Low incidence of nephrotoxicity following intravenous administration of iodinated contrast media: a prospective study.

OBJECTIVES: To estimate the incidence of contrast-induced acute kidney injury (CI-AKI) after intravenous (iv) iodinated contrast material (ICM) exposure. METHODS: This prospective cohort study included all consecutive patients who underwent radiological investigations using low-osmolar iopamidol 370 mg/ml in a regional hospital over a period of 36 months, without any exclusion criteria. The estimated glomerular filtration rate (eGFR) was evaluated using the MRDR equation before (2-10 days) and after (24-36 h) radiological investigations. CI-AKI was defined as a ≥ 25% decrease in eGFR from baseline. CI-AKI incidence was estimated using a binomial distribution. The association between CI-AKI and demographic and clinical characteristics was modeled using logistic regression. RESULTS: The study included 1541 patients with a median age of 68 (1st-3rd quartiles 58-76) years with various comorbidities, 30% of whom had pre-existing CKD. Patients affected by stage III or IV chronic kidney disease (CKD) received an infusion of 0.9% normal saline (1.0-1.5 ml/kg/h) before and after iso-osmolar iodixanol administration. CI-AKI was observed in 33 patients (2.1%, 95% CI 1.5-3.0). The logistic regression analysis showed that antibiotic and statin therapies were significantly associated with CI-AKI. The probability of developing CI-AKI decreased by 80% in patients taking statins (OR = 0.20, 95% CI 0.03; 0.68) and increased approximately three times in patients with antibiotic therapy compared with those who did not take statins and antibiotics (OR = 2.92, 95% CI 1.21; 6.36). CONCLUSIONS: Our data suggest that low-osmolar iopamidol carries a low incidence of nephrotoxicity, even in subjects with various comorbid conditions or reduced renal function. KEY POINTS: • IV administration of ICM carries a low incidence of nephrotoxicity, which was transient in observed patients. • Statin therapy is negatively associated with AKI in patients exposed to ICM. • Pre-existing impairment of renal function is not associated with AKI in patients exposed to ICM.

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.

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.

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.

[Prevention of chronic allograft nephropathy]. / Prevenzione della nefropatia cronica del rene trapiantato.

Chronic allograft nephropathy, characterized by interstitial fibrosis and tubular atrophy, is one of the main causes of allograft failure in the long term. It may be induced by several factors, immunogical or not in nature, which nephrologists must recognize in order to establish the appropriate treatment strategy and prevent progressive loss of graft function. Extensive use of graft biopsy, whether carried out by protocol or suggested by the clinical setting, is recommended for an accurate diagnosis of renal lesions and prompt identification of calcineurin inhibitor-induced toxicity or signs of immunological activity (i.e., subclinical rejection or chronic antibody-mediated rejection) requiring changes of immunosuppressive strategy.

[Kidney transplant: a mere stage of CKD?]. / Il trapianto è uno stato di malattia renale?

At present, renal transplantation is the best treatment for end-stage renal disease but not the cure. The main factors limiting a full recovery after transplantation include the need for lifelong immunosuppressive therapy (which may lead to severe side effects in the long term), and only partial recovery of renal function after grafting. The latter event is not infrequent nowadays due to the increasing age of donors, who frequently die of cerebrovascular accidents and may have subclinical renal vascular lesions despite a GFR >60 mL/min, with increased susceptibility to calcineurin inhibitor toxicity. As a consequence, uremic alterations such as anemia, arterial hypertension and bone disease may persist at various degrees after surgery and affect the patients' outcome in the long term. The outcome of renal transplantation may be improved if, in addition to accurate tuning of immunosuppressive regimens, we take into account the prevention and treatment of all conditions that may impair the clinical course of transplant recipients.

Genetic variant of C1GalT1 contributes to the susceptibility to IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition that leads to mesangial proliferation and chronic glomerular inflammation. Analyses of serum IgA1 from IgAN patients revealed an abnormal galactosylation of the O-linked carbohydrate moieties of IgA that may be a result of altered activity of core 1 beta1,3-galactosyltransferase (C1GalT1). To evaluate the association between C1GalT1 single nucleotide polymorphisms (SNPs) and IgAN, we performed a case control study on cohorts from the Italian population. METHODS: We sequenced C1GalT1 coding and promoter regions in 284 IgAN patients and 210 healthy controls. The functional role of 3' untranslated region (3'UTR) SNPs was studied using electrophoretic mobility shift assays and real-time quantitative PCR. RESULTS: We analyzed 8 SNPs in the C1GalT1 gene: 5 SNPs were in the promoter region and 3 SNPs in the 3'UTR. The allele 1365G in the 3'UTR was significantly more frequent in IgAN patients than in healthy controls. CONCLUSION: The 1365G allele and 1365G/G genotype seem to confer susceptibility to IgAN.

[Renal transplantation from living donor in Italy and Europe]. / Il trapianto da vivente in Italia e in Europa.

Renal transplantation from a living donor shows a better graft and patient survival when compared with cadaver donor grafts. Moreover, since surgery can be planned in advance when a living donor is available, the time spent on dialysis while awaiting transplantation can be greatly reduced and dialysis treatment can be completely avoided in some cases. Only few risks for the donor have been reported as a consequence of nephrectomy, both in the short and long term. Nevertheless, despite these advantages, the number of living donor renal transplants carried out in Europe each year varies greatly from country to country and is particularly low in Spain and Italy. Several factors account for these differences, mainly the effectiveness of the organ procurement system, which could make people reluctant to living donation, and doctors' and patients' limited knowledge about living donor transplants. Nephrologists have the responsibility to identify patients eligible for transplant early in the course of the disease, and to inform them and their relatives about living donor transplantation, enabling them to make informed choices among the various treatment options in end-stage renal disease.

Kidney transplantation in patients with previous renal cancer: a critical appraisal of current evidence and guidelines.

Due to the increasing occurrence of renal cell carcinoma (RCC) in the general population and the high prevalence of chronic kidney disease among cancer patients, many people with a previous RCC may eventually require renal replacement therapy including kidney transplantation. They should accordingly be evaluated to assess their life expectancy and the risk that the chronic immunosuppressive therapy needed after grafting might impair their long-term outcome. Current guidelines on listing patients for renal transplantation suggest that no delay is required for subjects with small or incidentally discovered RCC, while the recommendations for patients who have been treated for a symptomatic RCC or for those with large or invasive tumours are conflicting. The controversial results reported by even recent studies focusing on the cancer risk in kidney graft recipients with a prior history of malignancy do not help to clarify the doubts arising in everyday clinical practice. Several tools, including integrated scoring systems, are currently available to assess the prognosis of patients with a previous RCC and, although they have not been validated in subjects receiving long-term immunosuppressive drugs, they can be used to identify patients suitable to be listed for grafting. Among these, the Leibovich score is currently the most widely used as it has proved simple and reliable enough and helps categorize renal transplant candidates. According to this system, subjects with a score from 0 to 2 are at low risk and may be listed without delay, while those with a score of 6 or higher should be excluded from grafting. In addition, other factors have an established positive prognostic value, including chromophobe or clear cell papillary tumour, or G1 grade cancer; on the contrary, medullary or Bellini's duct carcinoma or those with sarcomatoid dedifferentiation at histological examination should be excluded. All other patients would be better submitted to careful individual evaluation by an Oncologist before being listed for renal transplantation, pending studies specifically focusing on cancer risk evaluation in people already treated for malignancy receiving long-term immunosuppressive therapy.

IgA nephropathy: the presence of familial disease does not confer an increased risk for progression.

BACKGROUND: Immunoglobulin A (IgA) nephropathy is the most common form of glomerulonephritis worldwide. Familial and sporadic cases are recognized, and a locus associated with the familial form of the disease was mapped to chromosome 6. Recent data suggest the familial IgA nephropathy form may have a poorer outcome than the sporadic form. METHODS: We tested the hypothesis of unequal survival rates between the 2 forms of disease by analyzing time from biopsy to end-stage renal disease in patients of Italian ancestry; 589 patients with sporadic and 96 patients with familial IgA nephropathy. RESULTS: Overall 10- and 20-year renal survival probabilities of the cohort as a whole were 71% and 50%, respectively. Macroscopic hematuria was the modality of clinical presentation in 51% of patients with familial IgA nephropathy and 39% of patients with sporadic IgA nephropathy. At univariable analysis, the sporadic form of IgA nephropathy was associated significantly with increased risk for renal death. However, patients with the sporadic form tended to be more hypertensive and diagnosed later, with signs of more advanced renal disease than those with familial disease at baseline. In the regression model, form of disease lost any independent effect. Only male sex, lower baseline glomerular filtration rate, greater proteinuria, and histopathologic score proved to be independent predictors of disease progression. Treatment with steroids or angiotensin-converting enzyme inhibitors was associated with improved outcomes. CONCLUSION: Our study does not confirm that familial IgA nephropathy has a worse prognosis than the sporadic form. The similar renal phenotype may support a common pathogenic mechanism underlying familial and sporadic IgA nephropathy.

The molecular basis of lecithin:cholesterol acyltransferase deficiency syndromes: a comprehensive study of molecular and biochemical findings in 13 unrelated Italian families.

OBJECTIVE: To better understand the role of lecithin:cholesterol acyltransferase (LCAT) in lipoprotein metabolism through the genetic and biochemical characterization of families carrying mutations in the LCAT gene. METHODS AND RESULTS: Thirteen families carrying 17 different mutations in the LCAT gene were identified by Lipid Clinics and Departments of Nephrology throughout Italy. DNA analysis of 82 family members identified 15 carriers of 2 mutant LCAT alleles, 11 with familial LCAT deficiency (FLD) and 4 with fish-eye disease (FED). Forty-four individuals carried 1 mutant LCAT allele, and 23 had a normal genotype. Plasma unesterified cholesterol, unesterified/total cholesterol ratio, triglycerides, very-low-density lipoprotein cholesterol, and pre-beta high-density lipoprotein (LDL) were elevated, and high-density lipoprotein (HDL) cholesterol, apolipoprotein A-I, apolipoprotein A-II, apolipoprotein B, LpA-I, LpA-I:A-II, cholesterol esterification rate, LCAT activity and concentration, and LDL and HDL3 particle size were reduced in a gene-dose-dependent manner in carriers of mutant LCAT alleles. No differences were found in the lipid/lipoprotein profile of FLD and FED cases, except for higher plasma unesterified cholesterol and unesterified/total cholesterol ratio in the former. CONCLUSIONS: In a large series of subjects carrying mutations in the LCAT gene, the inheritance of a mutated LCAT genotype causes a gene-dose-dependent alteration in the plasma lipid/lipoprotein profile, which is remarkably similar between subjects classified as FLD or FED.

Transplantation of kidneys with tumors.

The shortage of donors in the face of the increasing number of patients wait-listed for renal transplantation has prompted several strategies including the use of kidneys with a tumor, whether found by chance on harvesting from a deceased donor or intentionally removed from a living donor and transplanted after excision of the lesion. Current evidence suggests that a solitary well-differentiated renal cell carcinoma, Fuhrman nuclear grade I-II, less than 1 cm in diameter and resected before grafting may be considered at minimal risk of recurrence in the recipient who, however, should be informed of the possible risk and consent to receive such a graft.

The IgA nephropathy Biobank. An important starting point for the genetic dissection of a complex trait.

BACKGROUND: IgA nephropathy (IgAN) or Berger's disease, is the most common glomerulonephritis in the world diagnosed in renal biopsied patients. The involvement of genetic factors in the pathogenesis of the IgAN is evidenced by ethnic and geographic variations in prevalence, familial clustering in isolated populations, familial aggregation and by the identification of a genetic linkage to locus IGAN1 mapped on 6q22-23. This study seems to imply a single major locus, but the hypothesis of multiple interacting loci or genetic heterogeneity cannot be ruled out. The organization of a multi-centre Biobank for the collection of biological samples and clinical data from IgAN patients and relatives is an important starting point for the identification of the disease susceptibility genes. DESCRIPTION: The IgAN Consortium organized a Biobank, recruiting IgAN patients and relatives following a common protocol. A website was constructed to allow scientific information to be shared between partners and to divulge obtained data (URL: http://www.igan.net). The electronic database, the core of the website includes data concerning the subjects enrolled. A search page gives open access to the database and allows groups of patients to be selected according to their clinical characteristics. DNA samples of IgAN patients and relatives belonging to 72 multiplex extended pedigrees were collected. Moreover, 159 trios (sons/daughters affected and healthy parents), 1068 patients with biopsy-proven IgAN and 1040 healthy subjects were included in the IgAN Consortium Biobank. Some valuable and statistically productive genetic studies have been launched within the 5th Framework Programme 1998-2002 of the European project No. QLG1-2000-00464 and preliminary data have been published in "Technology Marketplace" website: http://www.cordis.lu/marketplace. CONCLUSION: The first world IgAN Biobank with a readily accessible database has been constituted. The knowledge gained from the study of Mendelian diseases has shown that the genetic dissection of a complex trait is more powerful when combined linkage-based, association-based, and sequence-based approaches are performed. This Biobank continuously expanded contains a sample size of adequately matched IgAN patients and healthy subjects, extended multiplex pedigrees, parent-child trios, thus permitting the combined genetic approaches with collaborative studies.

[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.

Renal cancer in kidney transplanted patients.

Renal cancer occurs more frequently in renal transplanted patients than in the general population, affecting native kidneys in 90% of cases and the graft in 10 %. In addition to general risk factors, malignancy susceptibility may be influenced by immunosuppressive therapy, the use of calcineurin inhibitors (CNI) as compared with mammalian target of rapamycin inhibitors, and the length of dialysis treatment. Acquired cystic kidney disease may increase the risk for renal cancer after transplantation, while autosomal dominant polycystic kidney disease does not seem to predispose to cancer development. Annual ultrasound evaluation seems appropriate in patients with congenital or acquired cystic disease or even a single cyst in native kidneys, and every 2 years in patients older than 60 years if they were on dialysis for more than 5 years before transplantation. Immunosuppression should be lowered in patients who develop renal cancer, by reduction or withdrawal of CNI. Although more evidence is still needed, it seems reasonable to shift patients from CNI to everolimus or sirolimus if not already treated with one of these drugs, with due caution in subjects with chronic allograft nephropathy.

Post-dilution hemodiafiltration with a heparin-grafted polyacrylonitrile membrane.

The aim of this multicenter, prospective study was to explore the possibility of carrying out routine sessions of post-dilution hemodiafiltration with a polyacrylonitrile membrane grafted with heparin (HeprAN) and reduced anticoagulation. Forty-four patients from eight centers were included in the study and treated by means of post-dilution on-line hemodiafiltration with automatic control of TMP, according to three different modalities tested consecutively: phase 1, polyethersulfone filter primed with heparinized saline and anticoagulated with continuous infusion of unfractionated heparin 1000/h; phase 2, HeprAN membrane filter primed with saline without heparin. Anticoagulation: a 1000-unit bolus of unfractionated heparin at the start of session followed by a second one at the end of the second dialysis hour; phase 3, same filter and priming procedure as in phase 2; anticoagulation with nadroparin calcium at the beginning of treatment. Partial or massive clotting of the dialyzer occurred in less than 1% of sessions in phase 1; 10% and 7% in phase 2; and 1% and 2% in phase 3. Clotting limited to the drip chambers was observed in 13%, 34% and 12%, respectively. The study of coagulation parameters showed a better profile when low-molecular weight heparin (LMWH) was used in association with HeprAN membrane, while the generation of TAT complexes did not differ from that observed with the standard anticoagulation modality used in phase 1. Our results suggest that the HeprAN membrane can be used safely in routine post-dilution hemodiafiltration with reduced doses of LMWH.

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.

Thin basement membrane disease in patients with familial IgA nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) can exist as a primary glomerulonephritis (GN) or in association with various clinical conditions, suggesting that it could include several heterogeneous disorders. The familial form of IgAN has been increasingly recognized, supporting the suggestion that genetic factors could be involved in the disease pathogenesis, although it remains unclear whether the familial form is itself heterogeneous. METHODS: This study included 24 patients with a biopsy-proven IgAN from 11 unrelated families coming from five geographically distinct regions of Italy, and 90 of their relatives investigated for the presence of nephritis. Families were included in a genome-wide linkage analysis to identify loci responsible for the disease. RESULTS: Liver or systemic disease was not found in any case, and no hearing loss or ocular alterations were detected. Renal biopsy showed mesangial expansion at light microscopy, with glomerular sclerosis involving from 11 to 35% of glomeruli in eight patients. Ultrastructural examination revealed mesangial electron dense deposits along with a diffuse glomerular basement membrane (GBM) thinning typical of thin basement membrane disease (TBMD) in eight patients belonging to six families. Of the 90 relatives, 12 had "suspected IgAN", 73 were defined as "unaffected" and five as "probably unaffected". Families with co-existent TBMD failed to link to the IGAN1 locus. After a follow-up of 3-19 yrs, nine patients (37%) showed a progressive reduction in renal function and five of them reached end-stage renal disease (ESRD). CONCLUSION: These data demonstrate that familial IgAN is present outside geographically confined regions of Italy. Co-aggregation of IgAN with TBMD suggests that familial IgAN itself is a heterogeneous disorder and that inherited GBM abnormalities could be the first alteration, in some cases.

Plasma exchange treatment improves prognosis of antineutrophil cytoplasmic antibody-associated crescentic glomerulonephritis: a case-control study in 26 patients from a single center.

Twenty-six patients with Antineutrophil cytoplasmic antibody (ANCA)-associated crescentic glomerulonephritis (GN) were divided into two groups according to the acute phase treatment: drug therapy consisting of steroids and oral cyclophosphamide plus a plasma exchange (PE) course (group A, 13 patients) or drug therapy alone (group B, 13 patients). Group A patients had a more severe clinical picture and higher serum creatinine than group B (12.7 +/- 6.9 vs. 8.5 +/- 5.3 mg%); nine patients from group A (69%) and five from group B (38%) required dialysis. At follow up (mean 35 months) all patients treated with PE were alive: four of them were in end-stage renal disease. Among group B patients, three (23%) died in the acute phase; 6 (46%) needed renal replacement therapy at follow up. Of the dialysis-dependent patients, five out of nine from group A were free of dialysis, while in group B two out of five patients had died, two had entered a regular dialysis treatment and one had received a cadaver graft. These data suggest that PE may significantly improve the prognosis of patients with ANCA-associated crescentic GN even if they are not dialysis-dependent at the time of diagnosis.

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.