The objective of this completed, randomized, open-label trial across 11 hemodialysis centers in Shanghai, China, was to evaluate whether hemoadsorption combined with hemodialysis (HAHD) reduces mortality compared to hemodialysis (HD) alone in end-stage kidney disease patients (maintenance HD ≥ 3 months, Kt/V ≥ 1.2). We randomized 1362 patients 1:1 to receive HAHD (n = 683) or HD alone (n = 679; mainly low-flux HD plus intermittent HDF). All 1362 randomized patients were analyzed. The primary outcome was all-cause mortality, while secondary outcomes included cardiovascular mortality and major cardiovascular events. Over a median follow-up of 39.5 months, all-cause mortality occurred in 117 (17.1%) of HAHD patients compared to 144 (21.2%) of HD patients (hazard ratio [HR]: 0.778, 95% confidence interval [CI]: 0.609-0.994; P = 0.045). HAHD also significantly reduced cardiovascular mortality (HR: 0.659, 95% CI: 0.481-0.901; P = 0.009) and major cardiovascular events (HR: 0.772, 95% CI: 0.621-0.959; P = 0.019). Important adverse events, primarily infections and abnormal blood pressure, were comparable between the two groups. Adding hemoadsorption significantly reduced all-cause mortality, cardiovascular mortality, and major cardiovascular events compared to HD alone (mainly low-flux HD plus intermittent HDF). Trial Registration: ClinicalTrials.gov NCT03227770.

ObjectiveTo investigate the optimal protocol for a doxorubicin-induced chronic kidney disease mouse model used for studying human focal segmental glomerulosclerosis (FSGS). MethodsC57BL/6J and C57BL/6N mice were randomly assigned using a random number sequence into control groups (J0 and N0, 24 mice each) and FSGS model groups (J1, J2, N1, and N2, 24 mice each). J1 and N1 groups received a single tail vein injection of 15 mg/kg doxorubicin, J2 and N2 groups received two injections (with a two-week interval), and J0 and N0 groups received an equal volume of 0.9% sodium chloride injection. The overall condition and body weight changes of the mice were observed, and general data were recorded. Urine was collected to evaluate proteinuria through urinary protein and urinary creatinine. Kidney tissue proteins were extracted for Western blot analysis to detect the expression of podocyte marker proteins. Kidney histopathological manifestations were observed using hematoxylin-eosin staining, periodic acid-Schiff staining and transmission electron microscopy. ResultsAfter modeling, C57BL/6N mice showed worse general condition and more significant weight loss than C57BL/6J mice (P<0.001). In both strains, mice receiving two doxorubicin injections showed poorer general condition and more pronounced weight loss (P<0.001). The urinary protein-to-creatinine ratio in the doxorubicin-injected groups of both C57BL/6J and C57BL/6N was higher than that in the control groups at all time points (P<0.05). In the single-injection C57BL/6J group, the expression of some podocyte marker proteins [synaptopodin, Wilms tumor protein 1 (WT1)] showed no significant changes, while in the two-injection group, the expression levels of podocyte marker proteins (nephrin, synaptopodin, podocalyxin, WT1, α-tubulin, podocin) were all lower than those in the control group. Both single- and two-injection C57BL/6N groups showed lower expression level of podocyte marker proteins than that in the control group, with more significant decreases in the two-injection group (P<0.05). Light and electron microscopy both confirmed successful modeling in the single- and two-injection C57BL/6N groups, with more significant pathological changes in the two-injection group. ConclusionsIn the doxorubicin-induced FSGS model in C57BL/6 mice, the C57BL/6N substrain outperforms C57BL/6J substrain in modeling efficacy. The recommended optimal modeling protocol for FSGS is the single tail vein injection of 15 mg/kg doxorubicin in C57BL/6N mice.

Objective:This study aimed to identify and validate potential endoplasmic reticulum stress-related biomarkers of focal segmental glomerulosclerosis(FSGS). Methods:Five microarray datasets were downloaded from the GEO database. The endoplasmic reticulum stress-related genes were extracted from GeneCards database. GSE104948, GSE129973, and GSE121233 datasets were used to identify DEGs by limma R package. WGCNA was performed to obtain hub gene modules. We intersected the DEGs, genes from hub module of WGCNA, and ERSRGs. GO and KEGG pathway enrichment analyses were performed. LASSO, SVM-RFE, and RF algorithms were used to screen characteristic genes. Further, GSE108109 and GSE104066 were used as validated datasets. Box plots, ROC curves, and AUC were created to identify potential biomarkers. A novel nomogram model was constructed using potential biomarkers. Immunohistochemistry validated the expression of the potential biomarkers, and correlation analysis was used to assess the correlation between the integrated optical density(IOD) value of GADD45A and the levels of 24-hour urinary protein, eGFR, and blood urea nitrogen. Results:Intersecting DEGs, the brown module genes, and ERSRGs, we identified 15 hub ERSRGs of FSGS. AGO2, CCND1, GADD45A, TRAM2, and PTPN1 genes were screened by using Lasso, SVM-RFE, and RF. Further, CCND1, GADD45A, and TRAM2 were validated as significant in training and validation datasets. A nomogram based on CCND1, GADD45A, and TRAM2 expression was constructed. The calibration curves, decision analysis curve, and clinical impact curve showed that the nomogram had good consistency and clinical practical benefit. The expression of GADD45A is higher in FSGS than controls in immunohistochemical(IHC) results(P < 0.0001). The integrated optical density value of GADD45A shows a strong correlation with 24-hour urinary protein(r 2 = 0.8459,P < 0.0001), eGFR(r 2 = -0.8233,P < 0.0001), and blood urea nitrogen(r 2 = 0.8695,P < 0.0001). Conclusions:GADD45A may be a potential biomarker associated with endoplasmic reticulum stress in FSGS.With its potential applicability spanning both biomarker identification and therapeutic intervention, GADD45A offers a compelling avenue for improving FSGS detection and clinical management in subsequent investigations.

Calcium/calmodulin dependent protein kinase II inhibitor 1 (Camk2n1) is closely associated with a peak logarithm of odds score in quantitative trait loci for systolic blood pressure. Increased Camk2n1 mRNA expression has been specifically observed in the kidneys of hypertension mouse models. However, the precise role of Camk2n1 in the kidney remains unclear. We generated Camk2n1-/- mice using the CRISPR/Cas9 system. Compared to controls, Camk2n1-/- mice exhibited consistently lower systolic blood pressure across all measured time points. Deletion of Camk2n1 resulted in decreased apical labeling of phosphorylated and total thiazide-sensitive NaCl cotransporter (NCC) in the distal convoluted tubule. NCC phosphorylation is regulated by activated SPAK/OSR1 kinases, which act downstream of With-No-lysine (K) kinase (WNK). In Camk2n1-/- mice, the elevated abundances of key components of the Cullin 3 (CUL3) RING ubiquitin ligase, including neddylated CUL3 and the adaptor Kelch-like protein 3, promoted proteasomal degradation of WNK4. In renal tissues, Camk2n1 deletion led to increased mRNA and protein levels of ubiquitin-like modifier-activating enzyme 3 (UBA3) and ubiquitin-conjugating enzyme E2 (UBE2M). Conversely, Camk2n1 overexpression in HEK293 cells resulted in decreased levels of UBA3 and UBE2M, along with reduced CUL3 neddylation. Treatment with MLN4924 effectively suppressed CUL3 hyperneddylation and restored WNK4 levels in the kidneys of Camk2n1-/- mice. In summary, Camk2n1 deletion lowers blood pressure, likely by promoting WNK4 degradation through dysregulated CUL3 RING ubiquitin ligase activity, which leads to decreased NCC activity.

Key PointsDeficits in nephron numbers are associated with higher risk of adult-onset kidney disease seen in congenital anomalies of the kidney and urinary tract.Mouse model experiments suggested that absent, small, or homeotic 2-like was vital for kidney development by activating cell cycle genes through histone methylation.Our findings identified absent, small, or homeotic 2-like-regulated genes as a potential target for treating congenital anomalies of the kidney and urinary tract.BackgroundMany congenital anomalies of the kidney and urinary tract involve deficits in the number of nephrons, which are associated with a higher risk of hypertension and CKD later in life. Prior work has implicated histone modifications in regulating kidney lineage-specific gene transcription and nephron endowment. Our earlier study suggested that absent, small, or homeotic 2-like (ASH2L), a core subunit of the H3K4 methyltransferase complex, plays a role in ureteric bud morphogenesis during mammalian kidney development. However, the potential involvement of ASH2L in nephron formation remains an open question.MethodsTo investigate the role of ASH2L in nephron development, we inactivated Ash2l specifically in nephron progenitor cells by crossing Six2-e(Kozak-GFPCre-Wpre-polyA)1 mice with Ash2lfl/fl mice. We used RNA sequencing combined with Cleavage Under Targets and Tagmentation sequencing to screen for gene and epigenomic changes, which were further verified by rescue experiments conducted on ex vivo culture explants.ResultsInactivating ASH2L in nephron progenitor cells disrupted H3K4 trimethylation establishment at promoters of genes controlling nephron progenitor cell stemness, differentiation, and cell cycle, inhibiting their progression through the cell cycle and differentiation into epithelial cell types needed to form nephrons. Inhibition of the TGF-beta/suppressor of mothers against decapentaplegic signaling pathway partially rescued the dysplastic phenotype of the mutants.ConclusionsASH2L-mediated H3K4 methylation was identified as a novel epigenetic regulator of kidney development. Downregulation of ASH2L expression or H3K4 trimethylation may be linked to congenital anomalies of the kidney and urinary tract.

Background:A key goal in managing patients with heterozygous disease-causing COL4A3 and COL4A4 (COL4A3/4) variants, affecting individuals spanning a broad age range, is to slow the development of chronic kidney disease (CKD). Whether age of onset is associated with the risk of CKD has not been investigated. Methods:In 294 patients (118 males) with heterozygous disease-causing COL4A3/4 variants in the Shanghai Registry of Alport Syndrome, we made the comparison of risk of CKD between those showing disease onset before 18 years old (early onset) or from 18 years and older (late onset). CKD were defined as onset of persistent albuminuria (albumin-to-creatinine ratio ≥30 mg/g) or CKD G2 (estimated glomerular filtration rate <90 ml/min/1.73 m2). Results:147 (50.0%) of patients had initial presentation of symptoms of kidney diseases when they were <18 years old [median age at onset, 5.0 years (IQR, 3.0-8.0 years)], and in the remainder when they were older [median age at onset, 30.0 years (IQR, 26.0-38.0 years)]. During a median follow-up of 3.0 years (IQR, 0-10.3 years), earlier disease onset showed significant associations with higher risk of albuminuria [hazard ratio (HR) 7.08, 95% confidence intervals (CI) 4.59-10.93] and CKD G2 (HR 3.49, 95%CI 1.57-7.75). Risk of albuminuria increased by 64%, and risk of CKD G2 increased by 34%, per 5-year step toward younger age at disease onset. Conclusions:Earlier onset of disease may predict higher risk of CKD in patients with heterozygous disease-causing COL4A3/4 variants. This association, if verified in large prospective studies, may help stratify patients by risk of worse prognosis, which can guide their management and preemptive nephroprotective treatment.

Although hemoadsorption combined with hemodialysis (HAHD) is increasingly used in patients undergoing maintenance hemodialysis (MHD), the optimal treatment duration remains uncertain. This study compared the efficacy and safety of 2-hour versus 4-hour HAHD sessions, supported by in vitro kinetic modeling. An in vitro recirculation system was used to assess the adsorption kinetics of parathyroid hormone (PTH), β2‑microglobulin (β2‑MG), and tumor necrosis factor‑alpha (TNF‑α) over 4 h. Subsequently, 92 stable MHD patients were prospectively enrolled and assigned to receive a single HAHD session of either 2 h (n = 45) or 4 h (n = 47). Pre- and post-treatment blood samples were analyzed to determine the reduction ratios of inflammatory cytokines (IL-8 and TNF-α) and middle molecular toxins (PTH and β2-MG). In vitro results confirmed time-dependent adsorption, with 4-hour removal ratios for PTH (93.27%), β2-MG (93.36%), and TNF-α (50.54%) being significantly higher than those at 2 h (84.36%, 82.00%, and 27.56%, respectively; all p < 0.05). Clinically, the 4-hour group achieved significantly higher median reduction ratios for the inflammatory cytokines IL-8 (81.64% vs. 69.51%) and TNF-α (43.94% vs. 22.33%) and for the middle molecular toxins PTH (59.67% vs. 55.12%) and β2-MG (21.79% vs. 14.20%). Both durations were well tolerated, with no significant safety concerns. These findings indicate that prolonging HAHD to 4 h improves the clearance of inflammatory and middle molecular weight toxins without compromising safety and may offer clinical benefits for MHD patients with high inflammatory burdens.

Immunoglobulin A nephropathy （IgAN） is one of the most common type of primary glomerulonephritis in China. Due to the lack of effective intervention means for the etiology， optimal supportive treatment is still the mainstream method at present. The uncertain efficacy and safety of new targeted immunosuppressive drugs limit the further clinical application. In recent years， non-immunosuppressive treatments have gradually garnered the attention of scholars. This article aims to review the progress of optimized lifestyle management， symptomatic supportive treatment， and traditional and novel non-immunosuppressive treatments of IgAN， thus offering new directions for medical practice.

Background Many congenital anomalies of the kidney and urinary tract involve deficits in the number of nephrons, which are associated with a higher risk of hypertension and chronic kidney disease later in life. Prior work has implicated histone modifications in regulating kidney lineage-specific gene transcription and nephron endowment. Our earlier study suggested that ASH2L, a core subunit of the H3K4 methyltransferase complex, plays a role in ureteric bud morphogenesis during mammalian kidney development. However, the potential involvement of ASH2L in nephron formation remains an open question. Methods To investigate the role of ASH2L in nephron development, we inactivated Ash2l specifically in nephron progenitor cells by crossing Six2 -e(Kozak-GFPCre-Wpre-polyA)1 mice with Ash2l fl/fl mice. We utilized RNA sequencing combined with Cleavage Under Targets and Tagmentation sequencing to screen for gene and epigenomic changes, which were further verified by rescue experiments conducted on ex vivo culture explants. Results Inactivating ASH2L in nephron progenitor cells disrupted H3K4 trimethylation establishment at promoters of genes controlling nephron progenitor cell stemness, differentiation and cell cycle, inhibiting their progression through the cell cycle and differentiation into epithelial cell types needed to form nephrons. Inhibition of the TGF-β/SMAD signaling pathway partially rescued the dysplastic phenotype of the mutants. Conclusions ASH2L-mediated H3K4 methylation was identified as a novel epigenetic regulator of kidney development. Downregulation of ASH2L expression or H3K4 trimethylation may be linked to congenital anomalies of the kidney and urinary tract.

Background:Focal segmental glomerulosclerosis (FSGS) is an increasingly prevalent group of refractory glomerular diseases and a significant aetiology of end-stage renal disease. Podocyte injury and depletion significantly contribute to the pathogenesis and progression of FSGS. MicroRNAs (miRNAs) are noncoding RNAs that regulate the expression of specific genes in relevant cells, thereby playing crucial roles in the pathogenesis of FSGS. Many studies have shown that miRNAs can be secreted from cells into body fluids and that these miRNAs in the circulation are highly stable. The gold standard for FSGS diagnosis is kidney biopsy; however, the clinical heterogeneity of FSGS, along with variations in histology and nonspecific morphological features, can impact its diagnostic accuracy. Thus, the discovery of novel and efficacious biomarkers is crucial in facilitating the diagnosis of FSGS. In addition, the degree of kidney damage in patients with FSGS varies at different stages, necessitating individualized diagnosis and treatment approaches. Considering the side effects of glucocorticoids, determining whether a patient is steroid resistant is vital. Thus, ideal biomarkers should not only be specific and sensitive but also have the ability to accurately reflect the stage or prognosis of the disease to improve the treatment for patients. Summary:To date, numerous studies have shown that both urinary miRNAs and plasma miRNAs are potential biomarkers for FSGS. In addition, the identification of miRNA biomarkers specific for the FSGS disease state may provide new insights into the underlying pathological mechanism of FSGS. Key Messages:Here we summarize the currently available miRNA biomarkers that could help us better understand the diagnosis, disease activity, prognosis, and clinical features of FSGS.

AIMS:In diabetic kidney disease (DKD), Angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin receptor blockers (ARBs) are key treatments but may cause hyperkalemia. This randomized controlled trial (RCT) firstly evaluates sodium zirconium cyclosilicate (SZC) to optimize renin-angiotensin-aldosterone system inhibitor (RAASi) use in DKD, addressing evidence gaps in this field. METHODS:This 24-weeks prospective multicenter study enrolled 86 DKD patients at hyperkalemia risk to SZC + ACEIs/ARBs or ACEIs/ARBs alone. PRIMARY OUTCOME:ACEIs/ARBs dose up-titration at week 12. Exploratory outcomes included urinary albumin-to-creatinine ratio (UACR), serum creatinine, and blood pressure (BP). RESULTS:At week 12, 55.81 % of patients in the SZC + ACEIs/ARBs arm up-titrated their ACEIs/ARBs dosage (95 % confidence interval [CI]: 39.88 %-70.92 %), compared to 27.91 % in the ACEIs/ARBs arm (95 % CI: 15.33 %-43.67 %, P = 0.009). UACR decreased by 63.46 mg/g in the SZC + ACEIs/ARBs arm at week 24, while increasing by 316.87 mg/g in the ACEIs/ARBs arm (least squares mean difference [LSMD]: -333.63 mg/g [95 % CI: -1148.73 to 481.47]; Per-Protocol Set). BP reductions were greater numerically in the SZC + ACEIs/ARBs arm (systolic: -1.7 mmHg; diastolic: -1.4 mmHg). CONCLUSIONS:SZC reduced hyperkalemia-related RAASi discontinuation risk, improved proteinuria and BP, supporting its prophylactic use in DKD patients on RAASi.

COQ8B nephropathy, a mitochondrial disorder caused by mutations in the COQ8B gene, is a major pediatric genetic focal segmental glomerulosclerosis (GFSGS) etiology and stands out as one of the few treatable forms with good response to coenzyme Q10 (CoQ10) supplementation. As the diagnosis and clinical experience of COQ8B nephropathy were predominantly in the pediatric population, the long-term efficacy of CoQ10 supplementation and its application in the adult-onset patients remains largely unknown. Here, we report three cases of adult-onset FSGS from unrelated families, all carrying the Chinese common COQ8B mutation (c.737G > A; p.Ser246Asn) with divergent trajectories of renal function following CoQ10 supplementation initiated in different stages of renal dysfunction, providing valuable evidence on the implication of early disease diagnosis and prompt CoQ10 supplementation for the prognosis of adult patients affected with COQ8B nephropathy.

BackgroundPeritoneal dialysis (PD) and conventional in‐center hemodialysis (HD) are treatment options for patients with end‐stage kidney disease (ESKD). However, their impact on all‐cause mortality is unclear.MethodsWe conducted a multicenter, open‐label, randomized, non‐inferiority trial to determine the effect of dialysis modality on mortality in patients with ESKD. Eligible patients were recruited from 30 sites across China and assigned to receive either PD or HD in a ratio of 1:1. The primary outcome was all‐cause mortality. Non‐inferiority was defined as the upper bound of the one‐sided 95% confidence interval (CI) for the hazard ratio (HR) being ≤1.25.ResultsA total of 414 patients with incident ESKD were randomly assigned to PD (n = 213) or HD (n = 201). During a median follow‐up of 1.7 years, 37 patients in the PD group and 31 in the HD group died, giving respective event rates per patient‐year of 0.061 and 0.071. The HR for mortality on PD in comparison with HD was 0.76 (95% CI 0.47–1.24) after adjustment for age, sex, and diabetes status, achieving the limit for non‐inferiority. There were more adverse events (p = 0.003), serious adverse events (p = 0.009), and adverse events leading to hospitalization (p = 0.003) in the PD group than in the HD group; however, there was no significant between‐group difference in adverse events leading to death or discontinuation of treatment.ConclusionsPD was non‐inferior to conventional in‐center HD in terms of survival in patients with ESKD. Our findings underscore the need for shared decision‐making between physicians and patients regarding the selection of dialysis modality.Trial registrationRegistered at ClinicalTrials.gov (NCT01413074).

Aims To investigate the potential mechanisms of fatty acid metabolism (FAM)-related genes in IgA nephropathy (IgAN) and to explore its immune cell infiltration characteristic.Methods Datasets for IgAN and FAM-related genes were obtained from GEO and MSigDB database, respectively. We employed differential expression analysis and WGCNA to identify common genes. GO and KEGG analyses were performed to compare the differences between IgAN and control groups. Furthermore, LASSO logistic regression was applied to develop a predictive model based on FAM-related genes. The efficacy of this prognostic model was evaluated using ROC analysis. The infiltration of immune cells and immune-related functions were assessed with CIBERSORT tool. Finally, the identified key genes were validated in blood samples from IgAN and control patients, as well as in human mesangial cells (HMCs) following Gd-IgA stimulation using Real-time PCR.Results A total of 12 hub genes linked to FAM were identified in patients with IgAN. A predictive model consisting of four genes was conducted through COX and LASSO regression analysis, revealing AUC values that indicate a relatively strong diagnostic capability. Immune infiltration analysis indicated that various immune cells have significant associations with IgAN. Additionally, Real-time PCR assays confirmed that the expression levels of hub genes were markedly reduced in IgAN patients and in Gd-IgA treated HMCs compared to controls.Conclusion This study employed bioinformatics methods to unveiled the immune cell infiltration associated with IgAN and to explore the potential genetic connection between FAM and IgAN. This could aid in predicting the risk of IgAN and enhance both diagnosis and prognosis of this condition.

Introduction: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common complication associated with increased morbidity and mortality. Tissue inhibitor metalloproteinases-2 • insulin-like growth factor-binding protein 7 (TIMP-2•IGFBP7) determines tubular stress markers, which may occur prior to tubular damage. Previous studies on the use of TIMP-2•IGFBP7 for the prediction of CSA-AKI showed divergent results. Therefore, this study aimed to explore the predictive value of TIMP-2•IGFBP7 measurements for the early detection of acute kidney injury (AKI) and short-term adverse outcomes after cardiac surgery. Methods: In the prospective cohort study, blood and urine samples were collected 6–12 h after cardiac surgery. Blood samples to monitor serum creatinine levels were additionally extracted from days 1 to 7. AKI was defined based on the KDIGO consensus guidelines. AKI within 7 days following surgery was the primary outcome. The initiation of renal replacement therapy, in intensive care unit mortality, and the combination of both were secondary outcomes. Results: A total of 557 patients were enrolled, 134 (24.06%) of them developed AKI and 33 (5.9%) had moderate or severe AKI. AKI developed more frequently in elderly patients with diabetes or with higher baseline serum creatinine levels. Patients with AKI had higher EuroSCORE II, Cleveland clinical score, and simplified renal index than those without AKI. Urinary TIMP-2•IGFBP7 was significantly higher in patients with AKI. The area under the curve was 0.66 in predicting all AKI and 0.70 in predicting stages 2 and 3 AKI. The resulting sensitivity and specificity were 44.0% and 83.9%, respectively, for a calculated threshold TIMP-2•IGFBP7 value of 0.265 (ng/ml)2/1,000. The TIMP-2•IGFBP7 values, simplified renal index (SRI) Score and age were significantly associated with AKI within 7 days postoperatively. A total of 33 patients reached the composite endpoint, the percentage of patients who reached the composite end-point in the TIMP-2•IGFBP7 of >0.265 (ng/ml)2/1,000 group was significantly higher than that of ≤0.265 (ng/ml)2/1,000 group. Conclusions: Postoperative implementation of TIMP-2•IGFBP7 improved prediction of CSA-AKI and may aid in identifying patients at risk of short-term adverse outcomes. We identified an ideal calculated cutoff value of 0.265 (ng/ml))2/1,000 for the prediction of CSA-AKI among all AKI patients.

Background: Contrast agents can directly or indirectly induce renal tubular ischemia and hypoxic damage. Given that cobalt chloride (CoCl2) can protect renal tubules, the protective effect and potential mechanism of action of CoCl2 on contrast-induced nephropathy (CIN) warrant investigation. Methods: A CIN mouse model was established to determine the protective effect of CoCl2 on renal injury in vivo. Then, TMT-based proteomics was performed to determine the differentially expressed proteins (DEPs), following which, enrichment analyses of gene ontology and the KEGG pathway were performed. In vitro, a CIN model was constructed with renal tubular epithelial cells (HK-2) to determine the effect of CoCl2 on potential targets and the role of the key protein identified from the in vivo experiments. Results: CoCl2 treatment decreased the levels of BUN and serum creatinine (sCr), while increasing the levels of urea and creatinine (Cr) in the urine of mice after CIN injury. Damage to the renal tubules in the CoCl2 treatment group was significantly less than in the CIN model group. We identified 79 DEPs after treating the in vivo model with CoCl2, and frequently observed ferroptosis-related GO and KEGG pathway terms. Of these, Hp (haptoglobin) was selected and found to have a strong renoprotective effect, even though its expression level in kidney tissue decreased after CoCl2 treatment. In HK-2 cells, overexpression of Hp reduced the ferroptosis caused by Erastin, while knocking down Hp negated the attenuation effect of CoCl2 on HK-2 cell ferroptosis. Conclusion: CoCl2 attenuated kidney damage in the CIN model, and this effect was associated with the decrease in ferroptosis mediated by Hp.