Prediction of decreased estimated glomerular filtration rate using liver fibrosis markers: a renal biopsy-based study

www.nature.com/scientificreports OPEN Prediction of decreased estimated glomerular filtration rate using liver fibrosis markers: a renal biopsy‑based study Akira Mima Non-alcoholic fatty liver disease is the most common chronic liver disease and is associated with chronic kidney disease. The fibrosis-4 index and non-alcoholic fatty liver disease score are widely used as non-invasive diagnostic methods for non-alcoholic fatty liver disease. However, the relationship between these markers and specific renal histopathologies in chronic kidney disease remain unclear. This study included 179 patients aged between 16 and 80 years who underwent renal biopsy. We examined the association between the fibrosis-4 index or non-alcoholic fatty liver disease score and change in estimated glomerular filtration rate 12 months after kidney biopsy for each renal histopathology. Renal histopathologies were determined by renal biopsy. Our results showed that there was a significant negative correlation between the fibrosis-4 index and estimated glomerular filtration rate. In nephrosclerosis, the non-alcoholic fatty liver disease score and estimated glomerular filtration rate tended to have a negative correlation, albeit without significance. In IgA nephropathy, both the fibrosis-4 index and non-alcoholic fatty liver disease score were significantly negatively correlated with estimated glomerular filtration rate. Furthermore, the fibrosis-4 index was not associated with urinary protein-to-creatinine ratio or renal function markers such as urinary b2 microglobulin and urinary N-acetyl-d-glucosamine. Our kidney biopsy-based study showed that the liver fibrosis markers fibrosis-4 index and non-alcoholic fatty liver disease score were negatively correlated with the estimated glomerular filtration rate in nephrosclerosis and IgA nephropathy. Chronic kidney disease is associated with increased risks of mortality and morbidity. Furthermore, CKD is also associated with diabetes mellitus, including diabetic kidney disease (DKD)1. Obesity and insulin resistance are the most common causes of CKD2,3. It has been reported that non-alcoholic fatty liver disease (NAFLD) is a clinicopathological condition that encompasses a variety of chronic liver diseases ranging from asymptomatic hepatic fat accumulation to progressive liver disease, with clinical symptoms resembling alcoholic liver disease despite the absence of excessive alcohol c onsumption4,5. A recent study revealed that the prevalence of NAFLD diagnosed by ultrasound was estimated to be about 25%6. It is estimated that either NAFLD or non-alcoholic steatohepatitis (NASH) will be the most common indication for liver transplantation by 2 0307. NAFLD is a multisystem disease that is associated with various diseases such as diabetes mellitus, obesity, metabolic syndrome, cardiovascular diseases, and C KD8. The fibrosis-4 (FIB-4) index and NAFLD fibrosis score (NFS) are simple and validated diagnostic markers used to stratify the degree of liver fibrosis according to risk in patients with suspected NAFLD9. Moreover, these non-invasive fibrosis markers have been shown to be associated with the prevalence of CKD in recent s tudies10. However, there have been no reports on the association between these fibrosis markers and decreased estimated glomerular filtration rate (eGFR) by renal histopathology classification as determined by kidney biopsy. Thus, we performed this renal pathology-based study to elucidate whether the FIB-4 index and NFS can predict eGFR decline in CKD patients. Results We determined the clinical characteristics of the 179 cases after excluding patients who underwent kidney biopsy. The median age of the study participants was 51 years, and 96 patients (53.6%) were female. The median body mass index was 22.7, and the median FIB-4 index was 0.96. The other median values are as follows: systolic blood Department of Nephrology, Osaka Medical and Pharmaceutical University, Osaka 569‑8686, Japan. email: akira. Scientific Reports | (2022) 12:17630 | https://doi.org/10.1038/s41598-022-22636-9 1 Vol.:(0123456789) www.nature.com/scientificreports/ Variables All patients (n = 179) Age (years) 51 (16–80) Female gender 96 (53.6%) Body mass index 22.7 (14.3–45.7) SBP (mmHg) 129 (90–236) DBP (mmHg) 78 (40–142) BUN (mmol/L) 5 (2.5–35.7) Serum creatinine (µmol/L) 76.02 (26.69–38.13) eGFR (mL/min/1.73m2) 64 (9–140) Urinary β2 MG (mg/L) 198 (47–73,162) Urinary NAG (IU/L) 8.9 (1.0–221.1) Urine protein/creatine ratio FIB-4 index 0.538 (0.04–28.86) 0.96 (0.19–6.58) NFS − 1.78 (− 4.88 to − 2.74) Table 1.  Patient characteristics. SBP systolic blood pressure, DBP diastolic blood pressure, BUN blood urea nitrogen, eGFR estimated glomerular filtration rate, urinary β2 MG urinary β2 microglobulin, urinary NAG urinary N-acetyl-β-d-glucosaminidase, FIB-4 index fibrosis-4 index, NFS non-alcoholic fatty liver disease score. Underlying disease Number (%) Nephrosclerosis 10 (5.6) IgA nephropathy 74 (41.3) Minimal change disease 24 (13.4) Diabetic nephropathy 7 (3.9) Lupus nephritis 12 (6.7) Membranous nephropathy 18 (10.1) ANCA-associated glomerulonephritis 9 (5.0) Interstitial nephritis 9 (5.0) Others 16 (8.9) Table 2.  Underlying diseases in study. pressure (SBP), 129 mmHg; diastolic blood pressure (DBP), 78 mmHg; serum creatinine (Cr), 76.02 mmol/L; blood urea nitrogen (BUN), 5 mmol/L; estimated glomerular filtration rate (eGFR), 64 mL/min/1.73 m 2; urine protein-to-creatinine ratio, 0.538; N-acetyl-β-d-glucosaminidase (urinary NAG), 8.9 IU/L; and urinary β2 microglobulin (urinary β2 MG), 198 mg/L (Table 1). The underlying diseases are as follows: nephrosclerosis (10 cases, 5.6%), IgA nephropathy (74 cases, 41.3%), minimal change disease (24 cases, 13.4%), diabetic nephropathy (7 cases, 3.9%), lupus nephritis (12 cases, 6.7%), membranous nephropathy (18 cases, 10.1%), ANCA-associated glomerulonephritis (9 cases, 5.0%), interstitial nephritis (9 cases, 5.0%), and others (16 cases, 8.9%) (Table 2). We calculated the FIB-4 index and eGFR before renal biopsy for all diseases. The results showed that there was a weak but negative correlation between the FIB-4 index and eGFR ( R2 = 0.1458, P < 0.01, Fig. 1a). In contrast, the FIB-4 index was not correlated with the urinary protein-to-creatinine ratio (R2 = 0.0164, P = 0.08, Fig. 1b) and urinary β2 MG (R2 = 0.0819, P = 0.08, Fig. 1c). Furthermore, there was a negative correlation between the FIB-4 index and urinary NAG ( R2 = 0.0483, P < 0.01, Fig. 1d). Next, we examined the relationship between FIB-4 index and NFS, and the rate of change in eGFR before and 12 months after renal biopsy. In nephrosclerosis, we found that the FIB-4 index was significantly negatively correlated with the eGFR ( R2 = 0.4362, P = 0.04, Fig. 2a). Additionally, the correlation between NFS and eGFR tended to be negative, albeit without statistical significance ( R2 = 0.1503, P = 0.27, (...truncated)