PURPOSE Over 80% of US patients initiate HD with a tunneled dialysis catheter (TDC). Published data on TDC outcomes are based on a case-mix of prevalent and incident TDCs. We analyzed factors affecting patency and complications of first TDCs ever placed in a large cohort of incident HD patients. MATERIALS AND METHODS We retrospectively queried a prospective, computerized vascular access database to identify 472 patients receiving a first ever TDC. Multiple variable survival analysis was used to identify clinical parameters affecting TDC patency (from placement to non-elective removal) and infection (from placement to first episode of catheter-related bacteremia). RESULTS The median patency of all TDCs was 202 days. Left-sided placement of TDCs was the only variable associated with inferior TDC patency (hazard ratio 1.98; 95% CI, 1.39–2.81, p<0.0001). The 6-month TDC patency was 37% for left interval jugular (LIJ) vein catheters vs 54% for right internal jugular (RIJ) vein catheters. The one-year patency was 6% for LIJ catheters vs 35% for RIJ catheters. Catheter patency was not associated with patient age, sex, race, hypertension, diabetes, coronary artery disease, peripheral vascular disease, cerebrovascular disease, or heart failure. The median time to the first episode of catheter-related bacteremia was 163 days. None of the clinical variables was associated with TDC infection. CONCLUSIONS TDCs are plagued by high rates of infection. Right IJ vein TDC should be used preferentially to maximize catheter patency.

Renal fibrosis is a common pathogenic response to injury in chronic kidney disease (CKD). The receptor-interacting protein kinase-3 (RIPK3), a regulator of necroptosis, has been implicated in disease pathogenesis. In mice subjected to unilateral ureteral obstruction-induced (UUO-induced) or adenine diet-induced (AD-induced) renal fibrosis, models of progressive kidney fibrosis, we demonstrate increased kidney expression of RIPK3. Mice genetically deficient in RIPK3 displayed decreased kidney fibrosis and improved kidney function relative to WT mice when challenged with UUO or AD. In contrast, mice genetically deficient in mixed-lineage kinase domain-like protein (MLKL), a downstream RIPK3 target, were not protected from UUO-induced kidney fibrosis. We demonstrate a pathway by which RIPK3 promotes fibrogenesis through the AKT-dependent activation of ATP citrate lyase (ACL). Genetic or chemical inhibition of RIPK3 suppressed the phosphorylation of AKT and ACL in response to TGF-β1 in fibroblasts. Inhibition of AKT or ACL suppressed TGF-β1-dependent extracellular matrix production and myofibroblast differentiation in fibroblasts. Pharmacological inhibition of ACL suppressed UUO-induced kidney fibrosis. RIPK3 expression was highly regulated in human CKD kidney. In conclusion, we identify a pathway by which RIPK3 promotes kidney fibrosis independently of MLKL-dependent necroptosis as a promising therapeutic target in CKD.

There is a growing recognition of the complex interplay between renal cell cancer (RCC), kidney function, mechanical reduction of nephron mass, and systemic agents targeting the cancer. Earlier detection of RCC and rising life expectancy of cancer survivors places a greater emphasis on preservation of renal function after cancer resection and during systemic therapy. Unique adverse effects associated with RCC drugs not only help reveal cancer pathophysiology but also expand our knowledge of normal cell signaling and metabolism. In this review, we outline our current understanding of RCC biology and treatment, their bidirectional relationship with kidney function, and unmet research needs in this field.

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Background Central venous catheters are frequently used for hemodialysis vascular access while patients await placement and maturation of an arteriovenous (AV) fistula or graft. Catheters may cause central vein stenosis, which can adversely affect vascular access outcomes. We compared the vascular access outcomes in patients with a history of ipsilateral and contralateral dialysis catheters. Study design Retrospective analysis of a prospective computerized vascular access database. Setting & Participants Patients at a large medical center who initiated hemodialysis with a catheter and subsequently received a fistula (n=233) or graft (n=89). Predictor History of central venous catheter placement ipsilateral vs. contralateral to the AV fistula or graft. Outcome & Measurements Primary access failure (access never suitable for dialysis) and cumulative access survival (time from successful cannulation until permanent access failure). Results Among patients receiving a fistula, the primary failure rate was similar for those with ipsilateral and contralateral catheters (50 vs 53%; HR, 0.94; 95% CI, 0.71–1.26; p=0.7), and the time to fistula maturation was similar (101±41 vs 107±39 days, p=0.5). However, the cumulative fistula survival was inferior in patients with ipsilateral catheters (HR, 2.48; 95% CI, 1.33–7.33; p=0.009). Among patients receiving a graft, the primary failure rate was similar for those with ipsilateral and contralateral catheter (35 vs 38%; HR, 0.92; 95% CI, 0.49–1.73; p=0.8), but the cumulative graft survival tended to be shorter with ipsilateral catheters (HR, 2.04; 95% CI, 0.92–5.38; p=0.07) Limitations Retrospective analysis, single medical center. Conclusions The primary failure rate of fistulas and grafts is not affected by the presence of an ipsilateral catheter. However, cumulative access survival is inferior in patients with prior ipsilateral catheters. Avoidance of ipsilateral catheters may improve long–term vascular access survival.