Is Totally Tubeless Percutaneous Nephrolithotomy a Safe and Efficacious Option for Complex Stone Disease?

Background: Percutaneous nephrolithotomy is the gold standard treatment for large, complex intrarenal stones. Historically, this was performed using a nephrostomy tube (PCN) and/or internalized ureteral stent at the end of the procedure. However, totally tubeless nephrolithotomy (tt-PCNL) is a novel technique where no tubes (no stent nor nephrostomy tube) are left post-operatively. We review the literature on this subject regarding peri-operative outcomes, post-operative outcomes, and potential complications of the procedure, discuss our technique, and make recommendations on implementation for centers not currently utilizing the procedure. Materials and methods: We performed a comprehensive search of the literature on totally tubeless nephrolithotomy using MEDLINE database search. Our search included prior review articles, meta-analyses, systematic reviews, primary research articles, case reports, and case studies. Results: In comparison to prior approaches where a stent or nephrostomy tube is placed, tt-PCNL has a similar complication rate and better post-operative outcomes. Totally tubeless PCNL has similar operative times and similar changes in hemoglobin. However, it had shorter length of stays across all studies. The mean difference in length of stay in the studies reviewed was 1.96 days. Additionally, tt-PCNL had decreased post-operative analgesic requirements and pain scores. Conclusions: This review highlights totally tubeless percutaneous nephrolithotomy as a safe and feasible surgical technique with improved outcomes in properly selected patients.

A Simple Fluorescent Cholesterol Labeling Method to Cryoprotect and Detect Plasma Lipoprotein-X.

Lipoprotein-X (LpX) are abnormal nephrotoxic lipoprotein particles enriched in free cholesterol and phospholipids. LpX with distinctive lipid compositions are formed in patients afflicted with either familial LCAT deficiency (FLD) or biliary cholestasis. LpX is difficult to detect by standard lipid stains due to the absence of a neutral lipid core and because it is unstable upon storage, particularly when frozen. We have recently reported that free cholesterol-specific filipin staining after agarose gel electrophoresis sensitively detects LpX in fresh human plasma. Herein, we describe an even more simplified qualitative method to detect LpX in both fresh and frozen-thawed human FLD or cholestatic plasma. Fluorescent cholesterol complexed to fatty-acid-free BSA was used to label LpX and was added together with trehalose in order to cryopreserve plasma LpX. The fluorescent cholesterol bound to LpX was observed with high sensitivity after separation from other lipoproteins by agarose gel electrophoresis. This methodology can be readily developed into a simple assay for the clinical diagnosis of FLD and biliary liver disease and to monitor the efficacy of treatments intended to reduce plasma LpX in these disease states.

ApoA-I-Mediated Lipoprotein Remodeling Monitored with a Fluorescent Phospholipid.

We describe simple, sensitive and robust methods to monitor lipoprotein remodeling and cholesterol and apolipoprotein exchange, using fluorescent Lissamine Rhodamine B head-group tagged phosphatidylethanolamine (*PE) as a lipoprotein reference marker. Fluorescent Bodipy cholesterol (*Chol) and *PE directly incorporated into whole plasma lipoproteins in proportion to lipoprotein cholesterol and phospholipid mass, respectively. *Chol, but not *PE, passively exchanged between isolated plasma lipoproteins. Fluorescent apoA-I (*apoA-I) specifically bound to high-density lipoprotein (HDL) and remodeled *PE- and *Chol-labeled synthetic lipoprotein-X multilamellar vesicles (MLV) into a pre-ß HDL-like particle containing *PE, *Chol, and *apoA-I. Fluorescent MLV-derived *PE specifically incorporated into plasma HDL, whereas MLV-derived *Chol incorporation into plasma lipoproteins was similar to direct *Chol incorporation, consistent with apoA-I-mediated remodeling of fluorescent MLV to HDL with concomitant exchange of *Chol between lipoproteins. Based on these findings, we developed a model system to study lipid transfer by depositing fluorescent *PE and *Chol-labeled on calcium silicate hydrate crystals, forming dense lipid-coated donor particles that are readily separated from acceptor lipoprotein particles by low-speed centrifugation. Transfer of *PE from donor particles to mouse plasma lipoproteins was shown to be HDL-specific and apoA-I-dependent. Transfer of donor particle *PE and *Chol to HDL in whole human plasma was highly correlated. Taken together, these studies suggest that cell-free *PE efflux monitors apoA-I functionality.