BMC Nephrology最新文献

Background: Diabetic kidney disease (DKD) is one of the most pervasive complications of diabetes worldwide. However, the pathogenesis of DKD remains poorly understood, due to limitations of the models. The hPSC-derived kidney organoids may offer a new possibility to solve the problem.

Methods: We generated human pluripotent stem cells (hPSCs) derived kidney organoids to model DKD injury by glucose intervention for 24 and 72 h, respectively. RT-qPCR was used to assess gene expression, while immunofluorescence was performed to evaluate protein expression. PAS staining was applied to examine organoid morphology, and Sirius Red staining was used to assess fibrosis.

Results: Firstly, qPCR results showed that glucose and lipid metabolism-related genes such as LDH, HK2, SGLT2, PLIN2, PPARA, PGC1A, and HSL mRNA expression were upregulated after glucose intervention. Secondly, qPCR and immunofluorescence staining results revealed that the expression of pro-inflammatory cytokines IL6, IL1B, TNFA, VCAM1 and IL-10 were increased, which suggested kidney organoids possess inflammatory responses in high glucose environments. Thirdly, KIM1, a kidney injury maker was upregulated after glucose intervention, and increased apoptosis cells in kidney organoids were confirmed by TUNEL assay. Finally, qPCR and immunofluorescence staining results revealed that the expression of fibrosis-related molecules TGF-β1 and COL4 were increased.

Conclusion: In general, diabetic kidney disease organoid models provide a valuable model for studying the onset, progression, and injury of DKD.

Clinical trial number: Not applicable.

Background: Few studies have analyzed the quality-of-life trajectories of CKD patients not receiving kidney replacement therapy, and the results are inconsistent. This study aimed to identify subgroups of long-term trajectories of the physical (PCS) and mental components summary (MCS) of the KDQOL-36 in patients with CKD stages 3-5 and to describe their associations with patient characteristics.

Methods: We used a joint latent class-mixed model to identify the PCS and MCS trajectories of 2716 patients with CKD stages 3-5 enrolled in the CKD-Renal Epidemiology and Information Network (CKD-REIN) cohort study. Quality-of-life was assessed annually using the Kidney Disease Quality-of-life-36. All the participants had scores for at least one-time point.

Results: During a median follow-up of 5.56 (4.77-6.16) years, 664 participants started KRT, and 465 died before KRT. We identified three profiles of PCS: a "High and declining PCS trajectory" which included 5.89% of patients, characterized by a higher initial score and a decline of more than 10 points over three years; a "High and stable PCS trajectory" in 50.96%, characterized by a higher initial score that remained stable; and a "Low and stable PCS trajectory" in 43.15%, characterized by a lower initial score that remained stable. For MCS, we identified a single, stable mean trajectory over time. A decline in eGFR was faster in participants with a "High and declining PCS trajectory" (-4.30 mL/min per years). Patients in the high and stable trajectory had a more favorable clinical and biological profile at baseline. The evolution of the specific dimensions of CKD within each PCS trajectory followed a pattern similar to that of the PCS itself.

Conclusions: The study highlights substantial heterogeneity in PCS evolution in patients with CKD, which contrasts with the stability of that for MCS.