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Background: Metformin-associated lactic acidosis (MALA) is a severe complication of drug administration with significant morbidity and mortality. So far no study in large population areas have examined the incidence, clinical profile and outcome of acute kidney injury (AKI)-MALA patients admitted in intensive care units (ICUs) and treated by renal replacement therapy (MALA-RRT). Methods: Retrospective analysis over a 6-year period (2010-2015) in Piedmont and Aosta Valley regions (5,305,940 inhabitants, 141,174 diabetics treated with metformin) of all MALA-RRT cases. Results: One hundred and seventeen cases of AKI-MALA-RRT were observed (12.04/100,000 metformin treated diabetics, 1.45% of all RRT-ICU patients). Survival rate was 78.3%. The average duration of RRT was 4.0 days at mean dialysis effluent of 977 mL/kg/day. At admission most patients were dehydrated, and experienced shock and oliguria. Conclusion: Our data showed that MALA-RRT is a common complication, needing more prevention. Adopted policy of early, extended, continuous and high efficiency dialysis could contribute to an observed high survival rate. Video Journal Club “Cappuccino with Claudio Ronco” at http://www.karger.com/?doi=471917.

Dabigatran is an oral direct inhibitor indicated for stroke prevention in patients with atrial fibrillation. Unlike warfarin, dabigatran's observed therapeutic window and minimal drug-to-drug interaction suggest that laboratory test and dose adjustments are not necessary; nevertheless, circumstances of excessive anticoagulation, decreased kidney function, and instances of significant bleeding and thrombosis require laboratory assessment. In order to gather experience in the management of global [activated partial thromboplastin time (APTT) and thrombin time (TT) with extended endpoint] and specific [ecarin chromogenic assay (ECA) and diluted thrombin time (dTT)] laboratory coagulation tests in patients receiving dabigatran with untoward effects, we describe a case in which hemodialysis was used in attempt to remove dabigatran in a patient with excessive anticoagulation, rectal bleeding, and severe anemia. Our experience confirmed that APTT is an unreliable method for the assessment of dabigatran in patients with acute complications because it was often normal in spite of the therapeutic drug plasma levels. Both ECA and dTT showed a linear correlation with dabigatran levels over a broad range, and identified therapeutic and supratherapeutic levels. TT assay, which is highly sensitive to dabigatran, correlated well and linearly not only with low drug levels, but also, because of the introduction of the extended endpoint (400 s), with high concentrations of the drug, and demonstrated to be a simple and reliable alternative to ECA and dTT to assess dabigatran in patients with acute complications.

Many recent papers analyze the association between renal stone disease and other diseases that are typical of industrialized countries. Epidemiology studies from large series indicate that the prevalence of nephrolithiasis is higher among patients with metabolic syndrome, diabetes, and hypertension. Patients with nephrolithiasis also have an increased risk of myocardial infarction and stroke. It has been hypothesized that the common underlying defect could be insulin resistance. This, in turn, alters the urine biochemistry (i.e. more acidic pH and less urine citrate) thereby increasing the propensity of stone forming. In the diabetic rat renal steatosis has been implicated in the reduced production of ammonia, which has been shown to be reversible after PPARγ administration. Furthermore, pioglitazone was shown to be effective in reducing ethylene glycol-induced renal injury.Another significant association concerns gout. Two recent papers report that both calcium and uric acid stone disease are more preval...

French speakers are very proud of their language, with its fine expressions, rare words and choice phrases. German speakers also undoubtedly love their language, but they fear the grandiloquence and even absurdity of a register that can quickly appear too elevated. This is particularly true in screenplays and often means translators face a difficult choice between language that is either too poetic or too banal. This article raises the question of faithfulness to the original from this perspective., Les francophones sont très fiers de leur langue dont ils apprécient les belles formulations, les mots rares, les expressions choisies. Les germanophones aiment la leur, certes, mais ils craignent le pathos, voire le ridicule d’un registre vite considéré comme trop élevé. Ceci est particulièrement vrai sur le plateau et met souvent le traducteur devant le dilemme entre le trop poétique et le trop banal. Cet article soulève la question de la fidélité au texte original sous ce point de vue., Berutti-Ronelt Silvia. Le pathos et le registre soutenu dans les traductions théâtrales du français vers l’allemand. In: Équivalences, 44e année-n°1-2, 2017. La traduction théâtrale. pp. 145-154.

Background: Unfractionated heparin (UFH) is the standard anticoagulant in regular dialysis treatments (RDTs), despite the fact that it may induce thrombocy- topenia, dyslipidemia, allergy and osteoporosis. Der- matan sulfate (DS) selectively inhibits thrombin, does not inhibit F-Xa and does not interfere with platelets (PLTS). Here we described an original protocol for the use of DS as anticoagulant in RDT and compared its effects with those of UFH. Methods: In 102 patients, 7,254 RDTs were performed using DS for anticoagulation (DS-phase) and 5,707 with UFH (UFH-phase). DS was supplied as initial bo- lus (80 ± 12 mg) and continuous infusion (14 ± 7 mg/ hour). With UFH, the initial bolus was 1,475 ± 141 IU and continuous infusion 576 ± 349 IU/hour. Activated par- tial thromboplastin time and its ratio were measured at least monthly, both before (pre-RDT APTT ratio) and af- ter (post-RDT APTT ratio) RDT sessions. With 41of 102 patients, both DS and UFH doses were not changed during study phases (stable patients). In this subset, the coefficient of variation (CV) of all pre-RDT APTT ratio and post-RDT APTT ratio values was calculated. Results: In DS and UFH phases, post-RDT APTT ra- tio increased by 61% and 50%, respectively, by com- parison with pre-RDT APTT ratio (p

A 85-year-old man, with CKD (e-GFR 35 mL/min), had been given Dabigatran (a direct thrombin inhibitor) at 110 mg daily dose because of atrial fibrillation. Due to intercurrent diarrhea and dehydration, renal function worsened (e-GFR 11 mL/min) and Dabigatran excretion decreased, thereby inducing drug overload. In this case, Dabigatran must be removed by dialysis, but the most appropriate schedule is still undefined. The effects of both continuous haemodiafiltration (CVVHDF) and intermittent haemodialysis (IHD) on plasma Dabigatran (Echarin Chromogenic Assay) were reported. Dialysis clearance of Dabigatran was reported as ratio to urea clearance (Dab/Urea(Cl)). Coagulation was assessed by both DOA-aPTTratio and Thrombin Time-ratio (TTratio). Dabigatran was elevated at 597 ng/mL predialysis (bleeding threshold being 30 ng/mL), and decreased to 96 ng/mL (-84%) after 20 hours of CVVHDF (Urea(Cl) = 67 mL/min). Dab/Urea(Cl) was 0.49. Three hours after dialysis, Dabigatran rebounded to 208 ng/mL. On IHD (Urea(Cl)=238 mL/min), predialysis Dabigatran was 52 ng/mL and decreased to 8 ng/mL (-85%) after 3.5 hours of treatment. Dab/Urea(Cl) was 0.47. Fourteen hours later, Dabigatran rebounded at 19 ng/mL. There was a positive correlation between Dabigatran and TTratio (r = 0.92; p0.0001), whereas DOA-aPTT did not increase above 2.5 times the reference values, even in face of the highest values of Dabigatran. Therefore, TTratio is more reliable than DOA-aPTT in detecting Dabigatran overdose. Post-dialysis rebound of Dabigatran occurred also with CVVHDF, thereby suggesting that accurate monitoring of both Dabigatran levels and bleeding risk are mandatory, also after long-lasting dialysis sessions.

The treatment of membranous glomerulonephritis (MGN) is controversial, especially in cases of no response to first-line treatment or multiple relapses. The Clinical Nephrology Group of Piedmont carried out a multicenter analysis of the treatment of patients affected by MGN in 15 nephrology units in Piedmont. The first treatment is usually started after a waiting period of 3-6 months in case of proteinuria in the nephrotic range but normal or slightly impaired renal function. A history of cancer, the presence of infectious disease, and secondary forms of MGN are criteria for exclusion from treatment. As first-line treatment, Piedmont nephrologists prescribe corticosteroids alternated with immunosuppressive drugs, generally preferring cyclophosphamide to chlorambucil. Only one nephrology unit uses cyclosporin A (CyA) as the first choice. In case of no response to treatment, a second therapeutic approach is undertaken after 2-12 months. Second-line treatment consists of CyA if immunosuppressive drugs were given before, and corticosteroids/ immunosuppressive drugs if CyA was the first treatment. A further choice may be ACTH or rituximab. In case of multiple relapses the treatment options are the same but previous immunosuppressive treatment, patient age, and the duration of kidney disease with a greater probability of renal failure and progression towards sclerosis require careful attention. Concern has been expressed regarding the potentially severe side effects of ACTH including myopathy, cataract and diabetes. In conclusion, the applied therapeutic approaches in Piedmont reflect the difficulty reported in the literature in identifying simple recommendations. ACTH and rituximab are increasingly preferred for the treatment of MGN and there is a need for prospective studies to determine the best protocol for rituximab and the safety profile of ACTH.

Conclusion. This short course of therapy with prednis- one and cyclophosphamide has been effective in a Background. IgA nephropathy is associated with a wide spectrum of possible lesions. Therefore, different subset of IgA nephropathy patients with florid glomer- ular changes and major urinary abnormalities, turning responses to anti-inflammatory or immunosuppressive therapies should be expected with acute inflammatory off phlogistic activity and preventing subsequent progression toward renal failure. changes, which are predominantly reversible, and with prevalently sclerotic lesions. Methods. The effects of a combined schedule of pred- nephropathy; renal disease progression nisone and cyclophosphamide was analysed in the specific subset of IgA nephropathy patients with acute inflammatory histologic changes associated with haem- aturia and proteinuria. Two groups of patients, with Introduction similar histologic lesions and clinical presentation, were considered. The first group (12 patients) was treated Due to its wide variability in clinical presentation and within 1 week after renal biopsy; starting with three histologic changes, IgA nephropathy has been defined pulses of methylprednisolone (1 g) followed by oral as a 'microcosmos of glomerular lesions' (1). Some prednisone (0.8 mg/kg body weight for 2 weeks, histologic lesions are irreversible and progress towards 0.6 mg/kg for another 2 weeks, 0.4 mg/kg for an obliteration of glomerular capillaries; others are additional 4 weeks, then slowly tapered by 5 mg each acute inflammatory processes, potentially susceptible month until discontinuation) and 1.5 mg/kg cyclophos- to reversal by means of antiphlogistic and immuno- phamide for 2 months. A second sample of eight suppressive therapies (1,2). Therefore, it is difficult to untreated patients served as a control group. Treated identify truly homogeneous subsets of patients for and untreated patients had diffuse mesangial prolifera- treatment trials (especially if the entry criteria are tion with florid crescents (8-60% in treated and based on a single variable such as urinary protein 10-40% in untreated patients) with mild degree of excretion). This possibly explains the conflicting results glomerular sclerosis and interstitial changes. Basal of reports on corticosteroids and cytotoxic drugs in creatinine (167 mmol/l, range 79-371 vs132 mmol/l, these patients (3). range 79-256) and proteinuria (3.0 g/24 h, 1.0-4.9 vs In order to assess the long-term effects of a combina- 3.3 g/24 h, 1.0-13.7) were not statistically different tion of prednisone and cyclophosphamide on renal between treated and untreated patients respectively. function in a subset of IgA nephropathy patients with Nine treated and six untreated patients were hypertens- acute phlogistic histologic changes associated with ive. Blood pressure treatment did not include ACE- haematuria and proteinuria, two samples of patients inhibitors. with similar histologic lesions and clinical presentation

Ascorbate supplementation for patients on regular dialysis treatment (RDT) is advised to obviate deficiency and improve epoetin response in those with functional iron deficiency. However, clear-cut safety concerns regarding hyperoxalemia are still poorly understood. This study tries to establish safety/efficacy profiles of ascorbate and oxalate during long-term intravenous ascorbate supplementation.A prospective study was performed in 30 patients on RDT showing ascorbate deficiency (plasma ascorbate2.6 mg/L [15 micromol/L]): 18 patients were administered intravenous ascorbate during 18 months (250 mg/wk, subsequently increased to 500 mg), and 12 patients were taken as reference untreated cases. Plasma ascorbate and oxalate assays and dialytic balance determinations were performed (ion chromatography and reverse-phase high-performance liquid chromatography, respectively) at baseline, during treatment, and 12 months after withdrawal.Plasma ascorbate levels increased dose dependently with supplementation (1.6 +/- 0.8 mg/L [9.1 +/- 4.6 mumol/L] at baseline, 2.8 +/- 1.8 mg/L [15.9 +/- 10.1 micromol/L]) with 250 mg of ascorbate, and 6.6 +/- 2.8 mg/L [37.5 +/- 16.0 micromol/L] with 500 mg/wk of ascorbate), but only normalized with greater dosages for several months in 94% of patients. Baseline plasma oxalate levels increased from 3.2 +/- 0.8 mg/L (35.8 +/- 8.8 micromol/L) to 3.6 +/- 0.8 mg/L (39.5 +/- 9.1 micromol/L) and 4.5 +/- 0.9 mg/L (50.3 +/- 10.4 micromol/L) with 250 and 500 mg, respectively ( P0.001). The calcium oxalate saturation threshold was exceeded by 7 of 18 patients (40%) during 6 months therapy with 500 mg/wk. Ascorbate dialysis removal increased from 37.8 +/- 23.2 mg (215 +/- 132 micromol) to 99.6 +/- 51.7 mg (566 +/- 294 micromol) during supplementation (P0.001), with corresponding increases in oxalate removal from 82.5 +/- 33.2 mg (917 +/- 369 micromol) to 111.2 +/- 32.6 mg/L (1,236 +/- 362 micromol; P0.01). Withdrawal reverted plasma levels and dialysis removal to initial values. Values for untreated patients did not change during 1 year of follow-up.Patients on RDT may resolve ascorbate deficiency with intravenous supplementation of 500 mg/wk, but this implies a significant risk for oxalate supersaturation. Oxalate measurements are strongly recommended during long-term ascorbate therapy.

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder that is caused by a deficiency of alanine: glyoxylate aminotransferase (AGT), which is encoded by a single copy gene (AGXT). Molecular diagnosis was used in conjunction with clinical, biochemical, and enzymological data to evaluate genotype-phenotype correlation. Twenty-three unrelated, Italian PH1 patients were studied, 20 of which were grouped according to severe form of PH1 (group A), adult form (group B), and mild to moderate decrease in renal function (group C). All 23 patients were analyzed by using the single-strand conformation polymorphism technique followed by the sequencing of the 11 AGXT exons. Relevant chemistries, including plasma, urine and dialyzate oxalate and glycolate assays, liver AGT activity, and pyridoxine responsiveness, were performed. Both mutant alleles were found in 21 out of 23 patients, and 13 different mutations were recognized in exons 1, 2, 4, and 10. Normalized AGT activity was lower in the severe form than in the adult form (P < 0.05). Double heterozygous patients presented a lower age at the onset of the disease (P = 0.025), and they were more frequent in group A (75%) than in the group B (14%; P = 0.0406). The T444C mutation was more frequent in the severe form (P < 0.05), and the opposite was observed for G630A (P < 0.05). G630A mutation homozygotes had a higher AGT residual activity (P = 0.00001). This study confirms the allelic heterogeneity of the AGXT, which could to some extent be responsible for the phenotypic heterogeneity in PH1.

To evaluate the role of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in the progression of immunoglobulin A glomerulonephritis (IgA-GN), genotype distribution in 81 biopsy-proven cases of IgA-GN was studied. A logistic regression model showed that the risk for homozygous DD was not significantly elevated in patients with IgA-GN compared with healthy subjects (odds ratio=1.16; confidence interval [CI], 0.4 to 3.3). However, the 5-year (78% v 90%) and 10-year (52% v 82%) renal survival rates for 47 patients with serum creatine (Cr) levels of 1.5 mg/dL or less at biopsy was significantly less in DD patients (n = 18; χ 2 = 5.41; P = 0.02). The hazard ratio (HR) for DD (multivariate analysis from Cox proportional model after adjustment for known factors of progression, such as hypertension [HPT] and proteinuria [PTO]) was 3.07 (CI, 1.1 to 9.4). The HR for heavy PTO was 6.1 (CI, 1.9 to 19). The association of DD genotype with progression was even more striking when patients with other risk factors (heavy proteinuria) were excluded, as shown by DD-related risk in the absence (HR = 3.6; CI, 1.1 to 12) and presence (HR = 2; CI, 0.4 to 10) of PTO. The risk ratio was further increased by the coexistence of DD + PTO (HR = 9.16; CI, 1.8 to 15.7). Furthermore, in a cross-sectional study among patients with IgA-GN, a logistic regression model showed that the risk for homozygous DD was greater, although not at a statistically significant level in the end-stage renal failure subgroup compared with the normal renal function subgroup (odds ratio=3.16; CI, 0.7 to 13.7) after adjustment by sex, age at biopsy, HPT, PTO, and therapy. Last, DD was significantly more frequent in those patients who started hemodialysis at an earlier age (χ 2 for trend=6.81; P = 0.009). Our study further supports that ACE genotype is a risk factor not for the development, but for the worsening of IgA-GN clinical course. However, on the basis of current knowledge, we cannot exclude that I/D polymorphism may simply serve as a prognostic marker, eventually linked with other discrete loci involved in the progression of renal damage.