Structural and functional analysis of retinal vasculature in HANAC syndrome with a novel intronic COL4A1 mutation.

PURPOSE: Mutations of the COL4A1 gene, a major structural protein of vessels, may cause hereditary angiopathy with nephropathy, aneurysms and muscle cramps (HANAC) syndrome. The vascular structure and function of patients with HANAC is poorly known. Here, we report a family with HANAC syndrome associated to a previously unreported mutation in COL4A1. The structure and function of retinal vessels were detailed by adaptive optics ophthalmoscopy (AOO) and optical coherence tomography (OCT) angiography. METHODS: Clinical data from six affected individuals (43 to 72 years old) from a single family comprising two generations were collected. Imaging charts including conventional fundus imaging, OCT-angiography and AOO in static and dynamic (flicker) mode were reviewed. DNA sequencing was done in the proband. RESULTS: DNA sequencing of the proband revealed a heterozygous deletion of COL4A1 (NM_001845) at position 1120 in the intron 20 resulting in the loss of splicing donor site for exon 20 (c.1120 + 2_1120 + 8del heterozygote). Four patients had arterial hypertension, and three had kidney dysfunction, one of which under dialysis. By fundus examination, five had typical retinal arteriolar tortuosity with arteriolar loops. Wall-to-lumen ratio of arteries was within normal limits, that is, lower than expected for hypertensive patients. Several foci of arteriolar irregularities were noted in the two oldest patients. In three affected subjects, evaluation of the neurovascular coupling showed a higher flicker-induced vasodilation than a control population (6 % to 11 %; n < 5 %). CONCLUSIONS: Structural and dynamic analysis of retinal vessels in a HANAC family bearing a previously unreported intronic COL4 mutation was done. In addition to arteriolar tortuosity, we found reduced wall-to-lumen ratio, arteriolar irregularity and increased vasodilatory response to flicker light. These abnormalities were more marked in the oldest subjects. This abnormal flicker response affected also non-tortuous arteries, suggesting that microvascular dysfunction extends beyond tortuosity. Such explorations may help to better vascular dysfunction related to HANAC and hence better understand the mechanisms of end-organ damage.

[The specific nutritionnal care in peritoneal dialysis]. / Les spécificités du soin nutritionnel en dialyse péritonéale.

Protein energy wasting is a major complication in peritoneal dialysis. It is leading to a poor quality of life and increasing mortality. Diagnosis must be early, according to criteria defined by the International society of renal nutrition and metabolism. It is necessary to appropriate the diagnostic tools with dialysis method. The nutritional care is difficult in peritoneal dialysis. Indeed, studies are limited and practical nutrition is complex. In this point of view, we propose to treat guidelines for protein energy wasting, in peritoneal dialysis patients.

Vasculitis associated with large granular lymphocyte (LGL) leukemia: presentation and treatment outcomes of 11 cases.

OBJECTIVE: The association between vasculitis and large granular lymphocyte (LGL) leukemia has rarely been reported or investigated. Thus, we assessed the clinical and biological phenotypes of LGL leukemia associated with vasculitis. RESULTS: We studied a series of 11 patients displaying LGL leukemia associated with vasculitis (LAV). The mean age at diagnosis of LGL leukemia was 60.3 years; there were nine women and two men. The mean follow-up period was 45 months. The main LGL lineage was T-LGL (10 patients), and only one NK-LGL was identified. Clinical and biological features of T-LGL leukemia were compared with those from the 2009 French T-LGL registry. We did not find any relevant differences except that patients with LAV were predominantly female (p < 0.05). The most frequently observed vasculitis was cryoglobulinemia (n = 5). Three patients presented with cutaneous leukocytoclastic angiitis, two patients had ANCA-negative microscopic polyangiitis, and one patient had giant cell arteritis. The main clinical features involved the skin, e.g., purpura (91%), arthralgia (37%), peripheral neuritis (27%), and renal glomerulonephritis (18%). The most frequent histologic finding was leucocytoclastic vasculitis (54%). The rate of complete remission was high; i.e., 80%. A minority of patients had a vasculitis relapse (27%). Three patients (27%) died; one death was related to LGL leukemia (acute infection) and the two other deaths were related to vasculitis (both with heart failure). CONCLUSION: We conclude that vasculitis is overrepresented in the population of LGL patients, LAV predominantly affects women, vasculitis preferentially affects the small vessels, and LAV has high rate of complete response.

How to avoid technique failure in peritoneal dialysis patients?

It is well established that technique failure is one of the main reasons for peritoneal dialysis cessation. Early PD failures occur during the first 6 months of PD and are mainly related to catheter dysfunction and psychosocial problems. Catheter malfunction should be treated by a video-laparoscopic procedure as this prolongs the catheter survival. Assisted peritoneal dialysis could help patients to cope with peritoneal dialysis. Preservation of residual renal function is of importance in peritoneal dialysis patients as it affects both patients and technique survival. Failure to obtain a sufficient ultrafiltration volume to maintain a euvolemic state without using large amount of hypertonic glucose solution can cause peritoneal dialysis failure. New approaches in the use of icodextrin to increase ultrafiltration and sodium removal are under investigation. A novel modality of prescribing automated peritoneal dialysis would improve ultrafiltration in peritoneal dialysis patients.

Adequacy in peritoneal dialysis.

Peritoneal dialysis (PD) adequacy is usually estimated by parameters based on the kinetics of small solutes as total Kt/V(urea) and total weekly creatinine clearance. However, other aspects (blood pressure, anemia, nutrition, inflammation, mineral metabolism and prevention of cardiovascular events) and, in particular, residual renal function must be taken into account. Although minimal levels are well defined, there are no optimal targets to be achieved. Clinical assessments are more and more relevant. In addition, fluid and sodium removal must be estimated, several studies showing that even in an uric patients adequacy can be obtained. Nutrition and inflammation have to be evaluated and their role seems to be more important than peritoneal membrane status in patient survival. Guidelines and recommendations are available to provide a better follow-up in patients on PD.

[Ecology and mechanisms of bacterial resistance to antibiotics in peritonitis]. / Écologie bactérienne et mécanismes de résistance aux antibiotiques lors des infections du liquide de dialyse péritonéale.

Peritonitis remains a common complication of peritoneal dialysis. The aim of our study is to describe the mechanisms of antibiotic resistance in bacteria isolated during peritonitis in peritoneal dialysis, to determine whether antibiotic therapy proposed by the International Society for Peritoneal Dialysis (ISPD) is adapted to the mechanisms of resistance. All causative microorganisms of peritonitis, isolated in 106 dialysis patients and reported 170 episodes of peritonitis, during the study period (01/01/2005 to 31/12/2010) were reviewed. According to the usual classification, twelve groups of microorganism were created. An interpretive reading of antibiograms was performed in each group to identify resistance phenotypes. The species most frequently isolated are coagulase-negative staphylococci (n=73) of which 46 had PBP2a (penicillin-binding protein). Many Enterobacteriaceae were also isolated (n=45), they are susceptible to third generation cephalosporins with the exception of Enterobacteriaceae producing an extended spectrum ß-lactamase (ESBL) or a cephalosporinase. Except for staphylococci, probabilistic antibiotic therapy recommended by the ISPD to treat peritonitis is effective. Indeed, many staphylococci producing a PBP2a, a first-generation cephalosporin cannot be administered in all cases. It is therefore necessary to identify patients with a strain of staphylococcus producing a PBP2a, it must be treated by vancomycin.

[Why and how to promote peritoneal dialysis?]. / Un plaidoyer pour la dialyse péritonéale.

The prevalence of peritoneal dialysis in France remains one of the lowest in Europe in spite of official recommendations in 2008. Progress in peritoneal catheter placement and a good knowledge of the management of catheter complications are essential. A more frequent use of biocompatible solutions should achieve a better preservation of the peritoneal membrane. Such physiological peritoneal fluids seem to decrease morbidity and mortality. Best peritoneal dialysis indications are mainly young patients waiting for a kidney transplantation, old patients without malnutrition and patients with cardiac insufficiency. Objective and complete information dedicated to both peritoneal dialysis and hemodialysis is necessary, even for patients seen in emergency or unplanned or late referral patients. A pre-end-stage renal disease education program has to be mandatory. Non-medical obstacles, mainly financial, are still common so that economic incitations are necessary for the development of peritoneal dialysis. A university formation of nephrologists is now available.

Lymphomatoid granulomatosis treated successfully with rituximab in a renal transplant patient.

Lymphomatoid granulomatosis (LYG) in renal transplant recipients is rare multisystemic angiocentric lymphoproliferative disorder with significant malignant potential. Here, we describe LYG in a 70-year-old renal allograft recipient who, 4 years after transplantation, on tacrolimus and mycophenolate mofetil and prednisone maintenance immunosuppression, complained of low-grade fever, persistent headache and gait disturbance. The MRI of the brain revealed diffuse periventricular cerebral and cerebellar contrast-enhanced lesions. The CT scan of the thorax showed multiple pulmonary nodular opacities in both lung fields. The patient was diagnosed LYG based on the cerebral biopsy showing perivascular infiltration of CD20-positive B-lymphocytes with granulomatous lesions and immunofluorescence staining with anti-EBV antibodies. With careful reduction of the immunossuppression combined with the use of rituximab, our patient showed a complete disappearance of LYG, and she is clinically well more than 4 years after the diagnosis, with good kidney function. No recurrence has been observed by radiological imaging until now. This is the first report of a durable (>4 years) complete remission of LYG after treatment with rituximab in renal transplantation.

Peritoneal dialysis in elderly patients: report from the French Peritoneal Dialysis Registry (RDPLF).

BACKGROUND: The number of elderly patients starting dialysis is increasing in developed countries. Older age is frequently associated with contraindication of peritoneal dialysis (PD). The aim of this study was to report the outcome of elderly patients on PD in a country where assisted PD is available. METHODS: This was a retrospective study based on the data of the French Language Peritoneal Dialysis Registry (RDPLF). We retrospectively analysed 1613 patients older than 75 years who started PD between January 2000 and December 2005. The end of the observation period was 31 December 2007. RESULTS: The mean age at dialysis initiation was 81.9 years; 545 patients had a Charlson comorbidity index (CCI) >9. Of these 1613 patients, 1435 were treated by continuous ambulatory peritoneal dialysis (CAPD) and 1232 were on assisted PD. The median patient survival was 27.1 months. In the multivariate analysis, patient survival was associated with sex, age, modified CCI, method of assistance and underlying nephropathy. The median pure technique survival was 21.4 months. In the Cox model, technique survival was associated with the modified CCI, but the association did not remain significant after adjustment for the centre size. The median survival free of peritonitis was 32.1 months. Neither the modality of assistance nor the centre size was associated with peritonitis risk. CONCLUSION: PD is a suitable method for elderly patients. In order to increase the rate of PD utilization in elderly patients, the need for the funding of assisted peritoneal dialysis has to be taken into account.