Cell therapy with a tissue-engineered kidney reduces the multiple-organ consequences of septic shock

Humes, H. David; Buffington, Deborah A.; Lou, Liandi; Abrishami, Simin; Wang, Min; Xia, Jun; Fissell, William H.

doi:10.1097/01.ccm.0000089644.70597.c1

Cited by 71 publications

(40 citation statements)

References 53 publications

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“…Plasma levels of HCO 3 Ϫ , P i , and K ϩ were maintained nearer to normal values; glucose, HCO 3 Ϫ , and K ϩ active transport as well as ammonia excretion, glutathione processing, and 25-hydroxyvitamin D 3 conversion were demonstrated (Humes et al, 1999a. Furthermore, in canine and porcine models of ARF with septic shock, RAD treatment was shown to modulate plasma cytokine levels, maintain better cardiovascular performance (as determined by cardiac output and renal blood flow), and increase survival times Humes et al, 2003).…”

Section: Full Renal Replacementmentioning

confidence: 95%

Stem Cell Approaches for the Treatment of Renal Failure

Brodie

Humes

2005

Pharmacol Rev

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Section: Full Renal Replacementmentioning

confidence: 95%

Stem Cell Approaches for the Treatment of Renal Failure

Brodie

Humes

2005

Pharmacol Rev

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“…Candidate biological markers that are known to be dysregulated in ESRD, correlated with poor outcome and linked to known mechanisms of disease, are markers of inflammation and oxidative stress. Pre-clinical animal models of septic shock have shown that treatment with a device containing metabolically active kidney cells decreases levels of inflammatory peptides compared with a sham device [45].…”

Section: Discussionmentioning

confidence: 99%

Renal Cell Therapy in the Treatment of Patients with Acute and Chronic Renal Failure

Humes

Weitzel

Fissell³

2004

Blood Purif

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Hemodialysis and hemofiltration have been important technologies in saving the lives of patients with acute (ARF) and chronic renal failure by clearing small solutes from plasma and thereby preventing death from acidemia, hyperkalemia, volume overload, and uremia. These therapeutic approaches, however, are still suboptimal, as patients with ARF have mortality rates exceeding 50%, and patients with end-stage renal disease (ESRD) have, on average, a life expectancy of 4–5 years. The preeminent cause of death in patients with ARF is the development of sepsis or the systemic inflammatory response syndrome with resulting systemic vasodilation, hypotension, ischemic injury to solid organs, multi-organ failure, and death. This vasodilation is due to persistent and excessive pro-inflammation. Similarly, the reduced survival times of patients with ESRD on chronic dialysis have been associated with a persistent and chronic systemic pro-inflammatory state. We have hypothesized that the loss of renal tubule cell mass acutely in acute tubule necrosis and chronically in ESRD results in an immunologically dysregulated state leading to excessive pro-inflammation. The replacement of renal tubule cell function may thus change the current dismal prognosis of patients with these disorders. In this regard, this report presents the first patient ever treated with a bioartificial kidney consisting of a synthetic hemofilter in series with a renal tubule assist device (RAD) containing approximately 10⁹ human renal tubule cells. This treatment in a critically ill patient with multi-organ failure and ARF in the intensive care unit was associated temporally with improved cardiovascular parameters and enhanced native kidney function. Multiple systemic plasma cytokine levels and gene expression profiles of peripheral white blood cells were also temporally changed with cell therapy. Clinical trials in patients suffering from either ARF or ESRD are currently ongoing to evaluate the influence of the RAD on the inflammatory response in these groups of patients.

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“…In vitro and ex vivo tests of renal assist devices have been conducted of animals and critically ill patients, with promising results that include better cardiovascular and hemodynamic parameters and improved survival (18 -20). Of particular interest is the potential differential beneficial effect in patients with acute kidney injury associated with sepsis (21)(22)(23)(24)(25).…”

Section: Living Membranes and Bioartificial Kidneymentioning

confidence: 99%

Technological Advances in Renal Replacement Therapy

Rastogi

Nissenson²

2009

Clinical Journal of the American Society of Nephrology

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The worldwide epidemic of chronic kidney disease shows no signs of abating in the near future. Current dialysis forms of renal replacement therapy (RRT), even though successful in sustaining life and improving quality of life somewhat for patients with ESRD, have many limitations that result in still unacceptably high morbidity and mortality. Transplantation is an excellent option but is limited by the scarcity of organs. An ideal form of RRT would mimic the functions of natural kidneys and be transparent to the patient, as well as affordable to society. Recent advances in technology, although generally in early stages of development, might achieve these goals. The application of nanotechnology, microfluidics, bioreactors with kidney cells, and miniaturized sorbent systems to regenerate dialysate makes clinical reality seem closer than ever before. Finally, stem cells hold much promise, both for kidney disease and as a source of tissues and organs. In summary, nephrology is at an exciting crossroad with the application of innovative and novel technologies to RRT that hold considerable promise for the near future.Clin J Am Soc Nephrol 4: S132-S136, 2009. doi: 10.2215/CJN.02860409 T he ongoing worldwide epidemic of chronic kidney disease (CKD) includes ESRD. According to recent US Renal Data System estimates, more than 900,000 patients worldwide have ESRD and are on renal replacement therapy (RRT) (1). The majority of these patients are on intermittent, diffusion-based hemodialysis (HD), with only a relatively small fraction able to receive kidney transplants because of the scarcity of available donor organs.Even though dialysis is touted as the only currently available successful therapy that replaces the functions of an organ ex vivo, it has several limitations. The advent of clinical dialysis in the 1950s has had a huge impact on the way in which ESRD and acute kidney failure are managed, but several decades later, the morbidity and mortality in patients with ESRD remain unacceptably high (1). One possible reason is that the equivalent clearance provided by three-times-a-week conventional HD or typical continuous ambulatory peritoneal dialysis (PD) is barely 15 to 20 ml/min, and the treatment by any criterion is unphysiologic (2). At the same time, the quality of life of patients who are on dialysis has remained suboptimal, and the cost of these procedures has remained high.Several attempts have been made to prove intramuscularly the efficiency of dialysis and outcomes in patients. In HD, these attempts include more biocompatible membranes, high-flux and high-efficiency membranes, more frequent and longer duration of dialysis, use of convective forms of therapy, and use of more user-friendly delivery systems. In PD, introduction of automated cyclers has improved convenience of the technique for some patients, increased the practical volume of dialysate, and, therefore, increased solute clearance and ultrafiltration capacity; however, none of these advances has had a substantial impact on patient outcomes.An ide...

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Cell therapy with a tissue-engineered kidney reduces the multiple-organ consequences of septic shock

Cited by 71 publications

References 53 publications

Stem Cell Approaches for the Treatment of Renal Failure

Stem Cell Approaches for the Treatment of Renal Failure

Renal Cell Therapy in the Treatment of Patients with Acute and Chronic Renal Failure

Technological Advances in Renal Replacement Therapy

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