CKD Nilang Patel Epidemiology of CKD - PowerPoint Presentation

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CKD

Nilang Patel

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Epidemiology of CKDDefinition of CKDStaging of CKD

Etiology of CKD

How to measure Kidney function

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Incidence of ESRD

(per million population, 1990, by HSA, unadjusted)

USRDS, 2000

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Incidence of ESRD

(per million population, 2000, by HSA, unadjusted)

USRDS, 2000

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ESRD Continue to Rise……..

Trends in the number of

prevalent cases of ESRD

, in thousands, by modality, in the U.S. population, 1980-2012

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A). How many US Adult Population has CKD ?

< 10%

10-15%

15-20%

20-25%

25-30%

B). Out of them, at what stage of kidney disease majority of them falls into?1). CKD 1-22). CKD 33). CKD 45). CKD 5 6). ESRDC). What is the cost of average dialysis patient to Medicare?

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Prevalence of CKD in U.S.

GFR

(mL/min/1.73 m

2

)

59-30

29-15

Number of People

7.7 Million

360,000

Thus, about

8 million Americans

have a GFR less than 60 mL/min/1.73 m2.

Plus 11 million

more have a GFR over 60 but have

persistent microalbuminuria

.

Coresh, et al., 2005

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Prevalence of CKD

Prevalence

is about

11-13 %

About 8 million US adult population has CKD

About 300,000 on HemodialysisNumber will expect to go high because of increasing prevalence of Diabetes, HTN, Aging population and Obesity ESRD patients related costs grew by 57% from 1999 to 2004 and now account for 7% of total Medicare expenditure and it will rise exponentially in future…

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Costs of Kidney Failure are High

(in $billions for 2002)

Kidney Failure

Care

Total NIH

Budget

25.2

23.2

Kidney Failure Accounts for 7% of Medicare Payments

Lost Income for Patients is $3-4 Billion/Year

USRDS, 2004

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Kidney Failure Compared to

Cancer Deaths in the U.S. in 2000

(in Thousands)

SEER Registry, 2004

Lung Cancer

Kidney

Failure

Colorectal

Cancer

Breast

Cancer

Prostate

Cancer

57

100

41

30

160

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What is the best way to measure kidney function ?

1). Loss of kidney mass (

ie

, nephron loss) is similar to the loss of GFR?

True or False

2). Stable GFR means stable kidney disease?

True or False

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How do you measure GFR?

The “gold standard” for measuring GFR is through the use of inulin, a carbohydrate produced by many plants, such as onions and garlic.

Inulin is useful as an indicator of GFR because the kidneys handle it in a unique way. Unlike most other substances in the blood, inulin is neither reabsorbed into the blood after filtration nor secreted through peritubular capillaries.

Thus, the amount of inulin cleared through the urine is indicative of the amount of plasma filtered by the body’s glomeruli. GFR can be calculated using Equation 1. 

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Urinary Inulin Clearance

Measurement of urinary 

inulin clearance

 requires a constant intravenous 

infusion

 to maintain a constant level of inulin over 3 to 4 hours. After an equilibration period, timed urinary specimens and plasma are collected every 30 minutes, and urinary and plasma inulin are measured to calculate urinary inulin clearance.

The mean clearance of 4 or 5 measurements determines the patient's GFR. Urinary catheterization is often required. To avoid this cumbersome procedure, two methods of plasma inulin clearance have been developed: the continuous infusion method and the single bolus method.Plasma Inulin Clearance: Continuous Infusion MethodThe continuous infusion method is based on the concept that once a marker has reached a steady state in the plasma and the volume of distribution is saturated, the rate of elimination of the marker will equal the rate of infusion (RI).

Clearance = Rate of Infusion/plasma concentration

Because the equilibration can take more than 12 hours in certain situations, a 

bolus injection

 can be given before the infusion to reach the steady state more rapidly.

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Endogenous Filtration maker for GFR estimation

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Serum Creatinine as Kidney Function

The serum creatinine concentration alone should not be used to assess the level of kidney function

.

The use of serum level of creatinine as an index of GFR is based on

3 assumptions

1. Ideal filtration marker

2. creatinine excretion rate is constant and

3. measurement is accurate and reproducible across clinical laboratories

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What are the problems of using Creatinine as filtration marker ?

Variation in creatinine production

Variation in creatinine secretion

 

Extrarenal creatinine excretion

 

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SHEMESH et al; Kidney International, Vol. 28 (1985)

Serum Creatinine vs. Inulin clearance

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Measured Creatinine Clearance

 Measured CrCl or GFR =  [UCr  x  V]  ÷  SCr

To correlate with GFR – need to adjust with BSA.

Problem:

Incomplete collection

Increase creatinine secreation with fall in GFR

Drug affecting tubular secreation of creatinine

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78 y/o male with h/o HTN, DM, CKD stage 3 with baseline

S.creat

of 1.8 admitted in hospital. His weight is 100 kg. He has presumed MRSA infection. His lab reported eGFR is 38 ml/min/1.73m2. You prescribed Vancomycin 1 gm IV. Pharmacist asked you to consider prescribing dose based on his Cockcroft-Gault equation estimated GFR. You advised him that…

1). Do whatever you want, why bother ?

2). Use CG equation since it has more accurate estimation of GFR than lab reported eGFR in elderly.

3). Call intern and asked him to do stat 24 hour creatinine clearance before adjusting dose.

4). Use Lab reported eGFR since it is more accurate than CG equation in elderly.

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Cockcroft-Gault equation

 

Estimate Creatinine clearance from the serum creatinine.

This formula takes into account assumptions

Patient has stable serum creatinine.

Creatinine production decreases with advancing age.

Creatinine production is greater in individuals with greater weight.The equation is not adjusted for body surface area.Developed on old S. Creat

assay (typically 20% higher)

With current standardized

S.Cret

assasy

it result in a 10 to 40 percent 

overestimate

 of creatinine clearance.

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The level of GFR is estimated from prediction equations based on the serum creatinine concentration

MDRD Equation

eGFR = 175 X (

Scr

)

-1.154

X age-0.203 X 0.742 (if female) X 1.212 (if

black),

where

Scr

is serum creatinine in mg/dl and age is expressed in years

CKD EPI formula

eGFR = 141 X min(

Scr

/k, 1)

α

X max(

Scr/k, 1)-1.209 X 0.993Age X 1.018(if female) X 1.159 (if black) Estimation of GFR

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People with near normal kidney function or mildly abnormal or elderly patient..

How MDRD estimate GFR compared to actual measured GFR?

1). Overestimate

2). Underestimate

3). Performed perfectly fine

4). All of the above.

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Performance of the CKD-EPI and MDRD Study equations in estimating measured GFR

Both panels show the difference between measured and estimated versus estimated GFR. A smoothed regression line is shown with the 95% CI (computed by using the lowest smoothing function in R), using quantile regression, excluding the lowest and highest 2.5% of estimated GFR. To convert GFR from mL/min per 1.73 m2 to mL/s per m2, multiply by 0.0167.

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-Although medial difference of estimated vs measured GFR low..

-CKD-EPI has ICR of 16.6 ml/min/1.73m2 and P30 is 84%

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Matsushita K et al,

JAMA. 

2012;307(18):1941-1951. 

A meta-analysis of data from 1.1 million adults (aged ≥ 18 years) from 25 general population cohorts, 7 high-risk cohorts (of vascular disease), and 13 CKD cohorts.

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Matsushita K et al,

JAMA. 

2012;307(18):1941-1951. 

-In estimated GFR of 45 to 59 mL/min/1.73 m

2

 by the MDRD Study equation, 34.7% of participants were reclassified to estimated GFR of 60 to 89 mL/min/1.73 m

2 by the CKD-EPI equationRe-Classified by CKD-EPI from MDRD Categories

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Matsushita K et al,

JAMA. 

2012;307(18):1941-1951. 

The CKD-EPI equation classified fewer individuals as having CKD and more accurately categorized the risk for mortality and ESRD than did the MDRD Study equation across a broad range of populations.

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60

y.o

. male with h/o C6-C7 tetraplegia since last 15 years after motor vehicle accident. He has h/o HTN, autonomic neuropathy, h/o frequent UTIs followed by Suprapubic catheterization, diet controlled diabetes and asthma. He is admitted at SCI for annual evaluation. His vitals are stable. BP at 130/80 mmHg, P 82, RR 20. His chemistry showed Na-140, K-3.6, Cl-110, Co2-22, BUN-6,

S.creat

0.8 and eGFR 97ml/min/1.73m2. His last

s.creat

was 0.5 in 2015 with eGFR of 122 ml/min/1.73m2. His U/A does not show any RBC/WBC. His urine ACR is 20 mg/gm. His renal USG showed 8.7 cm right kidney and 9 cm left kidney. Primary team called you for routine renal consult as part of hospital policy. What should you do?1). Call SCI attending, asked to discontinue consult as it’s not CKD.2). Get 24 Hour Creatinine Clearance.3). Get Serum Cystatin C and compared that to his previous readings.4). Just finish consult, why bother?

5). Get Serum Cystatin C, to estimated eGFR based on Cystatin C and Serum Creatinine value.

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Cystatin C, a low molecular weight protein. Cystatin C is believed to be produced by all nucleated cells. Its rate of production has been thought to be relatively constant, and not affected by changes in diet or weight.

Cystatin C is filtered at the glomerulus and not reabsorbed or secreted. However, it is metabolized in the tubules, which prevents use of cystatin C to directly measure clearance.

Estimation equations based on serum cystatin C have also been formulated. – useful in SCI, Poor muscle mass, Cirrhosis, Elderly.

Problem of Cystatin C: influence by Steroid, Infection, Variability of reporting result by different lab despite using standardized assay.

Serum cystatin C

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Inker et al, N

Engl

J Med 2012;367:20-9.

Panel A shows the median difference between measured and estimated GFR. Bias was similar among the three equations, with a median difference between measured and estimated GFR.

Panel B shows the accuracy

the three equations with respect to the percentage of estimates that were greater than 30% of the measured GFR (1 – P30). Precision was improved with the combined equation (interquartile range of the difference, 13.4 vs. 15.4 and 16.4 ml per minute per 1.73 m2, respectively [P = 0.001 and P<0.001]).

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60 y/o AA male with well controlled h/o HTN, referred to Nephrologist for evaluation of his kidney function. His BP is 130/82 mmHg. His weight is 180

lbs

and Height 68 inch. He is well built and muscular worked as professional Gym trainer. He also takes muscle milk daily. His chemistry showed Na-140, K-3.8, Cl-110, Co2-27,

S.creat

of 1.5, BUN 20, Glucose 90. His eGFR reported as 58 ml/min. His random Urine ACR – 10 mg/gm. His U/A is negative for protein, glucose,

rbc

and wbc. His Renal USG showed – 10.8 CM right kidney and 11.3 cm left kidney without any hydronephrosis, stone or mass. He is taking Lisinopril 40mg po daily for his BP. 1). Does this patient has CKD?

2). What is the stage of his CKD?

3). What other testing you want to do on him?

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Define Chronic Kidney Disease ?

The National Kidney Foundation has defined chronic kidney disease as:

The presence of markers of kidney damage, such as abnormalities in the composition of blood or urine or abnormalities on imaging tests ≥ 3 months

Or

The presence of a GFR of less than 60 mL/min/1.73 m

2

for ≥ 3 months with or without other signs of kidney damage.

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KDIGO Classification based on Prognosis

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Why GFR and ACR cut off? 

Meta-analysis by the CKD Prognosis Consortium demonstrated associations of eGFR < 60 ml/ min/1.73m2 with subsequent risk of all-cause and cardiovascular mortality, kidney failure, AKI, and CKD progression in the general population.

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55 y/o white male with well controlled HTN, referred to Nephrologist for evaluation of his kidney function. He has family h/of Polycystic kidney disease. His BP is 130/82 mmHg. His weight is 180

lbs

and Height 68 inch. His chemistry showed Na-140, K-3.8, Cl-110, Co2-27,

S.creat

of 1.3, BUN 20, Glucose 90. His eGFR reported as 73 ml/min. His random Urine ACR – 20 mg/gm. His U/A is negative for protein, glucose,

rbc

and wbc. His Renal USG showed – 12 CM right kidney and 12.3 cm left kidney with numerous cyst on both kidney suggesting PCKD. His blood pressure is well controlled on Lisinopril 40mg daily.  1). Does this patient has CKD?

2). What is the stage of his CKD?

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KADIGO (2013) (not graded)

Recognize that small fluctuation In GFR are common and are not necessarily indicative of progression. ( < 25% drop).

Rapid progression is defined as a sustained decline in eGFR of more than 5 ml/min/1.73 m2/year.

Alberta Kidney Disease Network (AKDN). In this analysis 598,397 adults with at

least two out-patient measures of

S.Cr

spaced at least 6 months apart were included. At least 4 year follow up.

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30% decline in eGFR over 2 years

Strongly correlate with ESRD & Mortality

Coresh et al, JAMA

. 2014;311(24):2518-2531.

Slide44

Trajectories of GFR decline are non-linear

12 year follow up of Individuals in AASK study.

41.6% of patients exhibited > 90% probability of having non-linear trajectory

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Diabetes mellitus

Hypertension

Glomerulonephritis

Polycystic kidney disease

Unrecovered AKI

CIN

Reno-vascular diseaseEtiology of CKD

Slide46

Causes of Stage 5 CKD in USRDS 2014

Slide47

Trends in ESRD incident cases

, in thousands, by primary cause of ESRD, in the U.S. population, 1980-2012

Non-diabetic CKD

Slide48

Diabetic Kidney Disease:

In most people with DM, CKD should be attributable to DKD in the presence of

Macro-albuminuria

Micro-albuminuria + retinopathy

Micro-albuminuria plus duration of type 1 DM >10 years

Hypertensive

Nephrosclerosis: Long history of hypertension with left ventricular hypertrophy, Relatively normal urine sediment,

Small kidneys,

if previous information is available, slowly progressive renal insufficiency with gradually increasing proteinuria that is usually non-nephrotic

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A persistent and progressive reduction in GFR.

Lack of proteinuria .

Findings that suggest the presence of

reno

-vascular disease

Severe hypertension that may be treatment resistant,

An acute rise in serum creatinine following the administration of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), Significant variability of serum creatinine concentration that may be due to changes in volume status, recurrent episodes of flash pulmonary edema and/or refractory heart failure, Presence of risk factors for atherosclerotic disease . Increased frequency of CAD and PVD.

Ischemic nephropathy

Slide50

Diabetic

CKD

Non-Diabetic HTN

CKD