Acute Kidney Injury

Board Review

AKI

• Basics of AKI

• New Biomarkers of renal injury

• Pathogenesis of AKI

• Treatment of AKI

• Clinical questions based learning

Acute Renal Failure

• Acute kidney Injury

• Defined as loss of renal function ,measured by the decline in GFR , developing over a period of hours to days.

• Clinically menifested by the retention of Nitrogenous products that are normally excreted by the kidneys

RIFLE Criterion for diagnosis of AKI

• Acute Dialysis Quality Initiative proposed a definition for AKI based on stratification of severity of renal injury.

AKI by AKIN

Usually abrupt increase in s/Cr >0.3 mg or 50% increase in Cr compared to baseline( usually within 48hrs)

• Decrease in urine output to 0.5ml/kg for 6 hrs

AKIN

• The diagnostic criterion should be applied only after volume status has been optimized

• Obstruction needs to be excluded if only oliguria was used as sole diagnostic criterion

• Has staging system(1-3)• Loss and ESRD are removed from AKIN

and used as outcome only.

AKI• Can be

• Oliguric

• Non oliguric

• Anuric

• Clinical expression of the disease is variable

• Sometimes diagnosed based on blood tests only.

Incidence of AKI

• Depends upon definition of AKI

• 0.5% if >2mg /dl increase in s/Cr

• 12% if 0.5 mg/dl increase in s/Cr

» Chertow JASN 2006

Markers of AKI

• Serum creatinine

• Cystatin C

• KIM 1

• NGAL

• IL-8

Treatment of AKI

• Medical Therapy

• Renal Replacement Therapy

Treatment of AKI

• Pharmacologic therapy of AKI

• Dopamine not recommended either as prophylaxis or treatment ( Lancet 2000) esp in critically ill pts as proven in ANZICS trial where renal dose dopamine was not associated with any decrease in s/cr or RRT.

Medical Therapy

• Fenoldopam esp in non diabetics( in comparison to dopamine may attain better s/Cr, improve GFR and shorten ICU stay

• Diuretics• Not recommended based on randomized clinical

trials ( Neph Dial Transplant 1997)• In comparion of lasix vs dopamine vs placebo, at

48 hrs intervals, no change in s/Cr.• High dose lasix 2gm/day vs placebo, no effect

on s/Cr and need for RRT

Medical Therapy

• ANP:

• Natriuretic peptides no sustained results

• In randomized control trial looking at 504 pts, primary outcome being at 21 day dialysis free survival, ANP group had no statistical difference.

• Insulin like growth factor

Only one clinical trial showing no benefit in critically ill pts ( Am J Physiology 2000 )

Thyroxine

No benefit in clinically ,may be harmful (KI 2000)

Renal Replacement Therapy

• Timing of RRT initiation

• Indications of RRT

• Prophylactic RRT ( Inten Care Med 1999 )

Modality of RRT

• Modality of RRT

• IHD

• CRRT

• PD

• EDD

• SLED

Question  A 77 year-old woman presents with weakness, anorexia, and fatigue for one week. One

month ago, she had symptoms suggestive of a viral infection; at that time the plasma creatinine concentration was 1.0 mg/dL. She is now admitted because of increasing symptoms.

• Physical examination reveals a blood pressure of 160/100. The remainder of the examination is noncontributory: there is no edema or rash.

• Initial laboratory data include:•       BUN  =  98 mg/dL

      Plasma creatinine  =  10 mg/dL       Plasma sodium  =  140 meq/L       Plasma potassium  =  4.6 meq/L       Hematocrit  =  29 percent       Urinalysis  =  trace protein by dipstick, benign sediment

•   A. Is this acute or chronic renal failure? What factors help to make this decision if no prior history is available?  

• B. What categories of renal disease (prerenal, postrenal, glomerular, vascular, or tubulointerstitial) can cause this type of renal failure with a normal urinalysis?

•   • C. Is the patient in sodium, water, and potassium balance? How might this be achieved in

the presence of a marked decline in glomerular filtration rate?

Question • A 74-yr-old man with diabetes, hypertension,chronic kidney disease,

and a baseline serumcreatinine of 1.7 mg/dl undergoes coronary angiography. Forty-eight hours after the procedure, his serum creatinine is 1.8 mg/dl. One week later, he is readmitted to the hospital with abdominal and lower extremity muscle pains. His serum creatinine is 3.6 mg/dl. His amylase is elevated at 320 U/L, with a creatinine kinase of 470 U/L. His urine specific gravity is 1.012, with 1 blood and 2 protein by dipstick. Microscopic examination reveals 3 to 5 red blood cells per high powered field, rare white blood cell, and moderate number of fine granular casts.

• What is the MOST likely etiology of his• ARF?• A. Contrast nephropathy.• B. Atheroembolic disease.• C. Myoglobinuric ARF.• D. Prerenal azotemia.• E. Vasculitis.

Radiocontrast Nephropathy

• Mostly hospital acquried

• Accounts for almost 10% cases of AKI

• Characterized by abrupt decline in renal function after IV administration of iodinated contrast material.

• Typically Cr begins to rise within 24-48 hrs of contrast

CIN

• Risks factors for CIN

• CKD

• DM

• CHF, AMI, PVD ,MM,

• Hct

Strategies to prevent RCN

• IV Hydration ( Arch Int Med 2000 )

• Low osmolality contrast medium ( KI 1995 )

• Acetylcysteine ( NEJM 2000, NEJM 2006 )

• Sodium Bicarbonate ( JAMA 2004)

• Miscellaneous agents

• Hemodialysis as prophylaxis

Question • A 43-yr-old woman with end-stage liver disease secondary to hepatitis C

infection is admitted to the hospital with worsening encephalopathy and ascites. Her serum creatinine on admission is 1.2mg/dl. She is treated with oral lactulose and neomycin with improvement in her mental status. Her ascites is treated with large volume paracentesis. Four days into her hospitalization, she is noted to be oliguric, with a serum creatinine of 3.6 mg/dl. Her BP is 98/60 mmHg, with a heart rate of 96 beats per minute. Jugular venous pulsation is visible 3 cm above the sternal angle with her head elevated 30°. She is markedly edematous, and she has a fine petechial rash over her lower extremities. Her urine sodium is 10mEq/L. Her urinalysis reveals moderate numbers of bile-stained granular casts.

• Which ONE of the following interventions or diagnostic tests is most important in differentiating between the potential etiologies of her ARF?

• A. Intravenous administration of 50 g of albumin.• B. Intravenous administration of at least 1.5 L of isotonic saline.• C. Measurement of central venous pressure.• D. Renal ultrasound.• E. Assay for serum cryoglobulins.

Hepatorenal syndrome

• AKI is common in pts with advanced liver disease.

• Mostly AKI is due to pre-renal ,HRS and ATN

• Differentiation between these entities may be difficult.

• Is usually of two types• Diagnosis is based on the following criterion

Treatment of HRS

Pharmacologic therapy includesVaspressin analogs 60-75% responseOctreotide with Midodrine not yet FDA approved for HRS ( Am J of Gas 2005 )

Octreotide , Midodrine with albumin Definite therapy is Liver transplantationRRT is usually not recommended

Question • A 57-yr-old man is admitted after a motor vehicle accident. He has sustained multiple

fractures and blunt chest and abdominal trauma. His BP is 95/60 mmHg. A left hemothorax is treated with a chest tube, an abdominal lavage reveals only minimal blood, and a non-contrasted CT of the abdomen is negative. He is volume-resuscitated with approximately 5 L of crystalloid, and his BP increases to 135/85 mmHg. Twenty-four hours after admission, he is noted to have marked abdominal distension, his amylase and lipase are elevated, his urine output has decreased to 10 ml/h, and his serum creatinine is 2.3 mg/dl. His central venous pressure is 18 mmHg. His urine sodium is 12 mEq/L. Urine sediment contains a few fine granular casts. A renal ultrasound demonstrates a small retroperitoneal hematoma without hydronephrosis and marked ascites. His intravesical pressure is 27 mmHg.

• Which ONE of the following choices is the• most appropriate next step in the management• of his acute renal failure?• A. Abdominal decompression.• B. Placement of bilateral ureteral stents.• C. Fluid resuscitation.• D. Watchful waiting.• E. Initiation of renal replacement therapy

Abdominal Compartment syndrome

uncommon cause of AKI ( Crit Care 2000)

Seen mostly in trauma pts

Menifested usually as oliguric AKI

Diagnosis requries high index of suspicion and measurement of intra-vesical pressure

Treatment is decompression of the abdomen

AKI usually resovles with relief of the high IBP.

Question• Which ONE of the following choices is not recognized as a risk

factor for the development of aminoglycoside nephrotoxicity?

• A. Volume depletion.• B. Biliary tract disease.• C. Elevated peak drug levels.• D. Elevated trough drug levels.• E. Age 65 yr.

Question• A 27-yr-old woman with HIV infection treated with highly active anti-

retroviral therapy (HAART) presents with nausea, vomiting, and• abdominal and flank pain. Her serum creatinine is 2.8 mg/dl

(baseline value was 0.7 mg/dl 2 wk previously). Urine microscopy is remarkable for rectangular plate-like and needle shaped crystals.

• Which ONE of the following medications is• most likely to have caused her ARF?• A. Adefovir.• B. Indinavir.• C. Nevirapine.• D. Ritonavir.• E. Zidovudine.

Question

• A 34-yr-old man receiving treatment for HIV infection presents with severe myalgias. His serum creatinine is 2.1 mg/dl, with a creatine phosphokinase of 7,4000 U/L. His urinalysis is strongly positive for blood on dipstick, but he has only 2 to 4 red blood cells per high-powered field.

• Which ONE of the following medications is MOST likely to be associated with his ARF?

• A. Acyclovir.• B. Adefovir.• C. Cidofovir.• D. Foscarnet.• E. Zidovudine.

HIV/AIDS

• Incidence is high in pts with CD4 cell count <200/mm3 and HIV RNA levels >10,000/ml and in men ( KI 2005, prospective cohort study )

• Most common causes are pre-renal and ATN associated with either opportunistic infections or drugs

• Rarely TTP/HUS ,Rhabdomyolysis and AIN

HAART

• Indinavir /Ritonavir usually associated with crystalluria and development of AKI .Nephrolithiasis can be seen as well.

• Tenofovir ,Cedoforvir are associated with Fanconi’s syndrome with severe acid base disturbances.

Question• A 23-yr-old Gravida 2, Para 1 woman presents at 32-wk gestation with

increasing lower-extremity swelling. Physical examination reveals the following: BP 145/95 mmHg, mild right upper quadrant abdominal tenderness with a gravid uterus, mild hyperreflexia, and marked lower extremity edema that has developed over the preceding two weeks. Laboratory studies are remarkable for a hemoglobin of 9.8 g/dl, platelet count of 83,000/mm3, prothrombin time 13 s, partial thromboplastin time of 41 s, serum creatinine of 1.8 mg/dl, alanine aminotransferase 120 U/L, aspartate amino transferase 92 U/L, bilirubin 3.4 mg/dl, and lactate dehydrogenase of 810 U/L. Urinalysis shows 3 protein. A peripheral blood smear has moderate schistocytosis.

• Which ONE of the following interventions is MOST appropriate?• A. Immediate delivery.• B. Intravenous methylprednisolone.• C. Intravenous heparin.• D. Plasma exchange.• E. Activated protein C.

Pre-eclampsia

• Usually seen after 20 weeks of gestation• Usually in very young or older primigravida• Can be superimposed on pre-existing

Hypertension or renal disease• Characterized by severe proteinuria, new

onset Hypertension and renal failure• Can progress to HELLP/Fatty liver of

pregnancy• Treatment is usually delivery of the baby

Question

• A 42 yrs old male with AML is admitted to the hospital for treatment of AML. His s/Cr is 0.7mg/dl on admission. He is started on chemotherapy. Pt becomes nauseous, loses appetite, starts vomiting, and on third hospital day, he becomes oliguric and repeat chemistries reveal K of 6.4meq/L, Co2 14, Cr of 3.0mg/dl. Calcium is 7.2mg/dl and PO4 is 6.4mg/dl. Pt is started on IV fluids with normal saline but urine output does not improve. Renal consult for further work up called.

• The most likely cause of this patient’s AKI is

• 1 Acute interstitial Nephritis from chemotherapy

• 2 Hydronephrosis due to prostatic hyperplasia

• 3 pre-renal AKI

• 4 Acute Glomerulonephritis

Tumor Lysis Syndrome

• Spontaneous and chemotherapy induced or radiation induced.

• Characterized by multiple electrolyte abnormalities.

• Diagonosis is clinical in conjunction with urine studies.

• Treatment is supportive.• Prevention is indicated in high tumor

burden conditions.

Question 1. A 37-yr-old man with a history of intravenous drug abuse is admitted with a 2-wk history of 2. fevers and malaise. Blood cultures on admission are positive for coagulase-negative 3. Staphylococcus, and an echocardiogram demonstratesa vegetation on his aortic valve.4. His serum creatinine is 1.1 mg/dl. He is started on antibiotic therapy with vancomycin 5. and gentamicin, his blood cultures resolve, and he is discharged to home to complete6. a 4-wk course of intravenous antibiotics. He is readmitted 2 wk later with recurrent fevers, 7. having been noncompliant with his outpatient antibiotic regimen. Blood cultures are again 8. positive for coagulase-negative Staphylococcus. His serum creatinine is now 2.4 mg/dl.9. Urinalysis reveals hematuria with some dysmorphic red blood cells but without any casts 10. noted. Serum complement levels are slightly below the lower limits of normal.

11. Which ONE of the following choices provides the most appropriate management12. for his acute renal failure?13. A. Continue current antibiotic therapy.14. B. Discontinue aminoglycoside antibiotic.15. C. Discontinue vancomycin.16. D. Begin a tapering course of oral prednisone.17. E. Begin intravenous methylprednisolone.

Question

• A 23yrs old female is admitted to the hospital with h/o sore throat. Admission labs reveal Cr of 2.5mg/dl, proteinuria of 5.6 gms of random quantification. Her PMH is unremarkable. Last blood test done three months ago revealed Cr of 0.8mg/dl. Family history is unremarkable.

• What is the most likely cause of her AKI

Contd

• Acute post infectious GN

• Hepatitis C related Cryoglobulinemia

• Acute Tubular Necrosis

• Microscopic Polyangitis

Question • A 57-yr-old woman with a history of mitral valve prolapse and no history of

renal disease develops Streptococcus viridans endocarditis. She is placed on intravenous ampicillin and gentamicin. Two weeks into her course of therapy, she develops worsening shortness of breath and lower extremity edema. On physical examination, she has an erythematous maculopapular rash across her legs and lower abdomen. Laboratory studies demonstrate a serum creatinine of 2.6 mg/dl. The leukocyte count is 9800/mm3, with 4% eosinophils. Urinalysis demonstrates microscopic hematuria and pyuria. The urine stain for eosinophils is negative.

• Which ONE of the following treatmentoptions would be most appropriate in this patient?

• A. Discontinue gentamicin, continue ampicillin.• B. Discontinue gentamicin and ampicillin, begin vancomycin.• C. Discontinue gentamicin and ampicillin, begin vancomycin and oral

prednisone.• D. Continue current antibiotics without change.• E. Continue current antibiotics and begin intravenous methylprednisolone.

Contd

• Plasmodium Ovale

• Schistosoma Hematobium

• Borrelia Burgdoferi

• Leptospira Interrogans

• Brucella Melitensis

Question• A 66-yr-old man develops acute renal failure(ARF) following operative repair of

a 5.6-cmabdominal aortic aneurysm. The aneurysm extended superiorly to the level of the right renal artery and the aorta was cross-clamped above the level of the right renal artery for approximately10 min. The left kidney was atrophic with severe atheromatous disease of the renal artery. He developed oliguric ARF postoperatively. Renal ultrasound1 d postoperative demonstrated a normal appearing right kidney without evidence hydronephrosis. The patient is begun on intermittent hemodialysis. On the 8th postoperative day,he notes an increase in his urine output. Dialysisis discontinued, and his serum creatinine spontaneously falls from 3.7 mg/dl to 3.4 mg/dl. The following day, however, he reports no further urine output, and his serum creatinine increasesto 4.1 mg/dl. Over the next several days, he describes a pattern of fluctuating urine output with occasional hematuria and has a progressive increase in his serum creatinine concentration to 6.5 mg/dl

Which diagnostic work-up is MOSTappropriate at this time?• A. Repeat renal ultrasound.• B. Computed tomography (CT) scan of abdomen.• C. Renal biopsy.• D. Abdominal exploration.• E. Resume hemodialysis for unresolved acute• tubular necrosis (ATN).