METHVEN S, MACGREGOR MS, TRAYNOR JP, O'REILLY DS, DEIGHAN CJ

NEPHROL DIAL TRANSPLANT,  SEPT 2010

Assessing proteinuria in chronic kidney disease: protein–creatinine

ratio versus albumin–creatinine ratio

SPEAKER : Dr. RAHUL CHAUDHARYSENIOR RESIDENT : Dr. ANURAG

Introduction

Identification and quantification of proteinuria are core elements in the diagnosis and management of CKD

Proteinuria is associated with an increased risk of progressive kidney failure

cardiovascular disease and death

monitor the progress of kidney disease

to assess response to therapy

Timed urine collections (usually performed over 24 h) are considered the gold standard

Urine formation

Urine proteins

TOTAL PROTEIN = 150 – 200mg/day ; ALBUMIN <30mg/day

How to assess the amount of protein in urine?

•24 – hour urine collection

•Poor compliance ; difficult in OPD set up

•Random urine protein/albumin concentration

•Variation in urine protein excretion (water intake ,rate of diuresis,exercise,diet….)

•Urine protein creatinine ratio

•Protein and creatinine excretion rates are fairly constant throughout the day as long as the GFR remains constant

Introduction

CONCLUSION :The protein : creatinine ratio on a random urine specimen provides evidence to “rule out” the presence of significant proteinuria as defined by a 24-h urine excretion measurement.

Guideline recommendations

Guideline Recommendation

KDOQI

( Kidney disease outcome quality initiative)

Monitor proteinuria using ACR unless ACR exceeds 500-1000mg/g, when TPCR is acceptable

NICE

(National institute for health and clinical excellence)

ACR for urine analysis

CARI( Caring for Australasians with renal impairment)

TPCR in patients with non-diabetic kidney disease

ACR for diabetic patients

Aim of the study

Examine the relationship between TPCR, ACR and 24-hr urinary protein

Compare the diagnostic performance of TPCR and ACR at various thresholds

To decide which is the optimal test to identify significant proteinuria

Materials and methods

Single centre study Kilmarnock, UK

Retrospective analysis Perusal of records in the electronic patient record Laboratory assays

Random spot urine samples sent for all patients attending the renal clinic

24 hr urine evaluation done only on requestAnalyser Urine albumin Urinary protein

Prior to Aug 2006 Bayer Advia 1650

Immunoturbidimetry using anti-human albumin antiserum

Pyrogallol red calorimetric method

After Aug 2006 Abbott Architect 2000

Immunoturbidimetry using anti-human albumin antiserum

Turbidimetric method using benzethonium

No significant difference in the precision and accuracy of two methods

Method of patient selection

Searched for patients with TPCR and ACR measured on the

same date

7830 patients were identified with simultaneous ACR and

TPCR results

Exclusions :

489 samples were analysed prior to 29 November 1999 and

laboratory assay details were unavailable

88 children <18 years old excluded

411 patients receiving renal replacement therapy

Data acquisition

Following details were recorded Gender Age at the time of urine collection Primary renal disease Use of ACE-I / ARB Weight / height / Blood pressure Serum creatinine eGFR using the 4 variable MDRD equation

Correlation was assessed using spearman’s rho

Bland-Altman analysis was used to compare different measures of proteinuria

Receiver operator curve were constructed to allow comparison of assays for key threshold values of proteinuria

ACE-I – angi0tensin converting enzyme inhibitors;ARB –angiotensin receptor blockers;eGFR – estimated Glomerular filtration rate;MDRD – modification of diet in renal disease

Baseline characteristics

Relationship between ACR and TPCR

Relationship was non-linear

ACR is always less than TPCR (as expected)

TPCR, ACR and 24h urine protein

Results were available for 1696 patients TPCR is more highly correlated with 24hr urine protein In the range 300-1000mg/day where clinical decisions are made, there is greater scatter with ACR

Ability of TPCR or ACR for prediction

TPCR is more sensitive than ACR but less specific

24hr urine protein used as a gold standard

ROC curve analysis

Discussion

LIMITATIONS Retrospective study Relationship demonstrated

may only apply to the assay used in this study

STRENGTH Large number of patients Representative nature of

unselected adult population attending a general nephrology clinic.

Discussion

TPCR is a highly sensitive and reasonable specific test for detection of significant proteinuria ie it can be used to rule out the presence of proteinuria and in those patients who have a positive result a full 24 hour collection and quantification is indicated.

ACR performs significantly less well by ROC curve analysis

Since these are screening tests, hence sensitivity is more important

Total proteinuria cannot be predicted from albuminuria because of the variable proportion of non albumin proteins

The diagnostic performances of both tests vary with age, gender, and to some extent eGFR, an effect that is related to muscle mass – hence clinician should interpret the result with the patient’s muscle mass in mind rather than rigidly sticking to a single cut off point.

THANK YOU.

Discussion

Both ratios have their own limitations

─ TPCR and ACR may underestimate 24hour protein excretion

─ Analysis must be immediately done in a fresh sample

─ Urine creatinine measurement is another source of error

─ Urine creatinine is variable and hence the ratio is variable.

THANK YOU.

Figure 26.8 The Renal Corpuscle

Figure 26.8a, b

Interpretation of Urine Albumin to Creatinine Ratio Normal Ratio (in general <30 mg/g is normal)

Men: < 0.017 (or 17 mg albumin to 1 gramCreatinine) Women: <0.025 (or 25 mg albumin to 1 gram Creatinine)

Microalbuminuria: 30-300 mg albumin/g Creatinine Macroalbuminuria: >300 mg albumin/g Creatinine

Comparison of different measures of urinary protein excretion for prediction of renal events. Heerspink HJ, et al.

J Am Soc Nephrol 21: 1355–1360,2010

Heerspink et al (2010) did a study on 701 participants of the Reduction In Endpoints in Non insulin Dependent Diabetes Mellitus with the Angiotensin-II Antagonist Losartan (RENAAL) trial

Four standard methods for measuring urine protein compared: 24-hour urine protein excretion 24-hour urine albumin excretion First morning void spot urine albumin conc First morning void spot urine albumin-to-creatinine ratio (ACR)

Study addressed which of the four methods most strongly associates with the clinical outcome of renal progression, defined by a doubling of serum creatinine or the development of ESRD

All four methods were strongly associated with renal progression

Associations for Spot urine ACR were modestly stronger than those for the

Other urine protein measurements and the superiority of urine ACR was consistent across subgroups defined by gender, race,and age