Approach to azotemic patients Case presentation

Shiva Seyrafian

Approach to azotemic patients

At the end of this class, you should be able to

Diagnose acute kidney injury (AKI)

Define the etiologies of AKI

Describe the evaluation of AKI

Diagnose chronic kidney disease (CKD)

Define the stages of CKD

Describe the evaluation of CKD

Discuss CKD risk factors and management of them.

Evaluation of Renal FailureIs the renal failure acute or chronic?

laboratory values do not discriminate between acute vs. chronic

Oliguria supports a diagnosis of acute renal failure

History of renal disease and azotemia helps to diagnose CKD.

Clues to chronic disease

Pre-existing illness – DM, HTN, age, vascular disease.

Uremic symptoms – fatigue, nausea, anorexia, pruritus, altered taste sensation, hiccups.

Small, echogenic kidneys by ultrasound.

5 Key Steps in Evaluating Acute kidney Injury

1. Obtain a thorough history and physical; review the chart in detail

2. Do everything you can to accurately assess volume status

3. Always order a renal ultrasound

4. Look at the urine

5. Review urinary indices

Case 1

A 42 year old male is admitted to the SICU after sustaining multiple trauma. His course is complicated by Enterobacter sepsis with profound hypotension requiring support with intravenous dopamine. The urine output has gradually decreased to only 300 ml per day. The urine sodium is 78.

Ischemic Acute Renal Failure

A form of ATN often following a prerenal insult

Late proximal tubule and medullary thick ascending limb most susceptible

Severity of renal failure correlates with duration of insult

Treatment is to optimize renal perfusion, avoid additional nephrotoxic insults and other supportive measures

Conditions that Lead to Pre-renal Acute Renal Failure

Generalizedor Localized Reduction in

Renal Blood Flow

IschemicAcute Renal Failure

Intravascular Volume Depletion

Decreased Effective Circulating VolumeCHF Cirrhosis Nephrosis

MedicationsCYA, TacrolimusACE inhibitors NSAIDSRadiocontrast Amphotericin BAminoglycosides

HepatorenalSyndrome

Sepsis

Large-vessel Renal Vascular DiseaseRenal Artery ThrombosisRenal Artery EmbolismRenal Artery Stenosis or Crossclamping

Small-vessel Renal Vascular DiseaseVasculitis AtheroemboliThrombotic MicroangiopathiesTransplant Rejection

Phases of Ischemic Epithelial Tubular Injury

Time

GFR

Pre-renal

Initiation

Extension

MaintenanceRecovery

Risk Factors for Ischemic Tubular Injury

Volume depletion

Aminoglycosides

Radiocontrast

NSAIDs, Cox-2 inhibitors

Sepsis

Rhabdomyolysis

Pre-existing renal disease

HTN

Diabetes mellitus

Age > 50

Cirrhosis

Case 2

A 56 y.o. male presents with complaints of persistent fever, chills, sore throat, and myalgias for the past 14 days. Ten days ago he started taking amoxicillin.

His physical exam is remarkable for fever to 38.6oC, an exudative pharyngitis and a diffuse maculopapular rash.

Laboratory Data Result Normal Range

Serum Na 134 mEq/L 135-145

K 5.7 mEq/L 3.5-5

Cl 106 mEq/L 100-111

Total CO2 14 mEq/L 24

BUN 46 mg/dL 4-15

Creatinine 3.8 mg/dL 0.6-1.0

Glucose 96 mg/dL 60-100

Whole blood

WBC 12 x109/L 4.5-11.0

Hgb 11 gm/dL 13.5-17.5

Hct 33 % 41.0-53.0

Platelets 216 x109/L150-440

Urine

Specific gravity 1.010 1.002-1.036

Protein 2+ Negative

Blood TraceNegative

Glucose Negative Negative

The urine sediment shows 3-5 RBC’s/h.p.f., 20-25 WBC’s/h.p.f., coarse granular and white cell casts, and rare red cell casts.

Case 2…

Acute Interstitial Nephritis-Etiology

• Allergic/Drug induced• Autoimmune

– Sarcoid -SLE– Sjogren’s

• Toxins– Chinese herb nephropathy -Heavy metals– Light chain cast nephropathy

• Infiltrative– Leukemia– Lymphoma

• Infections (Legionella, CMV, HIV, Toxoplasma)

Acute Interstitial NephritisClinical Presentation

• Non-oliguric ARF• Fever in allergic and infectious types (except NSAID type)• Rash in allergic type (except NSAID induced)• Eosinophilia• UA: WBC casts

Eosinophiluria (allergic)Hematuria (NSAID related)

Common Causes of Drug Induced AIN

• NSAIDS• Antibiotics

– Penicillins• methicillin• Ampicillin, amoxacillin, carbenacillin, oxacillin• Cephalosporins

– Quinolones (ciprofloxacin)– Anti-tuberculous medications (rifampin, INH, ethambutol)– Sulfonamides (TMP-SMX, furosemide, thiazides)

• Miscellaneous– Allopurinol, cimetidine, dilantin

Acute Interstitial NephritisTreatment

• Withdrawal of offending agent

• Treatment of underlying process if infectious/autoimmune etiology

• Trial of corticosteroids, especially in allergic presentations1 mg/kg/day or 2 mg/kg every other day– No randomized trials proving efficacy– Reversal of renal failure usually seen in < 6 weeks

Case 3

A 58 y/o woman referred to clinic due to abdominal pain, anorexia, fever and icterus. She had hx of HTN and DM. BP= 100/70, BW= 68 kg.T= 38.8 In US there was a common bile duct stone.

Lab: WBC= 20,000, Hb= 14.5, plt= 260000, BilT=5, Bill D= 4, AST= 70 ALT= 75, AlPh= 289, BUN= 25, Cr= 1.4

The physician admitted her and ordered gentamycin 80 mg tid for 7 days.

Patient recovered from fever and pain but 10 days later she developed nausea, vomiting, and edema. BP=160/100

Lab values

WBC 14500 Alb 3.9 U/A

Hb 11.5 pH 7.30 SG 1010

Plt 285000 HCO3 16 WBC 8-10

BUN 58 pCO2 38 RBC 6-8

Cr 5.4 AST 42 Ren epith 5-7

Na 139 ALT 57 Cast gran 5-6

K 5.2 AlPh 230

Ca 8.8 Bill T 1.8

P 5.6 Bill D 1

BS 186

What is the cause of vomiting?

How much is her eGFR? (First and last)

Calculations

Cockcroft-Gault Men: CrCl (mL/min) = (140 - age) x wt (kg)

SCr x72

Women: multiply by 0.85

MDRD GFR (mL/min per 1.73 m2) = 186 x (SCr x

0.0113)-1.154 x (age)-0.203 x (0.742 if female) x (1.12 if African-American

eGFR: (F, age= 58, BW= 68)

Cr= 1.4 Cr=5.4

CG 1= 47 ml/min CG 2= 12 ml/min

MDRD 1= 41 ml/min MDRD 2= 8.6 ml/min

What is the cause of azotemia?

Which kind of renal failure has she developed?

What is your prescription?

What would be her prognosis?

Aminoglycoside Nephrotoxicity

Generally presents 1 week after exposure

Non-oliguric

Low trough levels do not guard against nephrotoxicity

Incidence of ATN

10% after 1 week

40% after 2 weeks

Risk factors for ATN

Advanced age - Superimposed sepsis

Liver disease - Hypotension

CKD (DM-HTN)

Case

A 60 Y/O male patient with Hx of HTN and IHD, his cardiologist recommended coronary angiography due to recent chest pain.

Before angio: BUN= 23, Cr= 1.3, Na=138, K=4.5, Hb= 14.

3 days after angiography he developed edema, nausea and BP= 170/95, BUN=55 Cr=4.3 K=5.2 Na=132 U/A: SG= 1.011, Blood 1+, Pr 1+, WBC=5-7, RBC= 4-6, R epithelial cell= 3-4, cast granular+

What’s your diagnosis?

And what is his prognosis?

Case

A 60 Y/O male patient with Hx of HTN and IHD, his cardiologist recommended coronary angiography due to recent chest pain.

Before angio: BUN= 23, Cr= 1.3, Na=138, K=4.5, Hb= 14.

3 days after angiography he developed edema, nausea and BP= 170/95, BUN=55 Cr=4.3 K=5.2 Na=132 U/A: SG= 1.011, Blood 1+, Pr 1+, WBC=5-7, RBC= 4-6, R epithelial cell= 3-4, cast granular+

What’s your diagnosis?

And what is his prognosis?

Case

Radiocontrast-induced acute renal failure

10 days later: his sCr= 1.8, BUN= 25, K= 4.5

Radiocontrast-Induced Acute Renal Failure

Induces renal vasoconstriction and direct cytotoxicity via oxygen free radical formation

Risk factors:

Renal insufficiency - Diabetes

Advanced age - > 125 ml contrast

Hypotension

Usually non-oliguric ARF; irreversible ARF rare

Case 4

A 24 y/o renal transplant woman admitted to hospital for fever, tender vesicular rash on left side of abdomen and back in the spinal nerve root, from 4 days ago. T= 38.5, BP= 135/85 Her Cr= 1.8 mg/dl, BUN=28 mg/dl, WBC= 15000, Hb= 12g/dl. U/A: WBC= 3-4 RBC= 4-5

She received acyclovir 500 mg IV tid. After 5 days became anorectic and developed vomiting, but fever recovered.

Now Cr= 6 mg/dl, BUN= 67, Na= 135, K= 5.3, Ca=8.2, P= 4.7, Alb=3.4, U/A: RBC= 8-10, WBC= 10-14, Cast granular=3-4.

Acute Renal Failure due toIntratubular Obstruction

CrystalluriaEthylene glycol: Calcium oxalate

Tumor lysis: Urate and Calcium phosphate

Medications Acyclovir

Methotrexate

Sulfonamides

Anti-retroviral agents

Myeloma cast nephropathy

Case 5

A 35-year-old female presents with a one month history of periorbital and lower extremity edema. Over two days prior to presentation she has experienced arthralgias in her wrists and elbows. On physical examination she is in no acute distress. Blood pressure is 162/94, temperature 37.4 . Her skin exam is significant for a malar erythematous rash. The heart and lungs are normal. There is 3+ edema to the thighs bilaterally.

Laboratory Data Result Normal Range

SerumNa 138 mEq/L135-145

K 4.2 mEq/L 3.5-5

Cl 108 mEq/L 100-111

Total CO2 17 mEq/L 24

BUN 75 mg/dL 4-15

Creatinine 3.5 mg/dL 0.6-1.0

Glucose 83 mg/dL 60-100

Anti-nuclear antibody1:160 Negative

Whole blood

WBC 5.9 x109/L 4.5-11.0

Hgb 11.9 gm/dL 13.5-17.5

Hct 34 % 41.0-53.0

Platelets 153 x109/L 150-440

Urine

Specific gravity 1.015 1.002-1.036

Protein 3+ Negative

Blood 3+ Negative

RBC >50/h.p.f . 0-4

Sodium 10 mEq/L Variable

Acute Glomerulopathies

RPGN most commonly seen with:

Lupus nephritis (DPGN, class IV)

Pauci-immune GN (ANCA associated)

Anti-GBM disease

less commonly: IgA, post-infectious

Nephrotic presentations of ARF

Collapsing FSGS (HIV nephropathy)

Minimal change disease with ATN

Thrombotic microangiopathies (HUS, TTP, malignant hypertension, scleroderma kidney, pre-eclampsia)

Atheroembolic Renal Disease

ARF in patient with erosive atherosclerosis. Often follows aortic manipulation (angiography, surgery, trauma) or anticoagulation.

Pattern is often an acute worsening of renal function due to showering of emboli, followed by more insidious progression over several weeks to months due to ongoing embolization of atheromatous plaques

. Livedo reticularis

. Nephritic sediment, eosinophilia, eosinophiluria, low C3. Poor prognosis

Livedo Reticularis

Case

47 y/o female presents for routine dental care

PMH: chronic renal failure, kidney transplant 4 yrs ago and doing well

Meds: prednisolone, cyclosporine, mycophenolate mofetil

VS: BP: 145/87, PR: 70

What are the potential problems to consider in this patient?

Susceptibility to infection

Management recommendation: Consultation with patient’s transplant

doctor

Antibiotic prophylaxis

Daily antibacterial mouth rinses(chlorhexidine)

Case

CKL is a 68 year-old woman with DM and HTN who presents for a routine visit. She complains of mild fatigue and leg swelling but is otherwise asymptomatic.

Case…

On physical examination: Weight 55 kg with BP 155/90 mm Hg Funduscopy reveals AV nicking with cotton-wool

exudates Unremarkable cardiac exam with diffusely reduced

peripheral pulses and a right femoral bruit Trace pedal edema

Medications: HCTZ 25 mg/d Insulin

Labs

18 months ago, her serum Cr: 1.5 mg/dL

One year ago, sCr: 1.6 mg/dL

How can we assess her degree of kidney dysfunction?

Calculations

Cockcroft-Gault Men: CrCl (mL/min) = (140 - age) x wt (kg)

SCr x72

Women: multiply by 0.85

MDRD GFR (mL/min per 1.73 m2) = 186 x (SCr x

0.0113)-1.154 x (age)-0.203 x (0.742 if female) x (1.12 if African-American

What is CKD?

Presence of markers of kidney damage for three months, as defined by structural or functional abnormalities of the kidney with or without decreased GFR, manifest by either pathological abnormalities or other markers of kidney damage, including abnormalities in the composition of blood or urine, or abnormalities in imaging tests.

The presence of GFR <60 mL/min/1.73 m2 for three months, with or without other signs of kidney damage as described above.

Stages of CKD

Stage 1*: GFR >= 90 mL/min/1.73 m2 Normal or elevated GFR

Stage 2*: GFR 60-89 (mild)

Stage 3: GFR 30-59 (moderate)

Stage 4: GFR 15-29 (severe; pre-HD)

Stage 5: GFR < 15 (kidney failure)Am J Kidney Dis 2002; 39 (S2): S1-246

Case cont.

Recheck her sCr: 1.7 mg/dL

CrCl (age 68 yrs; wt 55 kg): 27 mL/min

MDRD: 32 mL/min/1.73 m2

How can we quantify CKD?

What next doc?

Identify reversible causes

Think about volume contraction, urinary obstruction, or toxic effects of medications

Rx

ACEs/ARBs

NSAIDs

Aminoglycosides and amphotericin B

IV radiocontrast agents

Other etiologies

Renovascular disease

Glomerulonephritis

Nephrotic syndrome

Hypercalcemia

Multiple myeloma

Chronic UTI

Management

Identify and treat factors associated with progression of CKD

HTN

Proteinuria

Glucose control

Hypertension

Target BP <130/80 mm Hg <125/75 mm Hg

pts with proteinuria (> 1 g/d)

Consider several anti-HTN medications with different mechanisms of activity ACEs/ARBs Diuretics CCBs HCTZ (less effective when GFR < 20)

Proteinuria

Single best predictor of disease progression

Normal albumin excretion <30 mg/24 hours

Microalbuminuria 20-200 g/min or 30-300 mg/24 hours

Macroalbuminuria >300 mg/24 hours

Nephrotic range proteinuria >3 g/24 hours

Continue HCTZ; add ACE and consider CCB to maintain BP <125/75 mm Hg

What biochemical abnormalities are characteristic of CKD? Or which laboratory tests and radiographic studies would you order?

Evaluation for CKD

Blood

CBC with diff

SMA-7 with Ca2+ and phosphorous

PTH

HBA1c

LFTs and FLP

Uric acid and Fe2+ studies

Urine

Urinalysis with microscopy

Spot urine for microalbumin

24-urine collection for protein and creatinine

Ultrasound

Metabolic changes with CKD

Hemoglobin/hematocrit

Bicarbonate

Calcium

Phosphate

PTH

Triglycerides

Metabolic changes…

Monitor and treat biochemical abnormalities

Anemia

Metabolic acidosis

Mineral metabolism

Dyslipidemia

Nutrition

Metabolic changes…

Monitor and treat biochemical abnormalities

Anemia

Metabolic acidosis

Mineral metabolism

Dyslipidemia

Nutrition

Treating Anemia

Epoetin alfa (rHuEPO; Epogen/Procrit)

HD: 50-100 U/kg IV/SC 3x/wk

Non-HD: 10,000 U qwk

Darbepoetin alfa (Aranesp)

HD: 0.45 g/kg IV/SC qwk

Non-HD: 60 g SC q2wks

Metabolic acidosis

Muscle catabolism

Metabolic bone disease

Sodium bicarbonate Maintain serum bicarbonate > 22 meq/L 0.5-1.0 meq/kg per day Watch for sodium loading

Volume expansion

HTN

NEJM 2000; 342(20): 1478-83

Mineral metabolism

Calcium and phosphate metabolism abnormalities associated with:

Renal osteodystrophy

Calciphylaxis and vascular calcification

14 of 16 ESRD/HD pts (20-30 yrs) had calcification on CT scan

3 of 60 in the control group

JAMA 1993; 269(23): 3015-23

Dyslipidemia

Abnormalities in the lipid profile

Triglycerides

Total cholesterol

NCEP recommends reducing lipid levels in high-risk populations

Targets for lipid-lowering therapy considered the same as those for the secondary prevention of CV disease

Kidney Int 1995; 47(1): 186-92

CV disease

70% of HD patients have concomitant CV disease

Heart disease leading cause of death in HD patients

LVH can be a risk factor

Am J Kidney Dis 2001; 37(6): 1191-200

CV disease II

Patients with CKD (non-HD) have poor prognosis after MI

Prospective CCU registry of 1724 pts with STEMI

Graded increase in RR of post-infarct complications: arrhythmia, heart block/asystole, acute pulmonary congestion, acute MR, and cardiogenic shock

Decreased survival over 60 months (RR 8.76; p<0.0001)

Key points

The serum creatinine level is not enough!

Target BP for CKD

<130/80 mm Hg

<125/75 mm Hg in proteinuria

HTN and proteinuria are the two most important modifiable risk factors for progressive CKD