Common Investigation tests for

renal disease including approach

to proteinuria and haematuria
September 2021

Presented by: Dr Yuen Sze Kit

MBChB (CUHK) DFM (Monash) Dip Ger Med RCPS (Glasg) PDipID(HK) DPD (Cardiff) MFM (CUHK)
MRCP (UK) FHKCP FRCP (Edin) FHKAM(Medicine)

Clinical Associate Professor (Honorary)

Department of Medicine & Therapeutics, The Chinese
University of Hong Kong

Associate Consultant
Department of Medicine & Geriatrics
Caritas Medical Centre
 need to be diagnosed by renal biopsy

before kidney

renal artery and vein for material exchange

divided into different renal unit called nephron
1-1.5million nephron

any cause of blocking ureter

causing hydronephrosis meaning the
swelling of kidney due to blocking of urine
Cause of
BPH pressing prostate press bladder

renal failure
blocking ureter: ureteric stone
• Fry AC et al. Management
of acute renal failure.
Postgrad Med J 2006;82:
106-116
bowman’s capsule is a part of the nephron that
forms a cuplike sack surrounding glomerulus.

from 1proximal convoluted tubules

to loop of henle
to distal convoluted tubules
to collecting duct
Screening of CKD

family hx of hypertension
dm and renal disease, better have regular noninvasive checking

Li PKT et al. Asian chronic kidney disease best

practice recommendations: Positional statements for
early detection of chronic kidney disease from Asian
Forum for Chronic Kidney Disease Initiatives
(AFCKDI). Nephrology 16(2011)633-641
 Prevalence of Combined Abnormalities
in the Asymptomatic Individuals

Age 20-40 41-60 >60 Total

No. (226) (641) (334) (1,201)

*Any BP or Urine 9.7% 24% 33.2%

abnormality

* HT (BP >140/90 mmHg) or Li PKT, et al. Kidney Int 2005 Apr;(94):S36-40

Microscopic hematuria or
Proteinuria or
Glycosuria
At the courtesy of Dr B Kwan
 Screening of CKD
important positive relationship between hypertension and CKD

Li PKT et al. Asian chronic kidney disease best practice recommendations: Positional statements for early detection of chronic kidney disease from Asian Forum for Chronic Kidney Disease
Initiatives (AFCKDI). Nephrology 16(2011)633-641
Insights from basic
investigations
 Blood tests
• Creatinine
• Creatinine clearance
• Estimated glomerular filtration rate (eGFR)
• albumin
important protein in blood
should not be low in health people
commonly affected by liver (production of albumin) and
renal function, also can be affected by intestine but rare

• Electrolytes
• Hemoglobin
 creatinine itself not toxic

Creatinine and creatinine

clearance
• Derived from metabolism of creatine
– Skeletal muscle for muscular and male, higher level of creatine inducing higher creatinine. normal creatinine can be 100
but for elderly and female, skinny one, normal creatinine can be 60

– Dietary meat
so it depends on the body build

• Creatinine production
– Meat intake
expected to be lower in these people

– Muscle mass (Amputation, muscle wasting)

– Muscle injury (Rhabdomyolysis) higher creatinine
 Creatinine and creatinine
clearance
filtered in bowman’s capsule and can be found in urine

• Creatinine secretion (10-40%)

but 10% may from tubules active secretion
with progression of renal failure, the proportion of active
secretion would increase as the GF% decreased
so it may be inaccurate using urine test to estimate the eGFR

– As CKD progresses… proportion of creatine being contributed by secretion rather than filtration would increase

– Nephrotic syndrome
– Trimethoprim, Cimetidine

• Measurement issue
– Alkaline picrate method (colorimetric)
– Recognizes other compounds as creatinine
chromogens (e.g. acetoacetate, flucytosine)
 Creatinine clearance
timed creatinine clearance

• UxV/P
usu. over 24hr
24味⼩便.
result would be presented in mins

• Unadjusted for drug dosing

• Adjusted to BSA for CKD comparison
body surface area
including body weight and body height

U = urine creatinine
V = urine volume
P = Plasma creatinine
 ideally substance in blood can be 100% filtered and tested in urine
GFR
also dont have active secretion like creatinine and reaborsptlon

• Inulin
• Iothalamate research only
rarely used in clinical purpose

• Iohexol
 Estimated GFR
calculated using formula

• Assume stable Renal function

• CKD-EPI
• MDRD
• Cockcroft-Gault (CrCl) traditional paper but used to
correlate with cr clearance

• Others
 CKD-EPI
• eGFR = 141 x min(SCr/κ, 1)α x
max(SCr /κ, 1)-1.209 x 0.993Age x 1.018 [if
female] x 1.159 [if Black]

Where:
eGFR (estimated glomerular filtration rate) = mL/min/1.73 m2
SCr (standardized serum creatinine) = mg/dL
κ = 0.7 (females) or 0.9 (males)
α = -0.329 (females) or -0.411 (males)
min = indicates the minimum of SCr/κ or 1
max = indicates the maximum of SCr/κ or 1
age = years

https://www.kidney.org/content/ckd-epi-creatinine-equation-2009
 MDRD
• GFR (ml/min/1.73m2)=170 x (SCr in mg/dL)exp
[-0.999] x (age)exp[-0.176] x (BUN in
mg/dL)exp[-0.170] x (alb in g/dL)exp[+0.318] x
(0.762 if female) x (1.18 if black)

• GFR(ml/min/1.73m2)=186.3 x SCr (exp[-1.154] x

age (exp[-0.203] x (0.742 if female) x (1.21 if
black)
 as it is troublesome and not measuring GFR so less

MDRD
commonly for 24hrs urine for cr clearance
for some stance would still do eg
renal transplant patient, bil. ureteric stone with PCN then
can do for bil. kidney function comparison

• Original MDRD study

– 51±12.7 y.o.
– Non-DM
– Mean GFR 40ml/min/1.73m2
• CKD
• DM
• Races
• Kidney recipients or donors
 Cockroft-Gault formula
• Measure creatinine clearance (not eGFR)
• Unadjusted CrCl (ml/min) = [(140-age) x lean body
weight in kg] / (Cr in mg/dL x 72) (*0.85 for women)

but all the formula are based on BLOOD cr level so affected by extreme muscle mass or body build

• Obesity uncommon by then

• Differential kidney function (e.g. PCN)
 cystatin test expensive!!
Others
• (Curea + CCr) /2
• Serum cystatin C common but not in HA setting

• CKD-EPI Cystatin Equation

• CKD-EPI Creatinine-Cystatin Equation
Action plan on management of CKD
Stage Description GFR Action
(ml/min/1.73m2)
1 Kidney damage with ≧90 Diagnosis and treatment
normal or ↑ GFR Treatment of comorbidities
Slowing progression
CVD risk reduction
2 Kidney damage with 60-89 Estimating progression
mild ↓ GFR

3 Moderate 30-59 Evaluating and treating

complications

4 Severe definite need nephrologist 15-29 Preparation for renal

replacement therapy

5 Kidney failure <15 Renal replacement therapy

(or dialysis)

K/DOQI guideline 2004

 Haematuria
kidney/bladder stone
pre, post and renal causes kidney/bladder CA (esp for elderly)
eg dm related RF TB causing hydronephrosis or attacking kidney

• Medical causes vs. surgical causes

shape changed

• Dysmorphic RBC (especially acanthocytes)

– glomerular bleeding
• Red cell cast
– glomerular bleeding > tubular bleeding
Dysmorphic RBC
supportive medical cause of haematurina with glomerular bleeding
RBC cast
protein wrapping around RBC
 Other cast
• Mostly non-specific
• Granular, hyaline
• Brown pigment cast
– Rhadomyolysis
 whit cell in the urine

Pyuria

• White cell cast infection

– Tubulointerstitial/interstitial nephritis
not related to bacteria infection but by body attacking kidney

– Pyelonephritis
need biopsy for diagnosis

• Eosinophils special white cell in pyuria

normally would be found in urine

– Drug-induced tubulointerstitial nephritis

 in some way a symptom

Proteinuria
• Glomerular proteinuria
– usu. >1g/d higher pressure so more
sieve itself broken

• Tubular proteinuria
– usu. <1g/d
tubule for reabsorption mainly
sieve normal and only with decreased
reabsorption so would be less

• Overflow proteinuria no problem in sieve and reabsorption

but protein in blood too much and too overwhelming

– usu. Paraprotein, not albumin

• Post-renal proteinuria
 Multistix/Dipstix
• Albumin
• RBC
• WBC
• Nitrite
infection if positive

• sugar
 Urine Dipstick
• Colorimetric reaction between albumin and
tetrabromophenol blue
• Misses non-albumin proteinuria
• Affected by urine concentration
• Specific but not sensitive

Negative <15mg/dL
Trace 15-30mg/dL
+ 30-100mg/dL
++ 100-300mg/dL
+++ 300-1000mg/dL
++++ >1000mg/dL
At the courtesy of Dr D Kwok
 Other tests
• Urine SSA
• Urine Lysozyme
• Quantitative
– Timed-urine collection
– Spot (morning) urine collection
 Protein in urine
• Normal proteinuria up to 150mg/day
• Normal albuminuria up to 10mg/day
• If albuminuria >30mg/day
– Impair renal & cardiac outcome
• If albuminuria >300mg/day
– Detectable by ordinary dipstick
• Therefore, define:
– Microalbuminuia: 30-300mg/day or 20-200 µg/min
– Macroalbuminuria: >300mg/day or 20-200 µg/min
 Microalbuminuria
• 30-300mg/day or 20-200 µg/min
• Needs 24 hours urine collection
– Albumin concentration, multiply by urine
volume
– Inconvenient to the patient
– Clumsy to the laboratory
 Good correlation……
• Albumin-creatinine ratio (ACR)
– 24hr albuminuria

• Protein-creatinine ratio (PCR)

– 24hr proteinuria
 Spot urine PCR vs. 24hr
collection proteinuria
early morning urine
protein over Cr resulting PCR help to estimate 24hr proteinuria
but not 100% correct

• Ginsberg JM. Chang BS. Matarese RA. Garella S. Use of single voided urine samples to estimate quantitative proteinuria. NEJM
309(25):1543-6, 1983 Dec 22
 cheaper!

Urine PCR & ACR

• For slight proteinuria
– Use ACR
• More sensitive detection method
• Allow diagnosis of microalbuminuria early stat of DM

• For gross proteinuria

– Use ACR
• Majority of protein in urine being albumin
– Use PCR
 Proteinuria
• 24hr urinary collection proteinuria and Cr clearance

• Albumin-creatinine ratio or
• Protein-creatinine ratio
– K/DOQI guideline
– Consensus statement of International Society
nephrology 2004 (Hong Kong)
• “It is recommended to use ACR to quantify
proteinuria and for follow-up”
renal function CR for eGFR
stock urine for microscopy for WBC, RBC, glucose
protein Cr ratio
 But remember…….
• Affected by creatinine
– Male vs. female
– Changing muscle mass

• Protein intake/proteinuria
– After exercise or fever

– Time
trace or one+ dipstix with incidental reason no need so worry
Approach to persistent
proteinuria/haematuria
 History
• HPI
– Symptoms
– Clinical course, especially onset (e.g. URTI)
• PH
– E.g. GDM
• FH
– DM, HT, PCKD
• Drugs (e.g. NSAID) causing RF and proteinuria eg minimal change nephropathy
 Physical examination
• Edema
• Rash
• BP more urgent

• Nephrotic vs. nephritic

 Investigations
• Basic investigation
– RFT
– Urine microscopy
- proteinuria

• Special investigation for those with persistent protein/haematuria and RF

– HBsAg, anti-HBs, anti-HCV

– syphilis EIA, malaria, anti-HIV, ASOT
– ANF, anti-dsDNA, C3, C4, anti-ENA
– ANCA, anti-GBM
– IgA/M/G
– SPE, BJP, FLC, tumor markers
 Others
• Imaging
– KUB
– USG, NCCT, IVP
– Nuclear scan (e.g. MAG3)

• Renal biopsy
Thank you!

Dr Yuen Sze Kit

yuensk@ha.org.hk