Renal Problems in the Surgical Patient

Dr. Bob RichardsonTGH Nephrology

2009

Agenda

Assessment of kidney function Acute renal failure Case studies of acute renal failure Chronic kidney disease

Causes and stages of chronic kidney disease Surgery in patients with chronic kidney

disease Surgery in dialysis patients Routine IV therapy in healthy patients

Assessment of Kidney Function A normal GFR and a normal

urinalysis rules out significant renal disease

How to estimate GFR?Serum creatinine

muscle

creatinine

serum kidney

Serum creatinine

GFR urine

Serum creatinine is an imperfect method of estimating GFR; there is no perfect method.

Determinants of Serum Creatinine

Muscle mass age (muscle mass falls with age) gender (women less muscle than

men) Weight, fitness (muscle vs fat) Nutritional state (muscle loss)GFR

How to Correct for Differences in Muscle Mass

Measure GFR directly: Creatinine clearance with 24 h urine Radionucleide GFR (nuclear

medicine – functional renal imaging)Estimate GFR Using Formulas Cockcroft-Gault MDRD (used by Ontario Labs to give

eGFR)

MDRD equation Serum creatinine, age, gender,

race (black or caucasian) Only useful for patients with known

kidney disease Ontario labs now report eGFR

using this formula GFR determines stage of CKD

Chronic Kidney DiseaseGFR ml/min

Stage 1 >90Stage 2 (mild) 60-90Stage 3 (moderate) 30-60 Stage 4 (advanced) 15-30Stage 5 End stage KD < 15

GFR measured or calculated using MDRD equation

Limitations of eGFR (MDRD) Cannot be used to determine if

kidney function is normal Not validated in acutely ill

hospitalized patients Not well validated in Asians Most useful for stable patients with

known CKD

Examples of Calculated Ccr

Two patients: same serum creatinine 100 umol/L:

20 yr old male, 80 kg, creatinine 100 umol/L Creatinine clearance: 115 ml/min

65 year old woman, 40 kg, creatinine 100 uM Creatinine clearance 30 ml/min

Moral: you need to look at more than the serum creatinine

Case 1: 67 year old man with large

abdominal mass Biopsy = sarcoma Encases right kidney, left kidney

atrophic Serum creatinine 140 umol/L What would the effect of surgery

be on residual GFR?

Case 1 Creatinine 140 uM

eGFR = 48 ml/min (stage 3 CKD) Functional renal imaging

Blood side GFR = 38 ml/min 75% function to right, 25% to left

Estimated residual GFR if right nephrectomy is 10-12 ml/min (stage 5 CKD)

Conclusion: patient will likely need dialysis post-op

Acute Renal Failure Renal response to reduced effective

circulating volume Prerenal ARF Ischemic and toxic acute tubular necrosis Obstruction Abdominal compartment syndrome Case studies Dialysis for ARF

Renal Response to Reduced Effective Circulating Volume

What is “effective circulating volume”? cardiac output vs peripheral vascular resistance how cardiovascular receptors “see” arterial

filling Effective circulating volume is reduced in:

volume depletion (hemorrhage, diarrhea etc) systemic vasodilatation (sepsis, liver failure) congestive heart failure

Consequences of Reduced Effective Circulating Volume on the Kidney

Arterial baroreceptors:

SNS circ. catecholamines ADH

JG apparatus renin, angiotensin II,

aldosterone

Effects on Kidney renal blood flow (BP +

renal vasc. resistance) GFR/RBF (efferent

constriction by AII, preserves GFR)

Sodium, chloride retention

urine [sodium] < 20 mMWater retention Uosm

>500

Angiotensin II and Regulation of GFR

Causes of Acute Renal Failure

1

23

4

1. Prerenal

2. Vascular

3. Glomerular

4. Tubulo-interstitial

5. Obstruction5

Prerenal Acute Renal Failure

GFR = arterial BP renal vascular resistanceBP depends on venous return, heart rate,

contractility, systemic vascular resistanceRVR may be increased by: catecholamines, angiotensin II sepsis, hepatic failure NSAID’s, Cyclosporine Renal arteriolarsclerosis (age,

hypertension)

Prerenal Failure-Clinical

Hypovolemia hemorrhage diarrhea, vomiting, burns pancreatitis, ascites SIRS/capillary leak

Septic shock Cardiogenic shock Drugs: cyclosporine, NSAID’s, etc

The Kidney In Prerenal Failure

Normal renal response to reduced effective circulating volume: oliguria (< 0.5 ml/kg/h) normal urinalysis (no protein or casts) high urine osmolality (ADH acting) low urine [Na] or [Cl-] increasing serum creatinine

Rapid improvement in urine flow and serum creatinine if prerenal state corrected

Ischemic Acute Tubular Necrosis

Causes: same as prerenal ARF - more severe or more prolonged

Factors that increase risk for ATN: sepsis (especially gram -) biliary obstruction with jaundice angiographic dye myoglobin (rhabdomyolysis) cardiopulmonary bypass CKD

Tubular proteins (markers of injury) in patients on bypass for < 70 minutes or > 90 minutes

Ann Thoracic Surg 2003;75:906

Pathophysiology of Ischemic ATN

Necrosis of cells of thick ascending limb and proximal tubule in outer medulla

Cells and cell debris enter lumen and cause obstruction and backleak of filtrate

Glomeruli are normal Continued hypotension causes

prolonged severe vascoconstriction

Debris in tubule lumens

Dilated tubules

Focal loss of tubule cells

lining tubular basement membrane

Interstitial edema

Urine in Ischemic ATN

Oliguria (if severe injury) or non-oliguric

Urine flow may increase with furosemide

Isotonic urine (300 mosmol/kg) High urine sodium ( > 30 mmol/L) hematuria, heme granular casts,

debris on urinalysis

Urine in ATN: note blood cells, tubular (white ) cells, debris and characteristic heme granular casts (muddy brown casts)

Toxic Acute Tubular Necrosis

Aminoglycosides, amphotericin, cisplatin etc

Aminoglycosides: accumulate in proximal tubule, cause

cell necrosis tubular obstruction and backleak non-oliguric, creatinine at 7-10 days toxicity most related to duration of

therapy prevent by limiting course to < 10 days

Obstruction and Acute Renal Failure

Males: prostate Females: pelvic malignancy Either:

single kidney and stone, clot retroperitoneal malignancy

lymphoma bladder, rectum

Retroperitoneal fibrosis

Obstruction (2)

Urine flow: anuric to polyuric Isotonic, high urine sodium Diagnosis by ultrasound Treatment:

bladder catheter! Unilateral or bilateral percutaneous

nephrostomy Ureteral stent (retrograde or antegrade)

Good prognosis if caught in < 1-2 months

Normal

Abdo U/S in Obstruction

Other Causes of Acute Renal Failure

Abdominal Compartment Syndrome Normal IP pressure 0-10 mmHg ACS when IP pressure > 25 mmHg Increased renal vein resistance

Reduced RBF and GFR Low urine [Na]

Causes: trauma, pancreatitis, liver transplant, bowel obstruction often with massive amounts of fluid resuscitation

Atheroembolic disease

obstruction and inflammation of small renal vessels due to cholesterol emboli

follows aortography, CABG, aortic OR usually elderly vasculopaths - aortic AS ischemic toes, livido reticularis, abdo

pain slowly progressive renal failure over

weeks bland urinalysis, eospinophilia

Contrast-induced ARF Non-oliguric ARF within 24 h of procedure Cause unknown (vascular vs toxic) Risk factors:

Stage 4-5 (GFR < 30 ml/min) diabetic nephropathy with GFR < 40 ml/min) Congestive heart failure

Prevention: IV saline or IV sodium bicarbonate N-acetylcysteine (controversial)

Prognosis: usually good except DM + CKD 4-5

Less Common Causes of ARF Allergic interstitial nephritis – drug

reaction penicillins, cipro, NSAID’s, Septra etc

Thrombotic Microangiopathy (hemolytic uremic syndrome) Toxemia of pregnancy Bone marrow transplant Cyclosporine Toxigenic E.Coli (Walkerton) Malignant hypertension etc.

Assessment of Patient with ARF History: prior renal function; BP, ECFV Drugs: diuretics, antibiotics, NSAID’s,

ACE inhibitors, angio dye, cyclosporine Physical Exam: BP, JVP, edema, ascites,

peripheral pulses, bruits, urine flow Lab: lytes, creatinine, urea, CBC, blood

film, urinalysis, urine lytes, osmolalityRenal U/S, renal biopsy if dg unclear

Consequences of Acute Renal Failure

ECF volume: pulmonary edema, edema Hyperkalemia if oliguria Uremia: anorexia, nausea, vomiting,

encephalopthy, etc Metabolic acidosis, hypocalcemia,

hyperphosphatemia, anemia Prognosis:

with multiorgan failure in ICU mortality 60-70%

with no other organ failure, prognosis is good

Dialysis for Acute Renal Failure

Indications: Pulmonary edema Hyperkalemia Serum creatinine > 500 umol/L Serum creatinine > 300 with oliguria Methods: Conventional HD (3-5 h, 3-6 days/wk) CRRT - using Prisma machine heparin vs

citrate SLED (sustained low efficiency HD) 8

hours 3-6 days/wk

Case History 1

65 yr old admitted 2 months post CABG+AVR fever, weight loss, dyspnea Febrile, JVP, aortic systolic and diastolic m blood cultures + for strep. Sp. Dg: bacterial endocarditis: gentamicin+ Pen Serum creatinine: Day 1 5 8 10 130 125 165

265 What is differential diagnosis?

Case 1

Differential: Post-infectious GN Ischemic ATN Athero-embolic disease GENTAMICIN-INDUCED

Case History 2 75 yr old with claudication; smoker,

hypertension Aorto-bifemoral graft for AAA + iliac disease 2 days post-op has 2 painful blue toes; good

distal pulses; abdominal pain Creatinine: preop day 1 7 14

28 135 145 165 225

450Urinalysis: trace blood, no protein, no casts?Cause of acute renal failure

Case 2

Differential Ischemic ATN Renal artery thrombosis ATHERO-EMBOLIC DISEASE

Case History 3

45 yr old woman with cholelithiasis 1 wk RUQ pain, pale stools, dark urine,

jaundice 2 days spiking fever, chills, vomiting BP 90/60, HR 110; temp 39; jaundice U/S: dilated bile ducts, distal duct stone Blood cultures: Klebsiella Creatinine 175 260 umol/L; urine=

blood, heme granular casts Diagnosis?

CASE 3

Ischemic ATN Obstructive jaundice Gram-negative bacteremia Hypotension

Case History 4 42 year old primigravida At 34 wks mild increase in BP (140/80) 35 wks: unwell, edema, proteinuria (3+) C-section

Creat HGB Plat ASTPreop 98 125 125 20024 h 175 80 25 150048 h 370 60 10 3500 ?Diagnosis

Case 4

Thrombotic Microangiopathy HELLP syndrome Post-partum acute renal failure

Case 5

50 year old man with known alcoholic cirrhosis Presents with 5 days of nausea, vomiting, severe

epigastric pain, distended abdomen Serum amylase 1,500 = necrotizing pancreatitis Given 3 L crystalloid and colloid for hypotension Requires intubation for acute respiratory failure In ICU: BP 95/65, CVP 25, oliguric

Differential?

Case 5

Differential Ischemic ATN Abdominal compartment syndrome

Summary: Risk Factors for ARF in Surgical Patients Obstructive jaundice Sepsis syndrome - especially with MOF Angiography

dye: renal failure/diabetes atheroembolic disease - vasculopaths

Prolonged use of aminoglycosides (> 7 d)

Hypotension with pre-existing renal disease especially in the elderly

Cyclosporine for transplantation

Chronic Kidney DiseaseGFR ml/min

Stage 1 >90Stage 2 (mild) 60-90Stage 3 (moderate) 30-60 Stage 4 (advanced) 15-30Stage 5 End stage KD < 15

GFR measured or calculated using MDRD equation

Causes/Risk Factors for CKD

Risk FactorsDiabetesHypertensionAgeSmokingHigh CholesterolOrgan

transplantation

CausesDiabetic nephropathyHypertension/

vascularGlomerulonephritisPolycystic KidneysObstructionMultiple myelomaCalcineurin-inhibitors

Patients with Chronic Kidney Disease

You are helping Dr. Robinette do a nephrectomy on a healthy living kidney transplant donor

You ask yourself: what is going to happen to this patient’s kidney function and why?

What Happens Post Donor Nephrectomy?

Serum creatinine rises by 50% (not 100%)

Increase in single nephron GFR of 50% Afferent and efferent arterioles dilate,

increased glomerular blood flow and pressure

Normal life expectancy, no increased risk of renal failure with loss of 50% of nephrons

What if More Nephrons are Lost?

Increased single nephron GFR by afferent and efferent arteriolar dilatation

If lose > 65% of nephrons, get structural changes in glomeruli and arterioles due to hyperfiltration and hypertension

Proteinuria and progressive renal failure Predictors of progessive disease?

Higher serum creatinine Hypertension Amount of proteinuria: > 1 g/d is bad, >3 g

worse

Impact of Chronic Kidney Disease on Surgical Outcomes (1)

Patients with stage 3-5 CKD are at risk:

Already maximally vasodilated Cannot further autoregulate in

response to hypotension: ATN Limited ability to excrete extra

sodium, water and potassium Limited ability to retain sodium and

water

Impact of Chronic Kidney Disease on Surgical Outcomes (2)

Patients with stages 3-5 CKD have increased risk of mortality with surgery

Higher death rates after CABG Higher death rates after aortic

surgery Higher death rates after MI

O.R. of Death at 30 d. Post CABG

>100 80-99 60-79 40-59 0-390

1

2

3

4

5

6

Lok et al:Am Heart J 2004

Creatinine Clearance ml/min

Impact of Renal Dysfunction on Outcomes of CABG

02468

1012141618

1 2 3 4 5

CKD Stage

DeathsStroke> 14 days

Circulation 2006;113:1063

485,000 US patients 2002-3

Mortality Following Arterial Surgery

Elective Urgent All0

10

20

30

40Renal FailureNormal

Gerrard et al:Br J Surg 2002;89:70

Type of Surgery

%

Why Increased Mortality in CKD?

Increased incidence of vascular disease (atherosclerosis)

Risk factors for kidney disease are risk factors for atherosclerosis

Reduced GFR promotes vascular disease: Vascular calcification Chronic inflammation Increased SNS, increased vascular stiffness Increased homocysteine

Case History 6 65 yr old woman assessed in vascular

surgery clinic for 5.5 cm AAA Hypertension (160/90), type 2 DM Urine: negative blood, 1 g/L

proteinuria Creatinine 275 umol/L (eGFR 20

ml/min) What are concerns regarding her low

GFR- what should you do?

Case History 6

Risks: If aortogram: contrast-induced ATN or

atheroembolic disease If OR: hypotension, aortic cross-clamp

inducing ischemic ATN If surgery: markedly increased mortality

riskPlan: (Nothing evidence-based!) request nephrology; cardiac assessment will renal disease progress anyway? -

operate when on dialysis?

Case History 6

Surgery is planned after cardiac assessment

Maintain as stable a BP as possible and avoid hypotension ( < 130 systolic in this patient)

Accurate fluid replacement to avoid volume depletion or overload

Monitor serum potassium (daily lytes)

Case History 7

A 79 year old man with a solitary kidney develops gross hematuria

CT = 2 cm mass in mid-zone of kidney consistent with renal cell Ca

Operate or not? Q: What is mortality rate annually

in 80 year old on dialysis? A: 20-30%

Management of HD Patient

Preserve HD access: lower or upper arm AV fistula or PTFE graft

No BP, IV or venesection in that arm

Call nephrology to arrange dialysis No IV fluids unless patient is

hypovolemic (ask nephrology) No IV potassium unless

hypokalemic (ask nephrology)

Peri-Operative Intravenous Fluid

What is normal intake of water, Na+ and K+? Water: 1.5-2 L/d Sodium: 150 mmol/day Potassium: 50 mmol/day

What is main risk of IV fluid post-op? Hyponatremia from large volume

hypotonic fluid

Prevention of Postoperative Hyponatremia

Avoid hypotonic fluid unless the patient is hypernatremic

Limit volume of I.V. fluid given to meet patient’s needs

Adjust volume to patient’s body weight

Peri-operative IV Fluid Annals Surgery 2003;238:641 RCT of standard vs restricted IV fluid

in patients undergoing colorectal resection

Multicenter study from Denmark Powered to detect a 20% difference

in complications with 80% power 86 patients per group

Peri-operative IV Fluid -Standard

Intra-op 500 ml HAES 6% in NS Third space loss: NS 7 ml/kg/h X1 h,

then 5 ml/kg/h X 2, then .3 ml/kg/h Blood loss: up to 500 ml: 1-1.5 L NS

then HAES Post-op

1-2 L crystalloid/day

Peri-operative IV Fluid: Restricted Intra-op:

No preloading No replacement of third space loss Blood loss: volume/volume with HAES

Post-op 1000 ml 5% D/W for remaining OR day Then oral fluid or IV if needed Furosemide if weight increased by 1

kg

Results

Standard

Restricted

IV fluid OR day

5.4 L 2.7 L*

IV fluid POD 1

1.5 L 0.5 L*

Max increase wt

0.9 kg 3.5 kg*

Complications

40 21*

Compl -major 18 8*

Complication frequency related to IV fluid and wt gain on operative day

A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit

NEJM 2004;350:2247 Previous meta-analysis suggested

albumin resuscitation increased mortality

RCT in 7,000 ICU patients 4% albumin vs crystalloid for fluid No difference in mortality

Summary Be familiar with stages of CKD Interpretation of serum creatinine Risks factors for ARF in surgical

patients Differentiation of prerenal failure

from ATN Impact of CKD stage 3-5 on surgical

outcomes