patients with anti-CysR-restricted activity were younger (P=0.008), had less nephrotic range proteinuria (P=0.02), and exhibited a higher rate of spontaneous remission (P=0.03) and lower rates of renal failure progression (P=0.002) and ESRD (P=0.01) during follow-up. Overall, 31 of 69 patients had poor renal prognosis (urinary protein/creatinine ratio >4 g/g or eGFR<45 ml/min per 1.73 m(2) at end of follow-up). High anti-PLA2R1 activity and epitope spreading beyond the CysR epitope were independent risk factors of poor renal prognosis in multivariable Cox regression analysis. Epitope spreading during follow-up associated with disease worsening (n=3), whereas reverse spreading from a CysRC1C7 profile back to a CysR profile associated with favorable outcome (n=1). We conclude that analysis of the PLA2R1 epitope profile and spreading is a powerful tool for monitoring disease severity and stratifying patients by renal prognosis.

Psychotropic Drug Use in Recreational Scuba Divers and its Effect on Severe Narcosis.

Recreational scuba diving is no longer reserved for young healthy individuals, and as a result, medical drug consumption is on the rise in the diving population. Due to the possible potentiation of nitrogen narcosis by psychotropic drugs, the latter are hence discouraged and are subject to contraindications for practice. However, there are no available experimental data to support this theoretical assumption. The objective of this study is to investigate whether psychotropic drug users are more at risk of severe narcosis. An online survey was sent to the licensed divers from the East of France registered with the French Underwater Federation. Divers were surveyed regarding their consumption of psychotropic drugs, the occurrence of nitrogen narcosis as well as their respective diver's curriculum vitae.1 608 divers responded to the survey of which 15.2% confirmed having used psychotropic drugs and 7.8% since they became divers. Overall, 40.0% and 5.5% experienced severe and critical narcosis. In multivariate analysis, neither severe nor critical narcosis was associated with psychotropic drug use (OR 0.97 [0.59-1.57] and 0.76 [0.29-2.00], respectively).In conclusion, despite the recommendations, a significant proportion of divers use psychotropic drugs but do not seem to be more prone to severe narcosis.

Multiphasic effects of blood pressure on survival in hemodialysis patients.

Dialysis patients exhibit an inverse, L- or U-shaped association between blood pressure and mortality risk, in contrast to the linear association in the general population. We prospectively studied 9333 hemodialysis patients in France, aiming to analyze associations between predialysis systolic, diastolic, and pulse pressure with all-cause mortality, cardiovascular mortality, and nonfatal cardiovascular endpoints for a median follow-up of 548 days. Blood pressure components were tested against outcomes in time-varying covariate linear and fractional polynomial Cox models. Changes throughout follow-up were analyzed with a joint model including both the time-varying covariate of sequential blood pressure and its slope over time. A U-shaped association of systolic blood pressure was found with all-cause mortality and of both systolic and diastolic blood pressure with cardiovascular mortality. There was an L-shaped association of diastolic blood pressure with all-cause mortality. The lowest hazard ratio of all-cause mortality was observed for a systolic blood pressure of 165 mm Hg, and of cardiovascular mortality for systolic/diastolic pressures of 157/90 mm Hg, substantially higher than currently recommended values for the general population. The 95% lower confidence interval was approximately 135/70 mm Hg. We found no significant correlation for either systolic, diastolic, or pulse pressure with myocardial infarction or nontraumatic amputations, but there were significant positive associations between systolic and pulse pressure with stroke (per 10-mm Hg increase: hazard ratios 1.15, 95% confidence interval 1.07 and 1.23; and 1.20, 1.11 and 1.31, respectively). Thus, whereas high pre-dialysis blood pressure is associated with stroke risk, low pre-dialysis blood pressure may be both harmful and a proxy for comorbid conditions leading to premature death.

Prognosis of patients with severe hyponatraemia is related not only to hyponatraemia but also to comorbidities and to medical management: results of an observational retrospective study.

BACKGROUND: The true cause of death in severe hyponatraemic patients remains controversial. The present study aimed to analyse the relationship between comorbidity, medical management and prognosis in severe hyponatraemic patients. METHODS: Medical records of all patients hospitalised in our institution in 2012 with a plasma sodium ≤120 mmol/l were retrospectively analysed. RESULTS: One hundred forty-seven of 64 723 adult patients (0.2 %) were identified with severe hyponatraemia. In-hospital mortality rate was 24.5 and 50.3 % after a median follow-up of 431 days. Patients with plasma sodium <110 mmol/l had less comorbidity (Charlson Comorbidity Index 2.2 ± 1.9 vs. 4.0 ± 3.1 (plasma sodium 110-115 mmol/l) and 4.2 ± 3.1 (plasma sodium 116-120 mmol/l); P = .02)) and a small trend for less mortality, respectively 40.0, 51.2 and 52.3 % (P = .64). At discharge, nonsurvivors and survivors had similar plasma sodium with 58.3 % of nonsurvivors being normonatraemic. Urine analysis was performed in 74.2 % of cases and associated with lower in-hospital mortality (20.2 % vs. 36.8 %, P = .05). In multivariate Cox analysis, mortality was significantly associated with plasma sodium normalisation (HR 0.35, P < 0.001), urine analysis (HR 0.48, P = .01), Charlson Comorbidity Index (HR 1.23, P < .001) and serum albumin (HR 0.88, P < .001). CONCLUSION: Mortality in severe hyponatraemia appears mainly due to comorbidities although the latter are potentiated by hyponatraemia itself and its management thereby exacerbating the risk of death.

Haemodialysis in patients treated with oral anticoagulant: should we heparinize?

BACKGROUND: Anticoagulation for the haemodialysis circuit in patients treated with oral anticoagulation poses additional haemorrhagic risk. The few available data suggest that tapering or even stopping heparinization is feasible and the HeprAN membrane with grafted heparin was developed to decrease heparin dose. The objective of our study was to evaluate the need for additional anticoagulation in patients on long-term oral anticoagulation, according to the type of membrane used. METHODS: This is a prospective, randomized, crossover bifactorial trial in haemodialysed patients on oral anticoagulation. Each patient had four haemodialysis sessions with two different membranes [HeprAN or polysulphone (PS)] and with or without enoxaparin. Clinical coagulation was evaluated by the need for premature ending and by a visual score (Janssen scale). Coagulation activation markers were also measured: d-dimers, prothrombin fragments 1 + 2, thrombin-antithrombin complexes, tissue factor pathway inhibitor and platelet factor-4. RESULTS: Ten patients were included (M/F = 4/6, mean age 63 ± 15 years). None of the 40 sessions ended prematurely. The clotting scores were similar with or without enoxaparin (dialyser: 1.49 ± 0.19 versus 1.53 ± 0.17, P = 0.97; bubble trap: 0.75 ± 0.19 versus 0.78 ± 0.22, P = 0.62) and with the polysulphone or the HeprAN membrane (dialyser: 1.54 ± 0.20 versus 1.47 ± 0.16, P = 0.65; bubble trap: 0.74 ± 0.22 versus 0.79 ± 0.19, P = 0.58). There was no significant difference in coagulation activation markers between dialysis modalities; however, dialysis efficacy was significantly greater with the PS membrane (1.58 ± 0.07 versus 1.43 ± 0.06, P = 0.02). CONCLUSIONS: These results suggest that haemodialysis without additional anticoagulation is possible in patients with oral anticoagulation. The HeprAN membrane did not provide any additional benefit compared with a PS membrane.

Continuous glucose monitoring in hemodialyzed patients with type 2 diabetes: a multicenter pilot study.

AIMS: Hemodialyzed patients with diabetes face an increased cardiovascular risk. Optimal glycemic control can reduce morbidity and mortality, but it is difficult to achieve because of the alternation between dialysis and non-dialysis periods. This study evaluated the contribution of continuous glucose monitoring (CGM) to the management of insulin regimen. METHODS: In this pilot prospective multicenter study, we performed CGM (Navigator®, Abbott, Rungis, France) for a total of 54 hours at baseline and for a 3-month follow-up period in a group of 28 hemodialyzed patients with type 2 diabetes treated by a basal-bolus detemir plus aspart insulin regimen. Insulin therapy was adapted to the CGM values. HbA1c and CGM parameters collected over the 3-month treatment period were compared using MANOVA for repeated measures. RESULTS: After 3 months, HbA1c significantly decreased from 8.4 ± 1.0% (65 ± 1 mmol/mol) to 7.6 ± 1.0% (60 ± 11 mmol/mol; p < 0.01). Similarly, mean CGM glucose values significantly decreased from 9.9 ± 1.9 to 8.9 ± 2.1 mmol/L (p = 0.05). The frequency of glucose values > 10 mmol/L significantly decreased from 41.3 ± 21.9% to 30.1 ± 22.4% (p < 0.05), without a significant increase in the frequency of glucose values < 3.3 mmol/L. Insulin requirements significantly increased from 70 ± 51 IU/d to 82 ± 77 IU/d (p < 0.001), without significant changes in body weight. CONCLUSIONS: CGM-adapted insulin regimen improves glycemic control without increasing hypoglycemic events in hemodialyzed diabetic patients. CGM could be a useful tool for the management of insulin therapy in these patients. These results need to be confirmed by long-term studies with larger sample sizes.

Percutaneous cryoablation for tuberous sclerosis-associated renal angiomyolipoma with neoadjuvant mTOR inhibition.

BACKGROUND: Renal angiomyolipomas (AMLs) are frequent in tuberous sclerosis and are responsible for a significant proportion of the morbidity in adulthood, mainly from bleeding complications, which are correlated to the size of the AMLs. We describe the case of a 19-year-old female with multiple bilateral renal angiomyolipomas. CASE PRESENTATION: The renal AMLs measured up to 6 cm in size. She was first treated with a low dose of the mammalian target of rapamycin (mTOR) inhibitor sirolimus (up to 3 mg/day over a 12-month period) and following significant AML size reduction, percutaneous cryoablation was performed. No side-effects of either treatment were reported. At 12 months post-cryoablation, no recurrence of the AML was noted. CONCLUSION: This is the first report of this treatment strategy and the case study reveals that combining a low dose of an mTOR inhibitor with percutaneous cryoablation to treat small tumors mitigates the side-effects while providing a good clinical outcome. This therapeutic approach is a novel tool for the clinician involved in the management of patients with tuberous sclerosis.

External validation of the 2-year mortality prediction tool in hemodialysis patients developed using a Bayesian network.

Background: In recent years, a number of predictive models have appeared to predict the risk of medium-term mortality in hemodialysis patients, but only one, limited to patients aged over 70 years, has undergone sufficiently powerful external validation. Recently, using a national learning database and an innovative approach based on Bayesian networks and 14 carefully selected predictors, we have developed a clinical prediction tool to predict all-cause mortality at 2 years in all incident hemodialysis patients. In order to generalize the results of this tool and propose its use in routine clinical practice, we carried out an external validation using an independent external validation database. Methods: A regional, multicenter, observational, retrospective cohort study was conducted to externally validate the tool for predicting 2-year all-cause mortality in incident and prevalent hemodialysis patients. This study recruited a total of 142 incident and 697 prevalent adult hemodialysis patients followed up in one of the eight Association pour l'Utilisation du Rein Artificiel dans la région Lyonnaise (AURAL) Alsace dialysis centers. Results: In incident patients, the 2-year all-cause mortality prediction tool had an area under the receiver curve (AUC-ROC) of 0.73, an accuracy of 65%, a sensitivity of 71% and a specificity of 63%. In prevalent patients, the performance for the external validation were similar in terms of AUC-ROC, accuracy and specificity, but was lower in term of sensitivity. Conclusion: The tool for predicting all-cause mortality at 2 years, developed using a Bayesian network and 14 routinely available explanatory variables, obtained satisfactory external validation in incident patients, but sensitivity was insufficient in prevalent patients.

The relationship of NT-proBNP and dialysis parameters with outcome of incident haemodialysis patients: results from the membrane permeability outcome study.

BACKGROUND/AIMS: The association of raised levels of natriuretic peptides with elevated risk of mortality was investigated in the present analysis of the Membrane Permeability Outcome study. METHODS: N-terminal probrain type natriuretic peptide (NT-proBNP) was measured in 618 incident haemodialysis patients, randomised to either high-flux or low-flux. Characteristics of patients with NT-proBNP levels below or above the median were descriptively analysed and survival analysis was performed. RESULTS: Median NT-proBNP value was 2,124 pg/ml, with 1,854 pg/ml in the high-flux and 2,919 pg/ml in the low-flux group. Survival probability was lowest in patients with both a history of cardiovascular disease and NT-proBNP values above the median (p < 0.001). A multivariate Cox proportional hazard model showed interaction between presence of cardiovascular diseases and NT-proBNP levels above the median. CONCLUSIONS: NT-proBNP is an independent predictor of mortality also in incident haemodialysis patients. Lower concentrations associated with high-flux dialysis suggest a possible biological link to improved survival in this group.

Evaluation of a predictive model of end-stage kidney disease in a French-based cohort.

BACKGROUND: The risk of ESKD is highly heterogeneous among renal diseases, and risk scores were developed to account for multiple progression factors. Kidney failure risk equation (KFRE) is the most widely accepted, although external validation is scarce. The objective of this study was to evaluate the usefulness of this score in a French case-control cohort and test the pertinence of the proposed thresholds. METHODS: A retrospective case-control study comparing a group of patients starting renal replacement therapy (RRT) to a group of patients with CKD stages 3-5. Multivariate analysis to assess the predictors of ESKD risk. Discrimination of 4-, 6- and 8-variable scores using ROC curves and compared with eGFR alone and albumin/creatinine ratio (ACR) alone. RESULTS: 314 patients with a ratio of 1 case for 1 control. In multivariate analysis, increasing age and higher eGFR were associated with a lower risk of ESKD (OR 0.62, 95% CI 0.48-0.79; and OR 0.72, 95% CI 0.59-0.86, respectively). The log-transformed ACR was associated with a higher risk of ESKD (OR 1.25 per log unit, 95% CI 1.02-1.55). The 4-variable score was significantly higher in the RRT group than in the CKD-ND group, and was more efficient than the eGFR (AUROC 0.66, 95% CI 0.60-0.72, p = 0.018) and the log-transformed ACR (AUROC 0.63 95% CI 0.60-0.72, p = 0.0087) to predict ESKD. The 6-variable score including BP metrics and diabetes was not more discriminant as the 4-variable score. The 8-variable score had similar performance compared with the 4-score (AUROC 8-variable score: 0.70, 95% CI 0.64-0.76, p = 0.526). A 40% and 20% score thresholds were not superior to eGFR < 15 and 20 mL/min/1.73 m2, respectively. A 10% threshold was more specific than an eGFR < 30 mL/min/1.73 m2. CONCLUSION: KFRE was highly discriminant between patients progressing to ESKD vs those non-progressing. The 4-variable score may help stratify renal risk and referral in the numerous patients with stage 3 CKD. Conversely, the proposed thresholds for creating vascular access or preemptive transplantation were not superior to eGFR alone.