Nierfunctiemeting en follow-up van chronisch nierlijden

Nierfunctiemeting en follow-up van chronisch nierlijden 12 Jan 2016 Patrick Peeters, M.D. Dept Nephrology Ghent University Hospital

Plan of presentation 1/ Renal function determination: Measured GFR Estimated GFR 2/ Follow-up Chronic Kidney Disease (CKD ) 3/ Nefrotoxic medication 2

1. Renal function measurement 3

Measured GFR is considered the gold standard. Exogenous markers Inulin clearance: gold standard Alternative: Unlabeled: iodine contrast media (iohexol) Radio-labeled: 125 I-iothalamate, 51 Cr-EDTA, 99 mtc- DTPA Limitations! 4

Measured egfr 5

Indication for use of mgfr 6

Relationship Screat vs. GFR is not linear 7

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Factors affecting Screatinine 9

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Chronic kidney disease is classified on basis of egfr Definition CKD: = egfr < 60 ml/min/1.73m² or kidney damage regardless the cause, for at least 3 months. K/DOQI-stages (2002) egfr < 60 ml/min: cut off : Increased risk Adverse outcome in general Progression ESRD Cardiovascular disease and death 14

Creatinine vs. Urea vs. cystatin C 15

Estimated GFR: egfr Creatinine-based Cockcroft-Gault age, weight, gender MDRD age, gender, race CKD-EPI age, gender, race Limitation: age, production rate, muscle mass, tubular secretion Cystatine-C based Stevens Rule Limitation: age, (muscle mass), inflammation, neoplasia, (no international standard) 16

egfr? Evaluation of formulae bias precision accuracy Which goal Which population 17

Cockcroft-Gault 1973 Population: 249, white, 96% male CrCl: 30-130 ml/min CrCl (male) = (140-age) x wt /scr x 72 CrCl (female) = CrCl (male) x 0.85 (ml/min) Non-standardized creatinine Arbitrary adjustment for female Not corrected for BSA Creatinine clearance, GFR 3 18

MDRD 1999 1628 patients, (94 % non DM, 60% male, 88% white) [1070: development, 558: validation] Mean GFR: ~ 40 ml/min egfr = 175 x (StdsCr) -1.154 x [Age] -0.203 x [0.742 if patient is female] x [1.212 if patient is black] (ml/min/1.73m²) Adjusted for BSA Standardized creatinine Good accuracy when GFR < 60 ml/min/1.73m², Underestimating egfr > 90ml/min/1.73m² Ethnicity? Age? 19

An external validation study of MDRDformula showed overall accuracy of 83%. egfr N Difference % Difference P30 (%) (ml/min/1.73m²) Median IQR Median IQR... 5504 2.7 5.8 83 90-119: 941 11.1 25.6 9.9 20.8 89 60-89: 1364 9.5 25.4 11.7 28.0 82 30-59: 1782 1.7 13.0 3.5 27.4 84 <15: 299 0.8 5.0 6.3 34.5 72 External validation,pop: 5504. mgfr 125 I-iothalamate (Stevens, JASN, 2007) 20

CKD-EPI 2009 Population: 8254 (development), 3896 (validation), 43% female, 30% black, 30% diabetes Mean mgfr: 68ml/min/1.73m² (sd: 40ml/min/1.73m²) egfr=141. min(scr/κ,1) α. max(screa/κ,1) -1.209. 0.993 Age. 1.018 (if female). 1.159 (if black) (κ: 0.7 if female, 0.9 if male; α: -0.329 if female, -0.411 if male) Elderly? Mean age: 47year >75year: < 1% Ethnicity 21

(Levey, Ann Int Med, 2009) 22

CKD-EPI is superior to MDRD, egfr > 60 ml/min/1.73m² Validation: egfr > 60 ml/min/1.73m² (external cohort, 3896 individuals, 16studies) Equation No. Median Bias Median % Bias Overall CKD-EPI 3,896 2.2 4.4 MDRD 3,896 5.4 10.3 >120 ml/min/1.73m² CKD-EPI 220-2.9-2.4 MDRD 159-8.0-6.7 90-119 ml/min/1.73m² CKD-EPI 784 1.9 1.9 MDRD 513 10.0 8.6 60-89 ml/min/1.73m² CKD-EPI 990 4.2 5.6 MDRD 1,124 11.9 14.3 (Levey, Am J Kidney Dis, 2010) 23

egfr: as follow up instrument -13,708 GFR measurements in 3635 subjects - mean follow up of 3.6 years. - mean mgfr, egfr (CKD-EPI) and error at baseline: 76, 76, and -0.3 ml/min/1.73 m2. - The mean change in mgfr, egfr and error were -2.3, -2.2 and - 0.1 ml/min/1.73 m2 per year (P <.0001, <.0001 and 0.6 respectively). Padala, ASN, 2011, PO 24

egfr and diabetes Normal GFRhyperfiltration: egfr overestimation of GFR Underestimation of rate of decline Reduced GFR Incongruent: over- /underestimation (Stevens, Am J Kidney Dis, 2010) Pop: 3896, 30%DM) 25

egfr and elderly? overestimate CKD = egfr < 60ml/min/1.73m²? (general population: 80+: 43-56% egfr > 60 ml/min/1.73m²) Stevens, JASN, 2007 26

egfr and transplantation Near-normal kidney function Corticosteroids, cyclosporine Accuracy within 10% (P-10) SCreat-based: (White, Clin Chem 2010) Overestimation (n =207) Median bias Precision(IQR) P- 30% 4v-MDRD: -8.2 14.5 77 CKD-EPI: (ml/min/1.73m²) -5.2 15.7 84 CystC-based: underestimation - Rule, LeBricon- formulae - Influence of corticosteroid 27

egfr and mortality, CV-complications CKD-EPI reclassification of patients in different CKD-stage (compared to MDRD) better categorized in terms of long term risk: mortality, stroke, coronary heart disease. Eg. egfr(mdrd): 30-60 ml/min/1.73m² CKD- EPI: reclassified upward adverse outcome risk Matsushita, Am J Kidney Dis, 2010 28

egfr risk prediction, elderly egfr 45-60 ml/min/1.73m²: no increased risk Mortality Low risk evolution ESRD egfr < 45 ml/min/1.73m² Increased cardiovascular mortality risk, HR 1.74 (P 0.09) egfr-slope > 3 ml/min/1.73m² Increased mortality risk Leiden 85+-study, Van Pottelbergh, BSN/BGGS joint meeting, 26nov 2011 29

egfr and mortality egfr + ALBUMINURIA (Matsushita, Lancet, 2010 Meta-analysis) Shaded 2008 Universitair areas represent Ziekenhuis 95% Gent CIs. Models included spline egfr, categorical albuminuria, and their interaction terms as well as adjustment 30 for age, sex, ethnic origin, history of cardiovascular disease, systolic blood pressure, diabetes, smoking, and total cholesterol.

Risk 31

CONCLUSION CKD-EPI Risk prediction: egfr + albuminuria 32

2. Follow-up chronic kidney disease CKD 33

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Chronic renal failure: CV morbidity-mortality 42

Chronic renal failure: CV morbidity-mortality 43

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Late versus Early Referral Lagere Karnofsky-score Lagere serum-albumine Hogere comorbiditeit Langere hospitalisatienood Meer overlijdens 1ste dialysejaar Minder keuze voor peritoneale dialyse Minder vaak transplantatie 47

3. Nefrotoxic medication 48

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EVOLUTION OF AKI Clin J Am Soc Nephrol, 2008. Cerda J 50

Dialysis ATN Urine l/dag Creatinine M/l Tijd / dagen 1. Acute toxicity 2. Oliguria/anuria Loss of GFR 3. Polyuria 4. Repair of injury 51

52 Nat. Rev. Nephrol. 2011, Murugam R

Prevention Who is at high risk? Chronic heart failure Chronic kidney disease Diabetes Older age Use of potential nephrotoxic drugs 53

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NSAID 55

Contrast-induced nephropathy (CIN) increase of > 25% or > 0,5 mg/dl in serum creatinine from baseline value at 48-72 h following the exposure to contrastmedia 56

CIN - pathophysiology Nature Reviews Nephrology, 2010. Calvin 57 Kidney International, 2007. Curtis

Contrastnephropathy prevention 1. Who is at risk? LVEF<40% egfr<60 ml/min + DM egfr< 40 ml/min Age > 75 y inflammation 2. Is there a validate alternative examination possible? 3. Preventive treatment : Bicarbonate /6 h or NaCl 0.9%/24h Stop NSAID, (diuretics) 58

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Conclusion Serum creatinine is not that easy egfr-epi is a good estimatation of renal function CKD with its multiple associated complications Acute renal failure: even small increases in creatinine have an effect on in-hospital mortality Prevention is the key 60