Clinical spectrum, prognosis and estimated prevalence of DNAJB11-kidney disease.

Monoallelic mutations of DNAJB11 were recently described in seven pedigrees with atypical clinical presentations of autosomal dominant polycystic kidney disease. DNAJB11 encodes one of the main cofactors of the endoplasmic reticulum chaperon BiP, a heat-shock protein required for efficient protein folding and trafficking. Here we conducted an international collaborative study to better characterize the DNAJB11-associated phenotype. Thirteen different loss-of-function variants were identified in 20 new pedigrees (54 affected individuals) by targeted next-generation sequencing, whole-exome sequencing or whole-genome sequencing. Amongst the 77 patients (27 pedigrees) now in total reported, 32 reached end stage kidney disease (range, 55-89 years, median age 75); without a significant difference between males and females. While a majority of patients presented with non-enlarged polycystic kidneys, renal cysts were inconsistently identified in patients under age 45. Vascular phenotypes, including intracranial aneurysms, dilatation of the thoracic aorta and dissection of a carotid artery were present in four pedigrees. We accessed Genomics England 100,000 genomes project data, and identified pathogenic variants of DNAJB11 in nine of 3934 probands with various kidney and urinary tract disorders. The clinical diagnosis was cystic kidney disease for eight probands and nephrocalcinosis for one proband. No additional pathogenic variants likely explaining the kidney disease were identified. Using the publicly available GnomAD database, DNAJB11 genetic prevalence was calculated at 0.85/10.000 individuals. Thus, establishing a precise diagnosis in atypical cystic or interstitial kidney disease is crucial, with important implications in terms of follow-up, genetic counseling, prognostic evaluation, therapeutic management, and for selection of living kidney donors.

Variables linked to hepatitis B vaccination success in non-dialyzed chronic kidney disease patients: Use of a bayesian model.

BACKGROUND: Hepatitis B vaccination is recommended for chronic kidney disease (CKD) patients before starting dialysis. We performed an analyis aimed to describe the clinical and biological parameters related to the success of vaccination in CKD patients before starting dialysis. METHODS: We extracted data of 170 non-dialyzed patients who were offered hepatitis B vaccination from a register. They received a first vaccination of 40µg followed by boosters after one, two and six months. Patients were considered protected if their hepatitis B antibody level was >10IU/L, three months apart. A logistic regression and a Bayesian model were used to describe the relationships between variables and the success of vaccination. RESULTS: Vaccination protected 50.6% of the patients. Model adjustment to the data was higher using the Bayesian model compared to the logistic regression (with area under the ROC curve of 0.955±0.007 vs 0.775±0.066 respectively). The Bayesian model's robustness studied using a 10 fold cross validation showed a percentage of misclassified subjects of 12.4±1.8%, a sensitivity of 87.7±0.3%, a specificity of 87.5±0.3%, a positive predictive value of 87.8±0.3% and negative predictive value of 87.4±0.2%. As classified by the Bayesian model, the variables most related to successful vaccination were, in descending order: age, eGFR, protidemia, albuminemia, cause of renal failure, gender, previous vaccination and weight. CONCLUSION: The Bayesian network confirmed that both kidney function and nutritional status of patients are important factors to explain the success of vaccination against hepatitis B in CKD patients before dialysis. For research purposes, before an external validation, the network can be used online at www.hed.cc/?s=Bhepatitis&n=ReseauhepatiteBsup10.neta.

[The recommendations of nephrologist are poorly followed by the primary care physician. The example of vaccination against hepatitis B]. / Les recommandations des néphrologues sont peu suivies par les médecins traitants. L'exemple de la vaccination contre l'hépatite B.

The relationship between specialist physician and primary care physician (PCP) has been poorly evaluated in France. We have studied the application of a specialist's recommendation by the PCP. Vaccination against hepatitis B in patients with chronic renal failure was the follow-up marker. After consultation, the nephrologist wrote in his report to the PCP that the vaccination was recommended. At the next nephrological consultation, the patient was asked if the PCP had proposed vaccination. The clinical, biological characteristics and history of the patients were recorded as well as number and location of the PCP consultations. Five nephrology centers recruited 315 patients. In 61.6% (194/315) of the cases, the vaccination was not proposed by the PCP. Only the estimated GFR (lowest in vaccinated patients, 29.5 vs. 34.5mL/min/1.73m2), the delay between the two consultations of the nephrologist (shorter in vaccinated patients, 18.7 vs. 22.9 weeks) and the nephrologist's practice center (17.5 to 52% vaccination rate) are statistically significant in univariate analysis. In multivariate analysis, only the center effect persists. The lack of vaccination was argued by a letter from the PCP in 2 cases (1%). In the absence of a direct questioning of the PCP, the reasons for not following the recommendation remain unexplained. Overall, the recommendation of the nephrologist was little followed. Our study can contribute to the reflection on the shared follow-up of patients suffering from chronic diseases.

Delayed renal dysfunction and flash pulmonary edema post endovascular abdominal aneurysm repair.

After endovascular aortic repair (EVAR), the deterioration in long-term renal function is probably multifactorial. Preoperative renal failure is an independent risk factor. Postoperative renal dysfunction can be associated with inadvertent renal artery occlusion, renal artery complications as stenosis, plaque dislodgement, or dissection. Ischemic nephropathy can accelerate hypertension and circulatory congestion. We report a case of coverage of the renal arteries symptomatic with flash pulmonary edema and renal failure 15 months after EVAR, suggesting a delayed endograft migration. The patient had complete resolution of symptoms and renal function after renal artery stenting with placement between endograft and aneurysm to the left renal artery.

Cytomegalovirus infection and chronic graft-versus-host disease are significant predictors of renal failure after allogeneic hematopoietic stem cell transplantation.

We investigated the frequencies and predictive factors of prolonged renal failure (PRF) in a retrospective study of 181 consecutive patients undergoing allogeneic hematopoietic stem cell transplantation. Twenty-six patients (23% of long-term survivors) developed PRF. We identified 4 independent prognostic factors; cytomegalovirus infection and chronic graft-versus-host disease appeared as major risk factors for PRF.

[Medical prescriptions in haemodialysis patients: critical analysis]. / Analyse critique des prescriptions médicamenteuses en hémodialyse.

AIM: The aim of the study is to analyse haemodialysis patients' prescriptions accordance with legal registrations in 64 chronic haemodialysis patients during a one-month follow-up period. RESULTS: Patients are taking 9.6+/-3 different drugs. A mean of 2.4+/-1.3 prescriptions per patient disagree with the recommended drug use. The directions for use in this specific population are defective in 89%. Moreover, at least one drug-drug interaction is found in 78% of our patients. CONCLUSION: Only 8% of the studied hemodialysis patients benefit from prescriptions in agreement with the legal recordings, as a consequence of the lack of drug studies in this particular population. Therefore, clinicians have to rely on their own experience to establish their prescriptions, which can involve their responsibility in case of litigation. Furthermore, the frequency of drug-drug interactions in these polymedicated patients implies that a close pharmaceutical follow-up should be implemented.

C-reactive protein and cardiovascular disease in peritoneal dialysis patients.

BACKGROUND: Elevated plasma concentrations of C-reactive protein (CRP) is a risk factor for cardiovascular disease (CVD) in the general population and in hemodialysis patients. The prognostic value of CRP is less well known in peritoneal dialysis (PD) patients. We examined the association between CRP and cardiovascular event (CVE) in a large population of PD patients. METHODS: Two hundred and forty patients starting PD were enrolled in this prospective study. The role of CRP was analyzed with respect to other known cardiovascular risk factors. RESULTS: The patients were followed for a mean duration of 41 +/- 21 months; the median value of CRP was 7 mg/L. Eighty-nine cardiovascular events (CVE; 37.1%) occurred in 84 patients and the CRP levels were higher in patients who experienced CVE (27 +/- 14 vs. 6 +/- 8 mg/L; P < 0.0001). In the Cox model, patients in the three lower quartiles of the CRP levels had a decreased risk of CVE compared with those in the highest quartile. Cox regression analysis also revealed that age, a previous history of cardiovascular disease, hyperhomocysteinemia and hypoalbuminemia were risk factors for CVE. CRP levels were higher in patients who died during the study period (25 +/- 12 vs. 5 +/- 8 mg/L; P = 0.003). In the Cox model, patients with CRP levels above the median had an increased risk of death compared with those in the lowest quartile. CONCLUSIONS: Chronic inflammation, as reflected by elevated CRP levels, is frequent in patients starting PD and independently contributes to an increased incidence of CVE in this population.