Assesment of renal function in Assesment of renal function in case of near normal creatinine case of near normal creatinine

(<1.5 )(<1.5 )

Naseer Khan MD Naseer Khan MD

Burden of CKD Stage II in USABurden of CKD Stage II in USA

According to the NHANES III-study the According to the NHANES III-study the prevalence of stage 2 chronic kidney prevalence of stage 2 chronic kidney disease is 3% in the American population disease is 3% in the American population i.e. about 9000000 persons are afflictedi.e. about 9000000 persons are afflicted

Prevalence of CKD by GFR in the USAPrevalence of CKD by GFR in the USA(There is a lot of CKD!)(There is a lot of CKD!)

StageStage DescriptionDescription GFRGFR

(mL/min/1.73m2)(mL/min/1.73m2)

PrevalencePrevalence Prevalence Prevalence (%) (%)

11 Kidney damage Kidney damage with normal or with normal or GFRGFR

> 90> 90 5.9 million5.9 million 3.3%3.3%

22 Mild Mild GFR GFR 60-8960-89 5.3 million5.3 million 3.0%3.0%

33 Moderate Moderate GFR GFR 30-5930-59 7.6 million7.6 million 4.3%4.3%

44 Severe Severe GFR GFR 15-2915-29 400,000400,000 0.2%0.2%

55 Kidney FailureKidney Failure < 15 or dialysis < 15 or dialysis

300,000300,000 0.2%0.2%

Coresh, et al, Am J Kidney Dis. 2003; 41: 1-12

What is GFR ?What is GFR ?

It is the volume of glomerular filtrate It is the volume of glomerular filtrate produced per unit of time, e.g. mL/minproduced per unit of time, e.g. mL/min

GFR Quality means the composition of GFR Quality means the composition of GFR in a patient relative to normal personGFR in a patient relative to normal person

Real GFR not measurable except in lab.Real GFR not measurable except in lab.

80,000 nephrons make it less easy80,000 nephrons make it less easy

Surrogate markers with limitations in useSurrogate markers with limitations in use

Gold Standard MethodsGold Standard Methods

Plasma clearance of inulin, iohexol, Plasma clearance of inulin, iohexol, 5151Cr-Cr-EDTA, EDTA, 125125I-iothalamate, I-iothalamate, 99m99mTc-Tc-diethylenetriaminepentaacetic acid diethylenetriaminepentaacetic acid

GFR markers are creatinine and Cystatin GFR markers are creatinine and Cystatin C which are now clinically usedC which are now clinically used

GFR equations are based on either GFR equations are based on either S.Creatinine and Cystatin CS.Creatinine and Cystatin C

AgeAgeGendGend

erer RaceRaceSCr SCr

(mg/dL)(mg/dL)

eGFR eGFR (mL/min/1.73 (mL/min/1.73

mm22))

CKD CKD StageStage

2020 MMB*B* 1.31.3 9191 11

2020 MMWW†† 1.31.3 7575 22

5555 MMWW

1.31.3 6161 22

2020 FFWW

1.31.3 5656 33

5555 FFBB

1.31.3 5555 33

5050 FFWW

1.31.3 4646 33

Problems with S.CreatinineProblems with S.Creatinine

Varies with age , sex , muscle mass Varies with age , sex , muscle mass

Also varied results with exercise and Also varied results with exercise and protein intake protein intake

Does not show or predict quality of GFR Does not show or predict quality of GFR like in cases of pre-eclempsia like in cases of pre-eclempsia

One equation alone cannot predict One equation alone cannot predict accurate GFRaccurate GFR

Both secreted and excreted Both secreted and excreted

Cystatin CCystatin C

All nuclear human cells produce this All nuclear human cells produce this protein protein 120 amino acid ( small Mol.weight)120 amino acid ( small Mol.weight)Removed from blood stream by filtration Removed from blood stream by filtration by kidneys; fully reabsorbed ( no urine by kidneys; fully reabsorbed ( no urine excretion)excretion)Decline in GFR results in rise of Cystatin CDecline in GFR results in rise of Cystatin CCross sectional studies show superiority to Cross sectional studies show superiority to creatininecreatinine

Emerging role of Cystatin CEmerging role of Cystatin C

Demonstrates the early, potentially Demonstrates the early, potentially reversible, decrease of GFR in the reversible, decrease of GFR in the “creatinine-blind” area“creatinine-blind” areaIndependent of muscle mass and dietIndependent of muscle mass and dietIndependent of sex and age for children Independent of sex and age for children above 1 yearabove 1 yearDemonstrates the decrease of GFR in old Demonstrates the decrease of GFR in old personspersons

No tubular secretionNo tubular secretion ; CV mortality data ; CV mortality data

Creatinine limitation with age Creatinine limitation with age

Age related Cystatin C levelsAge related Cystatin C levels

Creatinine blind areaCreatinine blind area

GFR-markers for patients with muscle GFR-markers for patients with muscle atrophyatrophy

GFR-markers for patients with muscle GFR-markers for patients with muscle atrophyatrophy

Non-parametric ROC plotsfor serum cystatin C (solid line)AUC = 0.912 and serum creatinine(dotted line) AUC = 0.507AUC = 0.50 equals the diagnosticefficiency of tossing a coin

Why use equations?Why use equations?

Equations estimate GFR taking into Equations estimate GFR taking into account creatinine; age ; gender; body account creatinine; age ; gender; body surface area ; race surface area ; race

Adults : Cockcroft-gault equation Adults : Cockcroft-gault equation

MDRD equation MDRD equation

Children :Schwartz & Counahan-Barratt Children :Schwartz & Counahan-Barratt equationsequations

Any value of 24 hours urine Any value of 24 hours urine collection collection

24 hr collection does not improve GFR 24 hr collection does not improve GFR estimation ( equations are better)estimation ( equations are better)

Helpful in persons with exceptional dietary Helpful in persons with exceptional dietary variation ( vegetarians; protein diet)variation ( vegetarians; protein diet)

Amputees Amputees

Muscle wasting /atrophy/ malnourished Muscle wasting /atrophy/ malnourished patientspatients

Criteria for starting dialysis Criteria for starting dialysis

GFR equations GFR equations

MDRD: MDRD: GFR = 186.3 x (creatinine/88.4)GFR = 186.3 x (creatinine/88.4)--

1.1541.154 x age x age-0.203-0.203

x 0.742 (if female) x 1.212 (if African x 0.742 (if female) x 1.212 (if African American)American)

GFRGFR(CC-estimate)(CC-estimate)= 84.69 x cystatin C= 84.69 x cystatin C-1.680-1.680 x x

1.384 (1.384 (if child<14yearsif child<14years))

Qualitative and quantitative measurement Qualitative and quantitative measurement of urine proteins more important in of urine proteins more important in paraproteinemiaparaproteinemia

Erythropoiten is a better marker for Erythropoiten is a better marker for hormonal function of kidneyhormonal function of kidney

GFR quality is altered in Pre-eclempsia GFR quality is altered in Pre-eclempsia which is not detected by creatinine but is which is not detected by creatinine but is better outline by Cystatin Cbetter outline by Cystatin C

Is GFR always the best marker Is GFR always the best marker for kidney disease/function?for kidney disease/function?

Is GFR always the best marker Is GFR always the best marker for kidney disease/function?for kidney disease/function?

Cystatin C in Pre-eclempsia Cystatin C in Pre-eclempsia

Creatinine in pre-eclempsiaCreatinine in pre-eclempsia

What do we do now ?What do we do now ?

Use History and Physical as Gold Use History and Physical as Gold StandardStandardKeep in mind limitations of serum Keep in mind limitations of serum creatinine measurement creatinine measurement Use more than one GFR marker Use more than one GFR marker Use more than one equation while using Use more than one equation while using S.Cr ( Lund University online equation)S.Cr ( Lund University online equation)Cystatin C seems promising esp. for Cystatin C seems promising esp. for qualitative analysisqualitative analysis

Identify High Risk GroupsIdentify High Risk Groups

DiabetesDiabetesHypertensionHypertensionHeart DiseaseHeart DiseaseFamily HistoryFamily HistoryHigh Risk Ethnic GroupHigh Risk Ethnic GroupAge > 60 yearsAge > 60 yearsScreening : eGFRScreening : eGFR UrinalysisUrinalysis Albumin / Creatinine RatioAlbumin / Creatinine Ratio

PCP Must be EngagedPCP Must be Engaged

1)1) 7.7 million people with GFR 30-60 mL/min/1.73 m7.7 million people with GFR 30-60 mL/min/1.73 m22

2)2) About 5,000 full-time nephrologists About 5,000 full-time nephrologists

3)3) Nearly 1,500 new patients per nephrologistNearly 1,500 new patients per nephrologist

Therefore, 7 new patients per day per nephrologist. Therefore, 7 new patients per day per nephrologist.

Obviously not possible.Obviously not possible.

Who should take the lead?Who should take the lead?

The primary care physician and the The primary care physician and the

nephrologistsnephrologists

PRIMARY CARE PHYSICIAN

Screening

Diagnosis

Treatment

NEPHROLOGISTS

Diagnosis

Management

Pre Dialysis care

Prevention Of Renal Failure

GoodGood doctordoctor relieve relieve diseasedisease

BetterBetter doctordoctor cure cure diseasedisease

SuperiorSuperior doctordoctor preventprevent diseasedisease

Old Chinese saying…….