The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients.

BACKGROUND: Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time. METHODS: Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many 'operationally tolerant' patients (TOL; defined as having a serum creatinine <1.7 mg/dL and proteinuria <1 g/day or g/g creatinine despite at least 1 year without any immunosuppressive drug) and 'almost tolerant' patients (minimally immunosuppressed patients (MIS) receiving low-dose steroids) as possible. We reported their number and the total number of kidney transplants performed at each centre to calculate their frequency. RESULTS: One hundred and forty-seven questionnaires were returned and we identified 66 TOL (61 with complete data) and 34 MIS patients. Of the 61 TOL patients, 26 were previously described by the Nantes group and 35 new patients are presented here. Most of them were noncompliant patients. At data collection, 31/35 patients were alive and 22/31 still operationally tolerant. For the remaining 9/31, 2 were restarted on immunosuppressive drugs and 7 had rising creatinine of whom 3 resumed dialysis. Considering all patients, 10-year death-censored graft survival post-immunosuppression weaning reached 85% in TOL patients and 100% in MIS patients. With 218 913 kidney recipients surveyed, cumulative incidences of operational tolerance and almost tolerance were estimated at 3 and 1.5 per 10 000 kidney recipients, respectively. CONCLUSIONS: In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival.

[Diagnosis of Alport syndrome]. / Il percorso diagnostico della sindrome di Alport e della malattia a membrane basali sottili.

Diagnosis of Alport syndrome or Thin basement membrane disease is suggested first of all by the clinical picture, the presence of neurisensorial hypoacusia and/or ocular abnormalities, and the family history which should be as accurate as possible involving the largest number possible of family members to recognize the transmission modalities, i.e. X-linked or autosomal. Renal biopsy remains the main tool to confirm the diagnosis and requires electron microscopy observation and collagen IV alpha chains investigation on renal tissue by means of specific antibodies. Skin biopsy is a useful and less invasive tool in families with X-linked Alport syndrome and can substitute renal biopsy in childhood as well as in patients with contraindication to renal biopsy. Confocal microscopy is mandatory to reduce the risk of false negative results in patients with segmental expression of alpha chains. Genetic analysis is at present indicated for studying subjects at risk for family planning or possible kidney donation but new techniques (Next Generation Sequencing) might increase their use in clinical practice.

m-TOR inhibitors may be useful in the treatment of encapsulating peritoneal sclerosis (EPS).

Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication of long-term peritoneal dialysis, often occurring after patients have been shifted to haemodialysis or undergone renal transplantation. EPS is still associated with high morbidity and mortality but, although various treatment modalities have been tried, the optimal therapy is still debated. The present paper reports a 16-year-old patient who developed EPS 6 months after shifting to haemodialysis and, following adhesiolysis, was successfully treated with a combination of steroids, tamoxifen and everolimus, this last drug chosen for its antiproliferative effect through mammalian target of rapamycin (mTOR) inhibition and its ability to block vascular endothelial growth factor and neoangiogenesis. EPS progressively improved and the patient successfully underwent renal transplantation 5 years later. The case suggests that, in view of their mechanism of action, mTOR inhibitors should be considered as an immunosuppressive agent after renal transplantation in patients at risk and merit investigation in future trials on this condition.

Effect of a plasma sodium biofeedback system applied to HFR on the intradialytic cardiovascular stability. Results from a randomized controlled study.

BACKGROUND: Intradialytic hypotension (IDH) is still a major clinical problem for haemodialysis (HD) patients. Haemodiafiltration (HDF) has been shown to be able to reduce the incidence of IDH. METHODS: Fifty patients were enrolled in a prospective, randomized, crossover international study focussed on a variant of traditional HDF, haemofiltration with endogenous reinfusion (HFR). After a 1-month run-in period on HFR, the patients were randomized to two treatments of 2 months duration: HFR (Period A) or HFR-Aequilibrium (Period B), followed by a 1-month HFR wash-out period and then switched to the other treatment. HFR-Aequilibrium (HFR-Aeq) is an evolution of the haemofiltration with endogenous reinfusion (HFR) dialysis therapy, with dialysate sodium concentration and ultrafiltration rate profiles elaborated by an automated procedure. The primary end point was the frequency of IDH. RESULTS: Symptomatic hypotension episodes were significantly lower on HFR-Aeq versus HFR (23 ± 3 versus 31 ± 4% of sessions, respectively, P l= l0.03), as was the per cent of clinical interventions (17 ± 3% of sessions with almost one intervention on HFR-Aeq versus 22 ± 2% on HFR, P <0.01). In a post-hoc analysis, the effect of HFR-Aeq was greater on more unstable patients (35 ± 3% of sessions with hypotension on HFR-Aeq versus 71 ± 3% on HFR, P <0.001). No clinical or biochemical signs of Na/water overload were registered during the treatment with HFR-Aeq. CONCLUSIONS: HFR-Aeq, a profiled dialysis supported by the Natrium sensor for the pre-dialysis Na(+) measure, can significantly reduce the burden of IDH. This could have an important impact in every day dialysis practice.

Search for genetic association between IgA nephropathy and candidate genes selected by function or by gene mapping at loci IGAN2 and IGAN3.

BACKGROUND: IgA nephropathy (IgAN) is not generally considered a hereditary disease, even though extensive evidence suggests an undefined genetic influence. Linkage analysis identified a number of genome regions that could contain variations linked to IgAN. METHODS: In this case-control association study, genes possibly involved in the development of IgAN were investigated. DNA samples from 460 North Italian patients with IgAN and 444 controls were collected. Candidate genes were selected based on their possible functional involvement (6 genes) or because of their location within linkage-identified genomic regions IGAN2 and IGAN3 (5 and 13 genes within chromosome 4q26-31 and 17q12-22, respectively). One hundred and ninety-two tag and functional single-nucleotide polymorphisms (SNPs) were typed with Veracode GoldenGate technology (Illumina). RESULTS: C1GALT1 showed an association with IgAN (rs1008898: P = 0.0019 and rs7790522: P = 0.0049). Associations were found when the population was stratified by gender (C1GALT1, CD300LG, GRN, ITGA2B, ITGB3 in males and C1GALT1, TRPC3, B4GALNT2 in females) and by age (TLR4, ITGB3 in patients aged <27 years). Furthermore, rs7873784 in TLR4 showed an association with proteinuria (G allele: P = 0.0091; GG genotype: P = 0.0077). CONCLUSIONS: Age and gender are likely to evidence distinct immunological and inflammatory reactions leading to individual susceptibility to IgAN. Overall, a genetic predisposition to sporadic IgAN was found. We might hypothesize that C1GALT1 and TLR4 polymorphisms influence the risk to develop IgAN and proteinuria, respectively.

Salt-precipitation method does not isolate to homogeneity Tamm-Horsfall glycoprotein from urine of proteinuric patients and pregnant women.

OBJECTIVE: Assessment of the degree of purification of Tamm-Horsfall glycoprotein from anomalous urine. DESIGN AND METHODS: Two methods have been compared: the method of Tamm & Horsfall (T&H method) consisting in the precipitation of THP by the addition to urine of NaCl up to 0.58 mol/L and the filtration of urine through a diatomaceous earth filter (DEF method) in which THP is selectively trapped because of its gelation/aggregation tendency. The purity of THP preparations has been evaluated by SDS-PAGE analysis and Western blotting developed with anti immunoglobulin G (IgG) antibodies and antichorionic gonadotropin antibodies. RESULTS: All THPs isolated by T&H method from proteinuric patients were contaminated by IgG and one of the five preparations from pregnant women even by chorionic gonadotropin. A smaller or no contamination was found in THPs isolated by DEF method. CONCLUSIONS: Although albumin is the most abundant protein in the anomalous urine, it never appears in THP preparations. The consistent contamination with IgG of THP prepared by salt precipitation-method might be related to the formation of a stable complex between the two proteins.