Introduction:
Rapid loss in kidney function is a hallmark of acute kidney injury (AKI), which can lead to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Dehydration, diarrhoea, infections, venomous snakebite, and other causes can cause AKI, which is usually community acquired in tropical countries like India. Recent research highlights the role of mitochondrial dysfunction in AKI. Urinary mitochondrial DNA was elevated in AKI patients and associated with AKI severity. However, there is no studies showing the link between urinary mtDNA with renal outcome of AKI. we aimed to find the association of urinary mtDNA with renal recovery from CA-AKI.
Methods:
In this prospective observational study, stable patients of either sex, aged between 18-70 years, and diagnosed with CA-AKI were enrolled at the time of hospital discharge. Patients with underlying CKD, urinary tract obstruction, decompensated chronic liver failure, malignancy or heart failure were excluded. The patients were followed at 4th months after hospital discharge to assess the outcome (recovery and non-recovery). Renal non recovery was defined as estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73m2. Total urinary DNA was isolated from urine samples collected at the time of hospital discharge. Levels of urinary mtDNA genes ND-1 and COX-3 were analysed by qRT-PCR method. mtDNA genes were normalised with β-actin gene.
Results:
A total 112 subjects with CA-AKI were enrolled. 35 (31.2%) patients were failed to recover completely from CA-AKI at 4 months with persistent eGFR <60 mL/min/1.73m2 after hospital discharge. Mean age of subjects was 38.8 ±13.6 years and gender were equally distributed in the study. There was significant difference in serum creatinine (3.23 ± 2.91 versus 0.9 ± 0.19 mg/dL, p<0.005, and in eGFR (33.2 ± 18.49 versus 98.8 ± 20.2 mL/min/1.73m2, p < 0.005) between renal non-recovery group and renal recovery group at 4th month after hospital discharge. Ct values of ND-1 gene (14.5 ± 1.1 versus 16.3 ± 4.0; p < 0.005) and COX-3 gene Ct (14.3 ± 1.2 versus 16.2 ± 3.2; p < 0.005) were significantly lower in renal non-recovery group as compare to renal recovery group. However, when β-actin was used to normalise both genes, there was no significant change (ND-1/β-actin Ct; 0.63 ± 0.1 versus 0.66 ± 0.1, p= 0.44 and COX-3/β-actin Ct; 0.62 ± 0.1 versus 0.65 ± 0.10, p=0.41) between the groups. Receiver operating characteristics analysis reveals that area under the curve value for ND-1 gene was 0.63 (95% C; 0.53 to 0.73, p=0.02) and for COX-3 was 0.67 (95% C; 0.57 to 0.77, p=0.003).
Conclusions:
The expression of urinary mtDNA genes, ND-1 and COX-3 were significantly higher in patients who were failed to recover from CA-AKI after the 4 month of hospital discharge. However, normalised gene expression was similar in both the group. Finding from this study needs further evaluation for the potential role of urinary mtDNA in renal recovery after AKI in with adequate sample size.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.