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Background. Blood flow (Qa) measurements are an important step in the surveillance protocol of haemodialysis vascular access (VA). The glucose pump test (GPT) is a new test for Qa measurement based on the dilution of a constant glucose infusion. The aim of this study is to verify the clinical accuracy of GPT in a graft surveillance protocol with sequential Qa measurements.Methods. In 30 chronic haemodialysis patients with graft, we compared monthly sequential Qa measurements performed with GPT in pre-dialysis and the ultrasound dilution technique (HD01 device Transonic Systems Inc., USA) during dialysis. The colour Doppler ultrasonography study (CDU) was our reference standard for the diagnosis of stenosis. The endpoints were the graft thrombosis or PTA treatment.Results. According to the K/DOQI guidelines we could identify the thrombosis high-risk grafts when Qa was <600 ml/min or <1000 ml/min with a decrease >25% in serial Qa measurements. HD01 yielded 27 of 112 high-risk Qa measurements (21 Qa <600 ml/min; mean 406±145 ml/min; 6 ΔQa >25%; mean 43±7%). In 12 of 27 cases the CDU control did not show haemodynamically significant stenoses (false positive); 15 of 27 cases were confirmed high-risk accesses by CDU and did PTAs (HD01 specificity 86%). GPT yielded 14 of 112 high-risk Qa measurements (8 Qa <600 ml/min; mean 404±135 ml/min; 6 ΔQa >25%; mean 38±8%) and all had severe stenoses and underwent PTA treatments showing a GPT specificity of 100%. The CDU study allowed us to correctly assess the Qa negative cases. HD01 method had 10 false negative cases (treated or clotted grafts with a Qa >600 ml/min and ΔQa <25%) with a sensitivity of 60%, while GPT had 11 false negative cases with a sensitivity of 56%. The diagnostic accuracy tested with the ROC curves was similar with both tests (area under the curve was 0.762 and 0.752 with GPT and ultrasound dilution, respectively; P = 0.985). The diagnostic efficiency (percentage of grafts with agreement between test result and factual situation) was 90 and 80% (P = 0.056) for GPT and HD01, respectively.Conclusion. Compared with HD01, the GPT had a lower false positive rate and similar diagnostic accuracy and efficiency. The clinical implication is a smaller number of unnecessary, invasive procedures (angiographies or PTAs), without increasing the thrombosis risk. This study has shown that GPT is an accurate, quick and economic test for Qa monitoring. [ABSTRACT FROM AUTHOR]

Background. The problem of pure red cell aplasia (PRCA) prompted nephrologists to revert to a wider intravenous (i.v.) utilization of erythropoeitin (Epo). Once weekly i.v. Epo administration has been suggested to be as effective as the twice/thrice weekly i.v. dose. The aim of the present study was to test whether once weekly i.v. Epo administration is equally as cost-effective as once weekly subcutaneous (s.c.) and 2–3 times weekly i.v. administration.Methods. We prospectively studied 41 patients (23 males, aged 28–82 years), on renal replacement therapy for 18–286 months, stabilized on twice or thrice weekly s.c. Epo-α (basal). The patients were treated for three consecutive 6 month periods with once weekly s.c. (OWSC), once weekly i.v. (OWIV) and twice/thrice weekly i.v. (TWIV) Epo-α. The initial dose for each period was equal to the final dose of the previous one; when necessary, the dose was adjusted according to DOQY guidelines. Iron, folic acid and vitamin B12 supplementations were given throughout all the study periods. At the end of each of the four study periods, the following parameters were evaluated: haemoglobin, haematocrit, hypochromic red blood cells (RBCs), iron, serum ferritin, transferrin, folate, vitamin B12, C-reactive protein (CRP), Kt/V, parathyroid hormone (PTH) and weekly dose of Epo-α.Results. Thirty-three out of 41 enrolled patients completed the study (there were five deaths, two renal transplants and one transfer). No significant changes were observed as regards iron, serum ferritin, transferrin, folate, vitamin B12, CRP, Kt/V or PTH level. Haemoglobin levels were not different at the end of the basal (11.7±1.21), OWSC (11.8±0.86) and TWIV (12.1±1.04) periods, while significantly lower levels were observed after the OWIV period (11.0±0.97, P<0.01). Weekly Epo consumption (Epo U/week/kg body weight/g haemoglobin) was: basal 11.57±5.96; OWSC 10.22±4.53; OWIV 15.99±7.7*a; and TWIV 11.89±6.3*a (*P<0.01 vs basal; aP<0.01 vs OWSC).Conclusions. From our results, the OWIV schedule seems to have less efficacy in the control of anaemia of chronic renal failure patients on dialysis treatment than either OWSC or TWIV schedules. [ABSTRACT FROM AUTHOR]

Minimal change disease (MCD) is a pathological condition characterized by subtle glomerular lesions causing massive and reversible proteinuria that is usually steroid sensitive. Recurrence of symptoms of active disease following successful treatment (including proteinuria, oedema and oliguria) and steroid toxicity requires the use of other drugs to attain or maintain remission. Unresolved MCD is considered the initial step in the pathological pathway leading to focal and segmental glomerulosclerosis (FSGS). Historically, cyclophosphamide, chlorambucil, mycophenolate and calcineurin inhibitors have been utilized with success in MCD; however, the chronic nature of the disease and the toxicity of long-term use of these medications has pushed the development of new therapies. Synthetic corticotropin (adrenocorticotropic hormone) and anti-CD20 monoclonal antibodies, for example, are currently under investigation in clinical trials. In addition, these new interventions have dramatically impacted our understanding of the mechanisms of the disease. Phase II-IV clinical trials targeting new mechanisms and/or molecules are in progress. The list is long and includes drugs blocking the adaptive immune system (abatacept and anti-CD40 antibodies), as well as retinoids and the sialic acid precursor N-acetyl-D-mannosamine (ManNAc), two agents that affect the sieving properties of the glomerular basement membrane. Other drugs are being tested against FSGS and, if successful, could also be utilized againstMCD. Clinical trials currently in progress should furnish a proper solution to what appears to be a solvable problem. [ABSTRACT FROM AUTHOR]

Background Agranulocytosis has been reported as a delayed-onset complication of rituximab treatment. However, the exact incidence and risk factors of this complication in patients with nephrotic syndrome remain unknown. Methods Records of 213 rituximab treatments for 114 patients with refractory nephrotic syndrome between February 2006 and April 2013 were reviewed to identify episodes of agranulocytosis (defined as an absolute neutrophil count of <500 mm3). Results Eleven episodes of agranulocytosis were detected in 11 patients. Median time of onset of agranulocytosis was 66 days (range, 54–161 days) after rituximab treatment. Nine patients experienced acute infections and received antibiotics. All but one patient received granulocyte colony-stimulating factor. Agranulocytosis resolved in all cases within a median of 3 days. The incidence of agranulocytosis was 9.6% in total patients and 5.2% in all treatments. Median age of the 11 patients who developed agranulocytosis was 6.4 years at the first rituximab treatment, significantly younger than the median age of the 103 patients who did not (median, 12.5 years; P = 0.0009). Five patients received re-treatment with rituximab. No recurrence of agranulocytosis was observed in any patient. Conclusions It is important to pay extra attention to this clinically serious delayed-onset complication as it may be accompanied by life-threatening infections such as sepsis. Further clinical studies are needed to clarify its pathogenesis. [ABSTRACT FROM AUTHOR]

Background Minimal-change nephrotic syndrome (MCNS) is a common cause of steroid sensitive nephrotic syndrome (NS) with frequent relapse. Although steroids and calcineurin inhibitors (CNIs) are the cornerstone treatments, the use of rituximab (RTX), a monoclonal antibody targeting B cells, is an efficient and safe alternative in childhood. Methods Because data from adults remain sparse, we conducted a large retrospective and multicentric study that included 41 adults with MCNS and receiving RTX. Results Complete (NS remission and withdrawal of all immunosuppressants) and partial (NS remission and withdrawal of at least one immunosuppressants) clinical responses were obtained for 25 and 7 patients, respectively (overall response 78%), including 3 patients that only received RTX and had a complete clinical response. After a follow-up time of 39 months (6–71), relapses occurred in 18 responder patients [56%, median time 18 months (3–36)]. Seventeen of these received a second course of RTX and then had a complete (n = 13) or partial (n = 4) clinical response. From multivariate analysis, on-going mycophenolate mofetil (MMF) therapy at the time of RTX was the only predictive factor for RTX failure [HR = 0.07 95% CI (0.01–0.04), P = 0.003]. Interestingly, nine patients were still in remission at 14 months (3–36) after B-cell recovery. No significant early or late adverse event occurred after RTX therapy. Conclusions RTX is safe and effective in adult patients with MCNS and could be an alternative to steroids or CNIs in patients with a long history of relapsing MCNS. [ABSTRACT FROM PUBLISHER]

Background Primary or secondary glomerulonephritis has been anecdotally reported in association with atypical haemolytic uraemic syndrome (aHUS). We here report a series of six patients who developed aHUS and glomerulopathy, and review the literature on aHUS and glomerulonephritis. Methods Out of all patients diagnosed at our unit with biopsy-proven glomerular diseases between March 2007 and October 2011, selected cases developing aHUS during the follow-up are presented. The following tests were performed in all six patients: serum C3 and C4 levels, ADAMTS13 activity, CFH levels and anti-CFH autoantibodies and genetic screening for CFH, MCP, CFI, C3 and CFHR1-3 mutations and risk haplotypes associated with aHUS. Results Two hundred and forty-eight patients received a biopsy-proven diagnosis of glomerulopathy and were followed for a median of 31 months (range 2–58). Of these, six developed aHUS, within a median of 15 months (range 1–36) of their initial diagnosis of glomerulopathy. One of these patients had focal segmental glomerulosclerosis (FSGS), two membranoproliferative glomerulonephritis (MPGN) type I, one C3 glomerulonephritis and two systemic small vessel vasculitis [one granulomatosis with polyangiitis (Wegener's), one Henoch–Schoenlein purpura]. Five patients (one of them heterozygous for a CFH mutation) carried, in homo- or heterozygosity, the risk haplotype CFH-H3 (CFH tgtgt), previously described to be associated with aHUS, while another one patient was homozygous for the MCPggaac risk haplotype predisposing to aHUS when present on both alleles. Conclusions Different types of glomerulopathies can be complicated by aHUS. Several mechanisms can contribute to this association, such as nephrotic-range proteinuria, mutations or aHUS-risk haplotypes involving genes encoding alternative complement regulatory proteins in some patients and inflammatory triggers associated with systemic immune-mediated diseases. [ABSTRACT FROM AUTHOR]

Background Recent advances in cell therapies have provided potential opportunities for the treatment of chronic kidney diseases (CKDs). We investigated whether human kidney structures could be preformed in vitro for subsequent implantation in vivo to maximize tissue-forming efficiency. Methods Human renal cells were isolated from unused donor kidneys. Human renal cells were cultured and expanded. Migration was analyzed using growth factors. To form structures, cells were placed in a three-dimensional culture system. Cells were characterized by immunofluorescence, western blots and fluorescence-activated cell sorting using renal cell-specific markers for podocin, proximal and distal tubules and collecting ducts. An albumin uptake assay was used to analyze function. Three-dimensional cultures were implanted into athymic rat kidneys to evaluate survival. Results Human renal cells were effectively expanded in culture and retained their phenotype, migration ability and albumin uptake functions. Human renal cell in three-dimensional culture-formed tubules, which stained positively for proximal, distal tubule and collecting duct markers, and this was confirmed by western blot. Polarity of the tubular cells was determined by the presence of E-cadherin, N-cadherin and Na-K ATPase. Colocalization of labeled albumin and proximal tubule markers proved functionality and specificity of the newly formed tubules. An in vivo study showed that cells survived in the kidney for up to 6 weeks. Conclusions These findings demonstrate that human renal cell grown in three-dimensional culture are able to generate kidney structures in vitro. This system may ultimately be developed into an efficient cell-based therapy for patients with CKD. [ABSTRACT FROM AUTHOR]

Background. In patients with refractory steroid-sensitive nephrotic syndrome (SSNS), treatment with rituximab has shown encouraging results; however, long-term follow-up data are not available. Methods. We performed a retrospective analysis of 37 patients (25 boys) with steroid-dependent nephrotic syndrome who were treated with rituximab (375 mg/m2 given weekly for one to four courses). Long-term follow-up data (>2 years, median 36, range 24–92.8 months) are available for 29 patients (12 boys). Results. Twenty-six of 37 (70.3%) patients remained in remission after 12 months. Relapses occurred in 24 (64.8%) patients after a median of 9.6 (range 5.2–64.1) months. Time to first relapse was significantly shorter in patients receiving one or two compared to three or four initial infusions. In the 29 patients with long-term follow-up for >2 years, 12 (41%) patients remained in remission after the initial rituximab course for >24 months, 7 (24.1%) patients without further maintenance immunosuppression. Nineteen children received two to four repeated courses of rituximab increasing the total number of patients with long-term remission to 20 (69%), remission including 14 (48%) patients off immunosuppression. The proportion of patients with long-term remission was not related to the number of initial rituximab applications. No serious side effects were noted. Conclusion. Rituximab is an effective treatment option in the short- and long-term control of treatment refractory SSNS. Further controlled studies are needed to address optimal patient selection, dose and safety of rituximab infusions. [ABSTRACT FROM AUTHOR]