Assessment of a Patient with Renal Disease

Dr Andrew SteinConsultant in Renal and General

Medicine, UHCW

Aims

• Anatomy• Function• Definitions

– eGFR, CKD, Creatinine• 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 mls

• Normal urine output– 2L/day (urinate 300 mls 6x in day, 1x/night ≈ 2000 mls)– Oliguria < 400 ml/day– Oligo-anuria < 200ml/day – Anuria = zero ml/day

Normal (basics)• There is a huge variation in fluids consumed

per day• Frail elderly may drink 500 mls tea a day• Students = 5L!• UO will be proportional to intake (minus 500

mls/day, insensible loss)• Important to ascertain, in history, change:

– UO – Urination (freq/noct, urgency, hesitancy, poor

stream, dribbling etc)

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 products2. Regulation of fluid state and electrolytes3. Acid-base balance

• Metabolic/endocrine (4)1. Erythropoitein2. Renin3. Prostagladins4. 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

• We use GFR to estimate renal function• GFR α 1/creatinine, ie mathematically linked• Whats wrong with creatinine?

– A normal creatinine concentration can occur even when the GFR has dropped by 50%

– So creatinine is a fairly insensitive indicator of early renal impairement

Creatinine clearance and the assessment of renal function

Nankivell, BJ. Aust Prescr 2001; 24: 15-7

CKD: GFR α 1/creatinine

Creatinine

GFR

120 mls/min

Creat <120 mcmol/L

Why GFR? Creatinine is rel specific but not very sensitive

Creat GFR/%800 2600 5500 10 Do400 20 Prepare300 30 Think200 50150 75120 100

Factors Affecting Serum Creatinine

• Age• Sex• Race• Muscle mass, useage• Diet• Drugs (eg?)

Creat 200GFR 60 mls/min

Creat 200GFR 15 mls/minNeeds dialysis

Other Problems with Creatinine

• Creatinine is an imperfect filtration marker, because it is secreted by the tubular cells into the tubular lumen, especially if renal function is impaired

• So, when the GFR is low, the serum creatinine and overestimates the true GFR

• Also, some drugs (such as cimetidine or trimethoprim) have the effect of reducing tubular secretion of creatinine. This increases the serum creatinine

Can Urea Be Used?

• Measuring the blood urea concentration 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 they are 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-150CKD3b – creat 150-200CKD4 – creat >200CKD5 – creat >400

When do symptoms start?Who to refer?

Another Way of Describing Renal Impairment

Classification of AKI: RIFLE

RIFLE (Bellomo, 2004) Creatinine

• R isk 1.5-2x baseline• I injury 2-3x• F ailure >3x• L oss (>4 wks)• E SRD (>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

Anuria

• V rare• Only 3 causes

– Obstruction– Vascular catastrophe– Severe acute glomerulonephritis

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

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)

Drugs + Allergies

DRUGS DRUGS DRUGS

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

Examination

• General• Limited cardiorespiratory• 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?

Dipstick – Blood, WC, Glucose

• Haematuria 2+ (ie microscopic) = ?– 80% sensitive, 65-99% specific– Need? ..

• 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

• Useful screening test, not diagnostic

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

Dipstick - Protein

• Detects albumin but not other proteins, such as immunoglobulin light chains (consequence? ..)

• Like creatinine, this 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 (<0.1g/L is normal). This is quite a lot

• Hence, concept of microalbuminuria developed

Dipstick – Protein (Other Problems)

• Semi-quantitative categories on the dipstick 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 = <0.1 g/L, <0.15g/24h (if 2L urine), PCR <15 mg/mmol

(ACR <10 mg/mmol)• PCR/100 ≈ 1g/24h• ACR 3-30 = microalbuminuria• Dipstick specific but not very sensitive (like creatinine)

Dipstick g/24h g/L PCR (ACR)0 <0.15g <0.1g <15 (<10)Microalb (ACR 3-30)Trace 0.5 0.25 50 (30)1 1.0 0.5 100 (70) low 2 2.0 1.0 200 (140) mod (nephrotic range,?Bx) 3 4.0 2.0 400 (280) high (nephrotic)4 6.0 3.0 600 (460) v high

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)– 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)

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

Investigation – Specialised(Nuclear Medicine Scans)

• DMSA – structure (eg looking for scars of reflux nephropathy)

• DTPA – function (including ‘% split function’)• MAG3 - both• Isotope GFR – more accurate measurement of

GFR than eGFR

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?

SummaryAssessment 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

Questions

Renalmed.co.uk

andrew.stein@uhcw.nhs.uk