Cyclosporin in idiopathic glomerular disease associated with the nephrotic syndrome : Workshop recommendations

Management of idiopathic glomerular disease associated with nephrotic syndrome (INS) remains controversial and one of the most complex areas relates to utilization of the drug cyclosporin. This is despite its demonstrated effectiveness in several histologic types of the INS in randomized controlled trials. Cyclosporin is effective in inducing remission of proteinuria in approximately 80% of steroid-sensitive cases of minimal change disease (MCD). Cyclosporin is also effective in both the induction of remission and long-term preservation of renal function in steroid-dependent/-resistant MCD and steroid-resistant focal segmental glomerulosclerosis (FSGS). The overall response rate in FSGS is lower than in MCD, and long-term therapy (>12 months) may be required to both achieve remission and sustain it. Cyclosporin therapy is also of benefit in reducing proteinuria in 70-80% of patients with steroid-resistant membranous nephropathy (MGN). In MGN, the maximum benefit is often delayed compared to MCD (>12 weeks). Cyclosporin is generally well tolerated and safe. The major concern remains the nephrotoxicity, but with careful monitoring of the patient's renal function; minimizing the maintenance dose and utilizing repeat renal biopsy in those receiving long-term therapy, this risk can be minimized. The algorithms have been developed derived from the best evidence in the literature in each of the histologic types to help provide a guide to the integration of cyclosporin into the management of INS for the practicing nephrologist

Immigrating progenitor cells contribute to human podocyte turnover

Podocyte depletion is a critical event in glomerular diseases in general and in the development of focal segmental glomerulosclerosis in particular. Progenitor cell immigration is a possible mechanism of podocyte replacement for the preservation of nephron function since, with rare exception, mature podocytes are thought to be incapable of replication. We examined eight paraffin-embedded renal biopsies from six male recipients of female transplant kidneys for receiver-derived podocytes. Fluorescent in situ hybridization for the Y chromosome was combined with immunofluorescence for the podocyte marker, Wilms tumor-1 antigen. Recipient-derived podocytes were found in 4 of 8 biopsies representing 3 of the 6 patients. Overall, 5 of the 740 podocytes examined in the female-donated kidneys were male derived. Our study suggests that immigrating progenitor cells are able to replace podocytes in humans; however, the importance of this process in physiologic and pathologic conditions is unknown

Paediatric acute liver failure and transplantation: the University of Essen experience.

To report our experience with 17 children who underwent a liver transplantation (LT) for acute liver failure (ALF). All LT procedures (deceased and living donor) were offered. Since 2003 Molecular Adsorbents Recycling System (MARS) was proposed as bridging procedure. We monitored the perioperative course and the short- and long-term outcomes. All children developed pretransplant hepatic encephalopathy (mostly grades II and III); six needed ventilator support and three haemodialysis. Median PELD/MELD score was 30. MARS was used in five children with poor pretransplant prognostic factors: all five survived the LT without sequelae. We performed 13 deceased donor LT (seven whole, five split and onr reduced) and four left lateral LDLT. Postoperative complications were observed in 10 children, requiring re-operation in seven. Two children developed irreversible neurological disorders. After a median follow up of 45 months, 16 children are still alive. About 1- and 5-year cumulative patient survival rates are 94% with a corresponding graft survival of 88% and 81%, respectively. The combination of experienced paediatric ICU management, the application of new liver support devices, and the capacity to offer both living and deceased donor transplant alternatives in a timely fashion represent the best formula to achieve optimal results in children with ALF

Cyclosporin A in steroid-sensitive nephrotic syndrome with frequent relapses.

Eight patients with steroid-sensitive nephrotic syndrome which frequently relapsed despite cyclophosphamide treatment were given cyclosporin A (7.5 mg/kg/day to 10 mg/kg/day) for 8 to 12 weeks. Six had minimal change glomerulonephritis and two had focal segmental glomerulonephritis. Cyclosporin A was given to 5 patients when their nephrotic syndrome was in relapse and to 3 patients when the nephrotic syndrome was in remission. Cyclosporin A induced a transient remission in only one patient