Because loss of podocytes associates with glomerulosclerosis, monitoring podocyte loss by measuring podocyte products in urine may be clinically useful. To determine whether a single episode of podocyte injury would cause persistent podocyte loss, we induced limited podocyte depletion using a diphtheria toxin receptor (hDTR) transgenic rat. We monitored podocyte loss by detecting nephrin and podocin mRNA in urine particulates with quantitative reverse transcriptase-PCR. Aquaporin 2 mRNA served as a kidney reference gene to account for variable kidney contribution to RNA amount and quality. We found that a single injection of diphtheria toxin resulted in an initial peak of proteinuria and podocyte mRNAs (podocin and nephrin) followed 8 d later by a second peak of proteinuria and podocyte mRNAs that were podocin positive but nephrin negative. Proteinuria that persisted for months correlated with podocinpositive, nephrin-negative mRNAs in urine. Animals with persistent podocyte mRNA in urine progressed to ESRD with global podocyte depletion and interstitial scarring. Podocytes in ectatic tubules expressed podocalyxin and podocin proteins but not nephrin, compatible with detached podocytes' having an altered phenotype. Parallel human studies showed that biopsy-proven glomerular injury associated with increased urinary podocin:aquaporin 2 and nephrin:aquaporin 2 molar ratios. We conclude that a single episode of podocyte injury can trigger glomerular destabilization, resulting in persistent podocyte loss and an altered phenotype of podocytes recovered from urine. Podocyte mRNAs in urine may be a useful clinical tool for the diagnosis and monitoring of glomerular diseases.

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As a result of the high rate of infection, the NKF-K/DOQI guidelines recommended that an uncuffed catheter (UC) should not be used for longer than three weeks. However, the findings of the Dialysis Outcomes and Practice Patterns Study recognized that 48% of new hemodialysis patients in the US and 75% in Europe used UC for temporary access during arteriovenous fistula or graft maturation. The antibiotic lock technique (ALT) has been recommended to prevent catheter-related bacteremia (CRB). Here, we prospectively evaluated the efficacy of catheter-restricted filling using an antibiotic lock solution in preventing CRB. A total of 120 new hemodialysis patients requiring a temporary catheter while waiting for placement and maturation of an arteriovenous fistula or graft were enrolled in this study. Patients with a UC were randomly assigned to receive either an antibiotic-heparin lock solution (antibiotic group: cefazolin 10 mg/ml, gentamicin 5 mg/ml, heparin 1000 U/ml) or a heparin lock solution (no-antibiotic group: heparin 1000 U/ml) as a catheter lock solution during the interdialytic period. The end point of the trial was CRB. CRB developed in seven (11.7%) patients in the no-antibiotic group (Staphylococcus aureus, two; Staphylococcus epidermidis, five) whereas only one patient in the antibiotic group had S. aureus bacteremia. CRB rates per 1000 catheter-days were 0.44 in the antibiotic group versus 3.12 in the no-antibiotic group (P=0.031). Kaplan-Meier analysis also showed that mean CRB-free catheter survival of 59 days (95% CI, 58-61 days) in the antibiotic group was greater than that in the no-antibiotic group (55 days; 95% CI, 50-59 days). The results suggest that ALT may be a beneficial means of reducing the CRB rate in hemodialysis patients with UC.