Assesment of renal function in case of near normal creatinine (<1 Naseer Khan MD

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

Prevalence of CKD by GFR in the USA (There is a lot of CKD!) Stage Description GFR (mL/min/1.73m2) Prevalence Prevalence (%) 1 Kidney damage with normal or  GFR > 90 5.9 million 3.3% 2 Mild  GFR 60-89 5.3 million 3.0% 3 Moderate  GFR 30-59 7.6 million 4.3% 4 Severe  GFR 15-29 400,000 0.2% 5 Kidney Failure < 15 or dialysis 300,000 Coresh, et al, Am J Kidney Dis. 2003; 41: 1-12

What is GFR ? It is the volume of glomerular filtrate produced per unit of time, e.g. mL/min GFR Quality means the composition of GFR in a patient relative to normal person Real GFR not measurable except in lab. 80,000 nephrons make it less easy Surrogate markers with limitations in use

Gold Standard Methods Plasma clearance of inulin, iohexol, 51Cr-EDTA, 125I-iothalamate, 99mTc-diethylenetriaminepentaacetic acid GFR markers are creatinine and Cystatin C which are now clinically used GFR equations are based on either S.Creatinine and Cystatin C

Age Gender Race SCr (mg/dL) eGFR (mL/min/1.73 m2) CKD Stage 20 M B* 1.3 91 1 W† 75 2 55 W 61 F 56 3 B 50 46

Problems with S.Creatinine Varies with age , sex , muscle mass Also varied results with exercise and protein intake Does not show or predict quality of GFR like in cases of pre-eclempsia One equation alone cannot predict accurate GFR Both secreted and excreted

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

Emerging role of Cystatin C Demonstrates the early, potentially reversible, decrease of GFR in the “creatinine-blind” area Independent of muscle mass and diet Independent of sex and age for children above 1 year Demonstrates the decrease of GFR in old persons No tubular secretion ; CV mortality data

Creatinine limitation with age

Age related Cystatin C levels

Creatinine blind area

GFR-markers for patients with muscle atrophy Non-parametric ROC plots for serum cystatin C (solid line) AUC = 0.912 and serum creatinine (dotted line) AUC = 0.507 AUC = 0.50 equals the diagnostic efficiency of tossing a coin

Why use equations? Equations estimate GFR taking into account creatinine; age ; gender; body surface area ; race Adults : Cockcroft-gault equation MDRD equation Children :Schwartz & Counahan-Barratt equations

Any value of 24 hours urine collection 24 hr collection does not improve GFR estimation ( equations are better) Helpful in persons with exceptional dietary variation ( vegetarians; protein diet) Amputees Muscle wasting /atrophy/ malnourished patients Criteria for starting dialysis

GFR equations MDRD: GFR = 186.3 x (creatinine/88.4)-1.154 x age-0.203 x 0.742 (if female) x 1.212 (if African American) GFR(CC-estimate)= 84.69 x cystatin C-1.680 x 1.384 (if child<14years)

Is GFR always the best marker for kidney disease/function? Qualitative and quantitative measurement of urine proteins more important in paraproteinemia Erythropoiten is a better marker for hormonal function of kidney GFR quality is altered in Pre-eclempsia which is not detected by creatinine but is better outline by Cystatin C

Cystatin C in Pre-eclempsia

Creatinine in pre-eclempsia

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

Identify High Risk Groups Diabetes Hypertension Heart Disease Family History High Risk Ethnic Group Age > 60 years Screening : eGFR Urinalysis Albumin / Creatinine Ratio

PCP Must be Engaged 7.7 million people with GFR 30-60 mL/min/1.73 m2 About 5,000 full-time nephrologists Nearly 1,500 new patients per nephrologist Therefore, 7 new patients per day per nephrologist. Obviously not possible.

Prevention Of Renal Failure Who should take the lead? The primary care physician and the nephrologists PRIMARY CARE PHYSICIAN NEPHROLOGISTS Screening Diagnosis Treatment Diagnosis Management Pre Dialysis care

Old Chinese saying……. Good doctor relieve disease Better doctor cure disease Superior doctor prevent disease