Acute kidney injury: Acute kidney injury is a common clinical problem,

affecting approximately 5% to 10% of hospitalized patients and up to

60% of patients admitted to the intensive care unit.

Renal causes : may be linked to nephrotoxic drugs, nephrotoxins,

infection, sepsis, renal ischemia, malignant hypertension or inflammation.
In the absence of a clear cause of AKI, inadequate response to treatment,
or findings of both hematuria and proteinuria in patients with AKI,
inflammatory diseases of the renal parenchyma such as
glomerulonephritis and vasculitis should be suspected.

Risk factors for drug nephrotoxicity in:

Drug factors:
 Prolonged exposure to nephrotoxic drugs.
 Potent direct nephrotoxic drug effects.
 Combinations of toxins and drugs promoting enhanced nephrotoxicity.
 Competition between endogenous and exogenous toxins for
transporters increasing drug accumulation within the tubular cell.
 Insoluble drug or metabolite with intra tubular crystal precipitation.
 Drug that accumulates in lysosome due to lack of enzymes to
metabolize the drug.
Kidney factors
 High rate of blood delivery to the kidneys (approximately 25% of
cardiac output).
 Increased drug concentrations within renal medulla and interstitium.
 Biotransformation of drugs to nephrotoxic metabolites and reactive
oxygen species.
 Proximal tubular uptake of drugs: Apical drug uptake via endocytosis
with drug accumulation or reduced drug efflux via apical transporters
with drug accumulation.
Patient factors
 Female sex and old age > 65 years.
 Nephrotic syndrome.
 Cirrhosis/obstructive jaundice (nephrotoxic bile acids).
 True or effective volume depletion (kidney hypo perfusion): Decreased
GFR, enhanced proximal tubular toxin reabsorption or sluggish distal
tubular urine flow rates.
 Hypokalemia, hypomagnesaemia or hypercalcemia.
 Immune response genes increasing allergic drug response.
 Pharmacogenetics favoring drug toxicity: Gene mutations in hepatic
and kidney P450 system or gene mutations in kidney transporters.

The incidence of acute kidney injury caused by nephrotoxic agents is

particularly notable among the elderly, and there are several reasons for
this:
1-There is an age-related decline in glomerular filtration rate in older
individuals, and this leads to decreased clearance of primary drugs or it 's
metabolites.
2-There may be a decrease in kidney blood flow and an increase in
concentration of some drugs in the cells of medulla.
3-Primary differences exist between the elderly and nonelderly
pharmacokinetics of drugs. For example, there may be an increase in
free-drug concentration in the elderly in conjunction with
hypoalbuminemia.
4- A decrease in total body water may also alter drug distribution in an
adverse way.
Certain drugs are commonly associated with nephrotoxicity and include
Aminoglycosides, Amphotericin B, Cisplatin, contrast dye,
Cyclosporine and NSAIDs (ibuprofen, naproxen, ketorolac). In
addition, medications that may accumulate with reduced GFR or
associated with crystal deposition "as Allopurinol, Baclofen, Colchicine,
Digoxin, Lithium, Fluconazole and Gancyclovir should be avoided or
dose should be adjusted as nephrotoxicity is dose dependent or related to
prolonged duration of treatment .

Most drugs found to cause nephrotoxicity exert their toxic effects by one
or more common pathogenic mechanisms. These include:

1- Altered intraglomerular hemodynamics,

2- Tubular cell toxicity,

3- Inflammation,

4- Crystal nephropathy,

5- Rhabdomyolysis,

6- Thrombotic microangiopathy.

Drug-induced renal injury is generally reversible, provided the

nephrotoxicity is recognized early and the offending medication is
discontinued.
General recommendations for prevention and treatment of critically ill
patients with AKI are based on:
(1) Correction of hypovolemia using isotonic crystalloids with avoidance
of hyper hydration,

(2) Regular monitoring of ions and acid base-balance with adequate

correction,

(3) Use of vasopressors as norepinephrine to maintain mean arterial

pressure 65–70mmHg,

(4) Use of diuretic agent to avoid fluid overload and preserve diuresis if
needed,

(5) Tight control of serum glucose,

(6) Therapeutic drug monitoring in initiation of therapy with highly

nephrotoxic antimicrobials (e.g., vancomycin, gentamicin),