Uremia Treatment & Management

The ultimate treatment for uremia is dialysis. Initiate dialysis when signs or symptoms of uremia (eg, nausea, vomiting, volume overload, hyperkalemia, severe acidosis) are present and are not treatable by other medical means. Patients with uremia must have dialysis initiated as soon as symptoms are present, regardless of GFR. For asymptomatic patients, dialysis is generally initiated when their creatinine clearance is 10 mL/min (creatinine level of 8-10 mg/dL) or less or, for diabetic patients, when their creatinine clearance is 15 mL/min (creatinine level of 6 mg/dL). Early referral to a nephrologist for evaluation (when creatinine level is > 3 mg/dL) is essential for patient education and preparation for dialysis or transplantation.

Patients may decide on peritoneal dialysis or hemodialysis, a decision dependent on their preference and level of motivation. Peritoneal dialysis is preferred for patients who are highly motivated, need flexibility in their dialysis schedule, and who may have underlying cardiovascular disease.^[10] Hemodialysis requires a functioning arterial venous dialysis access and may be accomplished at home or in a center.^[11] Regardless of whether a patient chooses peritoneal dialysis or hemodialysis, dialysis access must be discussed and placed early. Newer methods of dialysis include daily hemodialysis and nocturnal hemodialysis, the advantages of which include improved volume control, improved cardiovascular disease, improved calcium-phosphate balance, improved dietary parameters, and improved quality of life.

Renal transplantation is the best renal replacement therapy and results in improved survival and quality of life. Transplants from living, related donors are best, but transplants from living, unrelated donors should also be considered. Consider transplantation prior to the need for dialysis because the waiting list for cadaver transplants often exceeds 2-3 years.

• Hyperkalemia: Patients with renal failure associated hyperkalemia of 6.5 mEq/L or greater are candidates for emergent dialysis therapy, particularly if the hyperkalemia is associated with ECG changes (eg, peaked T waves, atrioventricular block, bradycardia). Short-term temporizing measures include intravenous infusion of calcium gluconate to stabilize cardiac membranes, bicarbonate, insulin and glucose administration, or inhaled or intravenous beta-agonists. Nonemergent hyperkalemia can be treated with oral potassium binders (eg, sodium polystyrene sulfonate [Kayexalate]). Correction of acidemia may improve potassium balance. Also, it is imperative to discontinue any medicine that might be contributing to the hyperkalemia, including ACE inhibitors, angiotensin-receptor blockers, beta-blockers, potassium-sparing diuretics, and nonsteroidal anti-inflammatory drugs.
• Anemia: Begin the workup for anemia when the hemoglobin level is less than 11 g/dL or the hematocrit value is less than 33% in premenopausal females and prepubertal patients or when the hemoglobin level is less than 12 g/dL or the hematocrit value is less than 37% in men and postmenopausal women. In patients found to have anemia of chronic kidney disease, it is important to check iron studies and to begin the initial treatment with iron replacement if there is evidence of iron deficiency. The serum ferritin level should be greater than 100 mcg/mL.

  • For patients with ESRD and CKD, the goal hemoglobin level should be 11-13 g/dL. There is insufficient evidence to recommend routinely maintaining hemoglobin levels at 13 g/dL or greater in ESA-treated patients, especially because several trials have demonstrated a potential for increased cardiac events in subjects treated to higher hemoglobin levels.^{[12, 13]}
  • If the anemia is not corrected, then begin treatment with 1 of 2 subcutaneous erythropoiesis stimulating agents, recombinant human erythropoietin (Epo) or darbepoetin, a unique molecule that stimulates erythropoiesis and has a longer half-life than erythropoietin.
  • Initiate iron therapy concurrently with dialysis therapy. Start with one of several intravenous iron preparations as these better absorbed than oral formulations. These can be administered with each dialysis treatment to load the patient with iron or once weekly to maintain iron stores.
  • For patients not yet on dialysis, oral iron preparations are used initially. For significant iron deficiency, intravenous iron (InFeD Injection) may be administered slowly (500 mg over 4-6 h) after the administration of a test dose (25 mg).
• Hyperparathyroidism, hypocalcemia, hyperphosphatemia, and renal osteodystrophy: Evaluate and treat secondary hyperparathyroidism, manifested by low calcium levels, high phosphate levels, and low levels of 1,25(OH)2 vitamin D-3, early because it is one of the first manifestations of renal osteodystrophy. Hypocalcemia can be treated with oral calcium carbonate or calcium acetate at a dose of 500 mg to 1 gram orally 3 times a day taken in between meals. If 1,25(OH)2 vitamin D-3 levels are depressed, calcium levels are decreased, and parathyroid levels are elevated (>300), consider initiating oral vitamin D therapy. The dosage of calcitriol is 0.25 mcg orally once daily or 3 times a week, depending on the levels of 1,25(OH)2 vitamin D-3 and PTH.
• When the creatinine clearance falls below 25-30 cc/min, the kidney begins to lose the ability to completely excrete excess amounts of phosphorus. Thus, it is not uncommon for many patients with CKD and ESRD to become hyperphosphatemic. Initial treatment is dietary counseling and modification. If this fails, treatment then consists of administration of oral phosphate binders given with meals. These can include calcium-based formulations, such as calcium carbonate or calcium acetate, or noncalcium-based formulations, such as sevelamer or lanthanum carbonate.
• Acidemia: Acidemia should be treated in patients with a serum bicarbonate level consistently less than 20 mEq/dL. Oral bicarbonate solution or tablets can be used, and most patients will require 0.5-1 mEq/kg of body weight of bicarbonate. Use this therapy cautiously in persons with significant fluid retention and hypertension because of the risk of worsening the fluid retention.

Surgical referral is necessary for dialysis access placement after the decision regarding dialysis has been made. Renal replacement therapy can be accomplished by hemodialysis, peritoneal dialysis, or transplantation. Referral to an appropriate surgeon (ie, vascular, general, transplant) is made after the modality for renal replacement therapy has been determined.

In general, referral to a vascular surgeon for consideration of dialysis access is initiated by the nephrologist early in the patient's course of renal failure to avoid emergent dialysis access placement. Dialysis access can be conducted through either an arteriovenous fistula for hemodialysis or a peritoneal dialysis catheter for chronic ambulatory peritoneal dialysis or continuous cycling peritoneal dialysis.

• Arteriovenous fistulas are the dialysis access of choice for hemodialysis.

  • Avoid arteriovenous Gore-Tex grafts if at all possible because of their poor longevity. Avoid long-term use of tunneled catheters because of the increased risk of infection and poor dialysis adequacy. Avoid subclavian catheters because of their association with increased venous stenosis, thrombosis, or both.
  • Peritoneal dialysis access can be accomplished by the placement of a Tenckhoff peritoneal dialysis catheter by either an experienced nephrologist or a surgeon. Direct visualization of the peritoneum is associated with fewer complications and better function of the catheter. Peritoneal dialysis allows patients more control and flexibility with their dialysis treatment regimen.
• Consider any surgery carefully in patients with uremia because of the increased risk for uremic bleeding, cardiovascular events, ARF, respiratory depression, and decreased metabolism of certain drugs. Vasopressin may be considered if uremic bleeding is substantial.

Consider consulting a nephrologist as soon as possible in the course of the patient's disease, particularly when renal function test results are only mildly abnormal. Acute hyperkalemia, volume overload, severe acidemia, or a change in mental status, which can progress to stupor or coma, requires emergent consultation with a nephrologist and, possibly, the initiation of dialysis.

Dietary changes should be made only with the help of a dietitian knowledgeable in renal diet treatment, particularly in patients who have not yet started dialysis therapy.

• A low-protein diet has been advocated for persons with mild-to-moderate renal failure, although this matter remains controversial. Low-protein diets may alleviate some of the symptoms of uremia, such as nausea; however, data regarding the renoprotective effect of low-protein diets are conflicting. The MDRD study analyzed 585 patients with nondiabetic chronic renal disease and a mean GFR of 39 mL/min. Patients were randomized to protein intakes of either 1.1 g/kg/d or 0.7 g/kg/d. Despite good compliance, there appeared to be little overall benefit with the low-protein diet. Also, low-protein diets can cause the patient to become malnourished, which has been associated with higher mortality upon the initiation of dialysis.
• On the other hand, in an analysis of studies comparing the consumption of different protein levels by nondiabetic adults with moderate to severe kidney failure, Fouque and Laville concluded that a low-protein diet can lower rate of "renal death" (which they defined as kidney transplantation, the need to begin dialysis, or the death of a patient) by 32%.^[14] Incorporating results from 2000 patients, including 1002 who had consumed a reduced-protein diet, the authors found that 113 renal deaths had occurred in the low-protein group and 168 in the higher-protein group. However, the authors stated that they were unable to confirm through their analysis an optimal protein intake level for persons with renal failure.
• Current recommendations for a low-protein diet prior to the initiation of dialysis are 0.8-1 gram of protein/kg of weight, with an additional gram of protein added for each gram of protein lost in the urine (for patients with nephrotic syndrome).
• Patients with advanced uremia or malnutrition are not candidates for a low-protein diet.
• Patients with CRF should be on a low-potassium (2-3 g/d), low-phosphate (2 g/d), and low-sodium (2 g/d) diet.

Activity for patients with uremia is self-restricted based on their level of fatigue.

• Early treatment of anemia with iron and EPO improves the quality of life and energy levels even before the patient needs dialysis.
• Bleeding secondary to uremia may occur; dangerous activities may need to be restricted and potential bleeding sites assessed in the event of a fall (eg, for a subdural hematoma).