Assessment of a Patient with Renal Disease

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Transcript Assessment of a Patient with Renal Disease

Assessment of a Patient with Renal Disease

Dr Andrew Stein Consultant in Renal and General Medicine, UHCW May 2015

Aims

• • • • • • • Anatomy Function Definitions – Creatinine, eGFR, CKD, AKI History Examination Investigation Likely Cases

Theme of Lecture: Basic Renal Principles

Assessment of a renal patient is not that complicated, need to be methodical ..

• • • • • • History, esp DRUGS Examination, esp fluid state Careful analysis of data Exclusion of non-renal causes of symptoms Re-assess patients daily (fluid state) Some technical knowledge of dialysis/Tx etc

7 Renal Syndromes

• • • • • • • AKI/AKI-CKD CKD-ESKD Nephrotic Syndrome Nephritic Syndrome Macroscopic haematuria Microscopic haematuria Hypertension

Anatomy

Surface Anatomy of Kidney

Nephron

Normal (Basics)

• • Normal bladder size – 300-400 mls Normal urine output – 2L/day (urinate 8x in day, 1x/night ≈ 200 mls) – Oliguria < 400 ml/day – Oligo-anuria < 200ml/day – Anuria = zero ml/day

Kidney Size

12 (10-14) x 6 x 3 cm, 150g, retroperitoneal How does that affect palpation?

Kidney Palpation

• • • Normal kidneys are not usually palpable However, in some slim women, lower pole of the right kidney can occasionally be felt during deep inspiration Large kidneys or masses can sometimes be felt

Function

Functions of Kidney

• • Execretory (3) 1. Excretion of waste products 2. Regulation of fluid state and electrolytes 3. Acid-base balance Metabolic/endocrine (4) 1. Erythropoitein 2. Renin 3. Prostagladins 4. Activation of vitamin D Consequences?

How Hard do 2 Kidneys Work?

• • • • 25% cardiac output GFR 120 mls/min = ~ 170 L /day Ie blood volume passes through kidneys 35x/day

What is GFR? Why Measure it?

• • • • • Glomerular filtration rate (GFR) is the rate (volume per unit of time) at which ultrafiltrate is formed by the glomerulus.

Approximately 120 mL are formed per minute eGFR can be used to estimate renal function eGFR α 1/creatinine, ie mathematically linked Whats wrong with creatinine?

– A normal creatinine concentration can occur even when the GFR has dropped by 50% – Creatinine fairly insensitive indicator of early renal impairment Creatinine clearance and the assessment of renal function Nankivell, BJ. Aust Prescr 2001; 24: 15-7

eGFR

• • • • = Estimated GFR Derived from serum creatinine. Proportional to 1/creatinine 4-variable MDRD formula currently used – Estimate only. May not be accurate in ethnic minority patients, elderly, pregnant women, malnourished, amputees, or children <16 years, or > 60 mls/min Men ≈ 130 mls/min; Women ≈ 120 mls/min

CKD: GFR α 1/creatinine

Why GFR? Creatinine is rel specific but not very sensitive 120 mls/min Creatinine Creat <120 mcmol/L GFR Creat GFR/% 800 600 2 5

500 400 300 10 Do 20 Prepare 30 Think

200 150 120 50 75 100

Factors Affecting Serum Creatinine

• • • • • • Age Sex Creat 200 GFR 60 mls/min Race Muscle mass, useage Diet Drugs (eg?) Creat 200 GFR 15 mls/min Needs dialysis

Can Urea Be Used?

• • Measuring blood urea has limitations because, as well as renal impairment, it is increased by: – Increased protein metabolism (raised in catabolic states, and high protein diet) – Dehydration – – – Heart failure RVD Steroids And, conversely, patients with renal impairment can have relatively normal blood urea concentrations if grossly malnourished and not eating

What About Tubular Function?

• • • • Although glomeruli control the GFR, damage to the tubulointerstitium is also an important predictor of GFR and progression towards renal failure Renal tubules make up 95% of the renal mass, do the bulk of the metabolic work and modify the ultrafiltrate into urine They control a number of kidney functions including acid-base balance, sodium excretion, urine concentration or dilution, water balance, potassium excretion and small molecule metabolism (such as insulin clearance) Measurement of tubular function is impractical for daily clinical use, so we usually use the GFR to assess renal function

Definitions

Definitions of Normal Renal Function, Renal Impairment and Failure in AKI/CKD (Creatinine + GFR) • • AKI/AKI-CKD • Creat >120 mcmol/L (normal range 60-120) • RIFLE (research mainly) CKD • Creat >120 mcmol/L (normal range 60-120) • GFR < 120 mls/min (not used in AKI) • • Renal impairment = CKD <60 mls/min (CKD3a) Renal failure = <15 mls/min (CKD4) Simple Definition of Renal Impairment = Creat > 120 mcmol/L (AKI, CKD, or AKI-CKD)

CKD, eGFR, Creatinine and Symptoms

CKD1 – creat N (<120) CKD2 – creat N (<120) CKD3a – creat N-150 CKD3b – creat 150-200 CKD4 – creat >200 CKD5 – creat >400 Suffix ‘p’ indicates significant proteinuria (ACR >30 or PCR >50) eg, CKD3p When do symptoms start?

Who to refer?

Another Way of Describing Renal Impairment

Epidemiology of CKD

• • • • • More common in women, but as renal function declines, men predominate >80% stable CKD that does not progress Very common = 5% of pop GP practice 10,000 pts (5 GPs, 2000 each) – CKD3-5 – CKD4 – CKD5 (dialysis/transplant) 500 15-20 5-10 (1-2 per GP) All cause mortality 30-60x gen pop

Causes of CKD

Small kidneys / idiopathic 30% Glomerular Disease - Primary (GN) - Secondary (eg DM 20%) Renovascular Disease - Atheroma - Fibromuscular Dysplasia Obstructive Nephropathy - Prostate (man) - Pelvic cancer (woman) Congenital eg PCKD Tubulo-interstitial Disease - Drugs eg Analgesic Nephropathy, Lithium - UTI eg Reflux Nephropathy - Autoimmune eg Sarcoidosis

CKD: Indications for Treatment with ACEi/ARB

• • • Hypertension and non-diabetic CKD with significant proteinuria (ACR >30, PCR >500 Non diabetic CKD with higher levels proteinuria (ACR >70, PCR >100), whatever BP Other uses – Diabetes and microalbuminuria. ACR > 2.5 (men) or >3.5 (women), whatever BP (no CKD) – Essential hypertension (no DM, no CKD) – Heart failure

ACEi/ARB Cautions

• • • • Can cause hyperkalaemia, AKI, AKI-CKD, permanent ESKF Especially in pts with known, suspected (or unknown) renovascular disease (or small kidneys) So, if start, check U+E after 2 wks + 6 wks, and after any dose change Stop if septic. ACEi/ARB and sepsis v prone to caused AKI, or AKI-CKD

CKD: When to Monitor and Treat Complications

• • • BP, fluid state – all stages Anaemia (Hb) – CKD3+ Renal bone disease (PTH) – CKD4-5

Age and CKD

• • • Controversial >40y there may be progressive loss of eGFR of 1ml/min/year. This may be normal, and not a disease If exists, may be consequence of (reno)vascular, rather than ageing itself

Classification of AKI: RIFLE

RIFLE (Bellomo, 2004) Creatinine • R isk • I injury • F ailure • L oss • E SRD 1.5-2x baseline 2-3x >3x (>4 wks) (>3 mths) Later: AKIN, KDIGO, NICE (2013)

History

Presenting Complaint

• • • Asymptomatic (routine bloods) Symptoms of fluid overload: – SOB = pulmonary oedema, pulmonary oedema and pulmonary oedema • Don’t forget pulmonary haemorrhage, acidosis (Kussmaul’s breathing) – SOA – Other: itching, nocturia, ‘uraemia’ Urinary symptoms – Frothy urine (nephrotic syndrome) – Macroscopic haematuria (IgA?)

HPC

• • Length of symptoms Associated symptoms Eg onset of SOA, frothy urine and red rash on face (Diagnosis ..?)

Urinary Symptoms (Surgical)

• • • • • Ask patient to describe urination (prostate) UTIs (reflux nephropathy) Loin pain “I cannot pass urine” (anuria) Macroscopic haematuria

PMH

• • • • • • • DM (esp DM2) Stones/UTIs Prostatic disease Autoimmune disease (SLE) Neoplasia (pelvic, myeloma) Atheroma (RVD) Previous AKI

SH

• • • • Smoke (RVD) Alcohol (IgA) IV drugs / sexual orientation (Hep B, Hep C, HIV) Home set-up (dialysis etc)

FH

• • PCKD (first case?) Rare (eg, Alports, other hereditary nephritis, thin basement membrane disease, nail-patella syndrome, cystinuria, hyperoxaluria)

Anuria

• • V rare Only 3 causes – Obstruction – Vascular catastrophe – Severe acute glomerulonephritis

Haematuria

• • Classified as: – Visible, also known as macroscopic or gross haematuria, or – Non-visible, also known as microscopic haematuria Haematuria can originate from numerous sites including: – kidney, ureter, bladder, prostate or urethra

Macroscopic Haematuria

• • • • Recurrent visible haematuria Age > 40 years, presume neoplasia Smoking History – UTI/stones or other urological disorders – Occupational exposure to chemicals or dyes – Pelvic irradiation – Excessive analgesic use – Cyclophosphamide

Microscopic Haematuria

• • • • • Present in approx 5% of population 50% of these will have glomerular disease of you look hard enough 5-10% of potential renal transplant donors Difficult presentation, as common and can be: – Benign disease of little significance, or – First sign of serious disease (intrinsic renal disease or urological malignancy) So .. who to investigate? ..

Microscopic Haematuria – Who to Investigate

• • • • If associated with: Stage 4 or 5 CKD Worsening CKD Significant proteinuria (PCR ≥ 50, ACR ≥ 30 mg/mmol (≥ 0.5 g/24h)) Uncontrolled BP ≥ 140/90 mmHg (3+ drugs) Or unexplained microhaematuria following urological assessment where no cause was found

Examination

Renal Examination

• • • General Cardiorespiratory (limited) GI+

General Examination

“Observation is 90% of Medicine” Prof Dan Hoyte • Walk into the room (DM?) • Face (eg SCCs (Tx-related), SLE) • Hands (radial/brachial fistula) • Skin (excoriation) • Uraemic frost = deposition of white/tan urea crystals on the skin after sweat evaporation (v rare) • Pulse (sign of LVF)

Cardiorespiratory

= Limited cardiorespiratory • BP BP BP • JVP JVP JVP • Auscultation (pericardial rub) • Pulmonary oedema (± pleural rub) • Sacral oedema • Leg oedema

GI+

• • • • • • • Observation (state the obvious, eg .. ) Light palpation Deep palpation Liver Spleen Kidneys + Bladder Bruits (epigastric, femoral)

Technical Signs (relating to HD, PD and Tx)

• • • • • • Dialysis catheter AVF (radial/brachial) PD catheter Urinary catheter/nephrostomy Tx scars Tx-related problems (eg NODAT, BCC/SCC)

Investigation

• Urine • Blood • Radiology + invasive

Urine Tests

Urine - MSU

• • • • • <5 WC <25 RC No casts (esp red cell) No growth “Mixed growth”?

.. which UTIs to investigate?

Urinary Dipstick

• • • • Useful screening test, not diagnostic Why?

Problems with – Microhaematuria – Leucs/nitrites – Glucose – Protein Ie, all of it!

Dipstick – WC, Glucose

• • • Leucocytes 1+ ≠ UTI (need? ..) Nitrites - produced when bacteria reduce urinary nitrates derived from amino acid metabolism Glucose - usually appears in urine when serum glucose increases to > 10 mmol/L and renal function is normal

Dipstick – Blood

• • • Haematuria (microscopic) – To confirm need? ..

As well as intact red blood cells (RBC), dipstick also detects Hb from lysed RBC caused by haemolytic conditions, or myoglobin from crush injuries, rhabdomyolysis or myositis – Therefore specificity is 65 – 99%, ie false positives occur Significant haematuria occurs at readings of 1+ or above, and trace levels should be considered negative – 80% sensitive

Proteinuria – what is it?

• • • • Albumin (20%) Tamm-Horsfall (muco) protein, derived from PCT (80%) Eat 80g /day Normal level proteinuria = <0.2 g/L, ie <0.4g/day, if 2L urine

Dipstick - Protein

• • • • Detects albumin but not other proteins, such as immunoglobulin light chains (consequence? ..) Like creatinine, his test is specific(ish), but not very sensitive for the detection of proteinuria Ie, it becomes positive (1+) only when protein excretion exceeds 0.5 g/L (upto 0.2g/L is normal). This is quite a lot Hence, concept of microalbuminuria developed

Dipstick – Protein (Other Problems)

• • • • Semi-quantitative categories on the dipsticks should be used with caution (esp ‘proteinuria’ = albuminuria) Only a rough guide since Albumin conc varies with urine volume, ie – Dilute urine underestimates degree of proteinuria – Concentrated urine may show ‘3+ proteinuria’ Different products

• • • • • • •

Proteinuria (quantification)

Eat 80g /day Heavy proteinuria is the hallmark of glomerular disease Normal = <0.2 g/L, ie <0.4g/day, if 2L urine Or PCR <15 mg/mmol (ACR <3 mg/mmol) PCR/100 ≈ g/24h ACR 3-30 mg/mmol = microalbuminuria Dipstick specific but not very sensitive (like creatinine) Dipstick 0 Trace 1 2 3 4 g/L <0.2

0.25

0.5

1.0

2.0

3.0

g/24h PCR (ACR) <0.4g <15 (<3) 0.5

50 (ACR 30) 1.0

2.0

100 (ACR 70) low 200 mod 4.0

6.0

400 600 high v high nephrotic range nephrotic

PCR and ACR

• • PCR and ACR are measured in mg/mmol – Both assume urinary creatinine conc 10 mmol/L (actually varies 5-30) Conversion – Low levels of proteinuria (<0.5g/24h), PCR = 2x ACR – Higher levels (>0.5g/24h), PCR = 1.3x ACR

CKD/Proteinuria Classification (Again!)

Blood Tests

Blood - Biochemistry

• • • • Sodium (135-145 mmol/L) Potassium (3.5-5.3 mmol/L) – Severe hyperkalaemia > 6.4 mmol/L Urea (3-7 mmol/L) – Severe level >50 mmol/L Creatinine (60-120 mcmol/L) – Severe level >400 mcmol/L

Hyperkalaemia

Blood – Bone Biochemistry

• • • • Calcium (2.2-2.6 mmol/L) Phosphate (0.7-1.4 mmol/L) Alk Phos (50-150 iu/L) PTH (<4.2 pcmol/L) Renal osteodystrophy? ..

Blood – Haematology

• • • • Hb – anaemia – MCV? ..

– ?EPO if HB < 100 g/L) WC - N Platelets – thrombasthenia Clotting - N

Blood – Immunology (‘Renal Screen’)

• • • • • • • • • • • Immunoglobulins (A, G, M) (IgA nephropathy, myeloma) Protein electrophoresis (myeloma) Serum free light chains (myeloma) ANA and dsDNA (SLE) Complement factors (C3 and C4) (SLE) Anti-neutrophil cytoplasmic antibodies MPO and PR3 (ANCA) (vasculitis) Anti-glomerular basement membrane antibodies (AGBM) (Goodpasture’s Syndrome) Anti-streptolysin O titre (ASOT) (post-infectious glomerulonephritis) Angiotensin converting enzyme (ACE) (raised in sarcoidosis) Cryoglobulins (mesangiocapillary GN) Hep B, Hep C, HIV (GNs and safety of patients and staff, esp HD)

Radiology + Invasive Tests

Radiology – Renal Ultrasound

• • • • 2 kidneys?

Prepare for biopsy Obstruction (treatable) Appearance – Size (chronicity) – Loss of cortico-medullary differentiation (chronicity) – Disparity size (RVD) – Scars (reflux nephropathy) – Very bright (HIVAN)

Radiology - Other

• • • • • • KUB (if known to have radio-opaque stones) CT-KUB (stones) is better CT MRI (MRA/CTA) Treatments (eg nephrostomy, antegrade or retrograde)

Radiology - Nuclear Medicine Tests

• • • • Tc99m-DMSA (Dimercaptosuccinic acid) – structure (eg scars in reflux nephropathy) Tc99m-MAG3 (Mercaptoacetyltriglycine) – function (split) Tc99m-DTPA (Diethylene Triamine Pentacaetic Acid) – both structure and function MAG3 is a better diagnostic agent than DTPA, particularly in neonates, patients with impaired function, and patients with suspected obstruction

Investigation – Specialised (Renal Biopsy)

• • • • AKI, normal sized kidneys, no obvious cause = biopsy CKD, normal sized kidneys, no obvious cause = biopsy Proteinuria (>1g/L = 2g/24h = ‘nephrotic range’), no obvious cause Transplant dysfunction

Investigation – Specialised (Renal Angiogram)

Rarely performed (now always with a review to intervention) • Hypertension (RVD) with poor BP control on 4 drugs • ‘Flash’ pulmonary oedema • AKI in single (or single effective kidney) • Fibromuscular dysplasia

Likely Cases

Case One

• • • • • • 47y year old Asian male Presents 2 wks SOB and SOA, O/E fluid overload DM2 2 years IHD/CCF Serum albumin 40 g/L Urinary protein 0.15 g/L 1. Other information?

2. Diagnosis?

Case Two

• • • • • 35y old female Investigated for BP Creat 68 mcmol/L FH grandfather died of kidney problem O/E large liver? 2 large kidneys? (both?) 1. Next investigation?

2. Diagnosis?

Case Three

• • • • • • 23 year old female 2 weeks SOA O/E SOA Serum albumin 25 g/L Urinary protein 4.3 g/L Creat 87 mcmol/L 1. Renal syndrome?

2. Diagnosis?

Case Four

• • • • • 67 year old Asian male PMH DM2 (20y), TURP C/O 6 mths SOB, O/E fluid overload, R fem bruit Creat 465 mcmol/L (198 mcmol/L, 2012) Urinary protein 0.1 g/L 1. Next investigation?

2. Diagnosis?

Case Five

• • • • • 87y old male C/O tiredness ESKF (2009) On CAPD (4 x 2L bags a day) Creat 877 mcmol/L and stable 1. Other information?

2. Diagnosis?

Summary

Assessment of a Renal Patient is not that complicated, need to be methodical ..

Summary - Usefulness of Tests

Creatinine eGFR Specific + + Dipstick (blood) (+) ACR (proteinuria) + Sensitive (+) ++ ++ ++ Notes Underdiagnoses CKD Overdiagnoses CKD. No use in AKI Screening Test No Yes Overdiagnoses microhaem (false +ves) Yes Overdiagnoses proteinuria (systemic causes) Yes

References

• • • • Creatinine clearance and the assessment of renal function, 2001. Nankivell, BJ Diagnostic tests in CKD. Alfzali et al CKD: frequently asked questions. De Lusignan S et al Interpreting urine dipsticks in adults, 2013. BPAC-NZ

Questions

Renalmed.co.uk

Acutemed.co.uk

[email protected]

Drugs + Allergies

DRUGS DRUGS DRUGS • NSAIDs (analgesic nephropathy) • ACEi-ARB • Lithium (chronic interstitial nephritis) • Chemotherapy • Prev drug allergies (eg .. ?)

Assessment of a Patient with Renal Disease

Transcript Assessment of a Patient with Renal Disease