Comment

Acute kidney injury

Rhabdomyolysis-induced acute kidney injury (AKI) is closely related to toxic reactive oxygen species (ROS), apoptosis, and inflammation. Excessive activation of poly (ADP-ribose) polymerase-l (PARP-1) by ROS can cause mitochondrial dysfunction and release of the proapoptotic protein AIF, which triggers an intrinsic PARP-1-dependent cell death program. Considering these characteristics of rhabdomyolysis-induced AKI, we developed a targeting nanodrug delivery platform by loading PJ34 and coupling anti-GPR97 with melanin nanoparticles (GMP nanoparticles) that could realize photoacoustic self-monitoring and triple-collaborative treatment (antioxidant, antiapoptotic, and anti-inflammatory). The nanoparticles exhibited good dispersibility, solubility, and broad-spectrum ROS scavenging ability. In vitro experiments revealed high biocompatibility of the GMP nanoparticles and strong ability of scavenging multiple toxic ROS, antiapoptotic activity, and anti-inflammatory activity. Because melanin nanoparticles possess inherent photoacoustic (PA) imaging capability, they can not only serve as a drug carrier but also perform self-monitoring for real-time tracking of GMP biodistribution and renal uptake in a murine AKI model through PA imaging. In vivo experiments showed that the GMP nanoparticles could effectively reduce oxidative stress, apoptosis, and inflammatory response in mice with rhabdomyolysis-induced AKI, and the mechanism of alleviation was verified through western blot experiments. These results indicated that the nanoplatform could realize the targeted delivery and curative effect monitoring under the guidance of PA imaging, which is of great significance for the prevention and treatment of AKI.

A targeting nanodrug delivery platform was developed by loading PJ34 and coupling anti-GPR97 with melanin nanoparticles (GMP nanoparticles) for photoacoustic self-monitoring and triple-collaborative treatment (antioxidant, antiapoptotic, and anti-inflammatory) of acute kidney injury (AKI). Further studies indicated that the Keap-1/Nrf2/HO-1 and PARP-1/AIF signaling pathways are involved in the therapeutic mechanisms to alleviate AKI. Immunohistochemical staining and routine blood test confirmed the anti-inflammatory performance of GMP nanoparticles. Compared to exogenous nanomaterials, we used endogenous melanin with broad ROS scavenging capacity as the nanocarrier and antioxidant, which not only overcomes the defects of high specificity, potential toxicity, low loading capacity, and high cost but also shows good biosafety and photoacoustic imaging performance in vivo.

To study how to effectively prevent or reduce renal injury caused by contrast agents in diabetic patients.

Sprague Dawley (SD) rats were bred with a high-fat diet for eight weeks, then intraperitoneally injected with Streptozotocin (STZ) to prepare the diabetes model. Rats were treated with Iodixanol to prepare a contrast-induced acute kidney injury (CIAKI) model. Moreover, 3-methyladenine (3-MA), an autophagy inhibitor, was administrated to diabetic rats with or without Rapamycin treatment. Serum creatinine (SCr) and blood urea nitrogen (BUN) were examined using Biochemical detector. Kidney injury molecule-1 (KIM-1), N-acetyl-β-D-amino glycosidase (NAG) in urine, inflammatory and oxidative stress factors in serum were determined by ELISA. The expression level of ROS was quantified by immunofluorescence (IF). The protein expressions of Bax, BCl-2, LC3, Beclin1, mTOR and p70S6K in renal tissue were detected by Western blot.

Rapamycin was demonstrated to improve renal injury induced by Iodixanol diabetic rats, decrease the levels of SCr, BUN, KIM-1, NAG, improve renal functions, reduce inflammatory response and oxidative stress injury, down-regulate Bax, while up-regulate BCl-2 and inhibit apoptosis. Moreover, Rapamycin could inhibit the phosphorylation of mTOR/p70S6K pathway-associated proteins, activate autophagy and increase the levels of LC3 and Beclin1. After treatment with 3MA, an inhibitor of mTOR/p70S6K signaling pathway, the protective effects of Rapamycin on CIAKI were weakened.

Rapamycin can alleviate renal injury induced by Iodixanol diabetic rats, and its regulatory mechanisms may be related to the regulation of mTOR/p70S6K signaling pathway and the activating autophagy.

Dialysis-requiring acute kidney injury (AKI-D) has increased substantially in the United States. We examined trends in and comorbid conditions associated with hospitalizations and in-hospital mortality in the setting of AKI-D among people with versus without diabetes.

Cross-sectional study.

Nationally representative data from the National Inpatient Sample and National Health Interview Survey were used to generate 16 cross-sectional samples of US adults (aged ≥18 years) between 2000 and 2015.

Diabetes, defined using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes.

AKI-D, defined using ICD-9-CM diagnosis and procedure codes.

Annual age-standardized rates of AKI-D and AKI-D mortality were calculated for adults with and without diabetes, by age and sex. Data were weighted to be representative of the US noninstitutionalized population. Trends were assessed using join point regression with annual percent change (Δ/y) reported.

In adults with diabetes, AKI-D increased between 2000 and 2015 (from 26.4 to 41.1 per 100,000 persons; Δ/y, 3.3%; P < 0.001), with relative increases greater in younger versus older adults. In adults without diabetes, AKI-D increased between 2000 and 2009 (from 4.8 to 8.7; Δ/y, 6.5%; P < 0.001) and then plateaued. AKI-D mortality significantly declined in people with and without diabetes. In adults with and without diabetes, the proportion of AKI-D hospitalizations with liver, rheumatic, and kidney disease comorbid conditions increased between 2000 and 2015, while the proportion of most cardiovascular comorbid conditions decreased.

Lack of laboratory data to corroborate AKI diagnosis; National Inpatient Sample data are hospital-level rather than person-level data; no data for type of diabetes; residual unmeasured confounding.

Hospitalization rates for AKI-D have increased considerably while mortality has decreased in adults with and without diabetes. Hospitalization rates for AKI-D remain substantially higher in adults with diabetes. Greater AKI risk-factor mitigation is needed, especially in young adults with diabetes.