Ckd Guideline

8/6/2019 Ckd Guideline

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Copyright 2005 by The Indian Society of Nephrology

Indian J Nephrol 2005;15, Supplement 1: S1-S6

Guidelines for the Management of CKD

Guidelines 1 and 2

Chronic Kidney is a new name for what was in the pastknown as Chronic Renal Failure. By redefining this entity,the National Renal Societies of western countries haveachieved the following objectives:

1. Chronic Kidney disease has been defined andclassified into 5 stages according to severity. Thishelps to make accurate epidemiological estimatesof the incidence and prevalence of CKD and itsstages, particularly in its early stages and alsoidentifies the populations at risk of developing CKD.

2. The complications associated with each stage of CKDhave been identified.

3. The clinical, laboratory and imaging parameters usedto define these stages have been standardized sothat the staging of disease is unambiguous.

4. The interventions recommended for the risk factorsassociated with progression of renal disease and theassociated cardiovascular morbidity and mortality arestandardized so that they can be uniformly appliedand critically evaluated for the claims they are creditedwith. This ensures uniform care of every CKD patient.

The two best and well known CKD best practice guidelinesare (1) the KDOQI of the NKF USA and the (2) 2002recommendations of the ERA/EDTA.

CKD in India differs from CKD in developed nations inthe following ways.

1. The incidence and prevalence of CKD is notaccurately known due to lack of epidemiologicalstudies.

2. Lack of financial resources, laboratory facilities andqualified personnel makes it difficult to practice withsame degree of depth of investigation in the Indianscenario.

3. Laboratory parameters of normal renal function arenot well defined in the Indian population and maydiffer from the western data. This is particularly trueof markers which are derived from the protein contentof the diet and the quantum of muscle mass such asurea and creatinine.

4. The Indian spectrum of renal diseases is clearlydifferent from that seen else where.

5. In view of the shortage of qualified nephrologists,the general physicians and less qualified doctors arealso practicing nephrology and they need to beinformed about good practice guidelines.

6. The insurance companies, TPAs and medical careproviders, are emerging as a large body who have asay in the management of nephrology patients. Theyneed to know and use standard practice guidelines.

7. The acceptability of the living donor for kidneytransplantation on the basis of renal function tests,particularly GFR estimation by creatinine clearanceis often questioned because Indian patients appearto have much lower values of GFR in the face ofnormal renal function. These guidelines would helpto define normalcy in the Indian population.

8. With increase in medico legal litigation in India, thestandard guidelines would help nephrologists todefend their appropriate actions taken in the interestof their patients. However these guidelines would notput the practicing nephrologists at risk if they are notadhered to, because they serve as guidance and arenot mandatory or binding.

9. Many recommendations made in western guidelines

are not possible to implement in Indian circumstancesdue to lack of facilities, infrastructure and resources.

Any guidelines must necessarily

1) Emerge from the deliberation of the national societyand be produced as a consensus.

2) Be along the lines of existing worldwide guidelines

3) Be suitably modified according to Indian researchand publications

4) Unfortunately the evidence available at present isnot always of the highest level and yet it ismeaningful. These limitations therefore need to beacknowledged even as recommendations are madeon the basis of this evidence.

The goals of the CKD work group would beas follows:

i. Definition of CKD and staging.

ii. Defining normalcy of renal function in India.

iii. Enumerate guidelines for management at eachstage of CKD and for each systemic


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Indian Journal of Nephrology Indian J Nephrol 2005;15, Supplement 1: S1-S6

derangement due to CKD.

iv. GCP recommendations when RRT should beinitiated and when AV fistula or CAPD cathetershould be put.

v. Recommendation for immunization schedules forCKD patients.

vi. Recommendations for measures to preventprogression of established CKD from lesser tomore severe stage.

Defining CKD

Chronic Kidney Disease is identified when the followingcriteria are fulfilled1.

Duration: 3 months or more

Kidney damage is either functional or structural with orwithout reduction in GFR as identified by any one or allof three criteria.

1. Abnormal gross or microscopic pathology.

2. Laboratory markers of kidney damage in blood, Urine,Imaging tests

3. GFR less than 60ml/min/1.73m in the absence ofany other renal abnormality

This definition propounded by the KDOQI guidelines isnow almost universally adopted and in the absence ofany significantly data emerging from our country, it needsto be adopted unchanged for the present. With the adoptionof this definition in the USA there has been a dramaticrealization of the large number of persons suffering fromCKD and the immense effect CKD will have on the healthcare budget of the nation, if CKD continues to progressrelentlessly. It has made the public health authorities situp and plan strategies to prevent the morbid outcomes.

The adoption of this definition followed by epidemiologicalstudies should help to identify the extent of the healthcare problem posed by CKD in India.

A major drawback is the identification of CKD due totubulointerstitial diseases and vascular renal diseases(such as ischemic nephropathy) is that the usual markersof CKD i.e low GFR, urinary, blood and imagingabnormalities are not sensitive and many patients withCKD due to these diseases cannot be identified at earlystages.

The classification has 3 unique grey areasthat deserve special attention.

a) Patients with low GFR between 60ml and 90ml withoutHBP, markers of kidney damage in urinary, blood orimaging tests.

A large number of normal Indians are likely to fall inthis category because of their small physical buildand low protein intake due to predominantvegetarianism. Every physician who has evaluatednormal renal donors for kidney living donor donationwill bear out the statement that in India, the normalpopulation has lower GFR than normal western

counterparts. The normal values in K-DOQI guidelinesfor CKD have been formulated for the US populations.Protein intake in the developed nations has beenfound to be 50% more than in developing countriesas India (105 g/day compared to 57.3 g/day)2.Furthermore, in those vegetarians who ingest noanimal products such as milk and eggs, the averageprotein intake is 20-40% less than in lacto-ovo-vegetarians3.Studies have demonstrated that thereis an acute and a delayed increase of GFR with aprotein load4. The GFR, renal plasma flow andsplanchnic blood flow increase within 1 hr after ameat meal and remains elevated for several hours.Habitually increased protein intake causes structuraland hemodynamic alterations leading to renalhyperemia and hyperfiltration in conjunction withdiuresis and natriuresis5. There are studies to confirmthat vegetarianism results in a low GFR which canbe stimulated by ingestion of a large protein meal.An infusion of aminoacids mimics a large protein


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meal and the resultant increase in GFR has beencalled the Renal reserve which may be as high as80-100% of the base line value6.

Other causes of chronically decreased GFR withoutkidney damage in adults include vegetarian dietsunilateral nephrectomy, extra cellular fluid volumedepletion and systemic illness associated with

decreased kidney perfusion such as heart failure andcirrhosis. Thus, in clinical practice, it is difficult todetermine whether the individual with decreased GFRhas chronic kidney disease. In this subset of patients,the presence of other markers for kidney diseasessuch as urinary abnormalities (hematuria, proteinuria,and pyuria) and hypertension help to differentiate theCKD patient from the non-CKD.

b) Patients with HBP and normal GFR without urinary,blood and imaging abnormalities of renal disease donot fall into the subgroup of CKD stage I; but shoulddefinitely be treated as a subgroup that needs closefollow up for future development of CKD. Theseindividuals would be considered at- risk fordevelopment of CKD. The other such patients requiringclose follow up are :

STAGE 0 CKD (patients at high risk of developingCKD)

Patients above 65

Those with family history of renal disease

Diabetics

Autoimmune diseases

Systemic infections 0Urinary tract infections

Urinary stones

Lower urinary tract obstruction

Drugs including NSAID abuses

c) Individuals with HBP and GFR values between 90and 60 ml / mt, although technically still not CKD inthe absence of urinary, blood and imagingabnormalities, are commonly those with essentialhypertension above 65 years of age and would oftenhave other target organ damage such as retinalchanges, LVH and remodeling on echocardiographyand history of cerebrovascular accidents. Thesepatients deserve the same management as stage ICKD.

Guideline I

1. The patient assigned a diagnosis of CKD shouldconform to the definition and fulfill the criteria of

Duration > 3 months

Urinary , blood and imaging abnormalities

Blood pressure

G F R

2. The patient must be assigned a stage for adequatemanagement (I-V).

3. In order to give specific treatment every possible

investigation should be done to determine theetiopathological cause of CKD.

4. Inspite of investigations a significant number ofpatients of CKD will be left without a confirmedetiopathological diagnosis due to limitations of theinvestigating techniques and their applicabilities.

5. Over and above the specific interventions, there arecertain interventions applicable to all cases of CKDirrespective of their etiology and pathology. There areappropriate interventions suggested for each stageof CKD.

These interventions are aimed at Reducing the rate of progression to stage V.

Reducing the incidence of complicationsassociated with each stage and in particularreducing the incidence of cardiovascularmorbidity and mortality.

6. CKD in India is different from CKD in the world in thewest and there is a need for Indian epidemiologicalstudies.

7. Until such time that Indian epidemiological studiesare developed, an attempt should be made to adoptwestern data in modified form.

Estimation of GFR

The level of GFR is a strong predictor of the time toonset of ESRD as well as the risk of CKD. GFR cannotbe measured directly the amount of a physiological,freely filterable and non-secreted or metabolized solute,such as inulin, in the urine is an indirect marker of theamount filtered at the glomerulus. The most widely usedmeasures of GFR are based on the 24 hrs creatinineclearance or serum creatinine concentration.

Laboratory evaluation of GFR

1. Insulin clearance (gold standard) This is the goldstandard but very difficult to carry out in clinicalpractice.

2. Blood urea / Blood urea nitrogen : Historically one ofthe earliest methods developed, it clearly does nothave a linear relationship with GFR because

a) Urea is not exclusively excreted only byglomerular filtration.



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b) Urea levels are influenced by dietary proteinintake, GI bleeds, volume depletion, steroidintake, liver disease and hypercatabolic states

c) Few symptoms of CKD have correlation with urealevels.These recommendations, however, do notsuggest that blood urea is not a useful test only that it has little value as a marker of CKD.

The test has many applications in other renalsituations such as ARF, Kidney transplantation,MHD and adequacy of dialysis but that is beyondthe perview of this study.

3. Serum creatinine and creatinine clearance

Creatinine is mainly derived from the metabolism ofcreatinine in muscle, and its generation is proportionalto the total muscle mass. Creatinine generation ishigher in men, younger individuals and in blacks thanin whites. Meat intake, low protein diets differencein S. creatinine according to age, gender and raceexist. Moreover, the traditional method of serum

creatinine estimation (alkaline picrate method) alsodetects non-creatinine chromogens compared tomodern autoanalysers (were such interference is notseen) leading to lab-variations in serum creatinineand overestimation of GFR when measured by thelatter method. Substances like ketones and bilirubinmay lead to spuriously elevated and decreasedcreatinine respectively.

The amount of creatinine excreted in the urine is acomposite of both the filtered and the secretedcreatinine. Creatinine clearance overestimates GFRby 10-40% in normal individuals, and is greater and

more unpredictable in patients with CKD. As muchas 2/3 of total daily creatinine excretion can occurby extra-renal creatinine elimination in patients withseverely reduced kidney functions.

The normal level of GFR varies according to age,gender and body size. After age 20-30 yrs, the GFRdeclines at the rate of 1ml/mt/1.73m2/year. Thus byage 70, it is approximately 70ml/mt/1.73m2. Thevariability of creatinine excretion with protein intake,muscle mass and sex have been dealt withearlier.That the GFR varies with race has not beenstudied extensively in populations of the developingcountries although certain ethnic groups like Hispanicand non-Hispanic blacks have higher creatinineexcretions than other populations7. Similar studiesfor the Indian populations have not yet beenconducted, but keeping in mind the lower creatinineproduction (due to a lower body mass index coupledwith a lower dietary protein intake in Indians), acomparatively lower creatinine excretion can beexpected. Whether ethnic origins and genetic make-up contributes to this difference remains to beevaluated.

The usual method of estimating GFR in clinicalpractice is by collection of the 24 hour urinary samplewith estimation of its creatinine content and usingthe formula ; creatinine clearance = uv/p, withcorrection for body surface area of 1.73sq.mts. Themajor drawbacks of this method are

a) Inaccurate collection

1) Samples are thrown away

2) Timing is wrong

3) Urine passed with faeces is lost

4) Most patients do not understand the collectionprocess as also many of the laboratory orward staff designated to do this

b) It is laborious, obnoxious due to smell, messyand time consuming.

c) It has been shown that the prediction equationsdescribed hereafter are equally accurate and

much easier to use in clinical practice.

Estimating the creatinine clearance from prediction equations

Equations used to predict GFR in Adults Based on SerumCreatinine\Equation

Cockcroft-Gault Equation

Cr.cl (ml/min) = (140-Age) x Weight x (0.85 if female)

72 x S. Cr

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MDRD, Serum VariablesGFR (ml/min/1.73m2) = 170 x (S.Cr.)-.999 x (Age)-

0.176 x (SUN)-0.170 x (Alb) +0.318

x (0.762 if female) x (1.180 if black)

Equations used to predict GFR in Children Based onSerum Creatinine Equation

_________________________________________________________________________________________________

Schwartz Formula

Cr.cl. (ml/min) = 0.55xLengthS.Cr

_________________________________________________________________________________________________

Counahan-Barratt Equation

GFR (ml/min/1.73 m2 ) = 0.43xLengthS.Cr

a. Cockcroft Gault equation

While the C-G equation provides an easy and readilyavailable estimate of the creatinine clearance, its majordrawback is that it does not take into account body size.


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The accuracy of the C-G equation has been validated inseveral studies, which indicated that the majority ofestimated GFRs were within 30% of the measured GFR,accuracy considered sufficient for good clinical decisionmaking8. Some studies have standardized the resultsfor body surface area, while others have suggested usinglean body mass (rather than total weight, especially forobese individuals) or ideal body wt calculated by the

Hamwi method9, as follows;

Females: 44 kg for the first 150 cms of height and 0.9 kgfor every cm beyond 150cm.

Males: 46.7 kg for the first 150 cms of height and 0.9 kgfor every cm beyond 150cm.

Other drawbacks of the CG include

1. Use of s.creatinine to estimate GFR relies on theindividual being in steady state and the ability toestimate the average rate of productions of creatinine.

2. Using prediction equation to estimate the degree of

kidney damage is not very accurate at the higherrange of GFR as in CKD stage 1-2. Early glomerularinjury may lead to compensatory hypertrophy andhyperfiltration in less affected nephrons, therebymaintaining or increasing GFR .Additionally, with amild decrease in kidney function, only a slight increasein the serum creatinine may be seen because of anincrease in tubular secretion.

3. Measurement of progression of kidney disease issubstantially more difficult than diagnosis of thepresence of kidney disease since the progression ofmany forms of kidney disease is slow. The C-G allows

for reliable detections of substantial progression (>25-50%) but may not satisfactorily differentiate the fallin GFR in those with slowly progressive kidneydisease

b. MDRD equation

The MDRD study equation has the advantage of havingbeen derived based on 10:

a. GFR measured directly by urinary clearance of I-125- Iothalamate.

b. A large sample of greater than 500 individuals with awide range of kidney diseases was done.

c. Inclusion of different ethnic groups in the study

d. It has been validated in a large separate group ofindividuals as part of its development.

This equation provides estimates of GFR standardizedfor the body surface area. The calculations, however,needs web based and downloadable medical calculatorswhich makes it difficult to implement on a day to daybasis for most physicians and nephrologists practicingin India.

The timed collection technique should be reserved forusage in the following situations:

1. Estimation of GFR in individuals with exceptionaldietary intake (veg-diet, creatine supplements) ormuscle mass (amputation, malnutrition, musclewasting and extremes of ages).

2. Rapidly changing kidney function.

3. Assessment of diet and nutritional status.

4. Prior to using drugs that one excreted by the kidneyand with significant toxicity.

5. To confirm the need to start dialysis when patientsare unable to accept this eventuality.

6. For research purposes.

Nuclear methods to measure GFR

When precise measurements of GFR are necessary, orwhen muscle mass may deviate substantially from valuespredicted by age, race, sex in adults or height in children,clearance measures using exogenous filtration markersmay be necessary. Nuclear methods to measure the GFRin such situations provides an easy and reliablealternative.

The radiolabelled compounds used for such measurementinclude I-125 iothalamate, Tc -99 diethylenetriaminepentaacetic acid etc.

I-125 iothalamate, the most reliable among the availablecompounds, can be used as a subcutaneous injectionwhich is followed by slow release to the circulationproviding stable plasma and urine concentration for some

hours. Its half life is 60 days and can safely be stored.Its efficacy in measuring GFR has been reported to becomparable to inulin clearance in adults and children.

The advantages of using radiolabelled compounds forGFR assessment include

Measurement of the compound at even very lowconcentrations using conventional counters isvery precise. Very small, non toxic amounts aregiven.

The disadvantages include its high cost andneed for supportive infrastructure.

In Indian circumstances, the utilization of these tests onregular basis is difficult because of lack of nuclearmedicine laboratories performing these tests on regularbasis with reliable reproducibility, and most Indianpractitioners therefore avoid their usage.

Guideline 2

GFR estimation

1. Blood urea / BUN is a poor estimate of GFR.

2. S. creatinine should not be used alone as an



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estimation of renal function and extent of renaldamage. Creatinine clearance by timed urinecollections or prediction equations provide additionalinformation in defining and staging CKD.

3. Every laboratory should supply estimated GFR byprediction equations using one of the two availableadult or child formulae derived from serum creatinine.

This would adjust for age, sex and body mass index.4. Timed urinary collections of creatinine clearance may

be reserved for the specific circumstances outlinedin the text.

1. K/DOQI Clinical Practice Guidelines for Chronic KidneyDisease: Evaluation, Classification, and Stratification

2. Young. V R, Pellett PL: Protein intake and requirementswith reference to diet and health. Am J Clin Nutr 1987:45: 1323 1343.

3. Taber LAL, Cook RA: Dietary and anthropometricassessment of adult omnivores, fish-eaters and lacto-ovo-vegetarians. J Am Diet Assoc 1980: 76:21-29.

4. Bosch JP, Lauer A, Glabman S: Short term proteinloading in assessment of patients with renal disease.Am J Med 1984: 77: 873 879.

5. Jones MG, Lee K, Swaminathan R: The effect of dietaryprotein on glomerular filtration rate in normal subjects .Clin Nephrol 1987: 27: 71- 75

5. Nuclear methods of GFR estimation are to be usedas confirmatory tests in confusing circumstances ifthe lab used inspires confidence.

6. Low GFRs in otherwise normal individuals, commonlyseen in normal Indians are due to predominantlyvegetarian diet and low protein intake.

7. The GFR of such persons can be stimulated to

increase to values in the normal ranges by infusionof amino acids followed by timed collections. Thismay help establish normalcy in the individual oncethe tests have been standardized.

References

6. Bosch JP, Saccaggi A , Lauer A, Ronco C, Belledonne M,Glabman S: Renal functional reserve in humans. Effectof protein intake on glomerular filtration rate. Am J Med1983: 75: 943-950.

7. James GD, Sealy JE, Alderman M, Ljungman S, Laragh

JH: A Longitudinal study of urinary creatinine andcreatinine clearance in normal subjects: Race, sex andage differences. Am J Hypertens 1988; 1: 124- 131

8. Levey AS: Use of measurements of GFR to assess theprogression of renal disease. Semin Nephrol 1989; 9:370- 379.

9. Gurney JM, Jelliffe DB. Anthropometry in nutritionalassessment: Am j Clin Nutr 1998: 26: 913: 435-452.

10. Klahr S : The modification of diet in renal disease study.N Eng J Med. 1989: 320, 864-866.

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