Problem: Uremia (A constellation of signs and symptoms associated with loss of renal excretory failure. Usually accompanied with anemia, malnutrition, impaired metabolism of carbohydrates, fats, and proteins, and defective utilization of energy. There is no specific BUN or creatinine level that marks uremia.)

Symptoms / Recognition:
Fatigue, Shortness of breath, Pruritus, Headache, Peripheral edema, Ascites, Ausculatory rales, Pericardial rub, Bruising, Uremic frost, Hyperpigmentation, Asterixis, Peripheral neuropathy, and Altered mental status.

Goal:
The primary goal is to recognize the early onset of decreased renal function so that conservative measure can be implemented before the need for dialysis or renal transplant.

Pathogenesis:
Loss of nephron function leads to the build-up of byproducts in the blood. These are most likely byproducts of protein and amino acid metabolism. BUN and creatinine only correlate in a rough and inconsistent way with uremic symptoms. The kidney normally catabolizes several circulating plasma proteins, including endocrine products. With decreased renal function, the levels of these products can rise. They include: PTH, insulin, glucagon, LH, and prolactin.
Disruption in renal function can lead to the following problems:

1. Fluid and electrolyte abnormalities: fluid overload, metabolic acidosis, sodium imbalance, hyperkalemia, hyperphosphatemia, hypocalcemia
2. Endocrine/Metabolic abnormalities: hypertriglyceridemia, Vit D deficiency, secondary hyperparathyroidism, osteomalacia, hyperuricemia, impotence
3. Cardiovascular disorders: hypertension, heart failure, pericarditis, accelerated atherosclerosis
4. Gastrointestinal disturbances: anorexia, nausea/vomiting, peritonitis, ascites
5. Dermatologic abnormalities: pruritus, uremic frost, hyperpigmentation
6. Hematologic/immunologic abnormalities: anemia (usually normochromic, normocytic), impaired platelet function, leukopenia, T-cell dysfunction
7. Neurologic/neuromuscular abnormalities: fatigue, asterixis, headache, altered mentation, coma
8. Medications: some medications can accelerate a decline in renal function. Common drugs include: aminoglycosides, NSAIDs, and allopurinol although all nephrotoxic agents should be held suspect in a patient with a newly added medication and a decline in renal function.

Therapeutic Stratagem:

1. Determination and control of the underlying etiology.
2. Monitoring changes in renal function
3. Conservative treatment of the effects of chronic renal failure.
   1. Dietary modification
      1. Protein restriction: Intake should be reduced to 0.6-0.7 g/kg/day of high biological value protein when the GFR falls below 30 ml/minute. Adequate caloric intake (35-50 kcal/kg/day) must be provided to avoid endogenous protein catabolism. Monitor patient for malnutrition.
      2. Potassium: should be restricted to 40 mEq/day when GFR falls below 20 ml/minute
      3. Phosphate and calcium: Dietary phosphorus should be restricted to 800-1000 mg/day when GFR is less than 50 ml/minute. As GFR falls, phosphate restriction becomes less effective, and phosphate binders are indicated. Calcium carbonate (500mg-2 g PO with meals) should be added.
      4. Sodium and fluid restriction: is dictated by the individual patient taking the patient's cardiovascular status into consideration. A no-added salt diet (NaCl, 8 g/day) is adequate. Once a patient has reached an adequate volume status, fluid replacement should equal urine output plus 500 ml for insensible losses.
      5. Magnesium: accumulates in chronic renal failure. Extra intake of magnesium (i.e. antacids) should be avoided.
   2. Hypertension: should be treated aggressively as it accelerates the rate of renal dysfunction. Target BP: 125/75. ACE inhibitors should be used whenever possible. Diuretics must be used carefully, and the patient must be monitored for volume depletion.
   3. Acidosis: treat with PO sodium bicarbonate, 325-650 mg TID when serum bicarbonate falls below 18-20 mEq/L
   4. Anemia: treat with erythropoietin when hematocrit is less than 30%. Initial dose of 50-100 units/Kg SC two to three times weekly with a target hematocrit of 31-36%.
4. Instituting more aggressive treatment (dialysis, and/or renal transplant) when appropriate. Dialysis is indicated when sever hyperkalemia, acidosis, or volume overload cannot be controlled by conservative measures. Additional indications include uremic pericarditis, encephalopathy, or nutritional requirements that would precipitate volume overload or uremia.

Baseline and Serial Monitoring:
GFR is normally about 125 ml/min. GFR can fall to 40 – 50% of normal function with only modest changes in creatinine. Azotemia occurs around 20-35% normal function. With less than 20% normal function, overt renal failure usually develops.
Two rough estimates of GFR:

1. 24 hour urine collection (U_Cr x V/P_Cr) / 1440
2. [(140 - age) x bodyweight (kg)] - [72 x P_Cr]

On presentation, the patient should have a CBC and Chem10 drawn to evaluate for anemia, infection, and electrolyte abnormalities.
The patient’s decline in GFR may be followed by plotting the reciprocal of serum Cr versus time. The plot is usually linear, unless there is a superimposed renal insult, and is useful in end-stage planning and in the predicting the time when dialysis is needed (GFR < 10 ml/minute in a non- diabetic and < 15 ml/minute in a diabetic).

Sentinel Events:
Conditions that may coexist with uremia:

1. Renal osteodystrophy
   1. Secondary hyperparathyroidism due to hyperphosphatemia, hypocalcemia, deficient production of calcitriol, and skeletal resistance to PTH.
   2. Low turnover bone disease (osteomalacia and aplastic bone disease), due to aluminum retention
   3. Mixed renal osteodystrophy
2. Hyper / hyponatremia
3. Hyper / hypokalemia
4. Metabolic acidosis
5. Hypocalcemia
6. Vitamin D deficient Osteomalacia
7. Secondary Hyperthyroidism
8. Malnutrition
9. Pericardidis
10. Nausea / Vomiting
11. Anemia (normoshromic/normocytic)
12. Leukopenia
13. Hypertension

Outcome Markers:
After determination of the etiology of the uremia and proper treatment, the BUN and creatinine levels should return to normal or a new baseline if the cause was irreversible. Dialysis or renal transplant maybe the endpoint for some patients if conservative measures were unsuccessful. The goal of dialysis is to reduce the patient’s urea level by 65%.

Resources:

• Harrison's Principles of Internal Medicine 14^th Edition
• The Washington Manual of Medical Therapeutics 29^th Edition