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D:\FILES\Review Articles\Internal Med Review\Dialysis and Transplantation.wpd
Dialysis and Transplantation in the Treatment of Renal Failure
Dialysis and
transplantation
are life-prolonging therapies for many patients with renal insufficiency. The term
end-stage renal disease 
(ESRD) describes the late stages of chronic renal failure. Initially, patients with ESRD are managed with conservativetherapy, but eventually they require hemodialysis, peritoneal dialysis, and/or
transplantation
. Because of limited success witheach of these modalities, chronic renal failure should be approached with the concept of moving from one form of therapy toanother as indicated by the degree of success and incidence of complications with each. Therapy for renal failure should
not 
be initiated when the patient is totally asymptomatic; however, dialysis and/or transplant should be started sufficiently early toprevent serious complications. Early dialysis is appropriate in patients with acute renal failure in whom resumption of renalfunction can be expected and in patients with chronic renal failure who have a good immunologic match with a related donorand are to be transplanted without prior long-term dialysis. In the remainder of patients, the clinical judgment to move fromconservative treatment to dialysis or
transplantation
is determined by the patient's quality of life and whether or not the benefitsof treatment outweigh the risks.The correlation of uremic symptoms with renal function varies from patient to patient depending on the cause of renal disease(earlier onset of symptoms in subjects with diabetes mellitus), muscle mass (large, muscular patients tolerate high levels ofazotemia), diet, nutritional status, and coexisting conditions. Therefore, it is ill-advised to assign a certain "usual" level of bloodurea nitrogen, serum creatinine, or glomerular filtration rate to the need to start dialysis. In the United States, the Health CareFinancing Administration has assigned levels of creatinine and creatinine clearance to qualify for reimbursement from Medicarefor patients receiving dialysis. The creatinine must be greater than or equal to 8.0 mg/dL (700 umol/L) and the creatinineclearance must be less than or equal to 10 mL/min (0.17 mL/s). The recently introduced regulations will undoubtedly affectphysician practice. Treatment with dietary protein restriction and aggressive control of hypertension, may prolong the time beforethe need for dialysis and/or
transplantation
but should be carried out only if complications of such therapy, specificallymalnutrition, do not occur.
DIALYSIS AND/OR TRANSPLANTATION
Selection of patients to receive dialysis and/or
transplantation
is a matter of some debate. Because of the reversible natureof acute renal failure, all patients with this diagnosis should be supported with dialysis, at least for some period of time, to allowreturn of renal function. In patients with irreversible or chronic renal failure, criteria for selection for
transplantation
aregenerally more stringent than those for dialysis (see below) and are guided by the possibility of complications related toimmunosuppressive therapy.
Transplantation
should be undertaken only when conservative treatment has failed, when thereare no reversible elements in the renal failure, and when the patient is too ill to be maintained comfortably with the usualmethods of treatment. However, morbidity is less if
transplantation
is performed before the patient is critically ill.
Transplantation
should not be utilized in an attempt to salvage patients, particularly the elderly, from failure to thrive ondialysis.The recipient should be free of life-threatening extrarenal complications such as cancer, severe coronary artery disease, andcerebrovascular disease. Provided that diffuse vascular involvement is not present, diabetes mellitus is not a contraindication.Oxalosis may recur in relatively short order in a transplanted
kidney
and is generally a contraindication for
transplantation
.Although advanced age may be a limiting factor, it is advanced "physiologic" rather than chronologic age that contraindicates
transplantation
. In general, patients reach a "physiologic" limit at approximately age 60 to 65 years, when the incidence ofcomplications due to glucocorticoids becomes much higher. Although abnormalities of the bladder and urethra present additional
 
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D:\FILES\Review Articles\Internal Med Review\Dialysis and Transplantation.wpdhazards, successful renal allografts have been placed in patients with these abnormalities by prior constitution of an artificialbladder (i.e., ileal conduit) into which the donor ureter is placed. Patients with any disease process that may be aggravated byglucocorticoids, cyclosporine, azathioprine, or other immunosuppressive agents or any patient with coexisting medical conditionsso severe that the risks of operation and drug therapy are high should not be offered
transplantation
.Criteria for treatment with hemodialysis or peritoneal dialysis are more liberal because dialysis has less morbidity than
transplantation
in older patients with the aforementioned medical complications. Because of the cost of these programs, somehave suggested that entry be restricted in patients of advanced age. Such decisions, based on moral, social, and economicissues, continue to be debated. In general, in the United States and some other countries, nearly all patients are accepted fordialysis if they or their families desire prolongation of life. The physician should inform the patient of the likelihood of successand review the complications and untoward effects. The patient and family should be given an estimate of prognosis andexpected quality of life. In most areas of the world, the cost of medical care for chronic renal failure is borne by government.In the United States, the mechanism of coverage is by Medicare, with all patients eligible regardless of age.
PREPARATION FOR THERAPY OF END-STAGE RENAL DISEASE
While conservative measures are being carried out in patients with chronic renal failure, it is important to prepare them with anintensive educational program, explaining the likelihood and timing of complete renal failure and the various forms of therapyavailable. The more knowledgeable patients are concerning hemodialysis, peritoneal dialysis, and
transplantation
, the easierand more appropriate will be their decisions at a later time. With hemodialysis, the major method of obtaining blood for treatmentis from an arteriovenous fistula. Since these devices often take months to develop, prophylactic placement of a fistula in apatient opting for hemodialysis is important in minimizing future complications of circulatory access. For those who selectperitoneal dialysis [continuous ambulatory peritoneal dialysis (CAPD) or continuous cyclic peritoneal dialysis (CCPD)], placementof the peritoneal catheter does not require prior preparation, and catheter placement and peritoneal dialysis can be institutedwhen uremic signs and symptoms develop. In those who may perform home dialysis or undergo
transplantation
, earlyeducation of family members for selection and preparation as a home dialysis helper or a related donor for
transplantation
should occur before the onset of symptomatic renal failure.In patients who have a good antigenic match with a willing donor,
transplantation
without intervening hemodialysis or peritonealdialysis should be considered. Approximately 25 percent of patients receiving renal transplants at our institution do so withouthaving had prior dialysis. In considering related-donor
transplantation
, the risk of unilateral nephrectomy in the donor, includingdevelopment of proteinuria and hypertension, should be considered by the family. As discussed below, the success rate ofcadaver-donor
transplantation
has improved sufficiently that this form of therapy should be considered both by the patient andby potential donors. Early referral of patients to ESRD programs will allow education of the patient and family and preparationfor an appropriate therapy. In recent years, unrelated living donors have become acceptable in most programs.
DIALYSISHEMODIALYSIS
Hemodialysis employs the process of diffusion across a semipermeable membrane to remove unwanted substances from theblood while adding desirable components. A constant flow of blood on one side of the membrane and a cleansing solution(dialysate) on the other allow removal of waste products by diffusive and convective transport. By altering the composition of
 
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D:\FILES\Review Articles\Internal Med Review\Dialysis and Transplantation.wpdthe dialysate, the method of exposure of blood and dialysate (geometry of the dialyzer), the type and surface area of dialysismembrane, and the frequency and duration of exposure (the dialysis prescription), patients without renal function can bemaintained in a relatively healthy state.Hemodialysis equipment consists of three components
:
the blood delivery system, the composition and delivery system of thedialysate, and the dialyzer itself. Blood is pumped to the dialyzer by a roller pump through lines with appropriate equipment tomeasure flow and pressures within the system; blood flow should be approximately 300 to 450 mL/min. Negative hydrostaticpressure on the dialysate side of the system can be manipulated to achieve desirable fluid removal, so-called ultrafiltration.Dialysis membranes have differing ultrafiltration coefficients (i.e., mL removed per mmHg/min), the selection of which, alongwith the hydrostatic pressure changes, determines fluid removal. The dialysate is delivered to the dialyzer from a storage tankor proportioning system that manufactures dialysate on-line. In most systems, dialysate passes once across the membrane,countercurrent to blood flow at a rate of 500 mL/min. The composition of the dialysate is similar to normal plasma water but maybe altered depending on need. The dialysate potassium is varied most often; the concentration of calcium, chloride, andbicarbonate generally remain unchanged in each dialysis unit. Sodium concentration may be varied during the course of dialysis(sodium modeling) in order to optimize fluid removal.The principal dialyzer in use in the United States is the hollow fiber or capillary dialyzer, in which membrane material is spuninto fine capillaries, thousands of which are packed into bundles with blood flowing through the capillaries while dialysate iscirculated on the outside of the fiber bundle. The type of membrane and surface area (size) are determinants of ultrafiltrationand clearance and are important in the immunologic (i.e., biocompatible) response by the patient. Cuprophan (Cupra-ammoniumcellophane) and cellulose acetate are "tighter" membranes with less diffusive and ultrafiltration capabilities and lessbiocompatibility. Polyacrylnitrile, polymethylmethacrylate, polysulphon, and certain newer cellulose derivatives are porous (highflux) and more biocompatible but are more expensive.With current dialysis techniques, most patients require between 9 and 12 h of dialysis per week, equally divided into severalsessions. The time depends on body size, residual renal function, dietary intake, complicating illnesses, and degree of anabolismor catabolism. The dialysis duration, frequency of treatments, type and size of dialyzer, dialysate composition, and blood ordialysate flow may all be altered to accomplish specific needs).Urea kinetic modeling is a technique to measure the delivered dose of dialysis. This may be determined by use of a pre- andpostdialysis urea sample [urea reduction ratio (URR)] or by determining the
KT/V 
(
K 
= clearance,
T 
= dialysis time, and
V 
=volume of distribution of the patient), which is a dimensionless measure of treatment. An acceptable URR is 65 percent, whichis equivalent to a
KT/V 
of approximately 1.0 to 1.2. The development of bicarbonate dialysis, sodium modeling, and high-fluxor ultraefficient membranes has resulted in the ability to reduce dialysis time. It is mandatory, however, that such decreasesin dialysis time be monitored by one of the above measures of adequacy. Reduction of dialysis time without documentation ofadequacy of treatment is associated with an increased mortality and morbidity.In addition to hemodialysis, a new method of treatment has been developed for patients with acute renal failure. Slow continuousultrafiltration, continuous arteriovenous hemodialysis (CAVHD), or continuous venovenous hemodialysis (CVVHD) aretechniques that employ high-efficiency dialyzers with continuous treatment utilizing very low blood and dialysate flow rates.These therapies are useful in the unstable, acute renal failure patient and are often preferable to intermittent hemodialysis.
Complications Of Hemodialysis
Complications of chronic dialysis should be thought of as those related to unresolved uremia,direct complications of clearance and ultrafiltration, and complications created by long-term dialytic treatment. Complications
of 00

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