Acute Kidney Injury

Educational Objectives

The goal of this program is to improve the management of chronic kidney disease (CKD) and acute kidney injury (AKI). After hearing and assimilating this program, the clinician will be better able to:

1. Identify the risk factors for AKI.
2. Limit or minimize the use of nephrotoxic drugs and exposure to contrast media to prevent AKI.
3. Manage and treat AKI to prevent adverse renal and cardiovascular outcomes.

Summary

Workup of acute kidney injury (AKI): history — risk factors; medications; acute or chronic illnesses; physical examination — vital signs and orthostatics; volume status; evidence of cardiac or liver conditions; rashes (suggesting concomitant glomerular or interstitial process); testing — urinalysis and urine indices; renal ultrasonography (US); kidney biopsy; urinalysis — elevated specific gravity (>1.015-1.50) in well-hydrated patient suggests volume depletion, although can be elevated by substances (eg, contrast) in urine; nonconcentrated urine in setting of AKI suggests acute tubular necrosis (ATN); protein for evidence of glomerular or tubular process; microscopic hematuria or blood on dipstick possibly indicative of glomerulonephritis or rhabdomyolysis; white blood cells (WBCs) — marker of inflammation; urine sediment — look for dysmorphic red blood cells (RBCs) and RBC casts for possible glomerulonephritis; if coarse granular or muddy brown casts present, and main prerenal or postrenal causes of acute renal failure ruled out, in 80% of cases attributable to ATN; WBC casts consistent with acute interstitial nephritis (AIN); renal US imaging test of choice (can rule out obstruction and provide evidence of chronicity)

Classification: prerenal AKI — to rule out, ensure that patient volume replete and does not have condition that affects renal perfusion; postrenal AKI — rule out with orthostatic vital signs or limited echocardiography to determine volume status; easily ruled out with imaging; intrinsic AKI

Diagnosis: Kidney Disease: Improving Global Outcomes guidelines — define AKI as increase in serum creatinine (SCr) by ≥0.3 mg/dL or 1.5 times baseline within 48-hr period or urine output <0.5 mL/kg/hr for 6 hr; AKI staging system — stage 1 (described by definition of AKI); stage 2 (SCr 2.0-2.9x above baseline or urine output <0.5 mL/kg/hr persists for >12 hr); stage 3 (SCr 3x baseline or increase in SCr to >4.0 mg/dL or urine output <0.3 mg/kg/hr for 24 hr or anuria for >12 hr)

Serum creatinine: problem with current definition of AKI is heavy reliance on SCr; poor marker of kidney injury, because of its dependence on muscle mass; creatine converted to Cr by liver, so level affected by poor liver function; because necessary to wait for SCr to rise, by time SCr doubled, injury likely occurred 24 to 48 hr before

Biomarkers: markers of tubular injury include kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin (NGAL); all have issues with sensitivity and specificity and can be falsely elevated in some clinical situations

Risk factors: preexisting kidney disease most important; advanced age; certain comorbid conditions and medications; active infection; exposure to nephrotoxic agents

Iatrogenic AKI: perioperative (cardiac surgery; prolonged general anesthesia; intraoperative hypotension or blood loss); drug-induced AKI; volume depletion; large-volume paracentesis in cirrhotics without albumin repletion

Contrast-induced nephropathy: defined as sharp decline in GFR within 24 to 48 hr after exposure to contrast material; SCr peaks within 2 to 3 days; NGAL rises within 3 to 6 hr of exposure; cystatin C rises ≤24 hr; GFR slowly improves over 5 to 10 days

Risk factors: concomitant acute kidney injury of other origins; reduced baseline kidney function (GFR <45 mL/min/1.73m2); diabetes; dehydration; anemia; poor hemodynamic status; concurrent use of other nephrotoxic agents; large doses or multiple administrations of contrast; contrast agents with higher osmolality

Mechanism of injury: in animal models, shown to cause injury at multiple sites; vasoconstriction in afferent artery; contrast agent itself, in vasa recta, affects delivery of O2 to tubules, further causing ischemic injury and cell damage; O2 free radicals also cause damage

Management: bicarbonate minimizes acidity in tubules; N-acetylcysteine acts against O2 free radicals; preventive strategies — limit exposure to patients at risk; avoid multiple administrations of contrast medium; consider alternative imaging method if possible; N-acetylcysteine 1200 mg orally (shown beneficial in small studies); bicarbonate infusion (speaker uses only if level low); vitamin C and vasodilators not beneficial

Drug-induced AKI: occurs mainly in intensive care unit (ICU); ≈20% of drugs prescribed in ICU considered nephrotoxic; nephrotoxic drugs contribute to 1 out of 4 AKI episodes in ICU; common causative agents include aminoglycosides; management — in high-risk patient without AKI, discontinue nephrotoxic medications and ensure adequate volume status; in at-risk patient with hemodynamic or cardiac issues or sepsis, consider hemodynamic monitoring; monitor urine output and SCr; since hyperglycemia exacerbates condition, start insulin drip early; avoid contrast agents for at-risk patients; in stage 1 AKI, noninvasive diagnostic work-up; in stage 2, consider changes in drug dosing (adjusting for lower GFR) and renal replacement therapy (RRT); if not in ICU, consider moving to ICU; in stage 3, dialysis, continuous RRT, or acute peritoneal dialysis

Renal replacement therapy: used only when unable to medically manage, eg, acidemia, hyperkalemia, or fluid overload, or evidence of uremia with pericarditis, encephalopathy, and intractable itching or nausea present; “renal support,” rather than RRT, newer approach; indications for early renal support — encephalopathy; volume overload; pulmonary congestion; pulmonary HTN; persistent acidosis; sepsis; acute respiratory distress syndrome; optimization for other organ transplantation; diuretic intolerance

Prognosis after AKI: if not reversible ≤48 hr, renal and cardiovascular prognosis worse and risk for future mortality increased; after AKI or ATN, patients remain in some degree of renal failure for 7 to 21 days after recovery from initial insult; short duration of renal ischemia leads to rapid recovery; longer ischemia can prolong recovery due to more severe tubular necrosis and apoptosis; renal outcomes after AKI — overall, patients more than twice as likely to develop CKD after one episode of AKI; elderly patient ≈7 times more likely to develop end-stage renal disease (ESRD) ≤2 yr after episode of AKI; if history of CKD present, 41-fold increased risk for ESRD; if patient has AKI requiring dialysis, 28-fold risk for CKD stage 4 or 5 and 2-fold increased risk for death over 8-yr follow-up; survival after AKI — mortality in ICU 40% to 60%; for non-ICU AKI, mortality 10% to 30%; posthospital mortality also increased (23% in one meta-analysis); cardiovascular outcomes after AKI — in matched study of patients that recovered from AKI requiring dialysis, AKI resulted in ≈67% higher risk for CV events in long term; partly driven by progression of CKD; those who recovered from AKI had 22% higher risk for HTN

Readings

Heung M, Chawla LS: Acute kidney injury: gateway to chronic kidney disease. Nephron Clin Pract, 2014;127(1-4):30-4; Kokkoris S et al: Novel biomarkers of acute kidney injury in the general adult ICU: a review. Ren Fail, 2013;35(4):579-91; Koza Y: Acute kidney injury: current concepts and new insights. J Inj Violence Res, 2016 Jan;8(1):58-62; Levey AS et al: Glomerular filtration rate and albuminuria for detection and staging of acute and chronic kidney disease in adults: a systematic review. JAMA, 2015 Feb 24;313(8):837-46; Paquette F et al: Acute kidney injury and renal recovery with the use of aminoglycosides: a large retrospective study. Nephron, 2015;131(3):153-60; Tolwani A: Continuous renal-replacement therapy for acute kidney injury. N Engl J Med, 2012 Dec 27;367(26):2505-14; Ward PA: Iatrogenic acute kidney injury: a challenge to renal physicians! Ren Fail, 2013 Aug;35(7):1060; Wetz AJ et al: Does sodium bicarbonate infusion really have no effect on the incidence of acute kidney injury after cardiac surgery? A prospective observational trial. Crit Care, 2015 Apr 22;19:183; Wichmann JL et al: Contrast-Induced Nephropathy. Circulation, 2015 Nov 17;132(20):1931-6; Wybraniec MT et al: Contrast-induced acute kidney injury: the dark side of cardiac catheterization. Pol Arch Med Wewn, 2015;125(12):938-49.

Disclosures

For this program, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Ghaffari was recorded at the 45th Annual USC Diagnostic and Therapeutic Skills in Internal Medicine, held February 27-March 3, 2017, in Maui, HI, and presented by the Keck School of Medicine of University of Southern California, Department of Medicine and Office of Continuing Medical Education. For information about upcoming activities from this sponsor, please visit their website at www.keck.usc.edu/cme. The Audio Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

IM643802

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.