Presentation on theme: "Detection, monitoring and referral of chronic kidney disease"— Presentation transcript:
1Detection, monitoring and referral of chronic kidney disease Canadian Society of NephrologyImplementation Committee2007This slide kit was developed for Primary Care givers by the Canadian Society of Nephrology Implementation Committee.A new position paper on the care and referral of adult patients with reduced kidney function was published on the CSN website in September of 2006 and the Society felt it was best if a document/presentation kit were to be prepared to complement this document dealing specifically with the issue of estimated GFR (eGFR) as it may be a new approach to following renal function to some clinicians.These recommendations address those at risk for chronic kidney disease and are not meant to consider all potential reasons to refer to nephrology (eg. hematuria).
2Key messages Who to test for chronic kidney disease What tests to orderWhat to do with the resultsThese are the three key points that we hope clinicians will remember.- use case-finding approach to CKD in high-risk individuals- test using eGFR (kidney function) and assessment of urine protein (kidney damage) to identify individuals with CKD as well as the subgroup at risk of progressive disease- abnormal findings need serial monitoring as many will improve on repeat testing and serial monitoring helps to identify those with progressive renal disease
3Identify patients in your practice at high risk for Chronic Kidney Disease Patients with hypertensionPatients with diabetes mellitusPatients with atherosclerotic coronary,cerebral or peripheral vascular disease- Patients with heart failurePatients with unexplained anemiaPatients with a family history of end stage renal diseaseFirst nations peopleseGFR <30eGFR 30-60eGFR >60Consider reversible factors:Medication - Volume depletionIntercurrent illness - ObstructionRepeat tests in weeksIndividualized follow upand treatmentCKD is diagnosed in this group onlyif other renal abnormalities are present(i.e. proteinuria, hematuria, anatomical)eGFR <30eGFR 30-60Nephrology referralrecommendedFollow eGFR at 3 months then seriallyAssess for persistent significant proteinuriaImplement risk reductioneGFR < 30or progressive decline in eGFRor persistent significant proteinuriaor inability to attain treatment targetsStable eGFR 30-60andno significant proteinuria
4What is Chronic Kidney Disease The presence of Kidney Damage or an eGFR < 60 ml/min/1.73m2 andPresent for ≥ 3 months andNot treated with dialysis or transplantKidney Damage is defined well in the Document on Identification, Evaluation and Management of Patients with Chronic Kidney Disease as pathologic abnormalities or markers of damage, including abnormalities in blood, urine or imaging tests studies*To be clear, the type of patient that is referred to is one where the renal function is stable and there is no significant amount of proteinuria present. Chronic kidney disease can be present in patients who have eGFRs over 60ml/min but who have abnormalities of urinalysis such as persistent proteinuria or hematuria. These patients should be referred to a NephrologistThere is no expectation of any Primary Care Physician to manage kidney disease that is progressive or with other complicating elements such as significant proteinuria.The diagnosis of CKD is only present in patients with eGFR ≥60ml/min if otherabnormalities (i.e. proteinuria, hematuria, anatomical) are also present.
5Who should be tested for CKD? CSN endorses a case finding approachto testing for CKD, which should befocused on high-risk groups.CSN does not endorsemass population screening for CKDwith either serum creatinine based tests or with urine dipstick testing.
6Who should be tested for CKD? Patients with diabetes mellitusPatients with hypertensionPatients with heart failurePatients with atherosclerotic coronary, cerebrovascular or peripheral vascular diseasePatients with unexplained anemiaPatients with a family history of ESRDFirst nations peoples
7Clinical case Joe is a 68 year old welder Past Medical History: appendectomy age 15, hypertension x 4 years, elevated cholesterol x 1 year, Type 2 DM x 1 yearSmoker- 1 pack a day since age 21Etoh- a case of beer on the weekendAllergy- none knownFamily History- father MI age 50, mother HTN age 48Medications- hydrochlorothiazide 25 mg po od, amlodipine 5mg po od, metformin 1000 mg po bidWeight 75 kgBP 149/84 mmHgIllustrating the power of eGFR using clinical cases
8Joe should be screened for CKD because he has several risk factors. Can you name them?Could discuss SCORED study (Arch Int Med Feb 2007; 167: )– Here Joe has a history of hypertension as well as DM. SCORED also considered age as a risk factor
9Which test would you choose to assess Joe’s renal function? Serum creatinine24 hour urine collectionNuclear medicine scaneGFREach item in this list has elements that preclude them from being dependably used and easily accessed in the day to day clinical assessment of patient renal function in a reliable and accurate manner.Commonly voiced concerns about 24hr urine collections include 1) instructions are routinely misunderstood leading to inaccurate collections and unreliable inaccurate results 2) Patients find it difficult to commit to an entire day’s worth of “testing” 3) routine under or over collections etcNuclear medicine tests are not practical nor cost effective ways in which to follow renal functionSerum Creatinine and urea measurements alone often are misinterpreted by health care professionals, the most common of which is that despite a value being in the “normal range” it reflects a GFR that is significantly reduced for that patient’s age , gender and body mass. This will be explored more in the presentation.
10Joe’s labs Na 138 mmol/L K 4.5 mmol/L Cl 103 mmol/L HCO3 23 mmol/L Glucose (R) 6.4 mmol/LUrea 10.1 mmol/LCreatinine 123 µmol/LCBC normalHgB A1C 5.6%Ca mmol/LPO4= mmol/LAlbumin 38 g/LTC 7.60 mmol/LTG 2.06 mmol/LLDL(C) 5.43 mmol/LHDL(C) 1.23 mmol/LUpper limit of Cr in this lab is 130umol/L
11Joe’s serum creatinine is in the normal range, doesn’t that mean his kidney function is also normal?
12Assessing Joe’s renal function using eGFR 54 ml/min / 1.73m2(Stage 3 CKD)Clearly, Joe’s renal function is not normaldespite a normal serum creatinineThis highlights some of the problems with eGFR in that the CG equation is recognized for overestimating renal function.The MDRD equation has been validated for use in the CKD population but it is not as easy to use and not everyone has access to a computer in their clinic area.The point is made however that despite either equation’s pitfalls the patient is better served by having their eGFR calculated and then repeated in a serial fashion to determine if it is changing. Stable chronically reduced eGFR with minimal proteinuria does not necessarily need to be seen by a nephrologist.The presenter can mention that this corresponds to Stage 3 CKD and that the staging system for CKD will be covered a little later on in the presentation
13Why use eGFR? It gives the health care practitioner a different sense as to a patient’s level ofrenal function that they may not haveappreciated by using simple serumcreatinine measurements.The advantage of these equations over serum creatinine measurements alone is that the latter are recognized as being poor indicators of early CKD.
15GFR Glomerular filtration rate (GFR): is the volume of fluid filtered from therenal glomerular capillaries into theBowman’s space per unit time.Normal for a 20 year old is ~ 120ml/min
16Methods to assess GFR Serum urea Serum creatinine Serum cystatin C Timed urine collectionsCreatinine clearanceInulin clearanceCalculated GFR calculationsbased on serum creatininemany formulas including Cockcroft Gault and MDRDNuclear medicine methodsThere is a great article in BMJ October 2006 that reviews all these methodsHow to measure renal function in clinic practice. Traylor, Mactier, Geddes and Fox, BMJ 2006; 333:
17The perfect marker doesn’t exist ! Endogenous Freely filtered Not secreted or reabsorbedInexpensive to measuredoesn’t exist !
18Problems with creatinine Stevens L et al, NEJM 2006; 354:
19Problems with timed collections CumbersomeProne to errorNo longer recommended in most situations
20Problems with other methods CystatinInulinNuclear medicine (iothalamate, EDTA etc)ComplexTime-consumingExpensiveNot practical for serial monitoring
21Creatinine based approximations 1) Cockcroft-Gault equationCrCl (ml/min)= (140-age) x actual weight (kg) x 1.2 (if male) SCreat (µmol/L)2) MDRD (Modification of Diet in Renal Disease)6 variable or abbreviated versionGFR(ml/min/1.73m2)=170 (PCr) x (Age) x (0.762 if female) x (1.21 if African American) x (serum urea) x (Albumin)+0.318Weight probably not available for lab to calculateCan use this slide to point out importance of adjusting for race in African Americans.These are the two main methods whereby an eGFR is generated by the lab.The CSN endorses the use of standardized methods to measure serum creatinine. Creatinine is measured in different ways in labs across Canada. It would be reasonable for the clinician to familiarize themselves with the methods employed in their local lab.Not all labs in Canada generate an eGFR value along with the serum creatinine. Pioneers in the area such as BC and Alberta have this but other areas do not have eGFR reporting at this time. Moreover, one lab may use the CG formula and another the MDRD equation. Again, the clinician is advised to familiarize themselves with the methods employed in their local lab.Both formulae have been validated in various populations with moderate to severe impairment of GFR; however they may be less reliable in patients with near normal (>60ml/min/1.73m2) GFR or in patients with markedly abnormal body composition (eg extreme obesity, cachexia, paralysis, amputations)There remain controversies as to the applicability of these equations to various ethnic groups, the very elderly and to the non-referred populations with modest decreases in renal function which are summarized on the next slide.Lab has patient age and gender – can do abbreviated version
22eGFR equation provisos eGFR calculations may be less reliable in:individuals with near normal GFR (>60 ml/min/1.73m2)individuals with markedly abnormal body compositionextreme obesitycachexiaparalysisamputationsControversies exist as to the applicability of these formulae to various ethnic groups and the very elderlyRemind them of adjusting MDRD for african-american race
23Estimate of Glomerular Filtration Rate (eGFR) It is not recommended that clinicians rely on serum creatinine measurements alone when assessing kidney function.CSN calls for the reporting of kidney function as an estimate of glomerular function rate (eGFR) using equations and standardized creatinine measurementsIf neither eGFR reporting, nor calculators are available to a physician, tables based on serum creatinine and other variables are available to provide approximations of eGFR.
24Developed by the BC Medical Services Commission, Guidelines and Protocols group
25Developed by the BC Medical Services Commission, Guidelines andProtocols group
26Is it just about GFR? Should also assess urine protein losses 24 hour urines are no longer recommendedFor same reasons as with GFRUrine dipsticks are affected by hydration statusQuantify protein excretion with random urine for:Urine albumin to creatinine ratio orUrine protein to creatinine ratioCan simplify it to explain that eGFR measures renal function (clearance) while proteinuria/albuminuria identifies renal injury and is associated with prognosis
27What do those values mean? ACR(mg/mmol)PCR24 hoururine>3N/A~30 mg day(albumin)<40<60~ 500 mg/day(protein)>60>100~900 mg/dayMicroalbuminuria(ie in diabetics)These examples were chosen since they are the numbers that people may already be familiar with and include values that should trigger referral to Nephrology.Can also use this slide to re-emphasize that microalbuminuria in diabetics shows evidence of renal injury despite preserved renal function. Demonstrates why need to look at function (eGFR) as well as injury (protein)Alarm valuesto refer
28Who should be tested for CKD? Patients with diabetes mellitusPatients with hypertensionPatients with heart failurePatients with atherosclerotic coronary, cerebrovascular or peripheral vascular diseasePatients with unexplained anemiaPatients with a family history of ESRDFirst nations peoplesSumming up what we’ve covered so far
29What tests to order? Assess kidney function with eGFR As reported by labAs calculated using equations (and PDA!)As estimated by tablesQuantification of protein with random urine samplesUrine albumin to creatinine orUrine protein to creatinineSumming up what we’ve covered so far
30What to do with the results Now that I know Joe’s GFR is not normal what should I do?
31What to do with the results Is one eGFR measurement enough?Consider reversible factorsAssess risk of progressive renal diseasewho needs referral to Nephrology
32Natural history of elevated creatinine levels Marcotte and Godwin, Canadian Family Physician 2006;52: ,e1-51434 patients in a family medicine practice57 patients had an elevated initial serum Cr levels (>130umol/L) and subsequent Cr levels within 4-5 years of follow-upInitial serum CrLatest serum creatinine (umol/L)<130>30026125231This article was referenced because it is a primary care population in the Canadian setting. Other examples could be used.More than half of those with initially elevated Cr levels saw them return to normal (including 50% of those with initial Cr >300)Only 7 patients progressed to a higher level over 4-5 years of followupIn all 1434 patients average age was 63, 18% were diabetic, 47% were hypertensive, only 4% were referred to Neph
33Is one eGFR measurement enough? Decisions about investigation, treatment or referral should not be made based on a single isolated test of kidney functionIn a primary care setting, many patients will show improvement or normalization of kidney function upon repeat testing.The diagnosis of CKD is based on serial measurements of kidney function and it is not possible to diagnose CKD on the basis of a single serum creatinine concentration transformed through equations.These are statements from the position paper
34For patients with a new finding of an eGFR between 30-60ml/min/1.73m2 CSN recommends that clinicians determinethe stability of the patient’s eGFRRepeat test within 2-4 weeks,and then in 3-6 monthsThere will always be cases that do not fit with these recommendations (for example in a 35 year old otherwise well individual a finding of an eGFR below 60 would probably lead to repeat testing sooner than 2-4 weeks). Primary care givers are still asked to use their clinical judgement
35Consider reversible factors Intercurrent illnessVolume depletionMedicationsNSAIDs, aminoglycosides, IV contrast dyeObstructionAn abdominal ultrasound may be indicated at eGFRs <60ml/min/1.73m2May also mention fibrates, different forms of NSAIDs (suppositories, creams)
36Back to JoeYou measure Joe’s eGFR in 2 weeks and then again in 3 months and it is unchangedYou order an ultrasound and it is normalHis urinalysis is normal
37Conclusions about JoeGiven the stability of these we can conclude that he has stable CKD.It is important to continue to serially follow his renal function.Serial measurement is a cornerstone of chronic kidney disease management.
38CSN recommends that most patients with non-progressive CKD can be managed bynon-nephrologists without referral.The recognition that many patients with an eGFR between 30 and 60 ml/min/1.73m2do not have a high risk ofprogressive kidney disease is important.Need to address two questions- why look for CKD if most will not be progressive- who does need referral to Nephrology
40Estimated prevalence of CKD in Canadians ≥ 20 years old Stage 1 CKD > 90 ml/min ,000Stage 2 CKD 60 – 89 ml/min 720,000Stage 3 CKD 30 – 59ml/min 1,032,000Stage 4 CKD 15 – 29 ml/min 48,000Stage 5 CKD < 15 ml/min 24,000This reference is an excellent one for Primary Care Physicians on CKD.It also outlined the scope of the problem when it extrapolated figures from US data (which was taken from K/DOQI) and gave an idea of the numbers of Canadians who had CKD and expressed these according to their stage of CKDThis slide also introduces the idea of the various stages of CKDNumbers are estimates based on an extrapolation of US dataStigant, C, et al. CMAJ 2003;168:
41Other common conditions also managed by primary care physicians CVD38.7% in diabetic men30.7 % in diabetic womenThyroid disease1/20 (Thyroid Fdn of Canada)Hypertension28%Type 2 DM8-10 % worldwideReferences for these figures areCVD:DM:BP: Hajjar, Kotchen and Kotchen. Annual Rev Public Health 2006; 27:465-90CKD is a common general health problem
42Estimated prevalence of CKD in Canadians ≥ 20 years old Stage 1 CKD > 90 ml/min ,000Stage 2 CKD 60 – 89 ml/min 720,000Stage 3 CKD 30 – 59ml/min 1,032,000Stage 4 CKD 15 – 29 ml/min 48,000Stage 5 CKD < 15 ml/min 24,000ESRD is not commonAim of slide is to demonstrate that although CKD is common (approx 1 in 10 adults) ESRD is not commonStigant, C, et al. CMAJ 2003;168:
43If many patients with CKD do not progress to end stage renal failure why then as a primary care physician should I even be looking for them using eGFR?
44Patients with CKD have high rates of cardiovascular disease ESRD is not the problemPatients with CKD have high rates of cardiovascular diseaseand many patients die before progressing to end stage renal failure thus it is important to screen for CKD.Risk of cardiovascular death is 100 X the risk of progressing to ESRD
45This study shows nicely why we must pay attention to those patients with CKD. In addition to their renal disease they are at significantly greater risk for health complications related to cardiovascular disease.This study published in the NEJM in 2004 looked at 1,120,295 adults (55% were female) where a serum creatinine had been measured between 1996 and 2000 who had no history of been treated with dialysis or renal transplant.They examined the multivariate association between the estimated GFR (eGFR) and the risks of death, risk of cardiovascular event and hospitalizations.They found an independent, graded association was observed between a reduced eGFR and the risk of death, cardiovascular events and hospitalizations in a large community based populationGo,A et al. NEJM 2004;351:
46Quick Tips on Management of CKD Implement measures to slow rate of CKD progressionTreat to target BP <130/80; most will need 3 or more meds, diuretics and salt restriction are very usefulTarget urine ACR <40 or PCR <60. ACEI and/or ARB are first line therapies for albuminuria or proteinuriaControl blood sugar in diabetes, target HbA1C <7%Implement measures to modify CV risk factorsFollow guidelines as per groups at highest risk for CV diseaseMinimize further kidney injuryIf possible, avoid nephrotoxins such as NSAIDs, aminoglycosides, IV and intra-arterial contrast etcIf contrast is necessary, consider prophylactic measures (if eGFR <60)Remember to adjust dosages of renally excreted medicationsFull guidelines on the management of CKD will be soon forthcoming from the CSN. In the mean time these “Quick Tips” are part of the CSN position paper on the Care and Referral of Adult Patients with Reduced Renal Function. This is an abbreviated version that fits on the algorithm. A full version is available as a one page handout (see CSN website for both algorithm and handout)
47Joe: three years later His CKD is no longer stable You have continued to follow his eGFR and notice that it is now 42 ml/min/1.73m2All clinical targets (BP, HBA1C, cholesterol) are stableNo intercurrent illnessesHis CKD is no longer stableRefer to Nephrology
48Who should be referred to a Nephrologist? Patients with acute renal failurePatients with eGFR <30ml/min/1.73m2Patients with progressive loss of renal functionPersistent significant proteinuria (present on 2 out of 3 samples)on dipstick orquantified PCR >100mg/mmol orquantified ACR >60 mg/mmol.Inability to achieve treatment targets or other difficulties in the management of the CKD patient
49Violet78 year old femalelongstanding patient of a colleague’s – followed for her hypertension and “mild” renal failureYou are on call and see her because she is c/o nausea and lethargyThis example illustrates the value of eGFR as opposed to Cr for assessment of renal function as well as the value of serial monitoringDatetoday1 yr ago2 yrs ago5 yrs agoSerum Creat(µmol/l)184168156138
50Using an “eGFR approach” Datetoday1 yr ago2 yrs ago5 yrs agoSerum Cr(µmol/L)184168156138eGFR(ml/min/1.73m2)24273035The presenter should use this table to illustrate how the patient’s renal function was never normal in the first place and that it may have been underestimated all along in her managementThe presenter should also point out that the serial measurement of the value shows that her renal function is in decline
51This woman’s renal disease may have been underdiagnosed Using eGFR may have given a moreaccurate measure of her renal functionSerial measurement of eGFRis a powerful tool for the clinicianMay also chose to discuss that her nausea and lethargy may signal decreased oral intake and her eGFR may be acutely low due to volume depletionNephrology referral is recommended for this patient
52Linda 54 yo female comes for routine annual physical no problems identifiednormal physical examinationfamily history of ESRDAll her labs are normal – serum creatinine is 90 µmol/lLab automatically reports an eGFR of 60 ml/min/1.73m2What do you do with this eGFR value?Should she be referred to a Nephrologist?This example illustrates the importance of proteinuria in the diagnosis of CKD90% confidence intervals on this eGFR calculation range from 42-78
53Identify patients in your practice at high risk for Chronic Kidney Disease Patients with hypertensionPatients with diabetes mellitusPatients with atherosclerotic coronary,cerebral or peripheral vascular disease- Patients with heart failurePatients with unexplained anemiaPatients with a family history of end stage renal diseaseFirst nations peopleseGFR <30eGFR 30-60eGFR >60Consider reversible factors:Medication - Volume depletionIntercurrent illness - ObstructionRepeat tests in weeksIndividualized follow upand treatmentCKD is diagnosed in this group only if other renal abnormalities are present(i.e. proteinuria, hematuria, anatomical)eGFR <30eGFR 30-60Nephrology referralrecommendedFollow eGFR at 3 months then seriallyAssess for persistent significant proteinuriaImplement risk reductioneGFR < 30or progressive decline in eGFRor persistent significant proteinuriaor inability to attain treatment targetsStable eGFR 30-60andno significant proteinuria
54Linda: continuedEvaluation of her urine shows no significant amount of proteinuria (ACR <40mg/mmol) and no hematuriaShe is followed annuallyTwo years latersame eGFRblood pressure is 146/94persistent proteinuria with ACR > 60mg/mmolProgressive CKD = referral to NephrologyHere the presenter could emphasize (again) the importance of serial monitoring of the eGFR and of proteinuria.Patients who have eGFR >60ml/min but no proteinuria or hematuria do not have renal disease. Serial monitoring of these patients and the important parameters of eGFR, BP and proteinuria allow for disease progression to be picked up using easy to do and relatively inexpensive means.Also emphasizes the importance of significant proteinuria in identifying patients more likely to develop progressive CKDProteinuria is a surrogate marker of renal disease
55Dave 81 year old man, new to your practice ASHD, stent placed 2 years agoPSA >100 led to biopsy and diagnosis of prostate cancer, being treated with hormone therapy aloneOn atorvastatin 40 mg, aspirin 81 mg, ramipril 5 mgBp 144/82, nil else on examCr 167, eGFR 36, ACR 0.7This example is used to demonstrate the role primary care docs have in following CKD that is non-progressive
56DaveOld labs from previous MD show Cr umol/L over last 3 yearsWhat would you do?Stable CKD, follow seriallyAchieve BP <130/80CV risk reduction – LDL at high risk levelWatch for renally excreted medications – adjust doses (metformin, glyburide, digoxin etc.) or avoidWould not need Nephro
57Summary Who should be tested for CKD? Patients with diabetes mellitus Patients with hypertensionPatients with heart failurePatients with atherosclerotic coronary, cerebrovascular or peripheral vascular diseasePatients with unexplained anemiaPatients with a family history of ESRDFirst nations peoples
58Summary What tests should be ordered? eGFR to assess kidney functionrandom urine sample to assess for significant persistent proteinuriaWhat should be done with the results?follow seriallyassess for proteinuriaimplement risk reduction strategiesMonitoring for evidence of progressive disease- declining eGFR- persistent significant proteinuria
59AcknowledgementsFinancial support for the development and distribution of these educational materials was provided by unrestricted grants from Amgen Canada and Bristol Meyers Squibb
60Quick Tips on Referral and Management of Chronic Kidney Disease Most patients with non-progressive CKD can be managed without referral to a nephrologist. The goals of therapy are listed below:Consider reversible factors, such as medications, intercurrent illness, volume depletion, or obstruction. An abdominal ultrasound may be indicated when eGFR <60 ml/min/1.73m2.Minimize further kidney injury by avoiding, if possible, nephrotoxins such as NSAID’s, aminoglycoside antibiotics, IV contrast, etc (if eGFR < 60 ml/min/1.73m2).Remember to adjust dosages of renally excreted medications.Implement measures to slow the rate of progression of CKD:Target BP is < 130/80 mmHg. Most patients will need 3 or more medications. Diuretics and salt restriction are very useful, and if needed, consider furosemide BID dosing when eGFR < 30 ml/min/1.73m2Target urine protein/creatinine ratio (mg/mmol) is < 60 (< ~ 500 mg/day) or target urine albumin/creatinine ratio (mg/mmol) is < 40. ACEI and/or ARB are first line therapies in patients with albuminuria or proteinuria.Control blood sugar in diabetes, target HbA1C < 7%.Implement measures to modify CV risk factors (NB: CV risk >> ESRD risk).Follow the Canadian Hypertension Education Program, the Canadian Diabetes Association, and the Canadian Cardiovascular Society guidelines as per groups at highest risk for CV disease.Referral to a nephrologist is recommended for:acute kidney failureeGFR < 30 ml/min/1.73m2. (CKD stage 4 and 5)progressive decline of eGFRurine protein/creatinine ratio (PCR) > 100 mg/mmol (~900 mg/24 hours) or urine albumin to creatinine ratio (ACR) > 60 mg/mmol (~500 mg/24 hr)inability to achieve treatment targetsNOTE: detailed CSN CKD management guidelines are under development, these quick tips should be considered as an interim approach.Insert Quick Tips sheet from the CSN CKD documentThis slide is obviously too hard to read but serves as a reminder to show participants the one page handout which features this information on one side as well as a summary of the key messages from this slide setThe CSN Guidelines committee is producing a document regarding the management of patients with CKD which will provide more detailed and evidenced based information (expected winter 2007)