Hemodialysis and Hemofiltration

1. INTRODUCTIONReplacement of renal function through artiﬁcial meanswas a substantial development in clinical medicine andenabled prolongation of life in diseases formerly almostuniformly fatal. Renal replacement therapies include ex-tracorporeal techniques using artiﬁcial membranes (e.g.,hemodialysis, hemoﬁltration) as well as techniques thatexploit natural membranes (e.g., peritoneal dialysis). Thefocus of this chapter will be on extracorporeal techniques.2. RENAL PHYSIOLOGYThe kidneys play a major role in the regulation of volumeand small solute concentration of extracellular ﬂuid, andthey participate in a number of other physiologic andmetabolic processes (Table 1). Although their weight isonly 0.5% of body weight, they receive approximately 25%of the cardiac output. The functional unit of the kidney forﬂuid and solute transport is the nephron (Fig. 1) whichnumber betweenoneandtwomillionineachkidney.Bloodis presented to the nephron via the afferent arteriole,which branches into the capillary network of the glomer-ulus, then reforms into the efferent arteriole before sup-plying the tubules.2.1. Renal Fluid and Solute HandlingThe nephron accomplishes its tasks by ﬁrst nonselectivelyﬁltering electrolytes and small molecules (but not pro-teins) through its glomerulus, selectively reclaiming ap-propriate amounts of water, electrolytes,and needed smallmolecules through its tubules and collecting system, thenexcreting the unreclaimed portions as urine. The glomer-ular ﬁltration rate in an adult is approximately 125ml/min (180L/day, or about 10 times the extracellular ﬂuidvolume), thus the ability to reclaim needed constituents isparamount.Both water and solute transport take place in thetubules of the nephron. The proximal convoluted tubulereabsorbs 60 to 70% of the ﬁltered water and electrolytesthrough the isoosmotic active transport of sodium into theinterstitial ﬂuid surrounding the tubules. The descendingloop of Henle absorbs an additional 20% of the ﬁlteredwater, driven by a sodium concentration gradient gener-ated by the ascending loop of Henle, which pumps sodiuminto the interstitial ﬂuid but is impermeable to water. Theproximal tubule is exposed to this increased interstitialtonicity, resulting in the water transport. The next adjust-ment of the renal excretion process takes place in thedistal convoluted tubule which also has an active sodiumpump. The ﬁnal adjustment of water balance takes placein the collecting tubule. The tubule is not permeable tosodium but is permeable to water under the control ofantidiuretic hormone (ADH). ADH increases water per-meability through aquaporin-2 channels mediatedthrough the vasopressin-2 (V2) receptor pathway, allow-ing water to move out of the collecting system driven bythe higher sodium concentration in the interstitial tissue.An absence of ADH results in loss of water reabsorption inthe collecting tubules and large increases in urine output,consisting of the 10 to 20% of water volume that is notreabsorbed prior to the collecting tubules.2.2. Renal FailureFailure of the kidneys to handle water and solute removalcan result from a number of insults and is traditionallyclassiﬁed into chronic and acute renal failure. Chronicrenal failure (CRF) is a slowly progressive decline in renalfunction over a period of months to years. While interven-tions can help slow the progression, it is generally anirreversible process. The advanced phase of chronic renalfailure is termed end-stage renal disease (ESRD), whichrequires chronic hemodialysis or renal transplantation for