Background: This study aimed to characterize the temporal trends of chronic kidney disease (CKD) burden in China during 1990–2019, evaluate their age, period and cohort effects, and predict the disease burden for the next 10 years. Methods: Data were obtained from the Global Burden of Disease (GBD) 2019 study. Join-point regression model was used to estimate the average annual percentage change (AAPC) of CKD prevalence and mortality, and the age-period-cohort analysis was used to estimate the age, period and cohort effects. We extended the autoregressive integrated moving average (ARIMA) model to predict the disease burden of CKD in 2020–2029. Results: In 2019, there were 150.5 million cases of (10.6%) and 196 726 deaths from (13.8 per 100 000 general population) CKD in China. Between 1990 and 2019, the prevalence and mortality rate of CKD increased significantly from 6.7% to 10.6%, and from 8.3/100 000 to 13.8/100 000. The AAPC was estimated as 1.6% and 1.8%, respectively. Females had a higher CKD prevalence of CKD but a lower mortality rate. Setting the mean level of age, period and cohort as reference groups, the risk of developing CKD increased with age [RRage(15–19) = 0.18 to RRage(85–89) = 2.45]. The cohort risk was significantly higher in the early birth cohort [RRcohort(1905–1909) = 1.56]. In contrast, the increase in age-specific CKD mortality rate after 60–64 years was exponential [RRage(60–64) = 1.24]. The cohort-based mortality risk remained high prior to the 1945–1949 birth cohorts (RRcohort ranging from 1.69 to 1.89) and then declined in the 2000–2004 birth cohort [RRcohort(2000–2004) = 0.22]. The CKD prevalence and mortality are projected to rise to 11.7% and 17.1 per 100 000, respectively, by 2029. Conclusions: To reduce the disease burden of CKD, a comprehensive strategy that includes risk factors prevention at the primary care level, CKD screening among the elderly and high-risk population, and access to high-quality medical services is required.

Acute kidney injury (AKI) has a critical role in the development of chronic kidney disease (CKD). Building on our previous findings, we explored the role of miR-382 in facilitating the transition of AKI to CKD using the Aristolochic acid (AA) nephropathy model, which was induced by intraperitoneal injection of aristolochic acid I salt (10 or 20 mg/kg). The effects of genetic depletion, pharmacologic inhibition, or overexpression of miR-382 on the PTEN/AKT signaling pathway were examined in vivo and in vitro. Changes in renal pathology and renal epithelial polarity were evaluated. A luciferase reporter assay was performed to investigate the reciprocal suppression relationship between miR-382 andPTEN. Renal fibrosis developed 14 d after AA exposure in a dose- and time-dependent manner. Renal abundance of miR-382 was upregulated following AA treatment, while genetic depletion or pharmacological inhibition of miR-382 partially reversed renal tubulointerstitial fibrosis. Expression of PTEN, a target of miR-382, was downregulated and subsequently its downstream AKT signaling pathway was activated during AKI to CKD transition induced by AA. Inhibition of PTEN in vitro resulted in the acquisition of the EMT phenotypes. Furthermore, upregulation of miR-382 in renal epithelial cells was partially mediated by the activation of NF-kB signaling, with a substantial elevation of proinflammatory cytokines. An in vivo study revealed that either miR-382 knockdown or miR-382 knockout was pivotal for inflammatory suppression, while an in vitro experiment confirmed that upregulation of miR-382 in cultured MTEC cells under AA exposure was remarkably reversed by NF-kB siRNA. These data indicated a novel role for the NF-κB/miR-382/PTEN/AKT axis in the pathogenesis of tubulointerstitial fibrosis following AA-induced acute renal tubular epithelial injury. Targeting miR-382 may lead to a potential novel therapeutic approach for retarding the AKT to CKD transition.

Background: The commonly used recommended criteria for renal recovery are not unequivocal. This study compared five different definitions of renal recovery in order to evaluate long-term outcomes of cardiac surgery associated acute kidney injury (CSA-AKI). Methods: Patients who underwent cardiac surgery between April 2009 and April 2013 were enrolled and divided into acute kidney injury (AKI) and non-AKI groups. The primary endpoint was 3-year major adverse events (MAEs) including death, new dialysis and progressive chronic kidney disease (CKD). We compared five criteria for complete renal recovery: Acute Renal Failure Trial Network (ATN): serum creatinine (SCr) at discharge returned to within baseline SCr + 0.5 mg/dL; Acute Dialysis Quality Initiative (ADQI): returned to within 50% above baseline SCr; Pannu: returned to within 25% above baseline SCr; Kidney Disease: Improving Global Outcomes (KDIGO): eGFR at discharge ≥60 mL/min/1.73 m²; Bucaloiu: returned to ≥90% baseline estimated glomerular filtration rate (eGFR). Multivariate regression analysis was used to compare risk factors for 3-year MAEs. Results: The rate of complete recovery for ATN, ADQI, Pannu, KDIGO and Bucaloiu were 84.60% (n = 1242), 82.49% (n = 1211), 60.49% (n = 888), 68.60% (n = 1007) and 46.32% (n = 680). After adjusting for confounding factors, AKI with complete renal recovery was a risk factor for 3-year MAEs (OR: 1.69, 95% CI: 1.20–2.38, P < 0.05; OR: 1.45, 95% CI: 1.03–2.04, P < 0.05) according to ATN and ADQI criteria, but not for KDIGO, Pannu and Bucaloiu criteria. We found that relative to patients who recovered to within 0% baseline SCr or recovered to ≥100% baseline eGFR, the threshold values at which significant differences in 3-year MAEs were observed were > 30% or > 0.4 mg/dL above baseline SCr or < 70% of baseline eGFR. Conclusions: ADQI or ATN-equivalent criteria may overestimate the extent of renal recovery, while KDIGO, Pannu and Bucaloiu equivalent criteria may be more appropriate for clinical use. Our analyses revealed that SCr at discharge > 30% or > 0.4 mg/dL of baseline, or eGFR < 70% of baseline led to significant 3-year MAE incidence differences, which may serve as hints for new definitions of renal recovery.

Redox imbalance plays an important role in the pathogenesis of CKD progression. Previously, we demonstrated that microRNA‐382 (miR‐382) contributed to TGF‐β1‐induced loss of epithelial polarity in human kidney epithelial cells, but its role in the development of renal tubulointerstitial fibrosis remains unknown. In this study, we found that with 7 days of unilateral ureteral obstruction (UUO) in mice, the abundance of miR‐382 in the obstructed kidney was significantly increased. Meanwhile, the protein expression of heat shock protein 60 (HSPD1), a predicted target of miR‐382, was reduced after 7 days of UUO. Expression of 3‐nitrotyrosine (3‐NT) was upregulated, but expression of thioredoxin (Trx) was downregulated. Anti‐miR‐382 treatment suppressed the upregulation of miR‐382, attenuated renal interstitial fibrosis in the obstructed kidney, and reversed the downregulation of HSPD1/Trx and upregulation of 3‐NT after UUO. Furthermore, in vitro study revealed that overexpression of HSPD1 significantly restored Trx expression and reversed TGF‐β1‐induced loss of E‐cadherin, while in vivo study found that direct siRNA‐mediated suppression of HSPD1 in the UUO kidney promoted oxidative stress despite miR‐382 blockade. Our clinical data showed that upregulation of miR‐382/3‐NT and downregulation of HSPD1/Trx were also observed in IgA nephropathy patients with renal interstitial fibrosis. These data supported a novel mechanism in which miR‐382 targets HSPD1 and contributes to the redox imbalance in the development of renal fibrosis.