15% av inneliggande patienter på svenska sjukhus är intagna på grund av felmedicinering ofta orsakad av ej identifierad njurfunktionsnedsättning dvs nedsatt GFR

According to the NHANES III-study the prevalence of stage 2 chronic kidney disease is 3% in the American population i.e. about 9000000 persons are afflicted

What is GFR? It is the volume of glomerular filtrate produced per unit of time, e.g. mL/min

Can GFR in humans be measured? No, because it is not feasible to measure the filtration flow in the 800,000 human glomeruli

“Gold standard” methods to estimate GFR Plasma clearance of inulin, iohexol, 51Cr-EDTA, 125I-iothalamate, 99mTc-diethylenetriaminepentaacetic acid

GFR markers Plasma creatinine Plasma cystatin C Creatinine clearance Creatinine-based GFR prediction equations Cystatin C-based GFR prediction equations

Advantages of cystatin C as a GFR-marker Demonstrates the early, potentially reversible, decrease of GFR in the “creatinine-blind” area Independent of muscle mass and diet Independent of sex and age for children above 1 year Demonstrates the decrease of GFR in old persons No tubular secretion

Creatinine-blind area

GFR-markers for patients with muscle atrophy Non-parametric ROC plots for serum cystatin C (solid line) AUC = 0.912 and serum creatinine (dotted line) AUC = 0.507 AUC = 0.50 equals the diagnostic efficiency of tossing a coin

Concensus recommendation of the National Kidney Foundation (US) “The serum creatinine concentration alone should not be used to assess the level of kidney function” Page 76, Am J Kidney Dis 2002;39Suppl.1

For Adults (MDRD) or

GFR-prediction equations Relative GFR in mL/min/1.73m2 MDRD: GFR = 186.3 x (creatinine/88.4)-1.154 x age-0.203 x 0.742 (if female) x 1.212 (if African American) GFR(CC-estimate)= 84.69 x cystatin C-1.680 x 1.384 (if child<14years)

Diagnostic performance of a cystatin C-based GFR prediction equation

Diagnostic performance of a creatinine-based GFR prediction equation (MDRD)

GFR (CC-estimat): 89 ml/min/1,73kvm Grubb, Anders 441021-4151 P-Cystatin C: 0,99 mg/L (ref. värde: 0,84 – 1,25 mg/L) GFR (CC-estimat): 89 ml/min/1,73kvm (ref.värde: 60 – 110 ml/min/1,73kvm)

“För dosering av njurutsöndrade läkemedel, speciellt hos barn, är det viktigt att känna till patientens absoluta (dvs ej kroppsyte-normaliserade) GFR i mL/min. Detta kan räknas ut från patientens estimerade, eller uppmätta, relativa GFR (i mL/min/1,73 kvm kroppsyta), vikt (kg) och längd (cm). På sajten http://www.klinkem.lu.se/GFR.htm finns ett hjälpmedel för snabb sådan uträkning.”

Is GFR always the best marker for kidney disease/function? No, for example: U-Protein HC is much better to demonstrate tubular damage P-Erythropoietin is much better to demonstrate renal anemia Altered glomerular filtration quality is much better to demonstrate preeclampsia

What does glomerular filtration quality mean? It describes the composition of the glomerular filtrate in a patient in relation to the composition of a “normal” glomerular filtrate

Hemodialysis (small pores)

Hemofiltration (large pores)

Difference in plasma clearance of marker molecules

How can glomerular filtration quality be assessed in the clinical practise? By the use of several GFR-markers differing in size and/or charge, e.g. Creatinine Cystatin C 2-microglobulin -trace 2-macroglobulin

S-Cystatin C in preeclampsia and normal pregnancy

S-Creatinine in preeclampsia and normal pregnancy

ROC-curves for demonstration of preeclampsia

Concluding suggestions Use more than one GFR-marker e.g. cystatin C, creatinine and -trace with cystatin C as the basic one Use GFR-prediction equations Use assessment of glomerular filtration quality for diagnostic purposes

Penning som föreställer Erik Emune, utropad till kung över Skånelanden och Danmark på Libers hög i Lund 1134 Visas på anmodan.