Acute kidney injury medical therapy

Pharmacologic medical therapies for acute kidney injury include supportive therapy, diuretics, correction of hyperglycemia.

• Pharmacologic medical therapies for acute kidney injury include supportive therapy, diuretics, correction of hyperglycemia.

• Although the pathogenesis of AKI often involves volume depletion especially in the context of prerenal azotemia, no trials have assessed the efficacy of fluids vs. placebo in preventing and treating AKI.
• The response to fluid resuscitation in AKI is very variable with studies showing that a positive balance is sometimes associated with higher mortality.^[1]
• This is true especially if the therapeutic window for treatment is missed and the in impairment progresses into a volume non-responsive AKI.^[2]
• Still, it is commonly agreed that fluid resuscitation is important to limit the extend of kidney injury and possibly facilitate recovery of renal function.
• Early fluid resuscitation is key especially in patients with severe hypotension (e.g: septic shock).
• However, the amount and duration of volume expansion has not been well elaborated.
• A recent protocolized approach to septic shock known as Early Goal-Directed Therapy (EGDT)has gained wide acceptance.^[3]
• The protocol aims to recognize septic shock early on and initiates resuscitation with the aim of reestablishing tissue perfusion in 6 hours.
• Goals are:^[4]

1. Return of mean arterial blood pressure to >65mm Hg
2. Central venous pressure between 8-12mm Hg
3. Improvement in blood lactate levels
4. Central venous oxygen saturation (ScvO₂)>70%
5. Urine output of >0.5 ml/kg/h

• Selection of the appropriate fluid types for resuscitation is also important for outcome. Isotonic saline (0.9%) is the standard of care for volume expansion due to the lack of support showing that colloids are a superior option.
• The Saline vs. Albumin Fluid Evaluation (SAFE) study, showed that albumin resuscitation is safe although doesn’t have any added benefit over normal saline.^[5]
• Hydroxyethylstarch is not a safe option for the concerns of coagulopathy, osmotic nephrosis especially with hypertonic HES, and increased AKI and 90 day mortality.^[6]
• Vasopressors are also important in the management of patients with sepsis and septic shock with hypotension refractory to fluid expansion.
• Clinical data is insufficient to differentiate between different vasopressors, although commonly used agents are norepinephrine, dopamine and vasopressin especially in patients unresponsive to norepinephrine.^[3]
• Other than appropriate fluid balance and volume resuscitation, correction of electrolyte imbalances particularly hyperkalemia and metabolic acidosis are important.
• Drugs should be monitored for any possible nephrotoxicity to prevent any aggravation of renal dysfunction. Drug doses should also be altered to follow the decline in eGFR.

• Loop diuretics in theory should help to improve AKI and prevent AKI in patients at risk. By inhibiting the Na/K/2Cl transporter they decrease oxygen consumption, and increase tubular fluids inducing a wash-out of necrotic debris.^[7]
• However, studies have shown that furosemide has no benefit and sometimes increases the risk of AKI.^[8][9]
• For that, it is recommended not to use diuretics to prevent or treat AKI except in cases of fluid overload where enhanced diuresis is required.^[3]

• Patients with AKI are usually in the critical care setting and are at high risk for developing stress hyperglycemia.
• Hyperglycemia by itself has been associated with a higher risk of developing and maintaining AKI.^[10]
• Van den Berghe et al showed significant improvement in morbidity and mortality, as well as a decrease in AKI and need for RRT in the group of patients with tight glycemic control.^[11]
• Thomas et al. also found in a meta-analysis of clinical trials a 38% risk reduction of AKI in patients on tight glycemic control.^[12]
• Thus, it is recommended that patients with AKI, especially those in the ICU setting, have their glucose levels monitored closely with insulin therapy in patients with hyperglycemia aiming at a plasma glucose between 110 and 149 mg/dL.^[3]

Renal failure with electrolyte imbalance is considered an absolute contraindication to the use of the following medications:

• Diclofenamide
• Spironolactone
• Aminosalicylic acid

Severe Renal failure (creatinine clearance (CrCl) < 30ml/min) is considered an absolute contraindication to the use of the following medications:

• Danazol
• Fondaparinux
• Sulfamethoxazole/Trimethoprim (oral)

Renal impairment (e.g., serum creatinine ≥1.5 mg/dL for men, ≥1.4 mg/dL for women, or abnormal creatinine clearance) is considered an absolute contraindication to the use of the following medications:

• Linagliptin and Metformin hydrochloride
• Metformin
• Saxagliptin hydrochloride and Metformin hydrochloride

Renal impairment is considered an absolute contraindication to the use of the following medications:

• Drospirenone and Ethinyl estradiol

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