Another TB patient with renal Another TB patient with renal failure - - PowerPoint PPT Presentation

Another TB patient with renal Another TB patient with renal failure failure

Inter Inter-

• hospital renal meeting

hospital renal meeting 21/3/2007 21/3/2007 KWH KWH

• Drs. SF Chan and SK
• Drs. SF Chan and SK Mak

Mak

Case presentation Case presentation

• 59/M

59/M

• Chronic smoker, nondrinker

Chronic smoker, nondrinker

• History of pulmonary tuberculosis in 2000

History of pulmonary tuberculosis in 2000 completed 6 months treatment with HRZM completed 6 months treatment with HRZM ( ( isoniazid isoniazid, , rifampicin rifampicin, , ethambutol ethambutol and and pyrazinamide pyrazinamide ) )

• Treatment course uneventful

Treatment course uneventful

History of present illness History of present illness

• Presented to chest clinic with chronic

Presented to chest clinic with chronic cough in 2006 cough in 2006

• Sputum culture positive for Mycobacterium

Sputum culture positive for Mycobacterium tuberculosis tuberculosis

• Started on TB treatment on 13/1/2007

Started on TB treatment on 13/1/2007

• isoniazid

isoniazid, , rifampicin rifampicin, , ethambutol ethambutol, , pyrazinamide pyrazinamide and streptomycin and streptomycin

• Tolerate treatment in the first week

Tolerate treatment in the first week

• However, on FU in the second week

However, on FU in the second week…

…

• Complained of

Complained of

• Fever, chills and rigor

Fever, chills and rigor

• Bilateral loin pain

Bilateral loin pain

• Dark

Dark coloured coloured urine with decreased urine output urine with decreased urine output

• Vomiting and

Vomiting and diarrhoea diarrhoea

• Blood streaks in sputum

Blood streaks in sputum

• Denial recent travel/insect bite/herbs nor over

Denial recent travel/insect bite/herbs nor over-

• the

the-

• counter drugs intake

counter drugs intake

• Septic looking with fever 38

Septic looking with fever 38-

• 39

39 0

0C

C

• Dehydrated with hypotension BP

Dehydrated with hypotension BP 98/60mmHg 98/60mmHg

• Sinus tachycardia with HR ~ 120bpm

Sinus tachycardia with HR ~ 120bpm

• Jaundice and mild pallor

Jaundice and mild pallor

316 316 327 327 238 238 AST AST 67 67 101 101 110 110 ALP ALP 11 11 93 93 101 101 Total Total bilirubin bilirubin 30 30 27 27 Globulin Globulin 26 26 30 30 31 31 Albumin Albumin 56 56 58 58 TP TP 883 883 573 573 247 247 170 170 Creatinine Creatinine 31.7 31.7 24.5 24.5 12.5 12.5 10.1 10.1 Urea Urea 108 108 110 110 106 106 106 106 Cl Cl 6.3 6.3 5.2 5.2 5 5 4.9 4.9 K K 138 138 140 140 142 142 140 140 Na Na 23 23 50 50 51 51 APTT APTT 1 1 1.8 1.8 1.6 1.6 INR INR 112 112 179 179 168 168 191 191 Platelet Platelet 11.9 11.9 14 14 14.6 14.6 14.7 14.7 Hb Hb 12.7 12.7 23.1 23.1 19.4 19.4 13.4 13.4 WCC WCC 24/1/2007 24/1/2007 23/1/2007 23/1/2007 22/1/2007 22/1/2007 21/1/2007 21/1/2007

Progress Progress

• Rapidly became

Rapidly became anuric anuric

• Haemodialysis started

Haemodialysis started

Further investigations Further investigations

• Bilirubin

Bilirubin: : unconjugated unconjugated mainly mainly

• LDH 3636 IU/L ( 94

LDH 3636 IU/L ( 94-

• 250 )

250 )

• Haptoglobin

Haptoglobin 0.18 mg/L ( 0.36 0.18 mg/L ( 0.36-

• 1.95 )

1.95 )

• Urine test:

Urine test:

• haemoglobulin

haemoglobulin 4+ 4+

• RBC 100/uL

RBC 100/uL

• myoglobulin

myoglobulin not detected not detected

• urobiliogen

urobiliogen: unfit for test : unfit for test

• No

No haemosiderin haemosiderin pigments pigments

• Direct

Direct coombs coombs’

’ test positive: Anti

test positive: Anti-

• IgG

IgG and Anti and Anti-

• c

c positive positive

• Uric acid 0.48

Uric acid 0.48 mmol mmol/L /L

• Schistocytes

Schistocytes negative negative

Further investigations Further investigations

• Malaria screening negative

Malaria screening negative

• Leptospira

Leptospira IgM IgM negative negative

• Hanta virus negative

Hanta virus negative

• G6PD activity normal

G6PD activity normal

• Anti

Anti-

• HCV negative

HCV negative

• Anti

Anti-

• HIV negative

HIV negative

• ANCA negative

ANCA negative

• ANF/Anti

ANF/Anti-

• GBM

GBM Ab Ab negative negative

• USG abdomen

USG abdomen

• Increased renal parenchymal

Increased renal parenchymal echopattern echopattern without focal renal mass without focal renal mass

• No renal stones or hydronephrosis

No renal stones or hydronephrosis

• No

No ascites ascites

Renal biopsy on Day Renal biopsy on Day 7 7

Renal biopsy Renal biopsy

• Glomeruli

Glomeruli

• 13/28

13/28 glomeruli glomeruli are are sclerosed sclerosed

• The vascular

The vascular glomeruli glomeruli show normal show normal cellularity cellularity and only mild increase in mesangial matrix and only mild increase in mesangial matrix

• Capillary loops are patent and basement

Capillary loops are patent and basement membrane is normal membrane is normal

• No

No vasculitis vasculitis or thrombosis is identified

• r thrombosis is identified
• IF:

IF: -

• ve

ve

Renal biopsy Renal biopsy

• Tubules

Tubules

• Interstitial edema with mild

Interstitial edema with mild lymphoplasmacytic lymphoplasmacytic cells and focal cells and focal intratubular intratubular mononuclear cells; mononuclear cells; eosinophils eosinophils not not conspicuous conspicuous

• Proximal tubules with prominent cell swelling

Proximal tubules with prominent cell swelling

• Many tubules contain fragmented red cells or

Many tubules contain fragmented red cells or granular casts and some contain necrotic granular casts and some contain necrotic cellular debris cellular debris

Iron stain Iron stain

Iron stain Iron stain

Fe deposit: Very fine blue dots in some of the tubular epithelial cells (intracytoplasmic)

Summary Summary

• Acute

Acute haemolytic haemolytic anaemia anaemia with acute with acute tubular necrosis 1 week after the second tubular necrosis 1 week after the second introduction of anti introduction of anti-

• TB treatment

TB treatment

Progress Progress

• Haemolysis

Haemolysis subsided soon after cessation of subsided soon after cessation of anti anti-

• TB treatment

TB treatment

• Normal

Normal Bilirubin Bilirubin on day 2

• n day 2
• Negative

Negative Coomb Coomb’

’s

s test day 9 test day 9

• Haptoglobin

Haptoglobin level raised to normal on day 9 level raised to normal on day 9

• Dialysis dependent, require HD 2X per week

Dialysis dependent, require HD 2X per week

• Gradual return of urine output with slowly

Gradual return of urine output with slowly improving renal function improving renal function

• Last HD session 3 weeks after presentation

Last HD session 3 weeks after presentation

Progress Progress

• Restarted on

Restarted on isoniazid isoniazid and and pyrazinamide pyrazinamide since 13/2/2007; later since 13/2/2007; later levofloxacin levofloxacin and and ethambutol ethambutol

• Polyuria

Polyuria up to 5000ml/day require fluid up to 5000ml/day require fluid replacement replacement

• latest RFT : Urea 9.1mmol/L, Cr

latest RFT : Urea 9.1mmol/L, Cr 128nmol/L 128nmol/L

128

Creatinine AST LDH

25/1

H aem

• dialy

sis

14/2

20/1 27/1 3/2 10/2 17/2 24/2 3/3

Haemoglobinuria Haemoglobinuria and Acute and Acute renal failure renal failure

Adult Adult haemoglobin haemoglobin

• Consists of two alpha and

Consists of two alpha and two beta globulin chain two beta globulin chain

• A

A haem haem group is bound to group is bound to each globulin chain each globulin chain

• The

The haem haem group has a group has a porphyrin porphyrin ring with a ring with a ferrous atom which can ferrous atom which can reversibly bind one oxygen reversibly bind one oxygen molecule molecule

Normal RBC breakdown Normal RBC breakdown

• In the

In the reticuloendothelial reticuloendothelial system system

• The

The haem haem group will be broken down into group will be broken down into Iron ( reutilized ) and Iron ( reutilized ) and Bilirubin Bilirubin ( excreted ( excreted via the via the biliary biliary system ) system )

• No free

No free haem haem pigments in the circulation pigments in the circulation

Intravascular Intravascular Haemolysis Haemolysis

• Destruction of RBC within the circulation

Destruction of RBC within the circulation liberate the liberate the haemoglobulin haemoglobulin

• The free plasma

The free plasma Hb Hb initially bound to initially bound to plasma plasma haptoglobulin haptoglobulin but soon become but soon become saturated saturated

• Filtered by the renal

Filtered by the renal glomerulus glomerulus and enter and enter the urine causing the urine causing haemoglobinuria haemoglobinuria

Pathogenesis of Pathogenesis of haeme haeme pigment pigment induced ARF/ATN induced ARF/ATN

1. 1.

intraluminal intraluminal cast formation cast formation

• When water is progressively reabsorbed from tubular fluid, the

When water is progressively reabsorbed from tubular fluid, the concentration of concentration of myoglobin/haemoglobin myoglobin/haemoglobin rises until it rises until it precipitates, causing obstructive cast formation precipitates, causing obstructive cast formation

2. 2.

renal vasoconstriction renal vasoconstriction

• Haemoglobin

Haemoglobin decreases the renal perfusion by inhibiting the decreases the renal perfusion by inhibiting the vasodilator effect of nitric oxide vasodilator effect of nitric oxide

3. 3.

direct direct haeme haeme-

• protein

protein-

• induced

induced cytotoxicity cytotoxicity

• intratubular

intratubular disintegration of the iron disintegration of the iron-

• carrying

carrying myoglobin/haemoglobin myoglobin/haemoglobin leads to the release of iron, which leads to the release of iron, which catalyses free radical production. These free radicals further catalyses free radical production. These free radicals further potentiate potentiate ischaemic renal damage ischaemic renal damage

Rhabdomyolysis Rhabdomyolysis and and myohemoglobinuric myohemoglobinuric acute renal failure acute renal failure

Kidney Kidney Int Int 1996 1996

Acute renal failure related to the crush syndrome: towards an er Acute renal failure related to the crush syndrome: towards an era of a of seismo seismo-

• nephrology?

nephrology?

Nephrology Dialysis Transplantation Nephrology Dialysis Transplantation 2000 2000

Staining for Staining for haemoglobin haemoglobin

Haemoglobin Haemoglobin cast filling tubular lumen cast filling tubular lumen

Haemoglobinuria Haemoglobinuria and ARF and ARF

• Etiology:

Etiology:

• Paroxysmal nocturnal

Paroxysmal nocturnal hemoglobinuria hemoglobinuria Nephron

Nephron 1984; 1984; Polskie Polskie Archiwum Archiwum Medycyny Medycyny Wewnetrznej Wewnetrznej [polish]1970 [polish]1970

• march

march haemoglobinuria haemoglobinuria Journal of the Association of Physicians of India

Journal of the Association of Physicians of India 1980; 1980; Vojnosanitetski Vojnosanitetski Pregled Pregled [Serbian] [Serbian] 1973 and 1972; New England Journal of Medicine 1973 and 1972; New England Journal of Medicine 1970 1970

• I nfections

I nfections

• typhoid fever

typhoid fever Transactions of the Royal Society of Tropical Medicine & Hygiene

Transactions of the Royal Society of Tropical Medicine & Hygiene 1988 1988

• malaria

malaria Semaine

Semaine des des Hopitaux Hopitaux 1979; Nouvelle 1979; Nouvelle Presse Presse Medicale Medicale 1973 1973

• Transfusion reaction

Transfusion reaction

• transfusion of accidentally frozen blood

transfusion of accidentally frozen blood JAMA 1976

JAMA 1976

• Delayed

Delayed haemolytic haemolytic transfusion reaction transfusion reaction Lancet 1971

Lancet 1971

• I nsect, spider and snake bites

I nsect, spider and snake bites

• scorpion sting

scorpion sting American Journal of Tropical Medicine & Hygiene 1978

American Journal of Tropical Medicine & Hygiene 1978

• Snakebite

Snakebite Nephrology October 2006

Nephrology October 2006

• Wasp

Wasp Nephrology 2005

Nephrology 2005

Haemoglobinuria Haemoglobinuria and ARF and ARF

• Drug

Drug-

• induced

induced

• Antibiotics

Antibiotics

• Rifampicin

Rifampicin British Journal of

British Journal of Haematology Haematology 2002; Reactions Weekly1998 2002; Reactions Weekly1998

• Ceftriaxone

Ceftriaxone Reactions Weekly 2004

Reactions Weekly 2004

• Halofantrine

Halofantrine Reactions Weekly 1992

Reactions Weekly 1992

• Chemotherapy

Chemotherapy

• Oxaliplatin

Oxaliplatin Reactions Weekly

Reactions Weekly 2007 2007

• Ambroxol

Ambroxol Reactions Weekly

Reactions Weekly 2007 2007

• Tretinoin

Tretinoin Reactions Weekly 1997

Reactions Weekly 1997

• I odine and

I odine and Mefenamic Mefenamic acid acid Clinical Nephrology 2001

Clinical Nephrology 2001

• Glycerol

Glycerol British journal of clinical pharmacology 1990; Lancet 1974/1975

British journal of clinical pharmacology 1990; Lancet 1974/1975

• Risedronic

Risedronic acid acid Reactions Weekly

Reactions Weekly 2006 2006

• Miscellaneous

Miscellaneous

• cold trauma

cold trauma Vestnik

Vestnik Khirurgii Khirurgii Imeni Imeni i i -

• i

i –

– Grekova

Grekova 1978 1978

• Arsine toxicity

Arsine toxicity British Medical Journal 1975

British Medical Journal 1975

• duct occlusion coils

duct occlusion coils Heart 1999

Heart 1999

• Henna

Henna International Journal of Clinical Practice 2004

International Journal of Clinical Practice 2004

Investigation of Investigation of red/brown urine red/brown urine

Treatment Treatment

1. 1.

Fluid repletion Fluid repletion

• Volume repletion with isotonic saline can enhance renal

Volume repletion with isotonic saline can enhance renal perfusion and increase the urine flow to wash out the perfusion and increase the urine flow to wash out the

• bstructing casts
• bstructing casts
• Up to 1.5L/hour to maintain urine output ~ 300ml/hour

Up to 1.5L/hour to maintain urine output ~ 300ml/hour

• Less effective after the first 6

Less effective after the first 6-

• 12 hours

12 hours Kidney Int. 1996 Kidney Int. 1996

2. 2.

Forced Forced diuresis diuresis with Alkaline with Alkaline-

• mannitol

mannitol ( No clear ( No clear clinical evidence ) clinical evidence )

• Alkalinization

Alkalinization of urine pH> 6.5:

• f urine pH> 6.5:
• increase solubility of

increase solubility of haeme haeme pigments pigments

• Minimizing the conversion of to the more toxic

Minimizing the conversion of to the more toxic methaemoglobin methaemoglobin

• Mannitol

Mannitol: :

• Induce

Induce diuresis diuresis which minimize which minimize intratubular intratubular haeme haeme pigments pigments deposition and cast formation deposition and cast formation

• Act as a free radical scavenger

Act as a free radical scavenger

Rifampicin Rifampicin-

• induced ARF

induced ARF

• First case reported in 1971 in Germany

First case reported in 1971 in Germany

• Approximate 60 cases published

Approximate 60 cases published

• Typically appears after discontinuous

Typically appears after discontinuous use/reintroduction of use/reintroduction of rifampicin rifampicin

Causes of Renal failure Causes of Renal failure

1. 1.

Tubular blockage by Tubular blockage by haemoglobin haemoglobin after after haemolysis haemolysis causing ATN causing ATN Pathogenesis: Pathogenesis:

• Rifampicin

Rifampicin-

• dependent

dependent IgM IgM and and IgG IgG Ab Ab

• Interact with the I antigen on the surface of the

Interact with the I antigen on the surface of the erythrocytes erythrocytes

• Leading to complement fixation and red blood

Leading to complement fixation and red blood cell cell lysis lysis

• Various interval between drug exposure and

Various interval between drug exposure and

• nset of disease (1 dose to months)
• nset of disease (1 dose to months)

Rif Rif asso

• asso. ARF:

. ARF: pathophysiology pathophysiology, immunological and clinical features , immunological and clinical features AJKD 1998 AJKD 1998

Causes of Renal failure Causes of Renal failure

2. 2.

Acute interstitial nephritis Acute interstitial nephritis

– –

Sudden deterioration of renal function in asymptomatic patients Sudden deterioration of renal function in asymptomatic patients

– –

Onset: days to weeks Onset: days to weeks

3. 3.

Rapidly progressive glomerulonephritis Rapidly progressive glomerulonephritis

– –

Deposition of Ag Deposition of Ag-

• Ab

Ab complexes in the complexes in the golmerulus golmerulus

– –

Uncertain causal relationship; 3 Uncertain causal relationship; 3 -

• 6 weeks after exposure

6 weeks after exposure

4. 4.

Light Light-

• chain proteinuria

chain proteinuria

– –

Polychonal Polychonal kappa and lambda light chains are detected in the urine kappa and lambda light chains are detected in the urine

– –

Biopsy: Biopsy: intratubular intratubular cast formation, tubular necrosis and interstitial edema cast formation, tubular necrosis and interstitial edema

– –

No typical light chain nephropathy features (LC deposition in GB No typical light chain nephropathy features (LC deposition in GBM / TBM) M / TBM)

– –

Onset: 1 Onset: 1 -

• 6 weeks

6 weeks

Rif Rif asso

• asso. ARF:

. ARF: pathophysiology pathophysiology, immunological and clinical features , immunological and clinical features AJKD 1998 AJKD 1998

Clinical picture of post Clinical picture of post-

• rif

rif ARF at ARF at presentations presentations

• 96% were

96% were anuric anuric at presentation at presentation

• Investigations:

Investigations:

• Anaemia

Anaemia -

• 96%

96%

• Intense

Intense haemolysis haemolysis –

– 25%

25%

• Haematuria

Haematuria –

– 33%

33%

• Haemoglobinuria

Haemoglobinuria –

– 16.6%

16.6%

• Proteinuria

Proteinuria –

– 60%

60%

Rifampicin Rifampicin-

• induced acute renal failure: a series of 60 patients

induced acute renal failure: a series of 60 patients Nephrology dialysis transplantation 1998 Nephrology dialysis transplantation 1998

• Progress

Progress

• Urine output returns in 10

Urine output returns in 10-

• 11 days ( mean )

11 days ( mean )

• Renal function recovery

Renal function recovery

• 40% in 30 days

40% in 30 days

• 96.6% in 90 days

96.6% in 90 days

• Mortality: 1.6%

Mortality: 1.6%

• Prognostic factors

Prognostic factors

1. 1.

Severity of the immune process Severity of the immune process

2. 2.

Duration of Duration of anuric anuric phase phase

Rifampicin Rifampicin-

• induced acute renal failure: a series of 60 patients

induced acute renal failure: a series of 60 patients Nephrology dialysis transplantation 1998 Nephrology dialysis transplantation 1998

Thank you! Thank you!