Trouble-shooting

Acute on Chronic Renal Failure

- A Case-based Discussion

Dr Grace Lee

Visiting Consultant

SGH & NUH

Cre

atinin

e

TIme

Acute Kidney Injury (AKI)

• Abrupt (within 48 h) absolute Cr 0.3 mg/dl (26.4 umol/L)

from baseline

• Cr 50%

• Oliguria 0.5 ml/kg/h for > 6 hours

(AKIN – Acute Kidney Injury Network)

DEFINITIONS

Chronic Kidney Disease (CKD)

• Evidence of structural or functional abnormalities

(abnormal urinalysis, imaging studies or histology) that

persists for at least 3 months, with or without

decreased GFR (<60 ml/min/1.73 m2)

OR

• in GFR, with or without evidence of kidney disease

(K/DOQI – Kidney Disease Outcomes Quality Initiative)

Acute on Chronic Renal Failure

Abrupt rise in serum creatinine in a patient with CKD Why is it important to diagnose acute on chronic renal

failure?

Prompt correction of the acute element will allow the serum

creatinine to return to baseline (albeit abnormal), and delay the

onset of renal replacement therapy

Renal perfusion

• Volume depletion – bleeding, GI,

urinary or cutaneous loss

• Effective volume depletion – heart

failure, septic shock, cirrhosis

• Acute tubular necrosis (ATN)

• Acute interstitial nephritis – drug

related, multiple myeloma

• Tumor lysis syndrome

• Vasculitis

• Thromboembolic disease

• HUS/TTP

• Malignant hypertension

• Idiopathic

• Secondary – neoplasm, drugs

• Stones

• Tumor (ureter, prostate)

PRE-RENAL

VASCULAR DISEASES

GLOMERULAR DISEASES

TUBULOINTERSTITIAL DISEASES

OBSTRUCTIVE UROPATHY

CAUSES OF ACUTE RENAL FAILURE

Wei SS, 1996

Common Causes of Acute on Chronic Renal Failure

Pre-renal

• Dehydration

• Hypotension

• Heart Failure

• Uncontrolled hypertension

• RAS Blocker

• Infection

Recent addition or in diuretic , vomiting, diarrhoea

Recent addition or antihypertensive agents

URTI, Chest Infection, Urinary Tract Infection

Particularly in volume depleted patients

Tubulointerstitial

• NSAIDs & Cox2 Inhibitors

• Radio-contrast

• Traditional Medicine

ACEi, ARB, renin inhibitor, esp in volume depleted patient

Case 1

8 Jan 2009

• 80 y Chinese male

• Referred by cardiologist for evaluation of Cr 501 umol/L

5 Jan 2009

Total volume 750 ml

24h protein 0.07 g/day

Creatinine 501 umol/L

CCl 6 ml/min

Past History

• HT, No DM

• Atrial fibrillation, Pacemaker X 12 years

• Enlarged prostate X 4 years on Avodart

• Informed that creatinine has been elevated X 3-4 years

Present History

• Right leg swelling with redness and pain

• Dryness of mouth and hand tremors

Oct 05 Feb 07 Sept 07 Feb 08 Nov 08

Cr (umol/L) 80 140 105 130 178

u/s kidneys (July 08) - normal

Case 1

Physical examination

• BP 100/60

• Tongue dry ++, No pedal odema

• Heart – S1,S2 with ESM, Apex beat 68 (AF), Lungs – clear

• Abd – unremarkable

• No vascular bruits

• Right big toe – bruised with blood clot on nail bed

• Right leg – swollen and red

Atacand 8 mg bd

( 6/52 ago)

Warfarin 2.5 mg om

Xanax 0.25 mg on, PRN

Allopurinol 300 mg om

Amitriptyline 25 mg on, PRN

Spironolactone 25 mg bd

Lasix 80 mg bd

Avodart 0.5 mg om

Fe fumarate 200 mg om

Flumicil 600 mg om

Folate 5 mg om

Recormon 4000U 1X/week

Case 1

What is the cause of the acute on

chronic renal failure?

A. Dehydration

B. Cellulitis of the right leg

C. Drug induced

D. All of the above

Case 1

What investigations to order?

• Urea/Electrolytes/Creatinine

• Urine microscopy and culture

• Full blood count

• Urine Bence-Jones protein

• Antinuclear antibody

• U/S kidneys/bladder

Case 1 - Results

Full blood count

• Hb 10.9, twc 7,090, Plt 199,000

No “obvious” infection

? Dehydration

No GN, UTI

Ultrasound kidneys – kidneys normal in appearance,

right renal cyst

U/E, Cr

• Urea 45.3, Cr 400, K 5.7, HCO3 27, Na 134

• TP 79, Alb 48

Urine FEME

• rbc nil, wbc 0-2, protein negative

Collagen screen

• ANA negative, ANCA negative

Urine Bence-Jones protein – negative

• ARB

• Spironolactone

Case 1 What is the cause of the acute on chronic renal failure?

A. Dehydration

B. Cellulitis of the right leg

C. Drug induced

D. All of the above

5/1/09 8/1/09 16/1/09 3/2/09 24/2/09

Cr (umol/L) 501 400 235 143 138

Urea (mmol/L) - 45.3 25.9 15.5 11.8

K (mmol/L) - 5.7 5.6 4.1 6.3

Treatment

• Stop Spironolactone

• Reduce Lasix 80 mg om (from bd)

• Reduce Atacand 8 mg om (from bd)

• Augmentin 625 mg bd

• Encourage oral fluids

0

50

100

150

200

250

300

Baseline 1 2 3 4

Weeks

Cre

ati

nin

e,

um

ol/

L ACEi or ATRA Started

A

C

B

A Individuals with normal renal function B Individuals with normal renal function with volume depletion, heart failure, or bilateral renal artery stenosis C Individuals with abnormal renal function

Bakris et al. Arch Int Med, 2000;160:685-693

0

50

100

150

200

250

300

Baseline 1 2 3 4

Weeks

Cre

ati

nin

e,

um

ol/

L ACEi or ATRA Started

A

C

B

Limited elevation in creatinine ie. 30% or less above baseline after initiation of ACEi or ATRA in patients with renal insufficiency

Increase will occur with first 2 weeks of therapy initiation and be stable within 2-4 weeks

Acute rise in previous stable patients due to (1)diuretics (2)NSAIDs (3)volume depletion

Case 2

18 Sept 2009

• 68 y Chinese male

• Referred by endocrinologist for evaluation of Cr 207 umol/L

Past History

• DM > 20 yrs, HT followed DM

• Cholesterol

• No admissions to hospital

Present History

• No complaints

Feb 07 Apr 08 Oct 08 May 09 Sept 09

Cr (umol/L) 143 157 141 131 207

A/C ratio (mg/mmol) 579 1782 6028

Novomix 26U om & 16U on

Metformin 250 mg bd

Cardiprin 100 mg om

Amlodipine 10 mg om

Simvastatin 20 mg om

Cozaar 50 mg bd

Case 2

Physical examination

• BP 130/60

• Pedal odema (to mid-shin)

• Right carotid bruit

• Heart – S1,S2 with ESM, Lungs – clear

• Abd – unremarkable, no bruits

What is the cause of the acute on chronic renal failure?

A. Heart Failure

B. Natural progression of diabetic nephropathy

C. De-novo glomerulonephritis

Case 2 - Investigations

Ultrasound kidneys – kidneys normal in appearance

TP/Alb

• TP 48, Alb 23

Urinanalysis

• rbc 3-5, wbc nil, Alb +++, casts – few granular

• 24 hour urine protein – 5.94 g/day

Collagen screen

• ANA negative, ANCA negative

Urine Bence-Jones protein – negative

Nephrotic syndrome with

bland urinary sediment

Renal biopsy – Diffuse mesangial proliferative GN with global

and segmental sclerosis, consistent with diabetic alterations

What is the cause of the acute on chronic renal failure?

A. Heart Failure

B. Natural progression of diabetic nephropathy

C. De-novo glomerulonephritis

Case 2

• Acute onset of nephrotic syndrome

• Histological changes can also be idiopathic

Treatment

• Screened for Hepatitis and HIV (all negative, HBSAb +)

• Started on Cyclosporin A (Oct 09)

30/12/09 27/2/10 8/9/10 31/1/11 29/8/11

Cr (umol/L) 179 194 159 147 151

Alb (g/L) 23 32 - 41 45

TUP (g/day) 5.40 - 0.87 0.80 0.60

Indications for renal biopsy in diabetic patients

• Onset of proteinuria < 5 yrs after onset of type 1 diabetes

(10-15 years for onset of overt diabetic nephropathy)

• Acute onset of renal disease

• Active urinary sediment (rbc, cellular casts)

• Absence of retinopathy and neuropathy in type 1 diabetes

• Signs / symptoms of another systemic disease

Important causes sudden increase in proteinuria in

diabetic patients

• De novo idiopathic GN

• Malignancy with associated GN (usually membranous)

• Multiple Myeloma

Avoiding acute on chronic renal failure

• Recognise patients at risk

- Abnormal creatinine

- Elderly

- Diabetes and other co-morbid conditions

• Avoid NSAIDS and Cox2 inhibitors

• RAS blockers - use with care

- Avoid introduction in volume depleted patient and/or hyperkalemia

- Monitor creatinine and potassium closely after initiation or increase in dose (with 1-2 weeks)

• Avoid using radio-contrast, when possible