Acute Renal Failure

James Paparello, MD

Division of Nephrology & Hypertension

Northwestern University

Goals:

I. Briefly Review Acute Renal Failure– New Definitions

II. Interpret Data regarding the questions:– What is the work up for new acute renal failure in a

hospitalized patient • What is appropriate follow up ?

– Who is at risk for contrast induced nephropathy• Can it be prevented ?

– What commonly used drugs in renal-impaired hospitalized patients need to be dose adjusted ?

I. Definitions and Physiology 101

Creatinine

• Released at steady rate from muscle, filtered by kidney

• In steady state, allows tracking of kidney function in individual

• Needs to be converted to GFR via formula (Cockcroft-Gault, MDRD)

Calculation of GFR

• Direct measurement of 24 hour urine creatinine clearance (cumbersome, inaccurate)

• Cockcroft-Gault Creatinine Clearance• Men: (140-age) * wt(kg) / 72 * SCr• Women: 0.85* [(140-age) * wt(kg) / 72 * SCr]

• MDRD GFR Formula*:170 x [SCr]-0.999 x [Age]-0.176 x [0.762 if female] x [1.180 if

black] x [Alb]+0.318

*From Levey et al, 1999,Ann Intern Med 130: 461-470

Stages of Chronic Kidney Disease

• Stage 1: GFR >= 90 ml/min, proteinuria

• Stage 2: GFR between 60 and 89 ml/min

• Stage 3: GFR between 30 and 59 ml/min

• Stage 4: GFR between 15 and 29 ml/min

• Stage 5: GFR less than 15 ml/min

Why GFR ?

• More accurate representation of renal function than serum creatinine, which can be misleading.

• 31 yo AA male in the office for life insurance physical:

• BUN: 18 Cr: 1.1 Alb: 4.0 GFR: 95 cc/min

• 80 yo Caucasian woman in nursing home:

• BUN: 18 Cr: 1.1 Alb: 4.0 GFR: 51 cc/min

Importance of the Steady State

Creatinine GFR= 0

Days Total Nephrectomy

Acute Renal Failure (ARF)

• Definition may depend on whom you ask– Surgeon -- low urine output

– Intensivist-- severe acidemia

– Nephrologist-- rising serum creatinine

• Frequency - depends on clinical setting– 1% of all admissions to hospital

– 2-5% of all individuals during a hospitalization

– 4-15% during cardiopulmonary bypass

– 10-30% of all admissions to ICU

Definitions:

• ‘…a sudden and severe decrease in the glomerular filtration rate (GFR) sufficient to cause increases in BUN and Scr (azotemia), Na/H2O retention (edema), and development of acidemia and hyperkalemia…’

• **review of 27 studies showed no 2 used the same defintion “chronic renal confusion”

New Definition:Mehta Crit Care 2007

• An abrupt (within 48 h) reduction in kidney function currently defined as:– an absolute increase in serum creatinine of

either >= 0.3 mg/dl, or

• a percentage increase of >= 50 %– or a reduction in UOP (documented oliguria of

< 0.5 ml/kg per h for > 6

RIFLE definitionADQI Group (Critical Care 2004, 8:R204-R212)

AKIN criteria for Acute Kidney Injury

Akin Stage Serum Creatinine Criteria

Urine output criteria

1 Increase in S Cr of 1.5 to 2, or >= 0.3 mg/dl

< 0.5 ml/kg per h for 6 h

2 Increase in serum creatinine of 2-3 fold

< 0.5 ml/kg per h for 12 h

3 Increase in S Cr > 3 fold, or baseline Cr > 4 with an acute rise > 0.5

mg/dl

< 0.3 ml/kg per h for 24 h, or

Anuria for 12 h

Does this affect your practice ?

• Slight changes in creatinine can represent renal failure (0.3 mg/dl)

• UOP is an important parameter

• More for research purposes

The New Creatinine:

• You may notice creatinines being reported with an extra decimal (accurate to the hundredth):

• BUN: 67• Cr: 2.42

• GFR, Non-African American, estimated: L 27• GFR, African American, estimated L 33

Comments Section

• Chronic Kidney Disease: Less than 60 ml/min/1.73m2

• Kidney failure: Less than 15 ml/min/1.73m2

• Stable renal function is required for accurate estimation of creatinine clearance.

• Efforts are underway to validate the equation in Hispanics, patients with diabetes, and individuals with normal renal function.

II. Evaluation of new Renal Failure

-Work up and Management

Categories of ARF

P re-R en a l3 0 - 7 0 %

In trin s ic2 5 - 6 5 %

P os t R en a l5 %

A cu te R en a l F a ilu re

Urinary Indices

Condition Prerenal ATN AGN Obs

U Osm > 500 <350 300-500+ 300-500*

U Na < 20 > 40 < 40 > 40

FE Na < 1 > 1 < 1 > 1

Prerenal ARF• Decrease in GFR secondary to poor

perfusion of kidney– GFR autoregulation impaired as MAP < 60-80

mmHg

• Clinically, may have– True hypovolemia– Decreased effective arterial blood volume

(EABV)

Prerenal ARF

• Clinical Presentation– Hemorrhage, diarrhea, vomiting, burns, fever– Heart failure, liver failure, nephrosis, sepsis– Meds: NSAIDs, ACE-I

• Labs– Conc. urine (s.g. > 1.015), Uosm > 500 mmol/kg, low

UNa (<10 mmol/l), FeNa < 1 %, BUN/Scr > 20 hyaline casts on microscopy

• Diagnosis– Rapid recovery of GFR after improved renal perfusion

Prerenal Renal Failure

• FeNa, U Na useful in setting of oliguria, and no diuretics

• Fe Urea, FE Uric acid can be used if patient on diuretics

Postrenal ARF~ Obstructive Uropathy

• Acute renal failure occurring with obstruction of both urinary outflow tracts or the outflow tract of a single kidney

• Etiologies:– Prostatic or cervical neoplasia– Neurogenic bladder– Intraluminal obstruction (crystals, stones,

blood)

Obstructive Uropathy

• Pathogenesis (not well understood)– Transmission of pressure to glomerulus, decreasing GFR

– Secondary renal vasoconstriction

• Urine output not a good guide to obstruction

Normal Obstruction

GFR 150 L/d 10 L/d

Tubular Resorp 148 L/d 8 L/d

Urine Output 2 L/d 2 L/d

• Urine Na low over first 24-48 hrs, then > 40

• Prognosis depends on duration ( < 1 week favorable, > 12 weeks poor)

Obstructive Uropathy

• Clinical:– May or may not be oliguric– Hyperkalemia– Diagnostic catheter placement or ultrasound

• Treatment:– Relief of obstruction– Recovery of renal function may be inversely

related to length of time obstruction persists– Recognize the possibility of a diuretic phase

Renal ImagingGeneral

• More helpful in evaluating patients with renal masses or urinary outflow disorders

• Less useful in parenchymal disorders (except cystic disease)

• May help direct further pathway of investigation or lead to specific diagnosis

• Choice: proceeds from less invasive to more invasive and/or expensive studies

ULTRASONOGRAPHY

• Safe, non invasive, does not require contrast

• Independent of renal function

• Technically difficult in large patients

• Most frequently used test

• Easily detect hydronephrosis

– Ultrasound can miss early obstruction, obstruction with retroperitoneal fibrosis, or dehydration

• Aid in Renal Biopsy; Aspiration and percutaneous Nephrostomy

IVP

• Non-invasive, inexpensive, widely available• Excellent detail of entire urinary tract, especially the

collecting system • Indications: hematuria, flank pain, papillary

necrosis, urothelial malignancies and congenital abnormalities

• Depends on renal function and contrast excretion: results poor if serum creatinine > 3 - 4 mg/dl.

• Uses contrast• Cumbersome

Plain Abdominal Radiograph (KUB)

• Standard scout film in all IVP studies

• Also useful for screening evaluation of patients with renal or ureteric stones

• Limited by other calcific lesions in abdomen: gall stones, phleboliths, aorta, etc.

CT Scan

• Offers much greater contrast resolution than conventional radiographs or tomograms

• Unaffected by overlying bone or gas

• Virtually entire urinary tract and retroperitoneum can be visualized

• Main role in staging neoplasms and structural abnormalities (cystic disease, calculi, pyelonephritis)

• Superseded IVP in trauma, biopsy and other interventions

• Risks: contrast and radiation

MRI

• Delineating complex renal masses where CT is not definitive

• Staging neoplasms, particularly evaluating renal vein and IVC invasion

• Renovascular lesions: RAS and RVT

• Beware Gadolinium with GFR < 30 cc/min

Isotope Renogram

• Radionuclide agents administered and then patient imaged with a gamma camera

• Records the number of counts emitted and their source

• Both functional and structural study: renal perfusion, urinary outflow tract obstruction and parenchymal integrity

• Useful in GFR and renal plasma flow estimation, renovascular disease, post-transplant, obstructive uropathy and in pts with contrast hypersensitivity

Categories of ARF

P re-R en a l3 0 - 7 0 %

In trin s ic2 5 - 6 5 %

P os t R en a l5 %

A cu te R en a l F a ilu re

Intrinsic Renal Failure

Intrinsic ARF

Tubular 85%Glomerular 5% Interstitial 10%

Ischemic 60% Toxic 40%

Intrinsic Renal Failure

• Glomerular will usually be in setting of a systemic disease if the evaluation is taking place in the hospital

• Dysmorphic RBC, RBC casts indicate glomerular hmaturia

Acute Interstitial Nephritis

“Many believe that AIN only occurs 2 - 3 weeks after initiation of therapy with an offending drug, that it is invariably associated with fever, rash, and eosinophilia/uria, and that prior tolerance of a medication eliminates that drug as a potential cause of AIN.”

“All of these assumptions are false.”

Michel and Kelly, JASN 1998.

Acute Interstitial Nephritis

• Clinical Presentation– Classic Triad of rash, fever, eosinophilia seen

in under 30 %– Can occur within 2-3 days of exposure to agent,

or after months (Classically, 10 - 20 days)– U/A: hematuria (invariable), sterile pyuria, mild

proteinuria, +/- eosinophils

Acute Interstitial Nephritis

• Remove offending agent

• Maintain adequate intravascular volume

• Steroids are believed beneficial, but no prospective, randomized trials support them– Recommended: In appropriate histological or

clinical presentation: 1 mg/kg x 2 weeks, rapid taper

Intrinsic Renal Failure

Intrinsic ARF

Tubular 85%Glomerular 5% Interstitial 10%

Ischemic 60% Toxic 40%

NEJM 357: 797-805

Radiocontrast Nephropathy

• Up to 11 % of hospital acquired acute renal failure

• Definition:– “acute decline in kidney function after the

administration of intravascular contrast material, in the absence of other causes”

– An increase of > 25 % or > 0.5 mg/dL in S Cr between 48-72 hours after administration of contrast

Risk Factors

• Pre-existing CKD (particularly GFR < 60)

• Diabetes Mellitus

• Heart Disease

• Hypotension

• Age

• Dehydration

• Consider: Kidney transplant, proteinuria

Quantifying Risk JACC 2004

Risk Factor Score

Hypotension 5

IABP 5

CHF 5

Age > 75 4

Anemia 3

Diabetes 3

Contrast Media 1 point every 100 cc

Serum Creatinine > 1.5 or 4

GFR 40-60, 20-40, or < 20 2, 4, or 6 points

Risk JACC 2004

Risk Score Risk of CIN Risk of dialysis

5 or less 7.5 % 0.04 %

6 to 10 14 % 0.12 %

11 to 16 26.1 % 1.09 %

16 or greater 57.3 % 12.6 %

Medications:

• Contrast – Volume– Type (High, Low, or Iso osmolar)

• Ace-Inhibitors

• Diuretics

• NSAIDs

Contrast Agents

Classification Name Osmolarity

High Ioxathalamte 2150

High Diatrozoate 2000

Low Iobitridol 915

Low Iopamidol 796

Low Iohexol 780

Low Iopromide 770

Low Ioxaglate 600

Iso Iodixanol 320

Guidelines:Consensus panel for CIN KI Suppl 100, 2006

1. Evaluate all patients for CIN risk2. Optimize volume status3. Prophylax high risk patients with evidence

supported therapies4. Use Low osmolarity media in all patients5. Hold medication that adversely affects renal

fuction6. Follow up S Cr in 24 –72 hours (high risk

patients)

Guidelines:CIN Consensus Working Panel Rev CV Med, 2006

1. CIN is common, and can be serious

2. GFR < 60, DM are risk factors of particular note

3. History can identify high risk patients when labs not available

4. In an emergency, the procedure may need to be done before labs are back

5. The more risk factors present, the higher the risk of the procedure (up to 50 % CIN, 15 % ARF requiring dialysis)

Guidelines:CIN Consensus Working Panel Rev CV Med, 2006

6. High OSM contrast the greatest risk. Current evidence suggests in high risk patients, particularly with DM, non-ionic iso-osmolar contrast is associated with the lowest risk

7. Higher contrast volumes (> 100 cc) associated with higher risk. Even small volumes (30 cc) can cause CIN

8. Intra-arterial more risky than intravenous

9. Volume expansion may decrease the risk

10. No adjunctive treatment has been proved to be efficacious in reducing the risk.

Summary Recommendations

• Assess risk– If high risk, avoid contrast if possible

• If contrast needs to be given– Use lowest amount, low- or iso – osmolar

– Insure adequate hydration

– Stop potentially nephrotoxic meds. (NSAIDs, diuretics, metformin)

– Avoid multiple repeat doses of nephrotoxins

– Mucomyst does not appear to hurt, and may help

Algorithmic ApproachMcCullough PA et al, AM J Cardiol 98:2k-4k, 2006

Appropriate Follow up

Medications in Kidney Disease

• Insulin– Decreased dose required:

• Kidneys metabolize up to 20 % of insulin

• Uremia may contribute to insulin resistance

• Anorexia with uremia may lower caloric intake

• Digoxin– CrCl 10-50 – dose is 25-75 % q 36 hours

– CrCl < 10 – dose is 10-25 % q 48

– Not removed with dialysis

Medications in Kidney Disease

• Coumadin– No dosing adjustment necessary, but patients with renal

failure at increased risk of bleeding

• Lovenox– Cr Cl > 30 mL/minute: No specific adjustment

recommended (per manufacturer)– Clcr <30 mL/minute:

•   DVT prophylaxis: SubQ: 30 mg once daily•   DVT treatment: SubQ: 1 mg/kg once daily

– Not recommended for patients on dialysis – if given requires careful follow up of anti-Factor Xa levels    

Medications in Kidney Disease

• NSAIDs:– Decrease GFR and can push a patient with marginal

GFR into acute renal failure. Associated with hyperkalemia.

– In dialysis, main concern is bleeding risk

• Antibiotics– Need to be dosed appropriately

– If on dialysis, be sure levels are therapeutic (e.g. 1 gm of Vancomycin at HD Q week is often not enough)

Medications in Kidney Disease

• Ace-I and ARBs may be beneficial

• There is no great evidence that they should be held in acute renal failure:– They may contribute to hyperkalemia– They confound interpreting changes in GFR

Efficacy of ACE-I in CKD Hou et al NEJM, 354 p: 131-140, 2006

Dialysis Patients (GFR < 15)

• Access is the bugbear of dialysis

Types of Access:Fistula

Graft

Having a catheter increases your chance of having a blood infection

Per 1000 CatheterDays

Relative Incidence

AVF .05 1X

Graft .20 4X

Catheter 1.5-3.9 40-80X

Marr, KI 1997

Tunneled Catheter

Take home points about access:

• Avoid PIC lines if possible– Labs can be drawn at HD– Some antibiotics (vancomycin, aminoglycosides) can

be dosed with HD

• If changing a catheter (or pulling a catheter without exchange) check with renal team

• Avoid subclavian lines• In predialysis patients, try to spare the veins of the

non-dominant arm

Imaging in Dialysis patients

• Dialysis must be done immediately after contrast studies (cath, CT) ?

• No good evidence to support this (unless volume is an issue) but it is routinely requested

Imaging in Dialysis patients

• Dialysis is necessary after MRI with gadolinium ?

Imaging in Dialysis patients

• Dialysis is necessary after MRI with gadolinium ?

• The FDA recommends dialysis in all patients with GFR < 30, who receive gadolinium, with 4 hours and another treatment the next day

• To prevent Nephrogenic Systemic Fibrosis

Summary

• Who is at risk for contrast nephropathy ?

Quantifying Risk JACC 2004

Risk Factor Score

Hypotension 5

IABP 5

CHF 5

Age > 75 4

Anemia 3

Diabetes 3

Contrast Media 1 point every 100 cc

Serum Creatinine > 1.5 or 4

GFR 40-60, 20-40, or < 20 2, 4, or 6 points

Summary

• How can contrast nephropathy be prevented ?

Recommendations

• Assess risk– If high risk, avoid contrast if possible

• If contrast needs to be given– Use lowest amount, low- or iso – osmolar

– Insure adequate hydration

– Stop potentially nephrotoxic meds. (NSAIDs, diuretics, metformin)

– Avoid multiple repeat doses of nephrotoxins

– Mucomyst does not appear to hurt, and may help

Summary

• What is the work up for new acute renal failure ? What is the follow up ?

Summary

• Work up and follow up are individualized.

• Use estimating equations for renal function– Remember to use them in the steady state

• 24 hour urine for protein and creatinine clearance is falling out of favor

Summary

• What commonly used drugs need to be dose adjusted in renal patients ?

Summary

• “Start low, go slow”

• Watch antibiotic dosing (both over and under) and anticoagulants

• Nephrologists like ACE-I