Focal segmental glomerular sclerosis can be effectively treated using an intensive B-cell depletion therapy.

Background: Focal segmental glomerular sclerosis (FSGS) is a histologic lesion rather than a specific disease entity and represents a cluster of different conditions affecting both children and adults that includes primary, secondary and genetically mediated forms. These forms can be distinguished by electron microscopy and genetic assessment and show different responsiveness to steroids and immunosuppressants. Despite some promising effects of rituximab in nephrotic syndrome in children, the results in adults with FSGS are disappointing. Our group previously explored the effectiveness of rituximab in eight adult patients with unselected forms of FSGS and achieved a consistent reduction in proteinuria in one case. Following this experience, we developed an alternative therapeutic option intended to enhance the potential of rituximab with the support of other synergic drugs. We herein report the results of this therapeutic protocol (six administrations of rituximab plus two of intravenous cyclophosphamide plus glucocorticoids) in seven prospectively enrolled patients with extensive podocyte effacement and recurrent relapses or steroid dependence. Results: Patients had a median baseline serum creatinine level of 2.2 mg/dl (range 1-4.7) that decreased to 1.1 mg/dl (range 0.9-2.2) and 1.1 mg/dl (range 0.75-2.21) after 3 and 6 months, respectively, and remained unchanged at 12 months. Three of five patients with renal failure turned to normal function while the other two patients maintained a stable impairment after 18 and 52 months. The median proteinuria decreased from 6.1 g/24 h to 3.5, 3.5 and 1.9 g/24 h at 3, 6 and 12 months, respectively. Specifically, five of seven patients had a partial response at 12 months and became non-nephrotic. One of them had a complete response at 18 months and was still in complete remission at the last follow-up visit at 36 months. Proteinuria persisted unchanged in two of seven patients with a genetic-related disease. No serious late adverse events were observed. Conclusions: Our results show that intensive B-cell depletion therapy is able to reverse the nephrotic syndrome of steroid-dependent or frequently relapsing adult patients with putatively idiopathic FSGS (i.e. with extensive podocyte effacement).

Increase of continuous treatments and regional citrate anticoagulation during renal replacement therapy in the ICUs of the North-West of Italy from 2007 to 2015.

BACKGROUND: Few reports have addressed the change in renal replacement therapy (RRT) management in the Intensive care Units (ICUs) over the years in western countries. This study aims to assess the trend of dialytic practice in a 4.5-million population-based study of the northwest of Italy. METHODS: A nine-year survey covering all the RRT provided in the ICUs. Consultant nephrologists of the 26 Nephrology and Dialysis centers reported their activities in the years 2007, 2009, 2012, and 2015. RESULTS: From 2007 to 2015 the patients treated increased from 1042 to 1139, and the incidence of RRT from 254 to 263 cases/10^6 inhabitants. The workload for dialysis center was higher in the larger hub hospitals. RRT for acute kidney injury (AKI), continuation of treatment in chronically dialyzed patients, or extrarenal indications accounted for about the stable rate of 70, 25 and 5% of all RRT sessions, respectively. Continuous modality days increased from 2731 days (39.5%) in 2007 to 5076 (70.6%) in 2015, when the continuous+prolonged treatment days were 6880/7196 (95.6% of total days). As to RRT timing, in 2015 only the classical clinical criteria, and no K-DIGO stage were adopted by most Centers. As to RRT interruption, in 2015 urine volume was the first criterion. Implementation of citrate anticoagulation (RCA) for RRT patients significantly increased from 2.8% in 2007 to 30.9% in 2015, when it was applied in all 26 Centers. CONCLUSIONS: From 2007 to 2015, current practice has changed towards shared protocols, with increasing continuous modality and RCA implementation.

Metformin-Associated Lactic Acidosis Undergoing Renal Replacement Therapy in Intensive Care Units: A Five-Million Population-Based Study in the North-West of Italy.

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.

Severe symptomatic hyponatremia during sibutramine therapy: a case report.

Sibutramine, a serotonin reuptake inhibitor, currently is used in treatment of obesity. The known side effects of sibutramine, ie, hypertension and tachycardia, depend on its adrenergic and serotoninergic effects. We describe a case of life-threatening hyponatremia associated with sibutramine use in an obese woman. We hypothesize that sibutramine, through its effect on neurotransmitters, may induce antidiuretic hormone secretion and lead to a syndrome of inappropriate antidiuretic hormone secretion. We advise careful monitoring of water-electrolytic balance during sibutramine therapy.

KCNA1 and TRPC6 ion channels and NHE1 exchanger operate the biological outcome of HGF/scatter factor in renal tubular cells.

Hepatocyte growth factor (HGF) is a glycoprotein that induces in vitro epithelial tubular cell growth, motility, scattering and branching morphogenesis. The cell machineries that account for HGF biological effects are still unclear. In previous study, we found that HGF upregulated in epithelial tubular cell line (HK2) 3 genes: potassium channel KCNA1, calcium channel (transient receptor potential channel, subfamily C, member 6, TRPC6) and Na(+)/H(+) exchanger-1 (NHE1). In this study, we validated these results with reverse transcription PCR and WB analysis. To investigate whether KCNA1, TRPC6, NHE1 mediate the changes induced by HGF in HK2, we studied the effects of their inhibitors: 4-aminopyridine, charybdotoxin, dendrotoxin K inhibitors of KCNA1, lanthanum, N-(p-amylcinnamoyl) anthranilic acid inhibitors of TRPC6, 5-(N-ethyl-N-isopropyl)amiloride, cariporide inhibitors of NHE1. The inhibitors prevented HGF-induced growth, migration, cytoskeletal reorganization and tubulogenesis in HK2. These results indicate that KCNA1, TRPC6 and NHE1 are cell machineries that are exploited by HGF to effect its biological outcome in renal tubular cells.