Another TB patient with renal failure. Inter-hospital renal meeting 21/3/2007 KWH Drs. SF Chan and SK Mak

Transcription

1 Another TB patient with renal failure Inter-hospital renal meeting 21/3/2007 KWH Drs. SF Chan and SK Mak

2 Case presentation 59/M Chronic smoker, nondrinker History of pulmonary tuberculosis in 2000 completed 6 months treatment with HRZM ( isoniazid, rifampicin, ethambutol and pyrazinamide ) Treatment course uneventful

3 History of present illness Presented to chest clinic with chronic cough in 2006 Sputum culture positive for Mycobacterium tuberculosis Started on TB treatment on 13/1/2007 isoniazid, rifampicin, ethambutol, pyrazinamide and streptomycin

4 Tolerate treatment in the first week However, on FU in the second week

5 Complained of Fever, chills and rigor Bilateral loin pain Dark coloured urine with decreased urine output Vomiting and diarrhoea Blood streaks in sputum Denial recent travel/insect bite/herbs nor over-the the- counter drugs intake

6 Septic looking with fever C Dehydrated with hypotension BP 98/60mmHg Sinus tachycardia with HR ~ 120bpm Jaundice and mild pallor

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8 AST AST ALP ALP Total Total bilirubin bilirubin Globulin Globulin Albumin Albumin TP TP Creatinine Creatinine Urea Urea Cl Cl K Na Na APTT APTT INR INR Platelet Platelet Hb Hb WCC WCC 24/1/ /1/ /1/ /1/ /1/ /1/ /1/ /1/2007

9 Progress Rapidly became anuric Haemodialysis started

10 Further investigations

11 Bilirubin: unconjugated mainly LDH 3636 IU/L ( ) Haptoglobin 0.18 mg/l ( ) Urine test: haemoglobulin 4+ RBC 100/uL myoglobulin not detected urobiliogen: : unfit for test No haemosiderin pigments Direct coombs test positive: Anti-IgG and Anti-c positive Uric acid 0.48 mmol/l Schistocytes negative

12 Further investigations Malaria screening negative Leptospira IgM negative Hanta virus negative G6PD activity normal Anti-HCV negative Anti-HIV negative ANCA negative ANF/Anti-GBM Ab negative

13 USG abdomen Increased renal parenchymal echopattern without focal renal mass No renal stones or hydronephrosis No ascites

14 Renal biopsy on Day 7

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18 Renal biopsy Glomeruli 13/28 glomeruli are sclerosed The vascular glomeruli show normal cellularity and only mild increase in mesangial matrix Capillary loops are patent and basement membrane is normal No vasculitis or thrombosis is identified IF: -ve

19 Tubules Renal biopsy Interstitial edema with mild lymphoplasmacytic cells and focal intratubular mononuclear cells; eosinophils not conspicuous Proximal tubules with prominent cell swelling Many tubules contain fragmented red cells or granular casts and some contain necrotic cellular debris

20 Iron stain

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

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

24 Progress Haemolysis subsided soon after cessation of anti-tb treatment Normal Bilirubin on day 2 Negative Coomb s test day 9 Haptoglobin level raised to normal on day 9 Dialysis dependent, require HD 2X per week Gradual return of urine output with slowly improving renal function Last HD session 3 weeks after presentation

25 Progress Restarted on isoniazid and pyrazinamide since 13/2/2007; later levofloxacin and ethambutol Polyuria up to 5000ml/day require fluid replacement latest RFT : Urea 9.1mmol/L, Cr 128nmol/L

26 LDH Haemodialysis AST 25/1 14/2 128 Creatinine 20/1 27/1 3/2 10/2 17/2 24/2 3/3

27 Haemoglobinuria and Acute renal failure

28 Adult haemoglobin Consists of two alpha and two beta globulin chain A haem group is bound to each globulin chain The haem group has a porphyrin ring with a ferrous atom which can reversibly bind one oxygen molecule

29 Normal RBC breakdown In the reticuloendothelial system The haem group will be broken down into Iron ( reutilized ) and Bilirubin ( excreted via the biliary system ) No free haem pigments in the circulation

30 Intravascular Haemolysis Destruction of RBC within the circulation liberate the haemoglobulin The free plasma Hb initially bound to plasma haptoglobulin but soon become saturated Filtered by the renal glomerulus and enter the urine causing haemoglobinuria

31 Pathogenesis of haeme pigment induced ARF/ATN 1. intraluminal cast formation When water is progressively reabsorbed from tubular fluid, the concentration of myoglobin/haemoglobin rises until it precipitates, causing obstructive cast formation 2. renal vasoconstriction Haemoglobin decreases the renal perfusion by inhibiting the vasodilator effect of nitric oxide 3. direct haeme-protein protein-induced induced cytotoxicity intratubular disintegration of the iron-carrying myoglobin/haemoglobin leads to the release of iron, which catalyses free radical production. These free radicals further potentiate ischaemic renal damage Rhabdomyolysis and myohemoglobinuric acute renal failure Kidney Int 1996 Acute renal failure related to the crush syndrome: towards an era a of seismo-nephrology? Nephrology Dialysis Transplantation 2000

32 Staining for haemoglobin

33 Haemoglobin cast filling tubular lumen

34 Haemoglobinuria and ARF Etiology: Paroxysmal nocturnal hemoglobinuria Nephron Nephron 1984; Polskie Archiwum Medycyny Wewnetrznej [polish]1970 march haemoglobinuria Journal of the Association of Physicians of India 1980; Vojnosanitetski Pregled [Serbian] 1973 and 1972; New England Journal of Medicine 1970 march Infections typhoid fever Transactions of the Royal Society of Tropical Medicine & Hygiene 1988 malaria Semaine des Hopitaux 1979; Nouvelle Presse Medicale 1973 malaria Transfusion reaction transfusion of accidentally frozen blood JAMA 1976 Delayed haemolytic transfusion reaction Lancet 1971 Insect, spider and snake bites scorpion sting American Journal of Tropical Medicine & Hygiene 1978 Snakebite Nephrology October 2006 Wasp Nephrology 2005

35 Haemoglobinuria and ARF Drug-induced Antibiotics Rifampicin British Journal of Haematology 2002; Reactions Weekly1998 Ceftriaxone Reactions Weekly 2004 Halofantrine Reactions Weekly 1992 Rifampicin Ceftriaxone Halofantrine Chemotherapy Oxaliplatin Reactions Weekly 2007 Ambroxol Reactions Weekly 2007 Tretinoin Reactions Weekly 1997 Iodine and Mefenamic acid Glycerol Risedronic acid Reactions Weekly acid Clinical Nephrology 2001 Glycerol British journal of clinical pharmacology 1990; Lancet 1974/1975 Reactions Weekly 2006 Miscellaneous cold trauma Vestnik Khirurgii Imeni Arsine toxicity British Medical Journal 1975 duct occlusion coils Heart 1999 Henna Imeni i - i Grekova 1978 Henna International Journal of Clinical Practice 2004

36 Investigation of red/brown urine

37 1. Fluid repletion Treatment Volume repletion with isotonic saline can enhance renal perfusion and increase the urine flow to wash out the obstructing casts Up to 1.5L/hour to maintain urine output ~300ml/hour Less effective after the first hours Kidney Int Forced diuresis with Alkaline-mannitol ( No clear clinical evidence ) Alkalinization of urine ph>6.5: increase solubility of haeme pigments Minimizing the conversion of to the more toxic methaemoglobin Mannitol: Induce diuresis which minimize intratubular haeme pigments deposition and cast formation Act as a free radical scavenger

38 Rifampicin-induced induced ARF First case reported in 1971 in Germany Approximate 60 cases published Typically appears after discontinuous use/reintroduction of rifampicin

39 Causes of Renal failure 1. Tubular blockage by haemoglobin after haemolysis causing ATN Pathogenesis: Rifampicin-dependent IgM and IgG Ab Interact with the I antigen on the surface of the erythrocytes Leading to complement fixation and red blood cell lysis Various interval between drug exposure and onset of disease (1 dose to months) Rif asso.. ARF: pathophysiology,, immunological and clinical features AJKD 1998

40 Causes of Renal failure 2. Acute interstitial nephritis Sudden deterioration of renal function in asymptomatic patients Onset: days to weeks 3. Rapidly progressive glomerulonephritis Deposition of Ag-Ab Ab complexes in the golmerulus Uncertain causal relationship; 3-6 weeks after exposure 4. Light-chain proteinuria Polychonal kappa and lambda light chains are detected in the urine Biopsy: intratubular cast formation, tubular necrosis and interstitial edema No typical light chain nephropathy features (LC deposition in GBM M / TBM) Onset: 1-66 weeks Rif asso.. ARF: pathophysiology,, immunological and clinical features AJKD 1998

41 Clinical picture of post-rif ARF at presentations 96% were anuric at presentation

42 Investigations: Anaemia - 96% Intense haemolysis 25% Haematuria 33% Haemoglobinuria 16.6% Proteinuria 60% Rifampicin-induced induced acute renal failure: a series of 60 patients Nephrology dialysis transplantation 1998

43 Progress Urine output returns in days ( mean ) Renal function recovery 40% in 30 days 96.6% in 90 days Mortality: 1.6% Prognostic factors 1. Severity of the immune process 2. Duration of anuric phase Rifampicin-induced induced acute renal failure: a series of 60 patients Nephrology dialysis transplantation 1998

44 Thank you!