Acute Kidney Injury Therapeutics and Drug-Induced Renal Disorders

an abrupt fall in kidney function over hours-days (sometimes weeks).

acute kidney injury

select all that apply:

what are some risk factors of acute kidney injury?

1. pre-existing kidney disease

2. use of nephrotoxic drugs or substances

3. advanced age

4. dehydration

5. pre-existing cardiovascular or respiratory disease

6. cardiovascular or major noncardiac surgery

select all that apply:

what are some symptoms of AKI?

1. no symptoms

2. malaise

3. edema

4. hypertension

5. abdominal pain

6. encephalopathy

7. anuria, oliguria, or nonoliguria

urine < 50 mL/day

anuric

urine < 500 mL/day

oliguric

urine > 500 mL/day

nonoliguric

perfusion problem before the kidney

pre-renal AKI

damage within the kidney

intrinsic/intrarenal AKI

ischemia or toxins

acute tubular necrosis

usually caused by drug allergy

acute interstitial nephritis

usually an autoimmune reaction

glomerulonephritis

obstruction after the kidney

post-renal AKI

select all that apply:

how do we treat the cause and restore flow in pre-renal AKI?

1. stop nephrotoxins

2. correct volume deficit

3. optimize cardiac output if needed

select all that apply:

what do we need to monitor in pre-renal AKI?

1. BUN/SCr

2. urine output

3. daily weight

4. fluid status

5. symptom resolution

6. whether stopping meds worsens the underlying disease

causes: severe ischemia; toxins/meds (e.g., aminoglycosides, vancomycin, cisplatin, radiocontrast, ethylene glycol, heavy metals).

management: remove the offending agent, supportive care, start renal replacement therapy (dialysis) if standard indications (refractory hyperK, acidosis, volume overload, uremic complications).

acute tubular necrosis

often drug-induced: penicillins/cephalosporins/sulfonamides, rifampin, phenytoin, NSAIDs, PPIs; also malignancy, infections, systemic diseases (lupus, sarcoid).

urine may show WBCs/WBC casts; eosinophils can occur.

management: stop the culprit, treat any infection; commonly steroids (e.g., methylpred 0.5-1 g IV daily ×3 days → prednisone ~1 mg/kg/day for 3-4 weeks).

acute interstitial nephritis

immune-mediated inflammation of glomeruli; post-streptococcal associations common.

can cause proteinuria/hematuria and reduced filtration.

management: suppress inflammation (steroids/immunosuppressants), antibiotics if infectious trigger, diuretics for edema—tailored to etiology.

acute glomerulonephritis

select all that apply:

how would we manage post-renal AKI?

1. relieve the obstruction

2. watch for post-obstructive diuresis

may help treat fluid overload, but do not lower mortality or prevent dialysis in AKI.

diuretics

can increase renal blood flow/diuresis but does not improve outcomes → not recommended.

low-dose dopamine

select all that apply:

no matter the cause of the AKI, you should...?

1. stop potential offending drugs.

2. adjust doses of medications that are cleared by the kidney.

prevention of AKIs:

avoid nephrotoxins/contrast when feasible; ensure good hydration.

in the critically ill, avoid ______________ (KDIGO ICU target ≈ 110-149 mg/dL).

hyperglycemia

select all that apply:

who is at risk for drug-induced renal disorders?

1. nephrotoxic drugs/substances

2. pre-existing CKD

3. older age

4. dehydration/volume depletion

5. heart/lung disease, major surgery

normally kept dilated by renal prostaglandins (PGE₂/PGI₂) to preserve GFR when perfusion is low. NSAIDs/COX-2 inhibitors ↓ prostaglandins → constriction → ↓ renal blood flow & ↓ GFR. risky when volume-depleted (vomiting, diuretics), heart failure, cirrhosis, elderly, or on ACEi/ARB ("triple-whammy": ACEi/ARB + diuretic + NSAID).

afferent arteriole

normally constricted by angiotensin II to maintain intraglomerular pressure and GFR.

ACE inhibitors / ARBs block Ang II → dilation → ↓ intraglomerular (hydrostatic) pressure and ↓ GFR.

in CKD this reduces hyperfiltration & proteinuria → slows progression (good).

in AKI risk states (dehydration, hypotension, bilateral renal artery stenosis) it can drop GFR too much (bad).

efferent arteriole

cause afferent vasoconstriction (↑endothelin, ↓NO/prostaglandins) → ↓ GFR; also dose-related tubular/interstitial toxicity.

calcineurin inhibitors (cyclosporine, tacrolimus)

a small rise (≤~30%) in SCr can be acceptable; more than that → evaluate volume status, diuretic/NSAID use, renal artery stenosis; hold or reduce if needed.

ACEI/ARB-induced functional AKI

stop; rehydrate; avoid in high-risk patients, consider acetaminophen

NSAID/celecoxib-induced AKI

iodinated dye given IV to make blood vessels and organs show up on imaging (CT angiography, coronary cath, some CT scans).

intravenous contrast

an acute drop in kidney function after iodinated contrast in the absence of another clear cause, usually defined as ↑ serum creatinine ≥0.5 mg/dL or ≥25% from baseline within ~48-72 h.

time course: SCr peaks at 3-5 days and often returns toward baseline by 7-10 days, but injury can occasionally persist.

contrast-induced AKI

select all that apply:

what are some non-modifiable risk factors for CI-AKI?

1. older age

2. diabetes

3. pre-existing CKD

4. advanced heart failure/low EF

5. recent MI

6. cardiogenic shock

7. post-renal transplant

select all that apply:

what are some modifiable risk factors of CI-AKI?

1. large or repeated contrast dose

2. dehydration

3. hypotension

4. anemia/blood loss

5. diuretics/SGLT2 inhibitors

6. ACEi/ARBs

7. NSAIDs

8. nephrotoxic antibiotics

select all that apply:

what do we need to do to prevent CI-AKI?

1. stop/avoid nephrotoxins around the study when possible

2. volume expansion

3. N-acetylcysteine

4. prefer lowest feasible contrast dose

5. monitor SCr 48-72 h post-exposure

obstruction anywhere from renal pelvis → ureter → bladder → urethra (stones, clots, tumors, BPH; anticholinergics can precipitate retention).

post-renal AKI

occurs in tubules → ATN, AIN, or physical obstruction.

drug crystalluria

select all that apply:

what are the culprit drugs of drug crystalluria?

1. acyclovir

2. allopurinol (oxypurinol)

3. methotrexate

4. quinolones

5. sulfonamides

6. triamterene

select all that apply:

what are some treatments for drug crystalluria?

1. hydration

2. supportive care

3. alternative drugs

often the result of repeated or unresolved AKI.

examples: aminoglycoside- or amphotericin B-induced ATN, captopril-induced glomerulonephritis.

management: stop the offender if possible; then treat CKD complications (BP, anemia, bone/mineral, acidosis) as needed.

drug-induced AKI