This article investigates the collaborative management of metabolic dysfunction-associated fatty liver disease （MAFLD） and chronic kidney disease （CKD）. As major public health issues worldwide， MAFLD and CKD are closely related in terms of epidemiology， pathogenesis， and management strategies， and however， there are still many challenges in the multidisciplinary collaborative management of the two diseases. This article systematically elaborates on the epidemiology of MAFLD and CKD， summarizes their common risk factors such as metabolic disorder， genetic susceptibility， and active metabolites， and reviews the mutual screening strategies and combined management models based on noninvasive imaging， serum markers， FIB-4 score， and liver stiffness measurement. In addition， this article summarizes the advances in the application of lifestyle intervention and new drugs （such as GLP-1 receptor agonists and SGLT-2 inhibitors） and emphasizes the importance of multidisciplinary collaboration in improving the prognosis of patients. Due to the close association between MAFLD and CKD， their joint management is crucial， and therefore， it is necessary to establish a multidisciplinary collaboration mechanism and implement the measures of precise screening， comprehensive treatment， and long-term monitoring， so as to improve the prognosis of patients and reduce the risk of complications. Finally， this article proposes that in the future， more effective combined treatment regimens should be explored to expand the clinical options for the co-management of the liver and the kidney.

Acute kidney injury (AKI) is a common clinical acute and critical condition. There is a lack of clinical interventions or therapeutic drugs that can significantly improve AKI outcomes. Lipids, including fatty acids, triglycerides, sphingolipids, phospholipids and cholesterol play crucial roles in energy metabolism, cell membrane composition, cell signaling, and cell homeostasis and survival. Recent lipidomics studies have revealed significant alterations in the content and composition of renal lipids during AKI, highlighting their important roles in the onset, progression, and outcomes of the disease. A common feature of AKI across multiple etiologies is altered lipid metabolism, characterized by insufficient energy generation due to mitochondrial damage and deposition of excess lipids in the kidney. The article summarizes the characteristics of renal lipid metabolism in physiological state, alterations of renal lipid metabolism in AKI and molecular mechanisms related to lipid metabolism disorders that aggravate AKI through mitochondrial damage, oxidative stress, autophagy dysfunction, activation of inflammatory and immune responses and regulated cell death, to provide new ideas and therapeutic targets for the clinical treatment of AKI.

Objective:To identify factors associated with depressive symptoms in maintenance hemodialysis patients and to examine the relationship between these symptoms and mortality.Methods:Between January and December 2019, patients who received maintenance hemodialysis in the Blood Purification Center of the Second Affiliated Hospital of Nanjing Medical University were enrolled in a prospective cohort study. Depressive symptoms were assessed using the internationally validated patient health questionnaire-8 (PHQ-8). Sleep quality and anxiety were measured with the Pittsburgh sleep quality index (PSQI) and the generalized anxiety disorder-7 (GAD-7) scale, respectively. Follow-up continued until December 31, 2022, with all-cause mortality as the primary outcome. Ordinal logistic regression was used to identify independent predictors of depression severity. Cox proportional hazards models evaluated the association between depressive symptoms and mortality.Results:A total of 532 maintenance hemodialysis (MHD) patients completed the study. Among them, 177 (33.3%) exhibited depressive symptoms. Compared with patients without depression, those with mild or moderate-to-severe depression were older [median age: 58 (50, 66) vs. 60 (55, 65) vs. 55 (46, 64)], more likely to smoke [35.9% (51/142) vs. 40.0% (14/35) vs.26.2% (93/355)], had poorer sleep quality [PSQI: 9 (6, 13) vs. 12 (9, 17) vs. 5 (3, 9)], and higher anxiety levels [GAD-7: 1 (0, 3) vs. 3 (1, 6) vs. 0 (0, 1)], the differences among the three groups were statistically significant (all P<0.05). Ordinal logistic regression identified smoking status, history of diabetes or cardiovascular disease, hemoglobin level, PSQI score, and GAD-7 score as independent predictors of depression severity ( OR=1.60, 1.80, 1.81, 0.98, 3.67, 8.67; all P<0.05). After a median follow-up of 40 (35, 44) months, 109 patients died, including 66 (60.6%) from cardio-cerebrovascular causes and 24 (22.0%) from infections. Kaplan-Meier analysis revealed significantly lower cumulative survival in the depression group compared to the non-depression group ( P<0.001). Cox regression analysis demonstrated that depressive symptoms remained independently associated with all-cause mortality after adjusting for confounders ( HR=1.06, 95% CI 1.00-1.13, P=0.048), with an even stronger association observed for patients with PHQ-8 scores≥2.9 ( HR=1.10, 95% CI 1.03-1.16, P=0.005). However, the associations between depression and cardio-cerebrovascular mortality ( P=0.111) or infection-related mortality ( P=0.509) were not statistically significant. Conclusions:Depressive symptoms are prevalent among maintenance hemodialysis patients and are independently associated with increased all-cause mortality. Smoking, comorbid diabetes or cardiovascular disease, low hemoglobin level, poor sleep quality, and anxiety are risk factors contributing to depression. Maintenance hemodialysis patients with PHQ-8 scores≥3 should be considered at heightened risk for mortality.

Objective:To analyze the clinical application of protocol biopsy (PB) during postoperative follow-up in recipients of allogeneic kidney transplantation.Methods:A prospective observational cohort study was conducted. Recipients who underwent allogeneic kidney transplantation at the Second Affiliated Hospital of Nanjing Medical University between January 2022 and September 2024 and received PB at 3 months (±1 week) and/or 12 months (±4 weeks) post-transplantation in the Department of Nephrology were enrolled. The implementation, complications, and pathological results of PB were summarized. The safety and diagnostic efficacy of PB were analyzed.Results:A total of 143 allogeneic kidney transplant recipients were included, and 200 PB procedures were performed. The overall implementation rate of protocol biopsy (PB) was 84.1% (143/170). Among them, 170 recipients completed 3-month follow-up, and 136 PBs were performed at 3 months (±1 week) post-transplantation, with an implementation rate of 80.0%. Seventy-nine recipients completed 12-month follow-up, and 64 PBs were performed at 12 months (±4 weeks), with an implementation rate of 81.0%. One major PB-related complication occurred (0.5%), presenting as gross hematuria and diagnosed as a transplant renal arteriovenous fistula. At 3 months post-transplantation, 58 biopsies (42.6%) showed pathological abnormalities, including rejection in 12 cases (8.8%), borderline changes in 18 cases (13.2%), BK virus nephropathy (BKVN) in 10 cases (7.4%), calcineurin inhibitor (CNI) nephrotoxicity in 13 cases (9.6%), and recurrent kidney disease in 5 cases (3.7%). At 12 months post-transplantation, 22 biopsies (34.4%) revealed pathological abnormalities, including rejection in 13 cases (20.3%), borderline changes in 4 cases (6.3%), BKVN in 3 cases (4.7%), CNI nephrotoxicity in 1 case (1.6%), and recurrent disease in 1 case (1.6%).Conclusions:Protocol kidney allograft biopsy after allogeneic kidney transplantation is highly safe and feasible in clinical practice. PB provides significant diagnostic value for the early detection of subclinical rejection and BKVN, thereby supporting its clinical utility in postoperative monitoring and management.

Acute kidney injury (AKI) is a common clinical acute and critical condition. There is a lack of clinical interventions or therapeutic drugs that can significantly improve AKI outcomes. Lipids, including fatty acids, triglycerides, sphingolipids, phospholipids and cholesterol play crucial roles in energy metabolism, cell membrane composition, cell signaling, and cell homeostasis and survival. Recent lipidomics studies have revealed significant alterations in the content and composition of renal lipids during AKI, highlighting their important roles in the onset, progression, and outcomes of the disease. A common feature of AKI across multiple etiologies is altered lipid metabolism, characterized by insufficient energy generation due to mitochondrial damage and deposition of excess lipids in the kidney. The article summarizes the characteristics of renal lipid metabolism in physiological state, alterations of renal lipid metabolism in AKI and molecular mechanisms related to lipid metabolism disorders that aggravate AKI through mitochondrial damage, oxidative stress, autophagy dysfunction, activation of inflammatory and immune responses and regulated cell death, to provide new ideas and therapeutic targets for the clinical treatment of AKI.

Objective:To identify factors associated with depressive symptoms in maintenance hemodialysis patients and to examine the relationship between these symptoms and mortality.Methods:Between January and December 2019, patients who received maintenance hemodialysis in the Blood Purification Center of the Second Affiliated Hospital of Nanjing Medical University were enrolled in a prospective cohort study. Depressive symptoms were assessed using the internationally validated patient health questionnaire-8 (PHQ-8). Sleep quality and anxiety were measured with the Pittsburgh sleep quality index (PSQI) and the generalized anxiety disorder-7 (GAD-7) scale, respectively. Follow-up continued until December 31, 2022, with all-cause mortality as the primary outcome. Ordinal logistic regression was used to identify independent predictors of depression severity. Cox proportional hazards models evaluated the association between depressive symptoms and mortality.Results:A total of 532 maintenance hemodialysis (MHD) patients completed the study. Among them, 177 (33.3%) exhibited depressive symptoms. Compared with patients without depression, those with mild or moderate-to-severe depression were older [median age: 58 (50, 66) vs. 60 (55, 65) vs. 55 (46, 64)], more likely to smoke [35.9% (51/142) vs. 40.0% (14/35) vs.26.2% (93/355)], had poorer sleep quality [PSQI: 9 (6, 13) vs. 12 (9, 17) vs. 5 (3, 9)], and higher anxiety levels [GAD-7: 1 (0, 3) vs. 3 (1, 6) vs. 0 (0, 1)], the differences among the three groups were statistically significant (all P<0.05). Ordinal logistic regression identified smoking status, history of diabetes or cardiovascular disease, hemoglobin level, PSQI score, and GAD-7 score as independent predictors of depression severity ( OR=1.60, 1.80, 1.81, 0.98, 3.67, 8.67; all P<0.05). After a median follow-up of 40 (35, 44) months, 109 patients died, including 66 (60.6%) from cardio-cerebrovascular causes and 24 (22.0%) from infections. Kaplan-Meier analysis revealed significantly lower cumulative survival in the depression group compared to the non-depression group ( P<0.001). Cox regression analysis demonstrated that depressive symptoms remained independently associated with all-cause mortality after adjusting for confounders ( HR=1.06, 95% CI 1.00-1.13, P=0.048), with an even stronger association observed for patients with PHQ-8 scores≥2.9 ( HR=1.10, 95% CI 1.03-1.16, P=0.005). However, the associations between depression and cardio-cerebrovascular mortality ( P=0.111) or infection-related mortality ( P=0.509) were not statistically significant. Conclusions:Depressive symptoms are prevalent among maintenance hemodialysis patients and are independently associated with increased all-cause mortality. Smoking, comorbid diabetes or cardiovascular disease, low hemoglobin level, poor sleep quality, and anxiety are risk factors contributing to depression. Maintenance hemodialysis patients with PHQ-8 scores≥3 should be considered at heightened risk for mortality.

Objective:To analyze the clinical application of protocol biopsy (PB) during postoperative follow-up in recipients of allogeneic kidney transplantation.Methods:A prospective observational cohort study was conducted. Recipients who underwent allogeneic kidney transplantation at the Second Affiliated Hospital of Nanjing Medical University between January 2022 and September 2024 and received PB at 3 months (±1 week) and/or 12 months (±4 weeks) post-transplantation in the Department of Nephrology were enrolled. The implementation, complications, and pathological results of PB were summarized. The safety and diagnostic efficacy of PB were analyzed.Results:A total of 143 allogeneic kidney transplant recipients were included, and 200 PB procedures were performed. The overall implementation rate of protocol biopsy (PB) was 84.1% (143/170). Among them, 170 recipients completed 3-month follow-up, and 136 PBs were performed at 3 months (±1 week) post-transplantation, with an implementation rate of 80.0%. Seventy-nine recipients completed 12-month follow-up, and 64 PBs were performed at 12 months (±4 weeks), with an implementation rate of 81.0%. One major PB-related complication occurred (0.5%), presenting as gross hematuria and diagnosed as a transplant renal arteriovenous fistula. At 3 months post-transplantation, 58 biopsies (42.6%) showed pathological abnormalities, including rejection in 12 cases (8.8%), borderline changes in 18 cases (13.2%), BK virus nephropathy (BKVN) in 10 cases (7.4%), calcineurin inhibitor (CNI) nephrotoxicity in 13 cases (9.6%), and recurrent kidney disease in 5 cases (3.7%). At 12 months post-transplantation, 22 biopsies (34.4%) revealed pathological abnormalities, including rejection in 13 cases (20.3%), borderline changes in 4 cases (6.3%), BKVN in 3 cases (4.7%), CNI nephrotoxicity in 1 case (1.6%), and recurrent disease in 1 case (1.6%).Conclusions:Protocol kidney allograft biopsy after allogeneic kidney transplantation is highly safe and feasible in clinical practice. PB provides significant diagnostic value for the early detection of subclinical rejection and BKVN, thereby supporting its clinical utility in postoperative monitoring and management.

AIM:This study investigates the protective effect of the selective peroxisome proliferator-activated receptor δ(PPARδ)agonist seladelpar on podocytes in a mouse model of diabetic kidney disease(DKD).METHODS:A DKD mouse model was established using streptozotocin and a high-fat diet.Mice were randomly assigned to three groups:control,DKD with vehicle treatment,and DKD with seladelpar treatment at dosages of 1,5 and 10 mg/kg(6 to 7 mice per group).After four weeks of treatment,mice were euthanized,and various parameters were measured,including urinary albumin,creatinine,blood urea nitrogen,serum triglycerides,and cholesterol using respective kits.Renal tissues were processed for histological examination through HE and PAS staining to assess glomerular pathology.The RNA from glomerular tissues was analyzed via RT-qPCR for podocyte marker(Nphs1,Nphs2,Wt1 and Synpo)expression,and the protein expression was evaluated using Western blot for PPARδ.Immunofluorescence staining of frozen renal cortical sec-tions was conducted to quantify WT1-positive cells and desmin protein levels.Transmission electron microscopy was used to observe glomerular ultrastructural changes.RESULTS:(1)PPARδ protein levels in the glomerular tissue of DKD mice were significantly lower than in controls.(2)Mice treated with 10 mg/kg of seladelpar showed reduced blood glu-cose,triglycerides,and cholesterol levels compared to the diabetic nephropathy group.(3)Both 5 mg/kg and 10 mg/kg se-ladelpar treatment groups exhibited decreased urine albumin/creatinine ratios,along with improvements in glomerular hy-pertrophy and mesangial matrix deposition.Increased mRNA expression levels of Nphs1,Nphs2,Wt1,and Synpo were also observed,alongside an increase in WT1-positive cells and a decrease in desmin expression.Additionally,there was a reduction in podocyte foot process fusion and glomerular basement membrane thickness.(4)RNA sequencing indicated that 5 mg/kg seladelpar treatment modulated PPAR signaling pathway and influenced various metabolic pathways,includ-ing bile acid metabolism,carbon metabolism,glutathione metabolism,glycerophospholipid metabolism,and fatty acid metabolism.CONCLUSION:Seladelpar,a PPARδ agonist,mitigates podocyte injury and reduces proteinuria in DKD mice.Notably,the protective effects of seladelpar are partially independent of its hypolipidemic properties.

AIM:This study investigates the protective effect of the selective peroxisome proliferator-activated receptor δ(PPARδ)agonist seladelpar on podocytes in a mouse model of diabetic kidney disease(DKD).METHODS:A DKD mouse model was established using streptozotocin and a high-fat diet.Mice were randomly assigned to three groups:control,DKD with vehicle treatment,and DKD with seladelpar treatment at dosages of 1,5 and 10 mg/kg(6 to 7 mice per group).After four weeks of treatment,mice were euthanized,and various parameters were measured,including urinary albumin,creatinine,blood urea nitrogen,serum triglycerides,and cholesterol using respective kits.Renal tissues were processed for histological examination through HE and PAS staining to assess glomerular pathology.The RNA from glomerular tissues was analyzed via RT-qPCR for podocyte marker(Nphs1,Nphs2,Wt1 and Synpo)expression,and the protein expression was evaluated using Western blot for PPARδ.Immunofluorescence staining of frozen renal cortical sec-tions was conducted to quantify WT1-positive cells and desmin protein levels.Transmission electron microscopy was used to observe glomerular ultrastructural changes.RESULTS:(1)PPARδ protein levels in the glomerular tissue of DKD mice were significantly lower than in controls.(2)Mice treated with 10 mg/kg of seladelpar showed reduced blood glu-cose,triglycerides,and cholesterol levels compared to the diabetic nephropathy group.(3)Both 5 mg/kg and 10 mg/kg se-ladelpar treatment groups exhibited decreased urine albumin/creatinine ratios,along with improvements in glomerular hy-pertrophy and mesangial matrix deposition.Increased mRNA expression levels of Nphs1,Nphs2,Wt1,and Synpo were also observed,alongside an increase in WT1-positive cells and a decrease in desmin expression.Additionally,there was a reduction in podocyte foot process fusion and glomerular basement membrane thickness.(4)RNA sequencing indicated that 5 mg/kg seladelpar treatment modulated PPAR signaling pathway and influenced various metabolic pathways,includ-ing bile acid metabolism,carbon metabolism,glutathione metabolism,glycerophospholipid metabolism,and fatty acid metabolism.CONCLUSION:Seladelpar,a PPARδ agonist,mitigates podocyte injury and reduces proteinuria in DKD mice.Notably,the protective effects of seladelpar are partially independent of its hypolipidemic properties.

Objective　To investigate the pattern of monocyte chemoattractant prolein-1 (MCP-1) distribution in the renal interstitium and evaluate its pathogenic role in tubulo-interstitial lesions in patients with lupus nephritis, the distribution of MCP-1 in renal tissue was observed. Methods　Eighteen female patients with biopsy-proven lupus nephritis were enrolled in this study. No intensive immunosuppresive therapy was used in these patients during the 3 months prior to renal biopsy. The distribution of MCP-1, infiltration of CD68+ (macrophage/monocyte), CD4+ and CD8+ cells in the tubulo-interstitium of patients with lupus nephritis was detected using immunohistochemical staining with specific antibodies. Renal specimens from patients with minimal change glomerulonephritis were used as controls. Results　MCP-1 protein was widely distributed in the renal tissue of patients with lupus nephritis, mainly located at the baso-lateral surface of tubular epithelial cells (16/18 biopsies), and on the wall of interstitial blood vessels (9/18 biopsies). In contrast, tubular MCP-1 staining was weak and rare in renal tissue from controls (7.4±6.2% vs 26.7±22.8%, P<0.01). Tubulo-interstitial infiltration of CD68+, CD4+ and CD8+ cells was markedly increased in patients with lupus nephritis as compared to controls. The tubular expression of MCP-1 was strongly associated with the amount of CD68+ cell infiltration in the interstitium (r=0.5420, P<0.05) and the extent of interstitial fibrosis. There was no correlation between MCP-1 production in tubules and the degree of urinary protein excretion in patients with lupus nephritis (r=0.0547, P>0.05). Conclusions　The expression of MCP-1 in the renal tubules and vascular wall was markedly increased in patients with lupus nephritis. The overproduction of MCP-1 in renal tissue may contribute to monocyte recruitment in the interstitium and thus result in tubulo-interstitial damage in lupus nephritis.