Diagnostik. Michael Rudnicki. Medizinische Universität t Innsbruck Univ. Klinik für f r Innere Medizin IV Nephrologie und Hypertensiologie 16.3.

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1 Diagnostik Michael Rudnicki Medizinische Universität t Innsbruck Univ. Klinik für f r Innere Medizin IV Nephrologie und Hypertensiologie ÖGN Wintermeeting, Fuschl,,

2 Kidney International Michael Supplements Rudnicki (2013) 2,1 150

3 KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease Kidney International Supplements(2013) 2,1 150 Chapter 1: Definition and classification of CKD Chapter 2: Definition, identification, and prediction of CKD progression Chapter 3: Management of progression and complications of CKD Chapter 4: Other complications of CKD: CVD, medication dosage, patient safety, infections, hospitalizations, and caveats for investigating complications of CKD Chapter 5: Referral to specialists and models of care

4 KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease Kidney International Supplements(2013) 2,1 150

5 CKD is classified based on cause, GFR category, and albuminuria category (CGA) Kidney International Supplements(2013) 2,1 150

6 Prevalence in the United States Kidney International Supplements(2013) 2,1 150

7 Evaluation of GFR Kidney International Supplements(2013) 2, : We recommend using serum creatinine and a GFR estimating equation for initial assessment. (1A) : We suggest using additional tests (such as cystatin Cor a clearance measurement) for confirmatory testing in specific circumstances when egfr based on serum creatinine is less accurate. (2B) : We recommend that clinicians (1B): use a GFR estimating equation to derive GFR from serum creatinine (egfr creat ) rather than relying on the serum creatinine concentration alone. understand clinical settings in which egfr creat is less accurate.

8 Determinants of the serum level of endogenous filtration markers Stevens LA, Levey AS. J Am Soc Nephrol 20: , 2009

9 Evaluation of GFR Kidney International Supplements(2013) 2, : We recommend that clinical laboratories should (1B):(gekürzt) report egfr creat in adults using the 2009 CKD-EPI creatinine equation. An alternative creatinine-based GFR estimating equation is acceptable if it has been shown to improve accuracy of GFR estimates compared to the 2009 CKD-EPI creatinine equation. We suggest measuring cystatin Cin adults with egfr creat ml/min/1.73 m 2 who do not have markers of kidney damage if confirmation of CKD is required. (2C) If egfr cys /egfr creat-cys is also <60 ml/min/1.73 m 2, the diagnosis of CKD is confirmed. If egfr cys /egfr creat-cys is 60 ml/min/1.73 m 2, the diagnosis of CKD is not confirmed.

10 CKD-EPI vs MDRD Levey AS, et al. Ann Intern Med 2009; 150(9):

11 Comparison of Risk Prediction Using the CKD-EPI Equation and the MDRD Study Equation for Estimated Glomerular Filtration Rate Matshushita et al. JAMA May 9;307(18):

12 Comparison of Risk Prediction Using the CKD-EPI Equation and the MDRD Study Equation for Estimated Glomerular Filtration Rate Matshushita et al. JAMA May 9;307(18):

13 N Engl J Med Jul 5;367(1):20-9.

14 Inker et al. N Engl J Med Jul 5;367(1):20-9. Estimating Glomerular Filtration Rate from Serum Creatinine and Cystatin C

15 Inker et al. N Engl J Med Jul 5;367(1):20-9. Estimating Glomerular Filtration Rate from Serum Creatinine and Cystatin C

16 Estimating Equations for Glomerular Filtration Rate in the Era of Creatinine Standardization Earley et al. Ann Intern Med. 2012;156:

17 Evaluation of Albuminuria Kidney International Supplements(2013) 2, : We suggest using the following measurements for initialtesting of proteinuria (in descending order of preference, in all cases an early morning urine sample is preferred) (2B): 1) urine albumin-to-creatinine ratio (ACR); 2) urine protein-to-creatinine ratio (PCR); 3) reagent strip urinalysis for total protein with automated reading; 4) reagent strip urinalysis for total protein with manual reading.

18 Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex: a meta-analysis Nitsch et al. BMJ Jan 29;346:f324.

19 Factors affecting ACR Kidney International Supplements(2013) 2,1 150

20 Definition and Identification of CKD Progression Kidney International Supplements(2013) 2, : Recognize that small fluctuations in GFR are common and are not necessarily indicative of progression. (Not Graded) 2.1.3: Define CKD progression based on one of more of the following (Not Graded): Decline in GFR category ( 90[G1], [G2], [G3a], [G3b], [G4], <15 [G5] ml/min/1.73 m 2 ). A certain drop in egfr is defined as a drop in GFR category accompanied by a 25%or greater drop in egfr from baseline. Rapid progression is defined as a sustained decline in egfr of more than 5 ml/min/1.73 m 2 /yr. The confidence in assessing progression is increased with increasing number of serum creatinine measurements and duration of follow-up.

21 Assess GFR and albuminuria at least annually in people with CKD.Assess GFR and albuminuria more often for individuals at higher risk of progression, and/ or where measurement will impact therapeutic decisions Kidney International Supplements(2013) 2,1 150

22 Within-Person Variability in Kidney Measures Selvin et al. Am J Kidney Dis Jan 18.

23 Longitudinal Progression Trajectory of GFR Among Patients With CKD Li et al. Am J Kidney Dis Apr;59(4):

24 y International Suppl. 2012; 2:

25 Definition of AKI Kidney International Supplements 2012; 2: : AKI is defined as any of the following (Not Graded): Increase in SCrby 0.3 mg/dl ( 26.5 umol/l) within 48 hours; or Increase in SCrto 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or Urine volume < 0.5 ml/kg/h for 6 hours.

26 Staging of AKI Kidney International Supplements 2012; 2:

27 AKI examples Michael Joannidis, Innsbruck Case Baseline Day 1 Day 2 Day 3 Day 7 Reference Creatinine A B C D E F? Max AKI Stage G? ? 1 H? ??

28 Conceptual model for AKI Kidney International Supplements 2012; 2:

29 Update on Markers Predicting CKD Progression

30 Urine neutrophil gelatinase associated lipocalin levels do not improve risk prediction of progressive chronic kidney disease Liu et al. Kidney Int Jan 23.

31 Periostin: novel tissue and urinary biomarker of progressive renal injury induces a coordinated mesenchymal phenotype in tubular cells Satirapoj et al. Nephrol Dial Transplant (2012) 27:

32 Identification of Periostin as a Critical Marker of Progression/Reversal of Hypertensive Nephropathy Guerrot et al. PLoS One. 2012;7(3):e31974.

33 Update on Markers Predicting CV-Events and CV-Mortality

34 Serum Bicarbonate and Mortality in Stage 3 and Stage 4 Chronic Kidney Disease Navaneethan et al. Clin J Am Soc Nephrol 6: , 2011.

35 FGF-23 and the Progression of Coronary Arterial Calcification in Patients New to Dialysis Khan et al. Clin J Am Soc Nephrol Dec;7(12):

36 Fibroblast Growth Factor 23, High-Sensitivity Cardiac Troponin, and Left Ventricular Hypertrophy in CKD Smith et al. Am J Kidney Dis Jan;61(1):67-73.

37 Proteomics, Microparticles, Exosomes and beyond

38 Urinary Proteomics for Early Diagnosis in Diabetic Nephropathy Zürbig et al. Diabetes Dec;61(12):

39 Urinary Proteomics for Early Diagnosis in Diabetic Nephropathy Zürbig et al. Diabetes Dec;61(12):

40 A urinary peptide biomarker set predicts worsening of albuminuria in type 2 diabetes mellitus Roscioni et al. Diabetologia Feb;56(2):

41 A urinary peptide biomarker set predicts worsening of albuminuria in type 2 diabetes mellitus Roscioni et al. Diabetologia Feb;56(2):

42 Microparticles Apoptotic Bodies - Exosomes Burger et al. Clinical Science (2013) 124,

43 Microparticles Apoptotic Bodies - Exosomes Burger et al. Clinical Science (2013) 124,

44 Microparticlesand micrornas of endothelial progenitor cells ameliorate acute kidney injury Bitzer et al. Kidney International(2012) 82,

45 Predictive value of circulating endothelial microparticlesfor cardiovascular mortality in end-stage renal failure: a pilot study Amabile et al. Nephrol Dial Transplant May;27(5):

46 Predictive value of circulating endothelial microparticlesfor cardiovascular mortality in end-stage renal failure: a pilot study Amabile et al. Nephrol Dial Transplant May;27(5):

47 Circulating and Urinary micrornas in Kidney Disease Lorenzen and Thum. Clin J Am Soc Nephrol Sep;7(9):

48 Summary KDIGO CKD-Guidelines: Cause, GFR, Albuminuria egfr: CKD-EPI (Creatinine + Cystatin C) GFR-Trajectory: Not linear! KDIGO AKI-Guidelines: Staging = Severity (novel markers not included) CKD Progression Markers: NGAL, Periostin, CKD Markers for CV-Events and Mortality: Bicarbonate, FGF23, Novel Markers Evolving: Proteomic Profiles, MultimarkerPanels, Microparticles, Exosomes, mirnas,