CREATININE AND CYSTATIN-C BASED GFRs VS 51 Cr-EDTA GFR IN PATIENTS WITH DECOMPENSATED CIRRHOSIS 1 4th Department of Internal Medicine, Hippokration General Hospital of Thessaloniki, Medical School of Aristotle University 2 Biochemical Department, Hippokration General Hospital of Thessaloniki

Renal dysfunction is a well-established predictor of increased mortality in both acute liver failure and cirrhosis Serum creatinine(Cr) is only an indirect marker of renal function, i.e. of glomerular filtration rate(GFR) Thus, most used GFR formulae (e.g. MDRD) use several corrections for age, gender, ethnicity and body weight BACKGROUND

Serum cystatin C (CysC) is a low molecular weight protein functioning as an extracellular inhibitor of cysteine proteases CysC is considered a more sensitive indicator of renal function compared to Cr, in several disease groups, including cirrhosis In cirrhosis, CysC has been proposed as a marker of liver disease stage BACKGROUND

OBJECTIVES Our aims were: (a)to compare ‘true’ GFR using a gold standard method and estimated GFR (eGFR) using Cr and CysC (b) to investigate if a new formula to estimate GFR in cirrhosis using parameters related to liver function could be derived.

Consecutive adult patients with stable decompensated cirrhosis admitted to our Department for liver transplant assessment In each patient demographic and clinical variables were prospectively recorded Measurement of “true” GFR was assessed with 51 Cr-EDTA MATERIALS & METHODS

Cr-based GFR was calculated using the 4 variable MDRD: - 186×(Cr) −1.154 ×(Age in years) −0.203 ×0.742(if female) Cystatin-based GFR was calculated using - Hoek formula: GFR= x1/CysC in mg/dL - Larsson formula: GFR=77.239xCysC in mg/dL MATERIALS & METHODS

Statistical analysis Univariate comparisons of demographic and baseline clinical and laboratory variables were performed Non parametric correlations were evaluated by Spearman and parametric ones by Pearson correlation We performed a stepwise multivariate linear regression analysis in order to derived the new eGFR specific for cirrhosis

Variable (unit)Patients, n=104 Age (years)54±11 Sex, male n, (%)75 (72) Cause of cirrhosis n, (%) Viral hepatitis (hepatitis B or C) Alcohol Others 53 (51) 32 (31) 19 (18) Refractory ascites and/or HRS, n, (%)15 (14) MDRD-estimated GFR (median, range)79 (range: ) “true” GFR by 51 Cr-EDTA (median, range)70 (range: ) Chid-Pugh score (mean±SD)8±2 MELD score, (mean±SD)11±4 Baseline characteristics of our cohort

Spearman r 2 =0.64, p<0.001 Correlation between Creatinine and Cystatin-C

Spearman r 2 =-0.66, p<0.001 Correlation between Creatinine and “true” GFR

Spearman r 2 =-0.68, p<0.001 Correlation between Cystatin-C and “true” GFR

Variable (unit)Spearman r 2 P value Age (years)-0.43<0.001 Protein (g/dL) Albumin (g/dL) Cystatin-C-0.68<0.001 Blood pressure (mmHg) Creatinine (mg/dL)-0.66<0.001 Urea (mg/dL)-0.65<0.001 Sodium (mean±SD, mmol/L) UNa24h (mean±SD, mmoL/day) 0.41<0.001 ALT (IU/L) CPK MELD score Correlations between baseline factors and “true” GFR

Variables95% Confidence Interval Coefficientp valuelowerupper Age Cystatin-C Creatinine Multivariable linear regression analysis to identify the independent factors associated with the “true” GFR in patients with decompensated cirrhosis New GFR: 163x (Creatinine) (-19.6) x (Cystatin C) (-11.8) X (age) (-0.86)

Spearman r 2 =0.78, p<0.001 Correlation between new-eGFR and “true” GFR

Spearman r 2 =0.69, p<0.001 Correlation between MDRD and “true” GFR

Spearman r 2 =0.73, p<0.001 Correlation between GFR-Larsson and “true” GFR

Spearman r 2 =0.72, p<0.001 Correlation between GFR-Hoek and “true” GFR

CONCLUSIONS Estimated GFR in cirrhosis is not better with CysC formulas compared to creatinine ones. In our cohort of cirrhotics, a specific formula perform better than the known eGFRs.