Efficacy and Safety of Renal Tubule Cell Therapy for Acute Renal Failure

Abstract

The mortality rate for patients with acute renal failure (ARF) remains unacceptably high. Although dialysis removes waste products and corrects fluid imbalance, it does not perform the absorptive, metabolic, endocrine, and immunologic functions of normal renal tubule cells. The renal tubule assist device (RAD) is composed of a conventional hemofilter lined by monolayers of renal cells. For testing whether short-term (up to 72 h) treatment with the RAD would improve survival in patients with ARF compared with conventional continuous renal replacement therapy (CRRT), a Phase II, multicenter, randomized, controlled, open-label trial involving 58 patients who had ARF and required CRRT was performed. Forty patients received continuous venovenous hemofiltration ϩ RAD, and 18 received CRRT alone. The primary efficacy end point was all-cause mortality at 28 d; additional end points included all-cause mortality at 90 and 180 d, time to recovery of renal function, time to intensive care unit and hospital discharge, and safety. At day 28, the mortality rate was 33% in the RAD group and 61% in the CRRT group. Kaplan-Meier analysis revealed that survival through day 180 was significantly improved in the RAD group, and Cox proportional hazards models suggested that the risk for death was approximately 50% of that observed in the CRRT-alone group. RAD therapy was also associated with more rapid recovery of kidney function, was well tolerated, and had the expected adverse event profile for critically ill patients with ARF. Acute renal failure (ARF) arising from acute kidney injury (AKI) and acute tubular necrosis (ATN) secondary to nephrotoxic and/or ischemic renal tubule cell injury commonly results in a cascade of events culminating in multiorgan failure and death. Mortality rates from AKI requiring renal replacement therapy range from 50 to 70%. 1,2 This high mortality rate has persisted over the past several decades despite greater understanding of the pathophysiology of the disorder and improvements in hemodialysis and hemofiltration therapy.The pathophysiology of this disease is initiated with injury to the cellular elements of the kidney,

Challenges and Advances in the Treatment of AKI

“…A phase II, multicenter, randomized trial involving 58 patients with AKI and who had required continuous RRT (CRRT) demonstrated that, at 28 days, the mortality was 33% in the RAD group and 61% in the CRRT group. 34 The Kaplan-Meier analysis revealed that survival through day 180 was significantly improved in the RAD group, and the Cox proportional hazard model suggested that the risk for death was approximately 50% of that observed in the CRRT-alone group. Tumlin et al reported substantial improvement in patients' outcomes over standard-care therapy with the use of a selective cytophoretic device.…”

Detrimental Cross-Talk Between Sepsis and Acute Kidney Injury: New Pathogenic Mechanisms, Early Biomarkers and Targeted Therapies

“…− , and glucose, as well as the excretion of ammonia and normal levels of 1,25-OH-vitamin D3 [50]. Moreover, the RAD modulates systemic inflammation by regulating circulating levels of several cytokines.…”

Renal replacement therapy review

“…150,155 This more "complete" renal replacement was felt to be safe 151 and to convey 180 day survival and return of renal function benefits to a small group of ICU patients enrolled in an open-label trial for CVVH with RAD augmentation. 156 Phase III trials have not been published but are planned according to the authors. However, the RAD is a long way from the criteria for ultimate renal replacement support, as it is used in conjunction with standard, machine-based hemofiltration whereby the ultrafiltrate is shuttled through the RAD with reclamation of approximately 25% of solute and fluid prior to return to the patient.…”