CREATININE AND CYSTATIN-C BASED GFRs VS 51Cr-EDTA GFR IN PATIENTS WITH DECOMPENSATED CIRRHOSIS

1 4th Department of Internal Medicine, Hippokration General Hospital of Thessaloniki, Medical

School of Aristotle University2 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 51Cr-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=-4.32+80.35x1/CysC in mg/dL

- Larsson formula: GFR=77.239xCysC -1.2623 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: 35-159)

“true” GFR by 51Cr-EDTA (median, range) 70 (range: 16-131)

Chid-Pugh score (mean±SD) 8±2

MELD score, (mean±SD) 11±4

Baseline characteristics of our cohort

Spearman r2=0.64, p<0.001

Correlation between Creatinine and Cystatin-C

Spearman r2=-0.66, p<0.001

Correlation between Creatinine and “true” GFR

Spearman r2=-0.68, p<0.001

Correlation between Cystatin-C and “true” GFR

Variable (unit) Spearman r2 P value

Age (years) -0.43 <0.001Protein (g/dL) 0.46 0.001

Albumin (g/dL) 0.25 0.033Cystatin-C -0.68 <0.001

Blood pressure (mmHg) 0.25 0.038Creatinine (mg/dL) -0.66 <0.001Urea (mg/dL) -0.65 <0.001Sodium (mean±SD, mmol/L) 0.44 0.013UNa24h (mean±SD, mmoL/day) 0.41 <0.001ALT (IU/L) 0.29 0.013CPK 0.010 0.32MELD score -0.45 0.001

Correlations between baseline factors and “true” GFR

Variables 95% Confidence Interval

95% Confidence Interval

Coefficient p value lower upperAge -0.86 0.001 -1.3 -0.37Cystatin-C -11.8 0.014 -21 -2.4Creatinine -19.6 0.038 -38 -1.1

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 r2=0.78, p<0.001

Correlation between new-eGFR and “true” GFR

Spearman r2=0.69, p<0.001

Correlation between MDRD and “true” GFR

Spearman r2=0.73, p<0.001

Correlation between GFR-Larsson and “true” GFR

Spearman r2=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.