Les facteurs pronostiques des néphropathies cryoglobulinémiques

INTRODUCTION : Le syndrome cryoglobulinémique est une vasculite rare. L'atteinte glomérulaire sous la forme d'une glomérulonéphrite membrano-proliférative est le mode d'expression rénale préférentiel de la cryoglobulinémie. OBJECTIFS : Déterminer les facteurs pronostiques de la survie rénale et décrire la cohorte des patients ayant une néphropathie cryoglobulinémique suivis au CHU de Bordeaux. METHODE : Les données étiologiques, cliniques, biologiques, histologiques de 24 patients présentant une biopsie rénale en rapport avec une glomérulonéphrite cryoglobulinémique ont été collectées de façon rétrospective entre 1997 et nos jours. Les différents traitements reçus par ces patients ont aussi été relevés. Ces données considérées comme des variables ont été testées pour en extraire les facteurs pronostiques de survie rénale de notre cohorte. RESULTATS : Il y a autant d'hommes que de femmes, l'âge moyen est de 58,4 ans +- 12,8(26 à 77 ans). L'atteinte rénale prédominante faisant faire le diagnostic est un syndrome néphrotique dans 38 % des cas. Les cryoglobulines de type II sont les plus fréquentes à 62 %. Une étiologie virale est retrouvée chez la moitié des patients, le virus de l'hépatite C est retrouvé chez 46 % d'entre eux. Le traitement le plus souvent proposé était les corticoides (75 %), les plasmaphérèses ont été utilisées dans 38 % des cas. La survie rénale (patients en vie non dialysés) est estimée à 58 % à 5 ans. Le modèle de Cox utilisé en analyse multivariée montre comme facteurs pronostiques le débit de filtration glomérulaire au diagnostic de la maladie ainsi qu'une hypogammaglobulinémie et un abaissement du C4 comme facteurs de bon pronostic. En analyse univariée, la présence d'un purpura, une pression artérielle systolique initiale inférieure à 158 mmHg, une atrophie tubulaire de moins de 50 % des tubules en histologie sont des facteurs de bon pronostic CONCLUSION : La particularité chez ces patients recrutés en néphrologie est une atteinte rénale sévère avec en conséquence une survie rénale inférieure à celle habituellement retrouvée. Les facteurs pronostiques retrouvés à type de débit de filtration glomérulaire initiale altéré, d'hypertension artérielle systolique ou d'atrophie tubulaire supérieure à 50 % en histologie était attendus. Les signes d'activité de la maladie cryoglobulinémique tels que la présence d'un purpura, une hypogammaglobulinémie et l'abaissement du C4 comme facteurs de bon pronostic font évoquer l'hypothèse que les traitements sont particulièrement efficaces quand la maladie est active. Pour étayer cette hypothèse, une étude prospective pluridiscuplinaire avec un nombre de patients plus important reste à réaliser.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Non HCV-related infectious cryoglobulinemia vasculitis: Results from the French nationwide CryoVas survey and systematic review of the literature

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The spectrum of type I cryoglobulinemia vasculitis: new insights based on 64 cases.

International audienceType I cryoglobulinemia vasculitis (CryoVas) is considered a life-threatening condition; however, data on the characteristics and outcome are scarce. To analyze the presentation, prognosis, and efficacy and safety of treatments of type I CryoVas, we conducted a French nationwide survey that included 64 patients with type I CryoVas between January 1995 and July 2010: 28 patients with monoclonal gammopathy of unknown significance (MGUS) and 36 with hematologic malignancy.Type I monoclonal CryoVas was characterized by severe cutaneous involvement (necrosis and ulcers) in almost half the patients and high serum cryoglobulin levels, contrasting with a lower frequency of glomerulonephritis than expected. The 1-, 3-, 5-, and 10-year survival rates were 97%, 94%, 94%, and 87%, respectively. Compared to MGUS, type I CryoVas related to hematologic malignancy tended to be associated with a poorer prognosis. Therapeutic regimens based on alkylating agents, rituximab, thalidomide or lenalinomide, and bortezomib showed similar efficacy on vasculitis manifestations, with clinical response rates from 80% to 86%.Data from the CryoVas survey show that the prognosis of type I CryoVas does not seem to be as poor as previously suggested. Besides alkylating agents, the use of regimens based on rituximab, thalidomide or lenalinomide, and bortezomib are interesting alternative options, although the exact role of each strategy remains to be defined

Apheresis in Adult With Refractory Idiopathic Nephrotic Syndrome on Native Kidneys

International audienceBackground: Apheresis is the gold standard for idiopathic nephrotic syndrome (INS) relapse after transplantation, but it remains unknown whether such treatment is useful for adults with refractory INS on native kidneys.Methods: This retrospective study included patients older than 16 years with biopsy-proven refractory (persistent nephrotic syndrome on corticosteroids plus at least 1 immunosuppressive drug) INS treated by apheresis and followed for at least 3 months.Results: Between September 1997 and January 2020, 21 patients (focal segmental glomerulosclerosis: 12, minimal change nephrotic syndrome: 9, men: 67%, median age: 34 years) were identified. At last follow-up (12 months), 7 of 21 patients were in complete or partial remission. Remission was associated with older age (51 vs. 30 years, P = 0.05), lower proteinuria (3.9 vs. 7.3 g/d, P = 0.03), and lower estimated glomerular filtration rate (eGFR) (28.0 vs. 48.5 ml/min per 1.73 m2, P = 0.05) at apheresis. The need for dialysis before apheresis (odds ratio [OR] 22.0 [1.00-524], P = 0.026), age ≥50 years (OR: 22.6 [1.00-524], P = 0.006), a marked (>4.5 g/d) decrease in proteinuria (OR: 9.17 [1.15-73.2], P = 0.041), and a short (<12 months) time between diagnosis and apheresis (OR: 10.8 [1-117], P = 0.043) were significantly associated with remission. Three of 7 patients in remission who were initially on dialysis became dialysis-free; by contrast, none of the 14 patients without remission was initially on dialysis, but 5 of 14 had become dialysis-dependent (P = 0.01).Conclusion: Apheresis may result in remission in adult patients with refractory INS, particularly in those at risk of renal failure, with limited sensitivity to medical treatments, if apheresis is initiated within a year of diagnosis

Predictors of early relapse in patients with non-infectious mixed cryoglobulinemia vasculitis: Results from the French nationwide CryoVas survey.

International audienceOBJECTIVE: Although in most patients induction therapy leads to complete or partial remission, relapses in patients with non-infectious mixed cryoglobulinemia vasculitis (CryoVas) remain a major problem. We aimed to identify predictors of early relapses occurring within the first 12months of treatment in such patients. METHODS: Patients included in the French CryoVas survey exhibiting complete/partial clinical remission and followed-up for at least 12months after induction therapy (n=145) were analyzed for predictors of early relapses. RESULTS: Forty out of 145 patients (28%) experienced early relapse. Relapses occurred after a median time of 9.5months after induction therapy (3-12) and involved skin (75%), joints and peripheral nerve (28% each), kidneys (25%) and gastrointestinal tract (5%). Baseline factors associated with an early relapse were purpura [HR 3.35 (1.02-10.97), P=0.046], cutaneous necrosis [HR 4.46 (1.58-12.57), P=0.005] and articular involvement [HR 2.20 (1.00-4.78), P=0.048]. The only factor negatively associated with an early relapse during follow-up was the achievement of complete immunological response [HR 0.07 (0.01-0.51), P=0.009]. The use of corticosteroids plus rituximab or cyclophosphamide tended to be associated negatively with early relapse [HR 0.43 (0.17-1.08), P=0.07]. CONCLUSION: In patients with non-infectious CryoVas, main predictors of early relapses after initial remission are purpura, articular involvement, and cutaneous necrosis. The absence of complete immunological response during follow-up was associated with early relapse. These findings may help in adapting future treatment strategies

Management of noninfectious mixed cryoglobulinemia vasculitis: data from 242 cases included in the CryoVas survey.

International audienceData on the clinical spectrum and therapeutic management of noninfectious mixed cryoglobulinemia vasculitis (CryoVas) in the era of hepatitis C virus screening are lacking. We analyzed data from 242 patients with noninfectious mixed CryoVas included in the French multicenter CryoVas survey. Baseline manifestations were purpura (75%), peripheral neuropathy (52%), arthralgia or arthritis (44%), glomerulonephritis (35%), cutaneous ulcers (16%), and cutaneous necrosis (14%). A connective tissue disease was diagnosed in 30% and B-cell non-Hodgkin lymphoma in 22%, whereas the CryoVas was considered to be essential in 48%. With the use of Cox-marginal structural models, rituximab plus corticosteroids showed the greater therapeutic efficacy compared with corticosteroids alone and alkylating agents plus corticosteroids to achieve complete clinical, renal, and immunologic responses and a prednisone dosage < 10 mg/d at 6 months. However, this regimen was also associated with severe infections, particularly when high doses of corticosteroids were used, whereas death rates did not differ between the therapeutic regimens. The role of each of these strategies remains to be defined in well-designed randomized controlled trials

Prognostic factors of survival in patients with non-infectious mixed cryoglobulinaemia vasculitis: data from 242 cases included in the CryoVas survey.

International audienceBACKGROUND: Data on the prognosis of non-infectious mixed cryoglobulinaemia vasculitis (CryoVas) in the era of hepatitis C virus screening are lacking. METHODS: The French multicentre and retrospective CryoVas survey included 242 patients with non-infectious mixed CryoVas. Causes of death and prognostic factors of survival were assessed and a prognostic score was determined to predict survival at 5 years. RESULTS: After a median follow-up of 35 months, 42 patients (17%) died. Causes of death were mainly serious infections (50%) and vasculitis flare (19%). One-, 2-, 5- and 10-year overall survival rates were 91%, 89%, 79% and 65%, respectively. A prognostic score, the CryoVas score (CVS), for the prediction of survival at 5 years was devised. Pulmonary and gastrointestinal involvement, glomerular filtration rate 65 years were independently associated with death. At 5 years the death rates were 2.6%, 13.1%, 29.6% and 38.5% for a CVS of 0, 1, 2 and ≥3, respectively. At 1 year the death rates were 0%, 3.2%, 18.5% and 30.8% for a CVS of 0, 1, 2 and ≥3, respectively. The CVS was strongly correlated with the Five Factor Score (FFS) 2009, another prognostic score validated in primary necrotising vasculitis (r=0.82; p65 years, pulmonary and gastrointestinal involvement and renal failure. A score including these variables is significantly associated with the prognosis

Urinary Sodium-to-Potassium Ratio and Blood Pressure in CKD

Introduction: In the general population, urinary sodium-to-potassium (uNa/K) ratio associates more strongly with high blood pressure (BP) than either urinary sodium or potassium alone. Whether this is also the case among patients with chronic kidney disease (CKD) is unknown. Methods: We studied the associations of spot urine sodium-to-creatinine (uNa/Cr), potassium-to-creatinine (uK/Cr), and uNa/K ratios with a single office BP reading in 1660 patients with moderate to severe CKD at inclusion in the CKD-REIN cohort. Results: Patients' median age was 68 (interquartile range [IQR], 59–76) years; most were men (65%), had moderate CKD (57%), and albuminuria (72%). Mean systolic and diastolic BP was 142/78 mm Hg. Spot uNa/Cr and uNa/K ratios were positively associated with systolic, mean arterial, and pulse pressures. The mean adjusted difference in systolic BP between the highest and the lowest quartile (Q4 vs. Q1) was 4.24 (95% confidence interval [CI], 1.53–6.96) mm Hg for uNa/Cr and 4.79 (95% CI, 2.18–7.39) mm Hg for uNa/K. Quartiles of spot uK/Cr were not associated with any BP index. The higher the quartile of uNa/K, the higher the prevalence ratio of uncontrolled (Q4 vs. Q1, 1.43; 95% CI, 1.19–1.72) or apparently treatment-resistant hypertension (Q4 vs. Q1, 1.35; 95% CI, 1.14–1.60). Findings were consistent in a subset of 803 individuals with 2 BP readings. Conclusion: In patients with CKD, higher urinary sodium excretion is associated with higher BP, but unlike in general population, lower potassium excretion is not. Urinary Na/K does not add significant value in assessing high BP risk, except perhaps for hypertension control assessment

J Am Med Dir Assoc

Objectives Renin-angiotensin system inhibitors (RASi) are recommended for slowing chronic kidney disease (CKD) progression to kidney failure. Their effectiveness and tolerance as patients age remain uncertain because older patients have often been excluded from clinical trials. Design CKD-REIN cohort study. Setting and Participants We studied 2762 patients with CKD stages 3 and 4 and a clinical indication for RASi enrolled between 2013 and 2016 in 40 nephrology clinics nationally representative in France. Methods The primary outcome was the occurrence of kidney failure or death. The secondary outcomes were the occurrence of cardiovascular events and hospitalizations with acute kidney injury (AKI) or hyperkalemia. A propensity score analysis was performed. We used Cox models to estimate hazard ratios (HRs) for each outcome associated with RASi prescription and tested interactions with age. Results Patients' mean age was 67 years, including 841 (30%) aged 75 years and older; 2178 (79%) were prescribed RASi's. During a median follow-up of 4.6 years, 33% of patients reached kidney failure or died. RASi prescription was associated with a lower risk of kidney failure or death (HR 0.79, 95% CI 0.66, 0.95), an association not modified by age (P for interaction = .72). It was not significantly associated with cardiovascular events. During the first 3 years of follow-up, 14% of patients were hospitalized with AKI or hyperkalemia, but risk was not higher among those prescribed RASi's (HR 0.75, 95% CI 0.55-1.02) and age did not modify its effect (P for interaction = .28). Conclusions and Implications This study shows that aging does not appear to modify either RASi's beneficial effects on major CKD outcomes or their potential adverse effects