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Introduction

Before the 1960s, death within days to weeks was inevitable in irreversible advanced uremia with the exception of recipients of kidney transplants from monozygotic twin donors, and the limited life extension afforded by tentative trials of cadaveric renal transplants. Over the next decade (1961-1970), the introduction of maintenance hemodialysis, intermittent peritoneal dialysis, and the combination of azathioprine and predisone in immunosuppressive regimens for renal transplantation established a choice for physician and patients of three different effective regiments, each capable of prolonging life in renal failure for years. Between 1971 and 1980, the technique of peritoneal dialysis was enhanced and modified to permit the patients to perform self -dialysis, either manually as CAPD or assisted as CCPD. At the same time, the introduction of cyclosporine for immunosuppression substantially improved the outcome of cadaveric renal transplantation. By the 1990's therefore the determination to treat chronic uremia entailed a series of decisions as to when and by what means therapy should be initiated.

Ideally, planning for treatment of ESRD ought to be contingent on selection by the physician-patient team of one or more modalities thought suitable to the patient’s whishes and real life circumstances. Determining when in the inexorable decline in renal function to start dialytic therapy or perform a renal transplantation is a key decision required for each patient approaching ESRD. No single guideline provides an answer for all patients.

 
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General indications to initiate renal replacement therapy

  1. Circulatory overload, congestive heart failure, or severe refractory hypertension.

  2. Neuropathy if severe, especially if fulminant motor neuropathy.

  3. Pericarditis, especially if substantial effusion.

  4. Osteodystrophy.

  5. Diabetic retinopathy if severe or progressive.

  6. Severe diabetic neuropathy, gastropathy or vascular disease.

  7. Progressive physical debility or malnutrition.

  8. Creatinine clearance < 4 ml/min.

  9. Bleeding diathesis.

  10. Non-compliant patient (danger of death from hyperkalemia or other complications).

  11. Progressive psychosis.

  12. No acceptable state of well-being or ability to work.

Choice of therapy

A. Hemodialysis:

Hemodialysis required access to the blood stream of removal and return of blood at a rate sufficient to effect clearance of uremic metabolites. The preferred hemaoaccess is a Brescia-Cimino internal fistula in which the radial artery is attached to the cephalic vein at the wrist. An interposition micropouous Teflon (Goretex) conduit may be placed in many locations, most commonly as a U-shaped conduit from the radial artery at the antecubitum to an antecubital vein. Bicarbonate dialysate is now widely employed. Dialysate composition can be varied to some extent to meet individual patient needs, particularly with regard to the concentration of potassium. The dialyzer consists of a semi-permeable membrane that separates the blood from the dialysate. The membranes are all quite permeable to small molecules but vary in their permeability to middle-sized molecules and in their ultrafiltration coefficients. Moderately permeable membranes and rapid rates of blood flow are often employed to increase the efficiency of hemodialysis and shorten the time of each treatment for patient and staff convenience. Very highly permeable membranes with high blood blow are sometimes employed in the belief that greater clearance of "middle" molecules may improve health.

  1. Efficacy, rehabilitation, and adequacy of dialysis Hemodialysis substantially prolongs life and invariably but reasonably restores health. A minority of patients feels entirely well, and their lives are primarily disrupted by the time required for treatment and for medical evaluation and supervision. The vast majority of patients are well enough to enjoy reasonably normal lives, and half continue full-time work, school or retirement activities.

    However, the adequacy of dialysis for an individual patient is difficult to assess particularly since some problems of under dialysis may be asymptomatic for long periods and may take years to develop. Nevertheless, clinical assessment of the control of uremic manifestations is a periodic necessity. it is also evident that different patients may benefit from somewhat different treatment regimens. By measuring generation and residual renal function and knowing dialyzer clearance, one may determine by computed mathematical computation the dialysis requirement of an individual patient. This "Kinetic modeling" allows the physician to prescribe an appropriate dialyzer and the protein intake, blood flow, and duration of dialysis thought to be optimal for an individual patient.

  2. Morbidity and Mortality from chronic hemodialysis
    Most patients undergoing chronic hemodialysis require periodic hospitalization or vascular access surgery, and some require hospitalization for intercurrent illness, but few are hospitalized for problems related directly to dialysis. A study several years ago revealed that following initial stabilization on dialysim patients spent a mean of 2 to 3 days per month (a median of 1 day/month) in the hospital. The same study revealed the leading causes of death to be sepsis; cardiac arrhythmia failure, or infraction, and stroke. Less than 1 patient in 10 died from dialysis or took his or her life. Nearly a third of deaths occurred in the first month of dialysis. Ten to twenty percent of patients died each year thereafter. This percentage has risen in recent years as more patients with diabetes and more elderly patients have been accepted for dialysis.

B. Chronic peritoneal dialysis:

The Conceptual change from chronic intermittent peritoneal dialysis to chronic continuous peritoneal dialysis and technologic improvements in dialysate bags, tubing, and tubing connectors (and a cycling machine for those who prefer the majority of exchanges to be performed at night) have made chronic peritoneal dialysis a fully acceptable alternative to transplantation or hemodialysis. In general, peritoneal dialysis is also preferable to hemodialysis. If the patient is an infant or if hemodialysis is not possible (lack of vascular access) or dangerous cardiovascular instability exists, or if the patient finds the side effects of hemodialysis too unpleasant.

  1. Continuous ambulatory peritoneal dialysis (CAPD)  
    is a technique in which three to five dialysis exchanges, usually of 2 to 3 liters, are performed each day emplying dialysate with varying concentrations of glucose as required to achieve ultrafiltration to remove ingested fluid and to thereby maintain body fluid balance. Dialysate is supplied in plastic bags of varied size and is infused and drained by gravity. This technique requires no machinery, no assistant, and only a short training period, and it is the least expensive form of dialysis.

  2. Continuous cycling peritoneal dalysis (CCPD)  
    relies on a cycling device for automatic delivery and drainage of a number of exchange of 2 liters in the nocturnal phase of 8 hours, followed by one 1-leter diurnal exchange of 16 hours.

    Morbidity and mortality of patients on chronic peritoneal dialysis: Much of the current assessment of peritoneal dialysis is derived from the National CAPD Registry, which has data from 1981 to the present. Peritonitis (turbid fluid with > 100 white blood cells/ul) continues to be the most trouble some complication. As stated before, an average of 1.3 episodes of peritonitis occur per patient per year. Advances in connection devices and technique have reduced to number of episodes and delayed the mean time of onset of first episode of peritonitis to 8.8 months. Twenty-seven percent of patients who transfer from peritoneal dialysis to hemodialysis do so because of peritonitis. Only 9 percent transfer because of exit site or tunnel infection. Although infections claim a large morbidity, 15 percent of transfers to hemodialysis are attributed to the stresses of self-dialisys on patient and family and their inability to cope.

C. Renal transplantation:

Major advances in transplantation in the past 15 years have decreased mortality and increases graft retention to the extent that transplantation is now preferable to dialysis for most patients between the ages of 1 and 70 years save those with contraindications. These advances include restraint in immunosuppressive therapy (especially that given for acute rejection episodes), the introduction of cyclosporine, DR histocompatiblity matching.



Morbidity and mortality of transplantation

Currently Many studies on the mortality of transplant and dialysis patients revealed significantly better survival in patients transplanted with a graft from a living related donor (98% at 1 year, 75% at 5 years) than in those transplanted with a cadaveric graft (85% at 1 years treated with azathioporine and prednisone) or in those undergoing chronic hemodialysis (90% at 1 year, 55% at 5 years). The differences in survival between cadaveric transplant and chronic hemodialysis were not significant in the past but appear to be today. This improvement in survival of cadaveric trasplant patients has occurred in association with the use of cyclosporine.