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1. Assessment of a Patient with
Renal Disease
Dr Andrew Stein
Consultant in Renal and General
Medicine, UHCW
May 2015

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

4. 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

5. 7 Renal Syndromes
• AKI/AKI-CKD
• CKD-ESKD
• Nephrotic Syndrome
• Nephritic Syndrome
• Macroscopic haematuria
• Microscopic haematuria
• Hypertension

6. Anatomy

7. Surface Anatomy of Kidney

8. Nephron

9. 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

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

11. 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

12. Function

13. 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?

14. How Hard do 2 Kidneys Work?
• 25% cardiac output
• GFR 120 mls/min =
• ~ 170 L /day
• Ie blood volume passes through kidneys 35x/day

15. 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

16. 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

17. 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 2
600 5
500 10 Do
400 20 Prepare
300 30 Think
200 50
150 75
120 100

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

19. Other Problems with Creatinine
• Creatinine is an imperfect filtration marker, because it is
secreted by tubular cells, esp if renal function impaired
• The amount excreted exceeds the amount filtered by 10-20%
• Fortunately this is balanced by a similar error in the chemical
assay used which overestimates creatinine
• So. >40 mls/min, creatinine is accurate and good reflection of
GFR. Under this level, it tends to overestimate GFR
• Note: some drugs (such as cimetidine or trimethoprim)
reduce tubular secretion of creatinine, increasing serum
creatinine

20. 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

21. 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

22. Definitions

23. 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)

24. 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?

25. Another Way of Describing Renal
Impairment

26. 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)
– CKD3-5 500
– CKD4 15-20
– CKD5 (dialysis/transplant) 5-10 (1-2 per GP)
• All cause mortality 30-60x gen pop

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

28. 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

29. 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

30. CKD: When to Monitor and Treat
Complications
• BP, fluid state – all stages
• Anaemia (Hb) – CKD3+
• Renal bone disease (PTH) – CKD4-5

31. 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

32. 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)

33. History

34. 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?)

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

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

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

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

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

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

41. 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

42. 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

43. 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? ..

44. 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

45. Examination

46. Renal Examination
• General
• Cardiorespiratory (limited)
• GI+

47. 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)

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

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

50. 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)

51. Investigation
• Urine
• Blood
• Radiology + invasive

52. Urine Tests

53. Urine - MSU
• <5 WC
• <25 RC
• No casts (esp red cell)
• No growth
• “Mixed growth”?
.. which UTIs to investigate?

54. Urinary Dipstick
• Useful screening test, not diagnostic
• Why?
• Problems with
– Microhaematuria
– Leucs/nitrites
– Glucose
– Protein
• Ie, all of it!

55. 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

56. 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

57. 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

58. 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

59. 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

60. 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 g/L g/24h PCR (ACR)
0 <0.2 <0.4g <15 (<3)
Trace 0.25 0.5 50 (ACR 30)
1 0.5 1.0 100 (ACR 70) low
2 1.0 2.0 200 mod nephrotic range
3 2.0 4.0 400 high nephrotic
4 3.0 6.0 600 v high

61. 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

62. CKD/Proteinuria Classification (Again!)

63. Blood Tests

64. 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

65. Hyperkalaemia

66. 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? ..

67. Blood – Haematology
• Hb – anaemia
– MCV? ..
– ?EPO if HB < 100 g/L)
• WC - N
• Platelets – thrombasthenia
• Clotting - N

68. 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)

69. Radiology + Invasive Tests

70. 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)

71. 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)

72. 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

73. 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

74. 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

75. Likely Cases

76. 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?

77. 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?

78. 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?

79. 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?

80. 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?

81. Summary
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

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

83. 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

84. Questions
Renalmed.co.uk
Acutemed.co.uk
andrew.stein@uhcw.nhs.uk

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