Rare cause of AKIM.C. Vasif Mayan

For theDept of NEPHROLOGY

APMC 2015

GMKMCH SALEM

HISTORY

• 28 year old female

• PRESENTING ILLNESS– Abdominal Pain 10 days– (Lumbar Pain)– Vomiting 10 days– Low grade fever– Myalgia

• No h/o oliguria• No h/o rashes• No h/o jaundice• No h/o cola coloured urine• No h/o dysuria

• No h/o loose stools

• No history of DM/HTN/CKD/CLD/SLE

HISTORY OF PAST ILLNESS

• Appendicectomy done 2yr back for recurrent abdominal pain. Biopsy revealed TB appendix

• Took Cat 1 ATT for 4 months

• Restarted on (intermittent) ATT for the past 10 days.

defaulted

EXAMINATION

• Conscious • GC stable• Afebrile• Mild Pallor +• No Icterus/ Cyanosis/ Clubbing• No Generalised LNE• No Bilateral Pitting Pedal edema

SYSTEM EXAMINATION• CVS S1, S2 + Normal

No murmurs

• RS BAE+, NVBSChest Clear

• ABDOMEN diffuse tenderness+bowel sounds +No organomegaly

• NS Consious,PEARLNo FND

Provisional Diagnosis

• ? DRUG INDUCED GASTRITIS• ? TB ABDOMEN

INVESTIGATIONS

• TC 9800• DC N77 L20 E3• Hb 10gm• ESR 30mm/1st Hour• PCV 30• RBC 3.2 million/mm3• RBS 52mg%

RFT and LFT• SGOT91 IU/L• SGPT 27 IU/L• Bilirubin Total 0.7 mg%• Bilirubin Direct 0.4 mg%

• S. Urea 130mg/dl• S. Creatinine 3.8 mg/dl

• USG Abdomen– Rt kidney 11x5cm– Lt Kidney 12x5cm– Increased Echoes, CMD absent

DAY S. Creatinine S. Urea S. Sodium S. Potassium

1 3.8 130 134 4.72 4.8 156 139 4.94 9.2 170 140 4.96 9.4 162 147 5.67 8.4 138 133 5.18 8.0 132 136 4.510 6.8 99 140 4.311 5.9 83 133 4.913 3.9 6914 2.4 66 137 4.617 1.0 34

1 2 3 4 5 6 7 8 9 10 110

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S. Creatinine

Axis Title

• ACUTE INTERSTITIAL NEPHRITIS• ACUTE TUBULAR NECROSIS• RIFAMPICIN INDUCED AKI

DISCUSSION

INTERSTITIAL NEPHRITIS

ACUTE TUBULAR NECROSIS

NEPHROTOXICITY

Methicillin – prototype drugCausing Interstitial nephritis

Renal disease – dose reduction

RIFAMPICIN INDUCED AKI

• Usually occur following re-treatment with an intermittent rifampicin regimen

• Intermission interval 5 months to 11 years• AKI manifested within 1st 10-20 days of re-

treatment• Withholding rifampicin and Supportive care

+/- dialysis can reverse the condition

• WHY???

MECHANISM

• Rifampicin dependent antibodies• Antibody accumulate during antigen-free interval• More in intermittent regimen and defaulters• immune complexes get deposited in the blood

vessels or interstitium and cause glomerular endotheliosis leading to tubular injury

• I antigen expressed on tubular epithelium through which immune complexes lead to tubular cell destruction

• Immune complex deposition in interstitium and blood vessels

• Predominant pattern = Acute tubular necrosis• Interstitial edema

Other pathogenic mechanisms

• Glomerular injury Nephortic syndrome(1 case)• Light chain proteinuria

(9cases)• Papillary necrosis• Crescent formation

CLINICAL FEATURES

• Abdominal pain, nausea, vomiting• Flu like illness

• Mild anemia 96%• Leukocytosis 63%• Thrombocytopenia 50%• IMMUNE HEMOLYSIS 25%• Sterile Leucocyturia 83%• Oliguria/Anuria 96%• Mild hepatic injury

Prognosis

• Usually self resolving with withdrawal of drug and symptomatic management

• ? Role of steroid

• Prognostic factors• Duration of anuria• Severity of immune complex deposition

Acute interstitial nephritis

• Most common etiologies are:– a) those related to the use of medications: 85% – b) those related to infectious agents: 10%– c) those associated to systemic disease or

glomerular diseases: 1%– d) idiopathic disease: 4%

Acute interstitial nephritis: drugs• Etiology: AB (penicillins and cephalosporins,

methicillin), diuretics, NSAID’s, chinese herbs, lithium• Pathogenesis:

T cell mediated allergic - immune reaction on drug or drug-self protein conjugate (hapten) later followed by accumulation of lymphocytes, plasmocytes and histiocytes

• Histology:– Early signs: oedema, lymphocytes focally– Later: eosinophils, lymphocytes, plasmocytes and

histiocytes with granuloma formation(with giant cells) in 30 %, especially after AB

– Tubulitis (distal tubules): with breaks of TBM, necrosis of tubular cells and atrophy and loss of tubules.

Acute drug induced interstitial nephritis

Granuloma

Oedema and focal inflammation

EOS

Granuloma

Acute drug induced interstitial nephritis

• Normally glomeruli not affected.• One exception: use of NSAID’s: can combine

ARF with Nephrotic Syndrome (effect of cell- mediated lymphokine directed reaction) inducing Minimal Lesions (effacement of foot processes of podocytes)

Acute interstitial nephritis

Acute Renal Failure and reduced glomerular filtration rate:

- depends on the severity of inflammation

- interstitial oedema causes elevated intratubular pressure

- intratubular obstruction through intra luminal cells

- tubular backleak- vasoconstriction- tubuloglomerular feedback

Outcome of drug- induced interstitial nephritis

• Recovery?

– Drug withdrawal: 60-90% in 1 to 12 mths– Irreversible with analgesics, NSAIDs, longterm use

• Adverse prognostic features– Marked interstitial inflammation– Granuloma (50% irreversible)– Tubular atrophy– Fibrosis