Managing acute kidney failure (Proceedings)

Treatment of acute kidney injury involves therapy for azotemia, extra renal manifestations, supportive care, and in some cases, therapy specific for the underlying disease process. Frequent monitoring of the patient is also necessary for a good outcome.

Fluid therapy

Fluid therapy is the mainstay of treatment for both acute and chronic kidney disease. Dehydration should be replaced with a balanced polyionic solution like LRS or Plasmalyte, but a solution with less sodium such as half-strength LRS is prudent for maintenance fluid needs. Sodium derangements should be reversed at the same rate at which they developed. Colloidal support (Hetastarch, Dextran, or plasma) may also be indicated depending on the clinical status of the patient.

Determining the amount of fluid to use in AKI is a challenge that requires frequent reassessment of the patient's status. Calculate an amount to rehydrate the patient (usually over 8 to 24 hours). If the patient appears hydrated, give 5% of body weight to account for undetectable dehydration. However, if the patient is anuric or oliguric, continued IV diuresis is not helpful and can be dangerous. For the oliguric or anuric patient, fluid administration may need to be guided by volume of urine output, or "Ins and Outs." The volume lost by a patient equals the insensible loss (respiration, stool) plus urine output plus ongoing losses (vomiting, fluid exudation into wounds, nasogastric suctioning, etc.). Insensible loss is 10 ml/lb/day (22 ml/kg/day). To measure urine output, use a urinary catheter and record volume produced at least every 4 to 6 hours, and replace this volume over the next 4 to 6 hours. Ongoing losses, like vomiting, diarrhea, gastric suction, etc. can be measured but are usually estimated.

If the patient is anuric, he will get only insensible loss. If he is overhydrated, withhold the insensible loss. Overhydration in an anuric patient or inability to start diuresis an oliguric or anuric patient is a clear indication for dialysis, which is the only other effective therapeutic option.

Converting oliguria to non-oliguria

There are a variety of methods to attempt to increase urine output. Before determining that oliguria is pathologic, ensure that the patient is adequately hydrated and has sufficient blood pressure to adequately perfuse the kidneys. The mean arterial pressure should be maintained above 60-80 mmHg, or the systolic pressure above 80-100 mmHg when measured by Doppler technology. Osmotic diuretics like mannitol are freely filtered at glomerulus but not reabsorbed by tubules. Increased osmolality of filtrate draws in water, increasing flow through the tubules without increasing GFR. The mannitol dose is 0.5 gm/kg over 5-10 minutes IV, up to a maximum of 2 gm/kg per 24 hours. Do not use mannitol in dehydrated or overhydrated animals; it can exacerbate pulmonary edema if the patient is overhydrated. Mannitol can also be used as constant rate infusion (CRI) of 1 mg/kg/min to decrease BUN in animals that are producing urine.

Chemical diuretics work by inhibiting Na+ carrier systems in tubules. Since different segments of tubules have different transport molecules, different drugs affect corresponding segment. Loop diuretics are most potent, since 25% of filtered sodium is resorbed in the loop of Henle. Thiazide diuretics work on the distal convoluted tubule, where 3-5 % of filtered sodium is resorbed. Spironolactone and other collecting duct diuretics are least potent, since only 1% of filtered sodium is available. Loop diuretics are the only ones helpful in converting oliguria or anuria. A starting dose for Furosemide (Lasix), a loop diuretic, is 2 mg/kg IV. If there is no urine production in 20-30 minutes, double the dose to 4 mg/kg. If there is still no urine in 20-30 minutes, increase the dose again (6-8 mg/kg). If still no response, add a second diuretic. High doses of furosemide (10 mg/kg) can cause ototoxicity. If the loading dose of furosemide induces urine production, it can be continued as a intermittent bolus (2 mg/kg q 6 hours) or a constant infusion (0.1 to 1 mg/kg/hr). Dehydration and electrolyte imbalances can be severe with higher doses of furosemide, if the patient is making urine. This increased urine flow does not increase GFR. In people, regardless of an effect on urine output, furosemide did not improve the outcome. IV diltiazem has been used to increase urine output.

Once a diuresis has been established, polyuria can be quite profound, and aggressive fluid support may be necessary to prevent additional prerenal insult from dehydration. Once the azotemia has resolved or reached a baseline, the fluid dose can be decreased by 10-20% per day. If the urine output diminishes by a corresponding degree and the azotemia does not return, continue tapering slowly. If the urine output does not diminish, the kidneys are unable to regulate fluid balance and further reduction in the fluid administered will lead to a dehydrated patient. It can take weeks for the kidneys to regain the ability to control fluid volume, but a rule of thumb used by some is to taper fluids over the same amount of time it took to diuresis them.

Acid-base and electrolyte disorders

There are a variety of acid/base and electrolyte disturbances that occur commonly in AKI. Hyperkalemia can be an immediately life-threatening electrolyte problem. Typical EKG changes include tall spiked T waves, a shortened QT interval, wide QRS complex, and a small or wide or absent P wave. Severe hyperkalemia can lead to a sine wave, ventricular fibrillation, or standstill. Treatment consists of insulin to drive potassium intracellularly. It takes up to 30 minutes to have an effect. The dose is 0.5 units/kg IV of regular insulin, and dextrose must be given concurrently to avoid hypoglycemia. Dextrose induces endogenous insulin release in nondiabetic patients and avoids hypoglycemia when insulin is administered. It is dosed at 0.5 gm/kg IV or 1-2 gm per unit of insulin given IV and 1-2 gm per unit in next dose of IV fluids. Metabolic acidosis causes extracellular shift of K+ as H+ increases intracellularly. Correction of metabolic acidosis with bicarbonate allows an intracellular shift of K+ as the H+ is combined with HCO3 and removed. The dose is based on base deficit or 2 mEq/kg IV. Calcium gluconate 10% can be used when death seems imminent. It restores membrane excitability without decreasing potassium concentration. It has an effect in 10 minutes, which can "buy" time for potassium lowering maneuvers to work. Calcium chloride is very irritating if perivascular and therefore is not used. The calcium gluconate dose is 0.5-1.0 ml/kg IV to effect, given slowly. During infusion the ECG must be monitored, and the infusion slowed or stopped if the arrhythmia worsens. Cation-exchange resins bind to potassium in the GI tract in exchange for sodium but are not useful in the acute setting. Dialysis is the only method that actually removes potassium.

Metabolic acidosis is a common acid-base disturbance in renal failure. With renal failure, the kidneys are unable to excrete H+ and cannot resorb HCO3. There may be some contribution from lactic acidosis from dehydration and poor perfusion. Treatment with sodium bicarbonate is geared toward causing acid (H+) to combine with bicarbonate (HCO3) to form H2CO3, which dissociates to H2O and CO2 according to the following formula: H+ + HCO3 ↔ H2CO3 ↔ H2O + CO2. An elevated PCO2 is a contraindication to bicarbonate administration because it can lead to paradoxical CNS acidosis. The bicarbonate dose can be calculated from this formula: 0.3 X body weight (kg) X base deficit, where the base deficit = 24 - patient HCO3. Give ¼ to ⅓ dose IV and additional ¼ in IV fluids over the next 4 to 6 hours. Adjust the dose based on serial evaluation of blood gas determinations. Therapy is usually reserved for pH less than 7.2 or HCO3 < 12.

Ionized calcium tends to be normal despite moderate to severely decreased total calcium. Treatment should be based on ionized calcium and clinical signs of hypocalcemia (tetany). Excessive treatment in the face of hyperphosphatemia leads to soft tissue mineralization when the calcium X phosphorus product exceeds 70. Calcium gluconate 10% can be used at a dose of 0.5 - 1.5 ml/kg IV over 20-30 minutes. As when treating hyperkalemia, monitor EKG during infusion.

Magnesium concentrations may be elevated in severe renal failure, as the kidneys are the major route of excretion of magnesium, but specific therapy is generally not necessary. Supplemental magnesium, such as that found in some phosphate binders, should be avoided in those situations. Hypomagnesemia may occur with polyuric renal failure. Hypokalemia may be refractory to therapy if concurrent hypomagnesemia is present. In those cases, correction of the magnesium deficit may be necessary in order to correct the hypokalemia. Magnesium sulfate or magnesium chloride can be used for intravenous supplementation, and various forms are available for oral supplementation.

Extra-renal signs

There are a variety of extra-renal manifestations of uremia, including anorexia, nausea and vomiting. Histamine blockers such as famotidine (Pepcid, 0.5-1.0 mg/kg IV q 24 hours), ranitidine (Zantac, 0.5 mg/kg IV q 24 hours), or cimetidine (Tagamet, 5-10 mg/kg IV slowly q 8 hours in dogs, q 12 hours in cats) are frequently prescribed. GI protectants help heal ulcers that have already formed. Sucralfate (Carafate, ¼ to 1 gm PO q 6 hours) works best in an acid environment and should be given 2 hours before antacids and separated from other drugs by 2 hours also. Centrally acting antiemetics are occasionally needed to control intractable vomiting. Metoclopramide (Reglan, 0.2-0.4 mg/kg SQ q 8 hours) should not be administered with concurrently with dopamine. Chlorpromazine (Compazine) (0.5 mg/kg IM q 8 hours) has hypotensive and sedative side effects. Experience with serotonin antagonists (i.e. odansetron, dolasetron) is limited, but these agents seem more potent than metoclopramide. Meropitant (Cerenia) appears to be quite effective as an antiemetic in patients with renal failure.

Acute hypertension can cause ocular damage (detached retina, hyphema, retinal edema), central nervous system signs from hemorrhage, cardiac abnormalities, or progression of renal damage. Treatment is indicated if the systolic blood pressure is over 180 mmHg. In patients with acute uremia with volume excess, control of volume status may improve the hypertension. If antihypertensive medications are required, the goal is to decrease systolic pressure to < 180 mmHg, but avoid a precipitous decrease. Amlodipine (0.18-0.3 mg/kg PO SID for cats, 0.2-0.4 mg/kg PO SID for dogs) may provide a response within 24-48 hours. Angiotension converting enzyme (ACE) inhibitors are generally avoided in acute uremia because they may decrease renal perfusion by causing afferent arteriolar constriction. If immediate control of hypertension is necessary, the onset of action of hydralazine (2.5 mg/cat PO or SQ once, 0.5-3 mg/kg PO BID dog) is 15 minutes (SQ) to 1 hour (PO). Blood pressure must be monitored closely after administration.

Nutritional support

Nutritional support in the early stages of AKI decreases morbidity in human studies. If enteral feeding is possible, nasoesophageal (NE), esophagostomy, or PEG tubes can be utilized. If vomiting cannot be controlled, partial or total parenteral nutrition (PPN or TPN) should be a consideration. In patients who are anuric or oliguric, the volume instilled, whether enterally or parenterally, must be taken into consideration.

Disease specific treatments

In many cases of AKI, the exact etiology is not known initially. However, there are some causes of acute renal failure that have specific treatments. When treating leptospirosis, penicillin G or ampicillin (22 mg/kg q 6 hours) is the antibiotic of choice for treating leptospiremia. The carrier state can be eliminated using tetracyclines (i.e. doxycycline 5 mg/kg q 12 hours for 2 weeks) or fluorquinolones (i.e. enrofloxacin). To minimize renal damage from antifreeze toxicity, emergency treatment with ethanol or 4 methylpyrazole (4-MP, Antizole-Vet) is indicated.

Monitoring

Critically ill patients should be considered at risk for developing acute kidney injury, and parameters that may be associated with renal damage should routinely be monitored in these patients. Patients with additional specific risk factors may need even more careful monitoring. Many of the parameters that should be monitored in patients at risk are useful in monitoring patients that have already developed acute kidney injury or uremia. Monitoring may allow for optimization of hemodynamic parameters, surveillance for common uremic complications, and evaluation of response to therapy. The frequency of monitoring will depend upon the severity of disease.

Monitoring hydration status is an ongoing process that is the key feature to an appropriate fluid plan. Blood volume can be measured using indicator dilution techniques, radioactive tracers, bioimpedance spectroscopy, or other methods. Unfortunately, readily available accurate measurement of blood volume is not feasible in general veterinary practice settings. Despite a lack of precise objective data, there are many ways to estimate hydration.

Physical examination provides a wealth of information about the patient. Diminished skin turgor may indicate dehydration (5% of body weight or greater), recent weight loss, or loss of elasticity due to aging. Dry mucous membranes or sunken eyes also suggest dehydration, although uremic patients may have xerostomia. Overhydration may manifest as wet mucous membranes, increased skin elasticity (heavy or gelatinous), shivering, nausea, vomiting, restlessness, serous nasal discharge, chemosis, tachypnea, cough, dyspnea, pulmonary crackles and edema, pleural effusion, ascites, diarrhea, or subcutaneous edema (especially hock joints and intermandibular space). However, patients with a low colloid osmotic pressure (i.e. hypoalbuminemia) or alterations in vascular permeability may appear interstitially overhydrated based on skin turgor assessment, yet have intravascular volume depletion. Body weight should be measured 3 to 4 times a day on the same scale to monitor fluid balance. Changes in body weight during hospitalization primarily reflect changes in body water. A sick animal may lose up to 0.5-1% body weight per day due to anorexia; changes in excess of this amount are due to changes in fluid status.

Central venous pressure (CVP) measurement through a centrally placed intravenous catheter may provide information about intravascular filling. A volume depleted animal will have a CVP less than 0 cm H20. A CVP over 10 cm H20 is consistent with volume overload or right sided congestive heart failure. However, pleural effusion falsely elevates the CVP. A 10-15 ml/kg bolus of crystalloid or 3-5 ml/kg of colloid will not change the CVP in hypovolemic patients, but will transiently increase the CVP by 2-4 cm H2O in the euvolemic patient, and cause a rise of over 4 cm H2O in the hypervolemic patient.

Blood pressure monitoring is important as both hypertension and hypotension are detrimental to renal function. Indirect methods, such as oscillometric methods or Doppler technology, are most commonly used. Although direct measurement is the most accurate method of assessing blood pressure, it is infrequently used because it involves arterial cannulation. A blood pressure measurement below 80 mmHg is insufficient for adequate renal perfusion and should be immediately addressed to avoid further renal damage. An increase in blood pressure may indicate a gain of fluid; conversely, a decrease in blood pressure may indicate a net loss of fluid. Because of the high percentage of patients with hypertension (80% of dogs with severe acute uremia and 20-30% of dogs and cats with chronic kidney disease), the trend rather than the absolute value is of more utility in assessing changes in hydration status. Similarly, changes in trends for PCV and total solids may reflect changes in volume, in the absence of bleeding or blood transfusion. Because each parameter is impacted by aspects beyond hydration status, these factors must be viewed in aggregate.

Cardiac output monitoring requires a pulmonary artery catheter and advanced equipment and is therefore rarely used in routine veterinary practice to monitor volume status. A continuous electrocardiogram (ECG) can also provide important information pertinent to the development of acute uremia (i.e., arrhythmias leading to a significant decrease in cardiac output) or in established renal failure (i.e., conduction disturbances due to hyperkalemia). Echocardiography may occasionally be necessary to assess myocardial performance and can provide information about volume status.

Venous blood gas analysis is useful for determining acid-base status in patients with acute uremia. Electrolyte abnormalities are both a risk factor for and an effect of acute uremia, and are frequently present in ICU patients. Therefore, regular electrolyte monitoring is advised. Blood urea nitrogen and creatinine concentrations are easily measured, but are insensitive markers of early renal dysfunction, since the GFR must be less than 75% of normal for these values to be elevated.

The importance of monitoring urine output and composition cannot be overemphasized. Urine production in a healthy animal is 1-2 ml/kg/hr. A decrease in urine volume may represent an appropriate renal response to hypovolemia or a pathologic change in renal function. Acute kidney injury may also result in polyuria (> 2 mL/kg/hr). Determining urine volume can be performed by a variety of methods, including placement of an indwelling urinary catheter with a closed collection system, collection of naturally voided urine, metabolic cage, or weighing cage bedding/litter pans (1ml of urine = 1 gm). An indwelling catheter is usually the most precise method, although technical issues such as urine leakage around the catheter or inadvertent disconnection may cause an artifactually low measurement. The risk of an iatrogenic urinary tract infection from the catheter can be decreased by careful attention to catheter and patient hygiene, including cleaning the external portions of the catheter with antiseptic multiple times daily and changing the collection bag and tubing daily. Complete collection of voided urine may be difficult in many patients, because of lack of patient cooperation, or urinary incontinence in obtunded or recumbent patients. An accurate scale is necessary to measure small volumes of urine in cats and small dogs, but weighing cage bedding or litter pans before and after use may provide an adequate assessment of urine volume noninvasively in some patients. Fluid losses from vomiting and diarrhea are usually estimated, and other losses such as body cavity drainage (ascites, pleural effusion) or nasogastric tube suctioning can be measured.

When renal damage has occurred, urine casts may appear before the urea or creatinine levels increase. Therefore, urine sediment should be evaluated daily in patients being treated with aminoglycosides or other potential nephrotoxic medications are at high risk for HARF.