Renal Failure

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[edit] Renal Failure

Sanford T. Reikes

Kevin J. Martin

[edit] EPIDEMIOLOGY AND ETIOLOGY

Acute renal failure is a commonly encountered problem characterized by a sudden reduction in function that limits the kidney's ability to maintain homeostasis and eliminate nitrogenous waste.Traditionally, causes of acute renal failure have been categorized into those resulting from impaired perfusion of the kidney, those resulting from injury to the nephron itself, and those resulting from the obstruction of urine flow.These broad categories have been termed prerenal, intrinsic, and postrenal acute renal failure, respectively.Clinical setting influences the frequency and etiology of acute renal failure, which complicates 2% to 5% of hospitalizations^[1][2] and is most often due to intrinsic factors, primarily acute tubular necrosis.In contrast, acute renal failure was found in 1% of patients at admission to the hospital, and these cases were most often of a prerenal etiology.^[3]

Chronic renal failure is a syndrome characterized by a slow, progressive decline in glomerular filtration rate (GFR) and other kidney functions.Various adaptations of the diseased kidney limit the clinical manifestations until the loss of kidney function is severe.In practice, it is convenient to divide chronic renal failure into stages such as mild, representing GFRs between 70 ml/min and the normal 120 ml/min; moderate renal insufficiency, representing GFRs from 30 to 70 ml/min; severe renal failure, with GFRs less than 30 ml/min; and end-stage renal disease (ESRD), representing GFRs less than 10 ml/min.

Uremia is the clinical syndrome associated with the retention of the end products of nitrogen metabolism that occurs with severe reductions in renal function.In uremia, the presence of symptoms is unusual before the blood urea nitrogen (BUN) level reaches 60 mg/dl or when the serum creatinine level is 8 mg/dl.

Uremic symptoms are more frequently associated with a BUN level higher than 100 mg/dl and a serum creatinine level higher than 12 mg/dl; the BUN value typically correlates most strongly with uremic symptoms.The metabolic derangements encountered in acute or chronic renal failure result in the dysfunction of several organ systems highlighting the kidney's central role in maintaining the internal environment of the body as a whole.

The overall incidence of new cases of ESRD in the United States is approximately 280 patients per million population annually and has been steadily increasing over the past decade.Approximately 304,000 Americans were receiving chronic dialysis treatment and almost 19,500 renal transplants were performed in 1997.Fig.149-1 depicts the causes of ESRD in the United States, with diabetes mellitus being the most common.^[4]

Figure 149-1 Causes of end-stage renal disease.

[edit] PATHOPHYSIOLOGY

[edit] Acute Renal Failure

Classically in acute renal failure, the GFR is reduced to 1 to 5 ml/min and is associated with a marked fall in urine output to less than 500 ml in 24 hours.The terms oliguria and anuria refer to urine output of less than 500 and 100 ml/day, respectively.Many patients, however, do not have such severe reductions in GFR, and severe acute renal failure may occur without significant reductions in urine output, giving rise to the term nonoliguric acute renal failure.

Renal function is assessed through measurement of the GFR.The normal GFR is 90 to 120 ml/min/1.73 m^[5] of body surface area.Although the measurement of insulin clearance is the “gold standard” for measuring GFR, it is usually more convenient to measure serum creatinine levels and creatinine clearance.An elevated serum creatinine value is frequently the first indication of renal failure, often preceding any overt symptoms.However, serum creatinine measurements must be interpreted with caution, since the proportion of creatinine secreted into the tubule increases as the GFR decreases,resulting in a nonlinear relationship between serum creatinine and GFR and in the overestimation of GFR by the creatinine clearance in the setting of renal impairment.Furthermore, the normal levels of serum creatinine depend on age, sex, and muscle mass, and thus a given level of serum creatinine may reflect a normal GFR in one patient but significant renal failure in another.(See Chapter 144 for further discussion of assessment of renal function.)

Differentiation of the principal causes of acute renal failure (Box 149-1)—prerenal, intrinsic renal, and postrenal—is of extreme importance, since the prognosis and treatment are radically different for each of the three causes.Thus severe acute renal failure from obstruction of the urinary tract requires relief of the obstruction.Acute renal failure caused by a marked reduction in intravascular volume requires treatment with replenishment of the extracellular fluid volume.Analysis of the specific intrinsic renal causes of acute renal failure is also important, since various conditions may be associated with this type of renal failure and require specific evaluation and treatment.

Most cases of acute renal failure occur in the hospital and are related to losses of extracellular fluid volume, the use of nephrotoxic drugs, sepsis or radiographic contrast diagnostic agents, or the effects of surgery or anesthesia.Cases of acute renal failure that occur outside the hospital often produce a great diagnostic challenge; these cases are often serious, and if a definite cause is not readily identifiable (see following discussion) or if the clinical course cannot be easily monitored, prompt referral to a nephrologist for detailed evaluation is required.

The laboratory assessment of acute renal failure is important for distinguishing between prerenal and intrinsic renal causes.In the presence of oliguria, the measurement of the concentrations of sodium and creatinine in serum and urine can provide valuable information regarding the cause of the renal insufficiency.In prerenal acute renal failure, the kidney's normal response is to conserve sodium and water.The conservation of sodium is manifested by a low concentration of sodium in the urine.Water conservation is manifested by an elevated concentration of the nonreabsorbable solute creatinine in the urine compared with the concentration of this solute in plasma; that is, the ratio of urine creatinine to plasma creatinine (U/P creatinine) is high.In the presence of intrinsic renal disease, these adaptations may not occur.Thus the finding of a relatively high urine sodium concentration and a low U/P creatinine ratio usually indicates intrinsic renal disease but is not invariable.These two parameters can be combined to yield the fractional sodium excretion (FE_Na), which has improved diagnostic value and is extremely useful in supporting the diagnosis of prerenal azotemia.The FE_Nais calculated from measurements of serum and urine concentrations of sodium and creatinine as follows:

As illustrated in Table 149-1, an FE_Naless than 1 suggests prerenal conditions, whereas an FE_Nagreater than 1 in the presence of oliguria indicates intrinsic renal insufficiency.Certain clinical situations may result in misleading FE_Navalues.For example, in urinary tract obstruction a wide range of urine sodium concentrations may be found, so obstruction must be excluded directly.In acute glomerular disease, the urinary excretion of sodium may be low, reflecting the marked decrease in GFR with preservation of tubular reabsorption of sodium.Prior administration of diuretics increases the urine sodium levels and renders the value of such determinations useless.If there is preexisting renal disease, the diseased kidney may not be able to reduce the urine sodium concentration maximally in conditions ofdecreased perfusion, resulting in an elevated FE_Nadespite prerenal pathophysiologic conditions.Finally, in metabolic alkalosis with alkaline urine, sodium bicarbonate excretion may raise urine sodium levels, so measurement of urine chloride may yield more useful physiologic information in this circumstance.Some cases of acute renal failure caused by allergic interstitial nephritis or secondary to radiographic contrast or cyclosporine toxicity may have low values for FE_Na.

Table 149-1 Urinary Chemistries in Acute Renal Failure✢

✢Although these laboratory tests are extremely useful, urine is not diagnostic in the following conditions: urinary tract obstruction, acute glomerulonephritis, prior administration of diuretics, preexisting chronic renal disease, and metabolic alkalosis.

[edit] Chronic Renal Failure

Although chronic renal failure may occur as a result of many disorders, the same signs and symptoms occur irrespective of the primary cause of nephron loss, and many of the pathophysiologic adaptations are similar.As the nephrons become damaged, the remaining nephrons undergo compensatory hypertrophy.Thus each tubule undergoes several adaptations in an effort to maintain the composition of the extracellular fluid.Although these adaptations maintain the constancy of the internal environment, the capacity of the residual nephrons to cope with the extremes of salt, water, or potassium excess or deficiency is limited.Thus, until renal insufficiency is severe, adaptations of tubular function can allow the excretion of relatively normal amounts of salt and water.

Serum potassium can be maintained within the normal range until renal insufficiency is severe (GFR <10 ml/min), and phosphorus excretion can be maintained by increasing the levels of parathyroid hormone.Although the increases in parathyroid hormone maintain the levels of phosphorus within the normal range, there are additional consequences of the high levels of this hormone on the skeleton, such as the development of hyperparathyroid bone disease (renal osteodystrophy).

As renal function decreases, the kidney's endocrine functions also become limited.Erythropoietin, which is essential for normal red blood cell (RBC) production, is produced in the kidney.The development of anemia is associated with progressive renal disease as erythropoietin production diminishes.Anemia may occur with reductions of renal function of 30% to 50% of normal values and tends to be progressive unless treated with recombinant erythropoietin.

An additional major endocrine function of the kidney is the production of calcitriol, the active form of vitamin D.As calcitriol levels decrease during progressive renal insufficiency, further stress is placed on efforts to maintain calcium and phosphorus homeostasis, which exaggerates the development of secondary hyperparathyroidism.

Impaired acid excretion by the kidney results in the demineralization of bone tissue directly and through the stimulation of osteoclasts and the inhibition of osteoblasts.^[6] Since alkali is then released from the skeleton, serum pH and bicarbonate concentrations may change little despite the significant dissolution of bone tissue.Since chronic metabolic acidosis and secondary hyperparathyroidism have a synergistic effect resulting in skeletal damage, patients with chronic renal failure are at particular risk for fractures, bone pain, and disfigurement.

[edit] HISTORY

Evaluation of the patient should include a comprehensive clinical history of not only the present complaint but also a previous history of systemic diseases, including those of childhood; a history or family history of hypertension or diabetes; and a careful history of drug ingestion, including over-the-counter medications such as analgesics, nonsteroidal antiinflammatory drugs, herbal or other naturopathic remedies, and other potential nephrotoxins.In women a full gynecologic and obstetric history is also required, including hypertension, proteinuria, or preeclampsia during pregnancy.The occupational history for exposure to potential nephrotoxins may be relevant in certain instances (see Chapter 11 ).Hospitalized patients should be evaluated for recent hypotensive episodes, sepsis, exposure to radiocontrast media or nephrotoxic drugs, and procedures that subject the patient to atheroemboli such as arteriography or surgery of the aorta.

Both acute and chronic renal insufficiency may present in a variety of ways, and the initial manifestations are often mistaken for primary problems in the affected organ system (Box 149-2).Thus patients may have nausea and vomitingthat may be evaluated as peptic ulcer disease but might represent manifestations of uremia.Presentations with vague symptoms such as weakness and tiredness can easily be attributed to anemia, the basis of which could be renal insufficiency.Difficulties with salt and water homeostasis, such as edema or dyspnea on exertion, may be mistaken for a primary cardiac problem.At the other end of the spectrum, significant renal disease may be present without significant clinical manifestations and may be detected only by routine urinalysis, which may reveal the presence of hematuria or proteinuria and should prompt further evaluation.Moderate to severe renal insufficiency may occur in the absence of symptoms.The patient should be asked questions to determine the etiology of acute renal failure (see Box 149-1) as well as its systemic effects.

[edit] PHYSICAL EXAMINATION

A complete physical examination should be performed to evaluate the patient with regard to the etiology of the renal disease and the assessment of complications (Box 149-3).Clues to the etiology of renal disease may be elicited by searching for manifestations of systemic problems such as hypertension, dehydration, diabetes, vasculitis, or leukemia and lymphoma.Hearing impairment may be associated with the hereditary Alport's syndrome.Large bilateral abdominal masses may indicate polycystic kidney disease.Peripheral vascular disease or the presence of abdominal bruits may raise the possibility of atheroembolic renal disease or renal artery stenosis.An enlarged bladder or abnormal prostate or pelvic examination may suggest obstructive uropathy.A rash may point to acute interstitial nephritis, and livedo reticularis is commonly seen in atheroembolic acute renal failure.

The physical examination should strive to assess complications of the chronic renal disease.Assessment of the extracellular fluid volume is important; the patient should be examined for elevation of neck veins, the presence or absence of edema, and ascites.Determination of blood pressure should be performed with the patient lying and standing, and cardiac and lung examinations should be performed.The optic fundi should be examined for evidence of hypertension or diabetes, the skin for bruising or signs of vasculitis, and the bones for tenderness or fracture.Gynecomastia may be seen in men with chronic renal failure, but the incidence of this complication appears to have decreased in recent years.Pericarditis, asterixis, Kussmaul's respirations, ecchymoses, uremic fetor (malodorous breath), and encephalopathy are manifestations of severe uremia.

Some of the presentations of renal disease are serious and require emergency management.Examples of such emergencies would include malignant hypertension; marked decreases in urine output; severe abnormalities in serum chemistries, including hyperkalemia, hypocalcemia, and acidosis; the presence of systemic vasculitis; acute pericarditis; pulmonary edema; encephalopathy; or the development of fever in the presence of urinary tract obstruction.

[edit] LABORATORY STUDIES AND DIAGNOSTIC PROCEDURES

If renal insufficiency is suspected, laboratory evaluation is indicated to assess the degree of the insufficiency and to monitor complications.Microscopic examination of the urine may reveal the presence of moderate numbers of hyaline and fine granular casts in prerenal azotemia.The presence of RBC casts indicates glomerular diseases such as glomerulonephritis or vasculitis.The presence of large amounts of cellular debris or brown muddy, coarsely granular casts is suggestive of ischemic or nephrotoxic acute renal failure.

As previously noted, the GFR may be estimated by measuring the creatinine clearance.Further laboratory evaluation should include a chemistry profile to evaluate serum electrolyte, calcium, phosphorus, uric acid, serum protein, cholesterol, and creatine kinase levels.Anemia and thrombocytopenia should be assessed with a complete blood count and evaluated further as appropriate.Serologic evaluation is useful when vasculitis is a consideration, whereas serum and urine protein electropheresis can detect multiple myeloma.As previously noted, the measurement of FE_Nacan aid in the diagnosis of acute renal failure.

Imaging of the kidneys and urinary tract, initially by ultrasound, is often helpful for evaluating the size of the kidneys and for excluding the possibility of urinary tract obstruction, which can be reversed with appropriate intervention.Small kidneys indicate chronic renal insufficiency with little possibility of reversal of renal dysfunction, whereas normal-sized kidneys in the presence of severe renal insufficiency should prompt urgent further evaluation for the possibility of reversal of renal dysfunction.Specific diagnoses such as polycystic kidney disease may be revealed by these techniques.In certain patients, renal biopsy is indicated for the specific diagnosis, particularly if a specific treatment might improve or stabilize renal function.

[edit] DIFFERENTIAL DIAGNOSIS AND DIAGNOSTIC EVALUATION

When a patient has renal insufficiency, the initial consideration should be to distinguish whether he or she has acute or chronic renal failure.This may be difficult in certain patients,and previous history and laboratory determinations may be useful.Factors that suggest chronicity include long duration of symptoms, severe anemia, bone disease (renal osteodystrophy), sexual dysfunction, skin pigmentation or calcification, neurologic complications, and small kidneys on imaging.Alternatively, patients with chronic renal failure may have few symptoms despite a very high BUN or serum creatinine level as a result of the gradual onset and worsening of renal failure.

In any patient with acute or chronic renal failure, factors must be sought that may exacerbate the degree of renal insufficiency, especially those that may be reversible (Box 149-4).Such reversible factors may represent the activity of the primary renal disease, which may require specific treatment.One common problem is contraction of the extracellular fluid volume because of overdiuresis or fluid loss from vomiting or diarrhea.The development of congestive heart failure as a result of primary cardiac disease or as a manifestation of an expanded extracellular fluid volume may result in decreases in cardiac output, leading to decreases in renal perfusion and worsening of renal insufficiency.Patients with underlying renal disease are predisposed to iatrogenic acute exacerbations of renal failure from angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), aminoglycosides, and radiocontrast media.Box 149-5 lists other risk factors for contrast-induced renal failure.

Urinary tract infections may lead to pyelonephritis and decreased renal function.Obstruction to the urinary tract may result from stones or sloughed renal papillae, in addition to prostatic disease.Allergic interstitial nephritis as a result of drug therapy may also cause decrements in renal function in the presence of preexisting renal disease (see Chapter 148 ).The development of metabolic derangements, such as hyperuricemia or hypercalcemia, may also result in a worsening of renal function.Vascular complications, such as the persistence of atheroembolic disease or cholesterol emboli to the kidneys, are often associated with generalized vascular disease and also the possible development of renal vein thrombosis in patients with heavy proteinuria.Acute renal failure in the setting of thrombocytopenia and hemolytic anemia suggest renal involvement in either hemolytic uremic syndrome or thrombotic thrombocytopenia purpura, known collectively as thrombotic microangiopathy. Finally, urinary tract obstruction by tumor, fibrosis, prostatic hypertrophy, or infection can result in acute or chronic renal failure.The underlying cause must be carefully sought in any patient with a sudden or unexpected decrement in renal function, since prompt correction of the abnormality may be successful in returning renal function to baseline.

[edit] MANAGEMENT

[edit] Acute Renal Failure

Acute renal failure is a serious condition has a considerable mortality rate ranging from 30% to 50%.If acute renal failure is suspected, prompt referrals should be made to specialized centers for specific diagnosis and management if resolution does not occur promptly or if the etiology is in doubt.Since the course of acute renal failure ranges from 7 to 21 days, dialysis may be required until renal recovery can occur.Absolute indications for prompt referral include volume overload with congestive heart failure, hyperkalemia, severe acidosis, bleeding, and uremic symptoms.If hyperkalemia is present with the electrocardiographic changes of peaked T waves, flattened P waves, prolongation of the PR interval, or widening of the QRS complex, urgent treatment is required.Immediate therapy should include the administration of calcium gluconate intravenously, followed by the correction of acidosis with the administration of intravenous bicarbonate.Additional therapy should include 50 ml of 50% dextrose with 10 units of regular insulin to shift extracellular potassium into the cells.Potassium removal from the body can be accomplished by the use of sodium polystyrene sulfonate (Kayexalate) given orally or as a retention enema.If renal failure is severe, arrangements should be made for the prompt institution of dialysis.

In patients with oliguric renal failure, a trial of diuretics may be undertaken to attempt to convert this situation to nonoliguric failure through the use of loop diuretics.In this way, fluid balance can be improved, and there may be some therapeutic benefit by increasing tubular urine flow.

[edit] Chronic Renal Failure

Box 149-6 lists the general principles of the management of chronic renal failure.In addition to monitoring the progression of renal failure and evaluating the response to specific therapies, complications of renal failure must be successfully anticipated and promptly treated.Chronic renal failure subsequent to systemic illness mandates attention to the underlying illness as well.Furthermore, routine medicalissues such as appropriate drug dosing and infection management must be approached within the context of the deranged physiology of renal failure.Finally, preparation for dialysis or transplantation involves attention to the special medical, social, emotional, and psychologic needs of the patient and the family.To accomplish these goals, a consensus conference of the National Institutes of Health^[7] has recommended referral to a nephrologist as soon as the creatinine level reaches 1.5 mg/dl in women and 2.0 mg/dl in men; the nephrologist can facilitate the management of the case with the primary care physician.

As already discussed, the mainstay of monitoring for the progression of renal failure is the measurement of serum creatinine levels supplemented with occasional determination of creatinine clearance.Some have advocated the use of plots of the reciprocal of the serum creatinine over time to monitor progression of renal failure, since a linear relationship often is found, making it possible to predict the time at which dialysis might be required and to evaluate deviations from the predicted course.

Serial serum chemistry determinations are important in the assessment of complications so that compliance with the diet can be evaluated and levels of potassium, bicarbonate, serum albumin, cholesterol, and uric acid and parameters of renal function can be monitored.This is also important in evaluating the efficacy of efforts to control serum phosphorus values and to maintain the levels of serum calcium.In diabetic patients, serial assessment of glycosylated hemoglobin determinations is useful for obtaining an index of the efficacy of blood sugar control between office visits.It is important to realize that renal insulin clearance decreases with increasing renal insufficiency.Therefore diabetic patients typically have decreasing insulin requirements as renal disease progresses.

As renal failure progresses, modest restriction of protein intake to 0.8 gm/kg/day can ameliorate symptoms of uremia and in some but not all studies has been shown to slow the progression of renal failure.It may become necessary to restrict phosphorus to 700 to 800 mg/day and potassium to 60 mmol/day based on frequent surveillance of the serum chemistry values.Sodium retention with signs of volume overload and sodium depletion with signs of dehydration and volume contraction are common in patients with chronic renal failure; therefore attention to salt and water intake is extremely important in their management.In general, only moderate salt restriction should be prescribed except with clear evidence of volume overload.Patients with chronic renal failure are usually able to maintain normal serum potassium levels until the GFR falls below 10 ml/min.

The incidence of hypertension increases with the increasing degree of renal failure, reaching 95% in patients with a GFR of 10 ml/min or less.^[8] Control of blood pressure in patients with renal disease prevents not only further deterioration in renal function but also the development of vascular complications of hypertension.The National High Blood Pressure Education Program Working Group^[9] recommends treating hypertension to a goal of 130/85 mm in patients with chronic renal failure.A target pressure of 125/75 Hg should be used for patients with urinary protein levels higher than 1 gm/day.Measurements of blood pressure with the patient both lying and standing are useful in diabetic patients, who may have autonomic dysfunction, and in patients receiving drug therapy for the evaluation of potential postural hypotension.This may also be valuable in patients with suspected extracellular volume contraction.

Although lowering the systemic blood pressure is beneficial, the choice of antihypertensive drugs may have an impact on the progression of renal disease.Data from numerous studies have demonstrated that ACE inhibitors slow the progression of renal failure independent of their effects on reducing blood pressure in several types of renal disease, with the most pronounced effects in patients with diabetes types I and II with urinary protein levels higher than 1 gm/day.^[10][11][12] Blood pressure measurements should be followed closely after the institution of antihypertensive therapy so that excessive reductions in renal blood flow do not further compromise renal function, especially in the presence of renal vascular disease.This may be seen with any agent that effectively lowers the blood pressure, but the use of ACE inhibitors has been particularly implicated in sucheffects.Serum potassium levels should be checked several days after the start of therapy with ACE inhibitors to exclude hyperkalemia.This is particularly important in diabetic patients and those using β-blockers and nonsteroidal antiinflammatory drugs, who may be particularly susceptible to the development of hyperkalemia.Although few studies have been undertaken, data suggest that calcium channel blockers, particularly verapamil and diltiazem, may attenuate the progression of diabetic nephropathy.^[5] These agents may be used as second-line antihypertensives for patients unable to tolerate ACE inhibitors.In animal models of renal failure, like ACE inhibitors, angiotensin II receptor antagonists such as losartan delay the progression of renal failure, but it must be stressed that long-term human trials have yet to be performed.As with ACE inhibitors, hyperkalemia may complicate therapy with angiotensin receptor blockers in patients with renal insufficiency.

Diuretics are often necessary in combination with other antihypertensives to control blood pressure in patients with renal insufficiency.Loop diuretics are used most commonly because thiazides tend to be ineffective at a GFR less than 25 ml/min and the use of potassium-sparing diuretics is frequently contraindicated as a result of predisposition for hyperkalemia in patients with chronic renal failure.

Hyperlipidemia is often associated with chronic renal failure and is often more severe in patients who have nephrotic syndrome or diabetes.Since cardiovascular complications are common in chronic renal disease and since experimental evidence shows that hyperlipidemia may have a deleterious effect on the progression of renal disease,^[13] the clinician should attempt to treat hypercholesterolemia.This can be done by attention to the diet, but many patients require drug intervention.

Histologic changes of hyperparathyroidism occur relatively early in the course of chronic renal failure.Early surveillance of intact parathyroid hormone levels and a low-phosphorus diet are the initial steps.Most patients eventually require therapy with phosphate binders such as calcium carbonate, calcium acetate, or cross-linked poly allylamine hydrochloride, also called Sevelamer or RenaGel, taken with meals, as well as calcium salts taken on an empty stomach to increase serum calcium levels in the setting of hypocalcemia.The use of aluminum-containing antacids as phosphorus binders is no longer recommended.The use of calcitriol, the physiologically active form of vitamin D, is also useful in treating mild to moderate hyperparathyroidism but often causes hypercalcemia, so such therapy should be undertaken with caution.Newly developed vitamin D analogs have the potential to reduce PTH levels without causing hypercalcemia.

Acidosis should be treated, if possible, with the awareness that bicarbonate supplementation may also lead to excessive sodium intake.Citrate-containing alkali salts should be avoided in advanced renal failure because of the possibility of enhancing the absorption of aluminum from the intestine.

The anemia of chronic renal failure is due primarily to low erythropoietin levels.When measured, erythropoietin levels are typically within the “normal” range of 15 to 30 mU/mL, reflecting an inappropriately low response to anemia.Intervention includes the institution of therapy with recombinant human erythropoietin (rHuEPO) with a target hematocrit of 33% to 36%.^[4] Supplementation of iron is frequently necessary in patients taking rHuEPO.Such therapy requires careful supervision because aggravation of hypertension and development of polycythemia may occur.

Since many drugs required for general medical management are handled by the kidneys for excretion, it is imperative that the dosing of any prescribed drug be verified for the degree of renal insufficiency.

[edit] End-stage Renal Disease.

It is usual to initiate dialysis when the creatinine clearance is less than 10 to 12 ml/min, which would usually correlate with a serum creatinine concentration of 8 to 12 mg/dl.Often, however, the initiation of dialysis depends on the development of symptoms of uremia.Excessive delay in starting dialysis can result in malnutrition and may delay ultimate recovery and rehabilitation.Most facilities provide hemodialysis and peritoneal dialysis and either perform transplantation or can refer to a transplantation center.The involvement of the nephrologist is important in the choice of dialysis modality and in the consideration for renal transplantation.Thus the patient may become both educated about the various forms of therapy and acquainted with the personnel involved in the management of the ESRD program.

Hemodialysis requires safe and reliable vascular access.The preferred access is through a primary arteriovenous fistula, which can usually be created under local anesthesia.The fistula requires 2 to 6 months of maturation before use.If the patient's vessels are inadequate, synthetic grafts can be inserted in the arm.These grafts can generally be used within 4 weeks of placement.The major complications of such vascular-access procedures are clotting and infection.It is usual to perform hemodialysis three times a week, with each session lasting approximately 4 hours.The annual mortality rate for hemodialysis patients is approximately 20% to 25%.This estimate varies according to comorbid conditions (e.g., diabetes, cardiovascular disease).^[10]

Continuous ambulatory peritoneal dialysis is an alternative treatment in which dialysis fluid is inserted through a catheter into the abdominal cavity, where exchange of solute occurs between blood and fluid.After a period of time, the fluid containing waste products and extra water is then removed through the catheter and discarded.A modified form of such therapy is the use of an automated cycling machine during the night.This continuous cycling peritoneal dialysis can be helpful to patients with limited mobility.Continued ambulatory peritoneal dialysis requires a minimum of four dialysis exchanges per day.The advantages of this form of dialysis is that it provides greater flexibility to patients, enabling them to work or travel and set their own schedules.Peritonitis is a potential complication of peritoneal dialysis, so strict attention to sterile technique is necessary.Since repeated connections of tubing are required, it is desirable that the patient's vision and fine-motor coordination be satisfactory; however, some devices can facilitate these connections.Although comparative survival statistics between hemodialysis and peritoneal dialysis are somewhat difficult to interpret in view of the unmatched patients, it would appear that under most conditions, survival rates are comparable.

Of the therapies for ESRD, a successful renal transplant provides the most complete correction of the uremic syndrome.Kidney transplantation from living related donors now has 1-year success rates above 90%, and that of transplantation with cadaveric kidneys now routinely exceeds 80%.Long-term success rates are somewhat lower, and somekidneys fail because of chronic rejection, but median graft survival in living donor transplants is 15 to 16 years and 9 to 10 years in cadaveric donor transplants.^[14]

[edit] REFERENCES