[Renal replacement therapy by hemodialysis: an overview]

Claude Jacobs
Néphrologie & Thérapeutique 2009, 5 (4): 306-12
The replacement of renal function by hemodialysis (HD) demonstrated for the first time that at least the most vital functions of a complex organ could be replaced by a man-made device. The Founding Father of dialysis is the Scottish chemist Thomas Graham who in 1861 found that colloid and crystalloid substances contained in fluids could be separated by diffusion of crystalloids through vegetable parchment acting as a semipermeable membrane. He coined this phenomenon as "dialysis". Fifty years later, using collodion as dialysis membrane and hirudin as anticoagulant (ATG), Abel et al. in Baltimore performed the first dialysis in dogs with a "vivi-diffusion" apparatus shortly after named "artificial kidney"(AK). In 1924, Haas in Germany treated for the first time uremia in man with dialysis using a collodion membrane and a new ATG: "heparin". Disappointed by unsuccessful results achieved with HD, Haas gave up his trials in 1928. HD revived in the early forties when Willem Kolff in the Netherlands built a "rotating drum kidney" using cellophane as dialysis membrane. The first recovery of a patient undergoing HD for acute renal failure (ARF) was reported by Kolff in 1945, paving the way for a rapidly worldwide expanding treatment of ARF with dialysis. The concept of applying HD to patients with end-stage chronic renal failure (ESRF), first pioneered by Alwall in Sweden as far back as 1948, became reality in 1960 when Scribner, Quinton et al. designed an external arteriovenous by pass made of Teflon tubing which allowed a permanent access to the bloodstream without requirement of permanent anticoagulation. The Teflon AV shunt, later improved with the use of a silicone rubber material (Silastic) has been the cornerstone for implementing the long-term treatment of ESRF patients with maintenance HD. The next major breakthrough in this area consisted in the surgically created AV fistula performed in 1966 by Cimino, Brescia et al. which considerably reduced the complications encountered with AV shunts. During the following decades technical advances rendered HD safer and easier thus allowing its management by patients themselves in their home. The concept of HD therapy being assimilated with a pharmacological treatment led to its rationalised prescription and the evaluation of its "adequacy" with the use of a normalised efficiency index (Kt/V). The long-term survival of HD-treated ESRF patients revealed previously unknown numerous clinical symptoms and complications. Many of them turned out as being linked to the global "unphysiology" of HD therapy due to the absence of the regulatory functions of the normal kidney and also to the iatrogenic adverse effects generated by various components of dialysis systems. Clinical and laboratory research attempted at identifying "uremic toxins" of various molecular size and stimulated the development of dialysis strategies aimed at their optimal removal by more biocompatible membranes designed for both diffusive and convective procedures and for reducing the chronic inflammatory state involved in several pathological manifestations of HD patients. The availability in the late eighties of human recombinant erythropoietin as treatment of uremic anemia greatly improved the quality of life of HD patients. HD will continue to be by far the most widely used treatment for patients with ARF and ESRF for many years to come. Most promising developments currently in progress, using optimal miniaturization and nanotechnologies, aim at adding a unit with regulatory "tubular" functions to the filtration "glomerular" process provided by the current AK systems, both being ultimately contained in a single, wearable, implantable device which would thus perform functions closer to that ensured by the normal kidney. Year 2009 is in no way "the end of History" of dialysis therapy for renal failure.

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