Acute Renal Failure aka Acute Kidney Injury

Acute Renal Failureaka Acute Kidney Injury

Dr H Bierman

RIFLE criteria for diagnosis of AKI based on The “Acute Dialysis Quality Initiative”

Increase in SCr Urine output

Risk of renal injury

Injury to the kidney

Failure of kidney function

0.3 mg/dl increase

2 X baseline

3 X baseline OR> 0.5 mg/dl increase if SCr >=4 mg/dl

< 0.5 ml/kg/hr for > 6 h

< 0.5 ml/kg/hr for >12h

Anuria for >12 h

Loss of kidney functionEnd-stage disease

Persistent renal failure for > 4 weeksPersistent renal failure for > 3 months

Am J Kidney Dis. 2005 Dec;46(6):1038-48

Increase in Creatinine without AKI

• Inhibition of tubular creatinine secretionTrimethoprim, Cimetidine, Probenecid

• Interference with creatinine assays in the lab (false elevation)

glucose, acetoacetate, ascorbic acid, cefoxitinflucytosine

Increase in BUN without AKI

• Increased productionGI BleedingCatabolic states (Prolonged ICU stay)CorticosteroidsProtein loads (TPN-Albumin infusion)

Major Disease Categories Causing AKIDisease Category Incidence

Prerenal azotemia caused by acute renal hypoperfusion 55-60%

Intrinsic renal azotemia caused by acute diseases of renal parenchyma: -Large renal vessels dis. -Small renal vessels and glomerular dis. -ATN (ischemic and toxic) -Tubulo-interestitial dis. -Intratubular obstruccttion

35-40%

*>90%*

Postrenal azotemia caused by acute obstruction of the urinary tract <5%

Prerenal Azotemia

• Intravascular volume depletionbleeding, GI loss, Renal loss, Skin loss, Third space loss

• Decreased cardiac outputCHF

• Renal vasoconstrictionLiver Disease, Sepsis, Hypercalcemia

• Pharmacologic impairment of autoregulation and GFR in specific settings

ACEi in bilateral RAS, NSAIDS in any renal hypoperfusion setting

Acute Kidney Injury• Prerenal and ATN encountered most often in the

hospital setting: 70-75% in many studies• Most common diagnostic consideration is

therefore between these two conditions• Prerenal:

1. Intravascular volume depletion2. Hypotension3. Edematous states4. Localized renal ischemia

• ATN:1. All causes for prerenal, leading to post-ischemic ATN2. Toxins

Intrinsic Renal Azotemia• Large Renal Vessel Disease

Thrombo-embolic disease• Renal Microvasculature and Glomerular Disease

Inflammatory: glomerulonephritis, allograft rejectionVasospastic: malignant hypertension, scleroderma crisis, pre-eclampsia, contrastHematologic: HUS-TTP, DIC

• Acute Tubular Necrosis (ATN)IschemicToxic

• Tubulo-interestitial DiseaseAcute Interstitial Nephritis (AIN), Acute cellular allograft rejection, viral (HIV, BK virus), infiltration (sarcoid)

• Intratubular Obstructionmyoglobin, hemoglobin, myeloma light chains, uric acid, tumor lysis, drugs (indinavir, acyclovir, foscarnet, oxalate in ethylene glycol toxicity)

Postrenal azotemia

• Stones• Blood clots• Papillary necrotic tissue• Urethral disease

anatomic: posterior valvefunctional: anticholinergics, L-DOPA

• Prostate disease• Bladder disease

anatomic: cancer, schistosomiasisfunctional: neurogenic bladder

Initial diagnostic tools in AKI• History and Physical exam• Detailed review of the chart, drugs administered,

procedures done, hemodynamics during the procedures.• Urinalysis

SG, PH, protein, blood, crystals, infection• Urine microscopy

casts, cells (eosinophils)• Renal imaging

US, Retrograde Pyelogram, CT etc• Markers of CKD

iPTH, size<9cm, anemia, high phosphate, low bicarb• Renal biopsy

AKI: Diagnostic studies-urine• Urinalysis for sediment, casts• Response to volume repletion with return to

baseline SCr 24-72 hr c/w prerenal event• Urine Na; FENa FENa (%) = UNa x SCr x 100 SNa x UCr

– FENa < 1%: Prerenal– FENa 1-2%: Mixed– FENa > 2%: ATN

• Hansel’s stain

Urinalysis in Acute Kidney InjuryBiomarkers: AMI versus AKI

PrerenalPostrenalOncotic AKI

GlomerulopathyVasculitisThrombotic MA

PyelonephritisInterstitial nephritis

AINAthero-

embolic AKI

ATNMyoglobinHemoglobin

Uric acidToxinsDrugs

Plasma cell dyscrasia

HematuriaRBC castsproteinuria

WBCWBC casts

Eosinophils RTE cellsPigmented

casts

Crystalluria Non-albumin

proteinuria

Abnormal sedimentNormal/bland

Acute Kidney Injury

IMAGING STUDIES• Ultrasound: evaluates renal size, able to detect

masses, obstruction, stones• CT: detects masses, stones; caveat exists when

IVCD is considered• MRI/MRA: can detect RAS; use of Gadolinium

carries uncertain R/B ratio in AKI 2° potential hemodynamic changes similar to IVCD, and NFD

• In the AKI setting, U/S provides most information with the most favorable R/B ratio

AKI: Acute Tubular Necrosis• Non-oliguric vs. Oliguric

• Prognosis worse with oliguric ATN in most series• Ischemic insult: medulla most susceptible to

hypoxic event, cellular ATP depletion, oxidative injury

• AKI/ARF phase of ATN: 7-21 days on average• Recovery phase of ATN: also known as diuretic

phase• High urine output (>3-4 L)• K, Mg, PO4 wasting

• Associated with high FENa

AKI: Acute Tubular Necrosis

• Saline loading effective in lowering ATN risk from drugs/pigments/toxins; sometimes limited in post-ischemic ATN, particularly if CO/CI compromised

• Maintenance of CO, BP, avoid new insults • Preventative agents have shown promise in

animal models, but poorly translated to clinical situations• Dopamine, fenoldopam, mannitol, statins, loop diuetics

• Identification of high risk AKI patients is essential to prevention: DM, CKD, CVD, poor nutrition

Acute Kidney Injury: AIN causes

DRUGS• ACEI• Allopurinol• Cephalosporins• Cimetidine• Fluoroquinolones• Loop diuetics• NSAIDS• PCN• Phenytoin• Rifampin• Sulfonamides• Tegretol• Thiazides

INFECTION• Bacterial

– Agents causing pyelonephritis– Legionella– Brucella– Yersinia

• Viral– Hantavirus– HIV– CMV,EBV,HSV

AKI: Glomerulonephritis (RPGN)/Systemic Vasculitis

• Immune-Complex Mediated

• SLE• Cryoglobulinemic vasculitis• Henoch-Schönlein purpura• Post-strep GN

• Direct Ab attack• Anti-GBM disease• Goodpasture’s syndrome

• Pauci-immune vasculitis• Microscopic polyangiitis• Wegener’s granulomatosis• Churg-Strauss syndrome

• Thrombotic Microangiopathy

• TTP• HUS• Scleroderma renal crisis• Preeclampsia• Malignant hypertension

Treatment of AKI• Treatment is largely supportive in nature!• Pharmacologic treatments under study:

– Dopamine: no benefit– Atrial Natriuretic Peptide (ANP) or ANP-analogue

(Anaritide): promising– Human Insulin like growth factor 1: no benefit

• Renal Replacement therapy remains the cornerstone of management of minority of patients with severe AKI

Nephron Clin Pract 2009;112:c222-c229

Is there a role for diuretics in the treatment of AKI in ICU setting?

• PICARD Study: Cohort study of 552 pts in 4 UC hospitals: no effect on in hospital mortality or longterm renal outcome

• Improved urine output and shorter duration of RRT (none has clinical relevance in ICU pts)

• But diuretics continue to be used for volume control in AKI in ICU setting!

JAMA. 2002 Nov 27;288(20):2547-53Crit Care Resusc. 2007 Mar;9(1):60-8

When to do renal biopsy in AKI ?

• Any evidence of glomerular disease -nephrotic range proteinuria-sub-nephrotic range proteinuria with hematuria -RBC cast

• AKI in renal allograft

• Determine the prognosis and chance of recovery of renal function in dialysis dependent AKI.

• Whenever potential Bx result can change the management or prognosis.

Acute Kidney Injury

INDICATIONS FOR RENAL REPLACEMENT THERAPY• Consensus generally includes:

1. Refractory volume overload2. Severe metabolic acidosis; HCO3 may be variable, but

declining level; also falling pH to 7.1-7.23. Hyperkalemia, with levels > 6.5, or documented rapid rise

refractory to medical therapy4. Major uremic target organ manifestations i.e. pericarditis,

progressive neuropathy, seizure, or unexplained AMS5. Platelet dysfunction, bleeding diasthesis6. AKI in setting of dialyzable drug/toxin

Acute Kidney Injury: conclusions• Major advances in understanding AKI, but no clear

definition that guides research on prophylaxis, prognosis• AKI still carries high M/M risk, especially in ICU setting• Improving volume status, hemodynamics rapidly aids in

minimizing ischemic AKI risk; volume resuscitation, relief of urinary obstruction can be done concurrently

• Patient history, hosp chart review, routine labs, UA may establish cause in 40-60% of AKI

• Serologies and consideration of Bx are also adjuncts• Advent of urinary biomarkers of ischemic tubular injury

i.e. urine NGAL, will be next front in redefining AKI

Thank you!