A presentation which taught us about “when to refer to a renal physician would be perfect,

in particular intrinsic renal failure not to be missed in an ICU presentation with AKI, and diagnostic work up prior to assessment by a

renal physician?”

Adam Kirk

Consultant Renal Physician

23rd October 2014

Difficult Topic

• The relationship between ICU and Renal; pathophysiologically

• What is there that renal physicians do that ICU do not?

• Key indicators– Renal input – single organ failure with on-going care needed– Weird brain

• Key interventions

• In the acute or more chronic setting

Chronic Kidney Disease

• Aims of referral to address– Establish diagnosis– Anaemia– Bone disease– Cardiovascular risk modification

• Hypertension• Hypercholesterolaemia

– Preparation for Renal Replacement Treatment• Psychologically• Modality• Physically (AVF/Tenckhoff)

80 yrs 120yrs??

eGFR

Age of patient

ESRD

Intervention

Managing CKD: what is our aim?

Death from something other than ESRD or CVD

CONTENTED

LIFE

Management in ICU: what is the aim?

Time (Yrs)

Ph

ysio

logi

cal R

eser

veICU Intervention

DEATH

Estate sorting/New lease

Acute Kidney Injury

• Defined in stages

• Often associated with hypoperfusion/oilgoanuria (<500ml/d)

• Linked to a different cause

– Pre-Renal

– Renal

– Post-Renal

Causes

• Pre-Renal

– Hypoperfusion

• Post-Renal

– Obstruction

NB: - Think age related.

Intrinsic Renal Disease

• Acute Tubular Necrosis (ATN)

• TubuloInterstitial Nephritis (TIN)

• Glomerular Nephritis (GN)

• Vasculitis

ATN• Common and predictable (in high risk scenarios)• Causes

– Oligoanuria– Rise in creatinine– Actual structural renal parenchymal damage

• Pointers– Bland urine (poss some proteinuria 1+)– Raised fractional excretion of Na and urinary concentration

• Prognosis– 60% expect full recovery– 30% suffer residual dysfunction– 5-10% go on to require RRTNB: - Mortality 19-37% in hospital

Tubular epithelial vacuolation

Tubular epithelial flattening

Tubular epithelial sloughing into the tubular lumen

ATN Histological changes(classically)

Tubulointerstitial Nephritis

• Acute usually allergic reaction causing parenchymal AKI with fever, arthralgia and rash (in F>M, 50-60’s)

• Chronology may be 3 – 21 days preceding the onset of symptoms

• Urine can have <modest haematuria and proteinuria (<1g/d), eosinophils present

• Biochem may reveal deranged U/Cr but also Ca.• Treatment

– Remove offending cause• Drug vs bug

– Consider steroids (no convincing evidence)

Causes and treatment

• Drugs• NSAIDS

• Penicillins, cephalosporins, rifampicin, sulphonamies

• Diuretics

• PPI’s

• Allopurinol

• Anti-retrovirals

• TB, Sarcoidosis, legionella, leptospirosis

• Autoimmune disease association

• Steroid consideration– HD needing

• Steroids

– HD independent, observe for 10d• No improvement – Pred

• Improvement – masterful inactivity

• Dose Pred 1mg/kg on reducing course for 3-6months

Inflammatory cell infiltrate- Mononuclear cells- Eosinophils

Note: - the presence ofinterstitial fibrosisimparts a worse prognosis

Tubulointerstitial Nephritis

GlomeruloNephritis

• Syndrome of– AKI

– Haematuria and proteinuria

– Salt and water retention

• General principals– TIGHT fluid balance

– Na/water restriction

– BP control <130/80

– Loop diuretics

– ACEi/ARBs

IgA vs Post-Infectious

• IgA – autoimmune condition– IgA1 deposition in the mesangium setting inflammation and fibrosis

– Onset at any point; can occur at the time of upper airways infections

“synpharyngetic haematuria”

NB: - Associated condition Henoch-Schonlein Purpura

– Tetrad – abdo pain, arthralgia, rash and AKI

– Rash buttocks, legs and arms – self limiting

– Adults – worse prognosis

• Post-infectious– Staph, strep, syphilis

– Influenza B, Mumps, coxsackie, HBV, EBV

– Malaria, toxoplasmosis, schistosomiasis

– IC mediated 3-21 days after infection

– Self limiting, requires symptomatic treatment and of the cause

IgA Glomerular deposition in Henoch-Schonlein Purpura

TTP vs HUS• TTP• ADAMTS13 cleaves vWF to mature smaller molecule

– Doesn’t in TTP causing TMA

• Classic pentad– Fever, MAHA, thrombocytopenic purpura, renal failure and

neurological symptoms

• Management – PEX

• HUS – MAHA, thrombocytopenia and AKI

• Diarrhoea positive – shiga-like toxin

• Diarrhoea negative – Factor H deficiency (or one of a multitude now)

• Supportive therapy inc PEX, Eculizumab (Mab C5complement)

Nephrotic Syndrome

• Triad – Hypoalbuminaemia, oedema and Proteinuria (>3g/d)

• Causes– Diabetic nephropathy – diabetes (!), do not miss other causes

– Minimal Change – Unchanged secretory renal function

– Membranous Nephropathy – malignant concern

– FSGS – rapidly progressive and long-term damaging

– MCGN – as above

– HIVAN – black HIV +ve

– Amyloid, myeloma, light chain disease – haemotology diagnosis, renal complications

– SLE – rheumatology diagnosis, renal complications

Considerations

• Protein loss

• Anticoagulation

• Causes

• Treatment

– Prednisolone

– Immune suppression

Vasculitis• Fever, weight loss, myalgia

• Flitting symptoms

• Multisystem – consider in situation where “nothing fits” and AKI

• Investigations– Full bloods inc

• Immunoglobulins, ANCA, ANA, complement, protein electrophoresis, coagulation

– AUSS

– CXR film

– Urine dip and quantification (protein)

ANCA Positive• Biopsy – FSGS, crescents ± granulomata

• Treatment– Prednisolone

• MP 500mg IV stat if Cr^, Cr>500 or pulm haemorrhage

• Pred 1mg/kg/day

– Cyclophosphamide• 1-2mg/kd/day

– PEX• Pulm haemorrhage

• Cr >500

• Anti-GBM +ve

• NB: Key difference with MP vs PEX, MP less risk and used at lower threshold.

Immunofluorescence demonstrating ANCApattern of labelling

P-ANCA Pattern(MPO)

C-ANCA Pattern(PR3)

Anti-GBM disease

• Pathogenic IgG binds α3 region of collagen IV (BM in glomeruli and alveoli)

• Usually more devastating

• Single hit disease – so make diagnosis and treat ASAP

• Biopsy – FSNGN, ruptured Bowman’s capsule

• Treatment– RRT

– Steroids (MP 1g x3, then Pred)

– PEX

Additional ones not to be missed

• Myeloma/Light chain abnormalities

– Require biopsy of some sort

• Lymphoma

– De novo OR Post-Transplant Lymphoproliferative Disorder (PTLD)

Key investigations

• Immunoglobulins

• Hepatitis Serology (B/C)

• Complement

• Protein Electrophoresis

• ± Bence Jones• Up to you. PE Strip should cover all eventualities of

secretory of non-secretory myeloma

Transplant

• Considerations when dealing with sick pt

– At time of transplant, ESRD

• This implies all renal complications are fair game

– Background viral activity becomes more central

• CMV/EBV/BK/HIV/Hepatitis

– Transplant career important

• Immune suppression levels

• Rejection episodes

– Time since and transplant and level of success

Acute Rejection

• Classic triad• Fever, Oliguria, graft tenderness

NB: - less available now with better immune suppressants

• Prompt assessment/treatment ESSENTIAL• Implications on long-term graft function/outcome

NB: - Successful treatment of AR within T+60d has little affect on graft outcome.

Risk Factors

• High Risk• African American

• Sensitization– Prev Tx

– Pregnancy

– Blood Transfusion

• Delayed Graft Function– Deceased donor source

– Increased donor age

– Prolonged ischaemic time

– Donor brain death

– Donor acute rejection

• HLA mismatch

• Positive PreTx Bcell Crossmatch

• ABOi/HLAi

• Co-existing infection

• Adolescent recipient

• Previous rejection episode

• Low Risk• Zero mismatch

• Elderly recipient of young healthy donor

• Pre-emptive transplant

• Living donor source

• First Transplant

Assessment/Treatment

• Assessment

– Urine dip

– Obs

– Biochemistry with trough IS levels

– AUSS

– Kidney biopsy

• Treatment

– Pulsed steroids

– Consider increasing the IS

– Continual review to ensure improvement

– Re-review with view to additional AR treatments

eg ATG

Differential diagnosis of Allograft dysfunction

• Week 1– ATN

– Rejection

– Obstruction/leak

– Clot art/vein

• <12 weeks post-Tx– AR

– CNI toxicity

– Volume depletion

– Obstruction

– Infection (inc virus)

– Interstitial disease

– Recurrent primary disease

• >12 weeks post-Tx– AR

– Volume contraction

– CNI Toxicity

– Obstruction

– Infection

– Chronic allograft nephropathy

– Recurrent primary disease

– RAS

– PTLD

Post-Transplant Infections

• 1-6 months• Opportunistic/non-

conventional– CMV/HHV-6/HHV-

7/EBV/VZV/influenza/RSV/adenovirus

• Aspergillus, cryptococcus, nocardia, listeria

• Legionella, TB, PCP

• HBV, HCV, HIV

• <1 month• Post –op bacterial

– UTI/ Resp/ Vascular related/ wound

• Nosocomial– Inc legionella

• HSV

• Candida

• Untreated undeclared disease (donor origin)

• >6 Months• Late opportunistic

• Cryptococcus, CMV retinitis or collitis, VZV, parvovirus B19, Polyoma (BK), HBV HCV

• Malignancy• EBV, Papilloma,

HSV, HHV-8• CAP/other infections

Summary

• Bloody difficult from ICU

• When to refer

– When there is a renal diagnosis requiring renal intervention/advice

– When there may be and further brains/interference may benefit the patient prognosis

– Known renal patient esp Transplant

To consider on referring

• PMH is essential to understanding how the patient got where they are

• PMH essential to understanding possible response to considered therapies

• Masterful, highly qualified, skilful inactivity is not always a bad thing

Thank youAny questions