RENAL SYSTEM
C. Laboratory Findings in AKI
1. Urinalysis. Common findings in AKI. Diagnostic laboratory values (urine and serum) are detailed in Table 5.6.
a. Urinary sediment
i. Intrinsic kidney failure b. Color
i. “Dirty” brown. Intrinsic kidney failure ii. Reddish brown. Acute glomerulone- phritis
iii. Bilious tinge. Mixed hepatic and renal failure
TABLE 5.6 Diagnostic Laboratory Values (Urine and Serum)
Diagnostic Labs Prerenal ATN
Urine output Decreased Decreased or normal
Urine sediment Normal Red blood cell casts, cellular debris
Specific gravity High (>1.020) Low (≤1.010)
Osmolality (urine-to-plasma ratio) >1.5 (>1.2 in neonates) <1.2
Urine sodium Low (<10 mEq/L) High (>30 mEq/L)
(>25 mEq/L in neonates)
Creatinine (urine-to-plasma ratio) >15:1 <10:1
FENa (%) <1 (<2.5 in neonates) >2 (>3 in neonates)
Creatinine Normal or slowly increasing High and increasing
BUN High High and increasing
ATN, acute tubular necrosis; BUN, blood urea nitrogen; FENa, excreted fraction of filtered sodium.
Note: Diuretic administration may affect results or measurement of urine sodium.
c. Proteinuria
i. Glomerulonephritis ii. Interstitial nephritis iii. Toxic and infectious causes d. Casts
i. RBC casts. Glomerulonephritis or vasculi tis
ii. WBC casts. Interstitial nephritis iii. Granular casts. Glomerulonephritis
iv. Uric acid crystals. Tumor lysis syn- drome (TLS)
v. Calcium oxylate crystals. Ethylene gly- col ingestion
vi. Acetaminophen crystals. Acetamino- phen toxicity (acute)
2. Serum Chemistries a. Hyperkalemia
i. Hyperkalemia occurs secondary to decreased renal excretion. Oliguric patients do not excrete sufficient potassium to maintain a normal balance. Hyperkalemia may be exac- erbated by metabolic acidosis, which causes a shift of potassium from the intracellular space.
Continued acid production occurs from cata- bolic cellular metabolism, despite loss of renal excretory function. Multiple blood transfu- sions and RBC hemolysis release potassium.
The longer the blood is stored, the higher the potassium content of the blood as a result of cell lysis and potassium release. Blood banks generally release the oldest unit of blood first. In an infant or child with hyperkalemia requiring blood transfusion, a specific request should be made for a fresh unit of blood.
ii. ECG changes secondary to hyper- kalemia can range from peaked T waves, prolonged PR interval, and complete heart block to ventricular fibrillation as the potas- sium level increases.
iii. Other clinical manifestations may include muscle cramps, muscle weakness, muscle twitching, abdominal cramps, diar- rhea, and ileus.
iv. Management of hyperkalemia depends on the severity of electrolyte imbalance.
Patients with a serum potassium level greater than 7 mEq/L and evidence of myo- cardial toxicity are at an extremely high risk for lethal arrhythmias. Prompt, aggressive intervention is critical for survival.
1) Treatment measures include the administration of insulin (0.1 units/kg regular insulin) and hypertonic glucose (0.5 to 1 mL/kg 50% dextrose) to promote cellular uptake of potassium. These med- ications essentially “move” the potassium around in the body and are not causing true potassium excretion. The effects of cel- lular shifts on serum potassium are short lived and require frequent monitoring of serum sodium and potassium. These medications may need to be redosed until potassium excretion occurs.
2) Albuterol is another pharmacologic strategy used to shift serum potassium into the cellular space, although it is not as potent as IV strategies. Its peak action is 90 to 120 minutes. Patients with hyper- kalemia may be placed on continuous inhaled albuterol.
3) Movement of the potassium into the cells can be facilitated by administration of sodium bicarbonate (1–3 mEq/kg) in the absense of acidosis. (Caution: Do not mix calcium and bicarbonate in IV solu- tions because precipitation will occur.) 4) Stabilize the myocardium with IV cal-
cium (10–20 mg/kg per dose cal- cium chloride [infants and children]
or 50–100 mg/kg per dose calcium glu- conate [infants and children]).
5) Eliminate exogenous sources of potas- sium (potassium-free hydration).
6) Remove potassium from the patient using resin exchange via the gastrointesti- nal tract with a sodium polystyrene sulfon- ate (Kayexalate) enema (1 g/kg per dose).
(Note: Repeat the enema two or three times per 24-hour period if necessary.) Sodium polystyrene sulfonate (Kayexalate) exchanges sodium for potassium in the gastrointestinal tract. It must be retained in the gastrointestinal tract to cause the renin exchange and ultimate removal of potas- sium. If it is not retained, the dose should be repeated. It may be instilled high in the rectum using a red rubber tube. Full effect is usually seen in 4 hours.
7) If kidney function is absent or severely impaired, or if hyperkalemia is severe, consider hemodialysis. Hemodialysis against a potassium-free dialysate can decrease serum potassium as rapidly as 1.5 mEq/hr. CRRT without potassium in the
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replacement fluid or dialysate is also an option if the patient is too hemodynami- cally unstable to tolerate hemodialysis.
b. Hyperphosphatemia
i. Hyperphosphatemia occurs primarily as a result of the kidney’s inability to excrete phosphate in mild to moderate renal insuffi- ciency. Phosphorus homeostasis is maintained by an increase in phosphorus excretion per nephron through the action of PTH. As renal failure progresses and GFR is less than 30 mL per minute, elevated phosphorus level will ensue. Hyperphosphatemia may also be sec- ondary to TLS, rhabdomyolysis, bowel infarc- tion, ileus, or the use of oral phosphates and/
or sodium phosphate enemas in the presence of gastrointestinal tract abnormalities.
ii. Hyperphosphatemia may not produce signs and symptoms until levels are very high (>10 mEq/L); however, a secondary hypocalcemia may develop as an attempt to compensate. See clinical manifestations in the discussion of hypocalcemia.
iii. Management of hyperphosphatemia may include IV fluid therapy to increase phosphorus excretion or administration of IV calcium. Use of enteral calcium-based phosphate binders should be considered.
Administration of phosphorus-containing agents and dietary phosphorus intake should be minimized. Acute situations can be man- aged initially with the administration of insu- lin and glucose by shifting phosphorus from the extracellular space to the intracellular space. Management of severe hyperphos- phatemia (greater than 10–12 mEq/L) may include hemodialysis or renal replacement therapy to decrease phosphate levels.
iv. Long-term sequelae include increased risk of mortality, cardiovascular disease, bone disease, and extraskeletal calcifica- tion of soft tissues, including blood vessels, lungs, kidneys, and joints.
c. Hypocalcemia
i. Pathophysiology. Serum calcium dec- lines reciprocally as phosphorus rises.
Alterations in calcium most often occur secondary to hyperphosphatemia. Other reasons for hypocalcemia include induced resistance to the action of PTH, crush injury (occurs early), severe muscle damage, large transfusions of citrate-containing blood products, sepsis, and hypomagnesemia.
ii. Clinical manifestations of calcium or phosphate imbalance include CNS changes (anxiety, tetany, and seizures), muscle cramps, hypotension, and Trousseau’s and Chvostek’s signs.
iii. Management of hypocalcemia includes decreasing the serum phosphate levels and replacing magnesium, if indicated, to increase PTH release. If the patient is symptomatic, administer IV 10% calcium gluconate (50–100 mg/kg per dose; maximum dose, 2 g). If a more rapid response is required, use calcium chloride (10–20 mg/kg per dose [infants and children] and 37–74 mg/kg per dose [neo- nates]; maximum dose, 1 g). Infuse slowly (do not exceed 1 mL/min), and monitor for bradycardia and asystole with IV calcium infusion. Because of high osmolar content, extravasation with IV administration can cause severe tissue damage.
iv. In AKI, PTH’s ability to serve as a reg- ulator of phosphorus and calcium balance is compromised because of the alteration in the renal absorption of calcium and excretion of phosphate. Decreased synthesis of the active form of vitamin D results in hypocalcemia.
d. Hypermagnesemia
i. Mild hypermagnesemia may occur in AKI secondary to decreased renal excre- tion of magnesium. It may be secondary to the use of magnesium-containing antacids (Maalox) or total parenteral nutrition (TPN).
ii. Clinical manifestations. Acute ele- vations may depress the CNS, peripheral neuromuscular junction, and deep-tendon reflexes. There is an increased potential for hypotension, hypoventilation, and cardiac arrhythmias.
iii. Management of hypermagnesemia usually does not require intervention other than discontinuing magnesium-contain- ing substances (e.g., Maalox). Calcium acts as a direct antagonist to magnesium. In life-threatening situations, IV calcium may be administered. Dialysis may be used for removal of magnesium because loop diuretics in particular enhance magnesium excretion. PTH stimulates reabsorption of magnesium from the tubules.
e. Glucose intolerance may develop second- ary to decreased peripheral sensitivity to insulin when renal excretion is decreased. Renal replace- ment therapy can remove glucose.
f. Uremia is related to the accumulation of tox- ins and waste products normally excreted in the urine and is measured as BUN.
i. Azotemia refers to a high serum concen- tration of nitrogenous wastes. Buildup of cre- atinine is not harmful to the body; however, uremia can have deleterious effects. Uremic pericarditis occurs only in the presence of prolonged severe renal failure and results from chemical irritation of the pericardium secondary to the metabolic abnormalities.
It may culminate in cardiac tamponade or cause recurrent hypotension during hemo- dialysis. If adequate relief of uremic peri- carditis does not occur with hemodialysis, pericardiectomy is recommended.
ii. Clinical manifestations are due to toxic effects of substances such as urea and ammo- nia. Neurologic symptoms include lethargy, confusion, seizures, and coma. Gastrointestinal tract symptoms include anorexia, nausea, vomiting, diarrhea, and gastrointestinal tract bleeding. Cardiovascular symptoms include hypervolemia and hypotension secondary to shifts of fluid into the extracellular space.
Hematologic compromise involves normo- chromic, normocytic anemia, thrombocyto- penia, platelet dysfunction, and increased bleeding time. Skin symptoms include pru- ritus and discoloration. Immunosuppression may result. Bone manifestations include osteodystrophies such as osteomalacia, ady- namic bone disease, and growth retardation in children. Endocrine manifestations include sexual dysfunction, hyperprolactinemia con- tributing to amenorrhea and galactorrhea in women, low total T4 and T3 and free T3, but normal free T4, reverse T3, and thyroid-stim- ulating hormone (TSH), suggesting a normal thyroid state. In early CKD, increased insulin resistance and glucose intolerance (azotemic pseudodiabetes), elevated triglycerides and very low-density lipoprotein (VLDL) and decreased high-density lipoprotein (HDL), and decreased protein synthesis and increased catabolism (Lerma, 2009).
iii. Initial management includes conserva- tive therapies related to diet and medications.
The goals of conservative treatment are to treat the cause of CKD if possible and detect/
treat any reversible cause of decreased kid- ney function, prevent/slow progression of CKD, prevent/treat complications of CKD, prevent/treat complications associated with other comorbid conditions such as diabetes
and cardiovascular disease, and prepare for replacement therapy. Referral to a nephrol- ogist should occur when estimated GFR is less than 30 mL/min (Stage IV; Lerma, 2009).
Management for symptomatic patients may include renal replacement therapy (either dialysis or transplantation).
g. Acid–Base Imbalance
i. Metabolic acidosis occurs in AKI because of alterations in renal function, including a decrease in GFR, decreased hydrogen ion secretion, decreased bicarbonate reabsorp- tion, decreased ammonia (NH3) synthesis, and ammonium (NH4) excretion. Acidosis in ARF results in an increase in the anion gap.
Anion gap = Sodium – (Chloride + Bicarbonate) ii. Clinical manifestations of acidosis sec- ondary to AKI include increased minute ventilation, a change in mental status as ammonium excretion decreases, and hyper- kalemia as potassium excretion decreases, causing an increased potential for lethal dys- rhythmias. Other manifestations can include decreased cardiac output, decreased tissue perfusion, and altered oxygen delivery.
iii. Management involves the correction of metabolic acidosis. Minor adjustments may be made by hyperventilation. IV adminis- tration of bicarbonate in the form of sodium bicarbonate or THAM may be necessary for significant correction (Table 5.7).
h. Hematologic changes include anemia and abnormal platelet function. Anemia is related to decreased erythrocyte production, changes sec- ondary to volume status (i.e., hemoconcentra- tion or hemodilution), frequent blood sampling, and bleeding. Patients with chronic renal failure require erythropoietin supplementation because of decreased erythrocyte production. Although platelet number is generally normal in ure- mia, the bleeding time is prolonged because of defective platelet activation and adhesiveness.
Coagulation tests are normal in AKI. Skin bleed- ing time is the best predictor of clinical bleeding.
Uremic bleeding is usually mild mucocutaneous bleeding. If a uremic patient bleeds, consider a structural or other hemostatic abnormality. If the hemostatic defect is thought to be related solely to the renal failure, peritoneal or hemodialysis can usually reverse the hemostatic disorder. Uremic patients who undergo surgery are always at risk for bleeding. Consider administration of desmo- pressin (DDAVP) before surgery.
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i. Infection is a risk for AKI patients, who have an altered immune response secondary to the suppression of macrophages by ure- mic toxins. Invasive lines increase the risk.
Prophylactic antibiotic therapy is generally not indicated.
j. Complications include potential multisys- tem complications (Table 5.8).