Objective To explore the relationship between hemoglobin variability (Hb?var) and risk of all-cause death and cardiovascular death in patients with peritoneal dialysis (PD), and to provide basis for reducing the risk of death in PD patients. Methods It was a multicenter retrospective cohort study. The clinical data of regular PD patients from Nanfang Hospital of Southern Medical University, Shunde Hospital of Southern Medical University, Foshan First People's Hospital and Ganzhou People's Hospital from July 1, 2008 to December 31, 2019 were collected. Hb?var was calculated based on hemoglobin at baseline before PD and in the first year after PD. The patients were divided into low Hb?var group, moderate Hb?var group and high Hb?var group according to the tertiles of first year Hb?var, and the differences of baseline clinical data among three groups were compared. Follow-up endpoints included death, transfer to hemodialysis, transfer to kidney transplantation, transfer to other centers, loss of follow-up, or on December 31, 2021. Cox regression analysis model was used to analyze the association of the first-year Hb?var with all-cause death and cardiovascular death. Fine-Gray competitive risk regression model was used to evaluate the impact of competitive events on mortality risk. Results A total of 1 562 patients with PD were included in the study, aged (47.6±13.8) years old, with 821 males (52.6%) and baseline hemoglobin of 81 (69, 94) g/L. Hb?var in the first year of PD was 26.6 (16.7, 40.3) g/L. There were statistically significant differences in age, body mass index, serum albumin, hemoglobin, serum creatinine, serum calcium, serum phosphorus, intact parathyroid hormone and the proportion of renin-angiotensin system inhibitors among low Hb?var group (<20.0 g/L), moderate Hb?var group (20.0-35.5 g/L) and high Hb?var group (≥35.5 g/L, all P<0.05). The follow-up time was 33 (19, 51) months, and 208 patients (13.3%) died, among which 111 patients (53.4%) died of cardiovascular death. Multivariate Cox regression analysis showed that the higher Hb?var in the first year, the lower the risk of all-cause death (HR=0.98, 95%CI 0.97-0.99, P=0.018) and cardiovascular death (HR=0.98, 95%CI 0.97-0.99, P=0.041) in PD patients. Compared with low Hb?var group, the risk of all-cause death (HR=0.56, 95%CI 0.37-0.82, P=0.003) and cardiovascular death (HR=0.54, 95%CI 0.31-0.95, P=0.032) was lowest in the high Hb?var group. The competitive risk regression model analysis showed that Hb?var in the first year was still negatively correlated with the risk of all-cause death (HR=0.98, 95%CI 0.97-0.99, P=0.041) and cardiovascular death (HR=0.98, 95%CI 0.97-0.99, P=0.039). Conclusion High Hb?var in the first year is associated with low risk of all-cause death and cardiovascular death in PD patients with severe anemia at baseline.

Objective To explore the value of combined detection of urinary kidney injury markers in the diagnosis of early-stage diabetic kidney disease (DKD), and to provide evidence for early-stage DKD screening. Methods It was a retrospective study. The clinical data of patients with type 2 diabetes mellitus (T2DM) from the Second Affiliated Hospital of Hainan Medicine University from January 2022 to August 2023 were collected. According to urinary microalbumin/creatinine ratio (UACR), the patients were divided into three groups: isolated diabetes group (UACR < 30 mg/g), early-stage DKD group (30 mg/g ≤ UACR < 300 mg/g) and clinical DKD group (UACR ≥ 300 mg/g), and the differences of clinical data among three groups were compared. Glomerular injury markers urinary microalbumin, transferrin, immunoglobulin (Ig) and α2 macroglobulin, and renal tubule injury markers α1 microglobulin (α1?MG), β2 microglobulin (β2?MG), retinol-binding protein (RBP), N-acetyl-β-D-glucosidase (NAG), neutrophil gelatinase-associated lipid carrier protein (NGAL) were measured. Spearman correlation method was used to analyze the correlation between urinary kidney injury markers and clinical indicators. Multivariate logistic regression analysis method was used to analyze the risk factors of DKD occurrence (UACR > 300 mg/g). Receiver-operating characteristic curve was used to analyze the value of individual and combined detection of urinary renal injury markers in the diagnosis of early-stage DKD (30 mg/g ≤ UACR < 300 mg/g). Results A total of 116 T2DM patients were enrolled in this study, aged (61.99±12.56) years old (30 to 91 years old), with 79 males (68.1%). There were 44 (37.9%) isolated diabetes patients, 27 (23.3%) early-stage DKD patients, and 45 (38.8%) clinical DKD patients. Serum creatinine (Scr, H=34.183, P<0.001) and blood urea nitrogen (BUN, H=34.082, P<0.001) in clinical DKD group were higher than those in isolated diabetes group and early-stage DKD group. Spearman correlation analysis showed that glomerular injury markers urinary microalbumin, transferrin, Ig and α2 macroglobulin were positively correlated with Scr, BUN and UACR, and negatively correlated with estimated glomerular filtration rate and serum albumin (all P<0.05). Renal tubule injury markers urinary α1?MG, β2?MG, NAG, RBP, and NGAL were positively correlated with Scr, BUN and UACR, and negatively correlated with estimated glomerular filtration rate and serum albumin (all P<0.05). Multivariate logistic regression analysis indicated that systolic blood pressure ≥ 140 mmHg (OR=1.033, 95%CI 1.008-1.060, P=0.010), high urinary microalbumin (OR=1.018, 95%CI 1.007-1.030, P=0.001), high urinary RBP (OR=1.309, 95%CI 1.086-1.577, P=0.005), high urinary NGAL (OR=1.004, 95%CI 1.000-1.008, P=0.037), low serum albumin (OR=0.833, 95%CI 0.749-0.926, P=0.001) and low urinary Ig (OR=0.994, 95%CI 0.990-0.999, P=0.018) were independent influencing factors of DKD occurrence. Receiver-operating characteristic curve revealed that the area under the curve (AUC) was the largest for diagnosing early-stage DKD when urinary microalbumin was detected alone (AUC=0.976, 95%CI 0.955-0.997, P<0.001), with sensitivity and specificity of 95.6% and 90.1%, respectively. The combined detection of urinary microalbumin + Ig + transferrin + α2 macroglobulin + α1-MG + β2-MG + NAG + RBP + NGAL had an AUC of 0.986 (95%CI 0.971-1.000, P<0.001), with sensitivity and specificity of 93.3% and 98.5%, respectively, which was better than each single index. Further optimized detection combination was urinary microalbumin combined with β2-MG and NGAL, which had the best diagnostic efficacy (AUC=0.978, 95%CI 0.958-0.999, P<0.001), with sensitivity and specificity of 95.6% and 93.0%, respectively. Conclusions Compared with the single detection of each index, the combined detection of urinary glomerular injury and renal tubule injury markers has higher value in diagnosing early-stage DKD. The combined detection of urinary microalbumin combined with β2-MG and NGAL has the highest value in diagnosing early-stage DKD.

Objective To investigate the efficacy and prognosis of rituximab (RTX) in the treatment of M-type phospholipase A2 receptor (PLA2R)-associated idiopathic membranous nephropathy (IMN). Methods It was a retrospective cohort study. The clinical data of PLA2R-associated IMN patients who received RTX treatment in the Shenzhen Second People's Hospital from September 2018 to March 2023 were collected. According to remission status of proteinuria, the patients were divided into proteinuria remission group (24-hour urinary protein quantity < 3.5 g) and non-proteinuria remission group (24-hour urinary protein quantity ≥ 3.5 g), and the clinical data between the two groups were compared. According to baseline 24-hour urinary protein quantity and estimated glomerular filtration rate (eGFR), the patients were divided into high-risk disease progression group [24-hour urinary protein quantity ≥ 8 g or eGFR < 60 ml·min^-1·(1.73 m²)^-1] and non-high-risk disease progression group [24-hour urinary protein quantity < 8 g or eGFR ≥ 60 ml·min^-1·(1.73 m²)^-1]. Kaplan?Meier survival curve was utilized to compare the differences of proteinuria remission rates and renal composite endpoint event survival rates between the two groups. Multivariate Cox regression analysis was utilized to identify the influencing factors of proteinuria remission and renal composite endpoint event. Results This study included 46 PLA2R-associated IMN patients, with 31 males (67.4%). The baseline eGFR was (78.4±34.1) ml·min^-1·(1.73 m²)^-1. The 24-hour urinary protein quantity was 8.33 (6.04, 12.85) g. After 14.95 (7.44, 22.15) months of follow-up, 29 patients (63.0%) achieved proteinuria remission, with remission time of 6.0 (5.0, 9.0) months. Six (20.7%) patients relapsed, with relapsed time of 17.25 (11.75, 18.28) months. CD20 in the proteinuria remission group was lower than that in the non-proteinuria remission group (Z=2.270, P=0.023). Eleven (23.9%) patients experienced renal composite endpoint events wtih occurrence time of 16.07 (7.87, 29.63) months. Kaplan-Meier survival curve analysis indicated that there was no statistically significant difference in proteinuria remission rates (log?rank χ²=0.26, P=0.612) and renal composite endpoint event survival rates (log?rank χ²=0.25, P=0.619) between baseline 24-hour urinary protein quantity ≥ 8 g and < 8 g groups. There was no statistically significant difference in proteinuria remission rates after RTX treatment (log?rank χ²=0.77, P=0.381) and renal composite endpoint event survival rates (log?rank χ²=1.41, P=0.236) between eGFR ≥ 60 ml·min^-1·(1.73 m²)^-1 and < 60 ml·min^-1·(1.73 m²)^-1 groups. Multivariate Cox regression analysis showed that hypertension history (HR=0.16, 95% CI 0.05-0.55), immunosuppressive therapy history (HR=0.08, 95% CI 0.01-0.50), baseline eGFR < 60 ml·min^-1·(1.73 m²)^-1 (HR=0.21, 95% CI 0.05-0.92), baseline PLA2R antibody titer ≥ 100 RU/ml (HR=0.20, 95% CI 0.06-0.69), long time between treatment and first diagnosis (HR=1.33, 95% CI 1.12-1.57), high baseline triglyceride (HR=1.46, 95% CI 1.02-2.08), and baseline 24-hour urinary protein quantity ≥ 8 g (HR=8.54, 95% CI 2.08-35.12) were independent influencing factors of proteinuria remission after RTX treatment. The baseline PLA2R antibody titer ≥ 100 RU/ml was an independent influencing factor of reaching the renal composite endpoint event (HR=7.31, 95% CI 1.23-43.62). Conclusions The proteinuria remission rate after RTX treatment of PLA2R-associated IMN is 63.0% and the recurrence rate is 20.7%. The incidence rate of renal composite endpoint event is 23.9%. The hypertension history, immunosuppressant medication history, baseline eGFR < 60 ml·min^-1·(1.73 m²)^-1, baseline PLA2R antibody titer ≥ 100 RU/ml, long time between treatment and first diagnosis, high baseline triglyceride, and baseline 24-hour urinary protein quantity ≥ 8 g are independent influencing factors of proteinuria remission, and baseline PLA2R antibody titer ≥ 100 RU/ml is an independent risk factor of renal poor prognosis in PLA2R-associated IMN patients.

Objective To detect and analyze the α-galactosidase A (GLA) gene mutations in Fabry disease patients and their family members, observe the clinical phenotype of the patients, and assess the therapeutic effect of agalsidase alpha. Methods It was a case series analysis. A total of 5 Fabry disease patients was diagnosed at the First Affiliated Hospital of Sun Yat-sen University from March 2022 to April 2023, and the clinical data and blood samples of the patients and their family members were collected. Genetic testing was performed using whole exome sequencing. GLA activity and substrate concentration were measured using the liquid chromatography-tandem mass spectrometry. Patients' clinical manifestations, family history, and auxiliary examination results were collected, and the therapeutic efficacy of agalsidase alpha and disease progression were followed up. Results A total of 5 GLA gene mutations were identified by gene sequencing, including 1 novel mutation. Among them, 4 mutations were missense mutation, and the other one was nonsense mutation. Common clinical manifestations included edema (4/5) and reduced sweating (4/5). Renal pathology biopsy of 4 patients showed varying degrees of kidney damage, one of which was combined with IgA nephropathy. Auxiliary examinations revealed ocular involvement in 4 patients, cardiac involvement in 4 patients, and hearing impairment in 2 patients. All 5 patients received agalsidase alpha treatment, with 4 male patients receiving (16.8±5.9) times administrations of agalsidase alpha, and their globotriaosylsphingosine (Lyso?GL?3) levels decreased by 45.6%±15.5% from baseline. Conclusions One novel GLA gene mutation is detected, which enriches the human gene mutation database. Fabry disease can be accompanied by kidney disease such as IgA nephropathy. When patients present with unexplained proteinuria combined with extrarenal manifestations such as reduced sweating, Fabry disease should be considered. Agalsidase alpha treatment can reduce Lyso?GL?3 concentration, and improve clinical symptoms.

Objective To explore the effects of G protein-coupled receptor 55 (GPR55) antagonist CID16020046 on renal fibrosis in mice, and provide a new method and idea for the treatment of renal fibrosis. Methods (1) GPR55 overexpression and GPR55 antagonist CID16020046 were used in renal fibroblasts (NRK?49F) of rats, respectively. Meanwhile,transforming growth factor-β1 (TGF?β1) was applied in the NRK?49F cells to observe the expression of fibrosis-related factors and inflammatory factors. (2) A mouse model of renal fibrosis with unilateral ureteral obstruction (UUO) was established in vivo. Eight-week-old male C57BL/6J mice (20-25 g) were randomly divided into three groups according to the random number table method: sham group (n=6), model group (UUO group, n=7), model + CID16020046 drug (UUO+CID group, n=8). The drug CID16020046 (10 mg/kg) was intraperitoneally injected 1 day before modeling, on the day of modeling and every day after surgery in UUO+CID group, and the corresponding dose of 0.9% normal saline was injected intraperitoneally in sham and UUO groups.The mice were sacrificed for sampling 7 days after UUO surgery, and their renal function indicators, liver transaminase, and cardiac markers were examined. Western blotting and quantitative real-time PCR were used to detect the expression of renal fibrosis-related factors and inflammatory factors. Immunohistochemistry staining, Sirius red staining and Masson trichrome staining were used to detect the pathological changes of renal tissues. Results (1) After NRK?49F cells were stimulated by TGF?β1, the mRNA and protein expression levels of GPR55 were significantly increased (both P<0.05). There was no statistically significant difference in the mRNA expression of fibrosis-related factors fibronectin and collagen Ⅰ, and inflammatory factors interleukin-1β and tumor necrosis factor-α between TGF?β1 group and TGF?β1 + GPR55 overexpression group (all P>0.05). Compared with the TGF?β1 group, the protein expression levels of fibrosis-related factors alpha-smooth muscle actin (α?SMA) and vimentin, and the mRNA expression levels of collagen Ⅰ and α?SMA were lower in the TGF?β1 + CID group (all P<0.05). (2) Compared with sham group, the mRNA and protein expression levels of GPR55 in UUO group were higher (both P<0.05). The serum creatinine in the UUO+CID group was lower compared to the UUO group (P<0.05). There was no statistically significant difference in blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and creatine kinase isoenzyme between UUO group and UUO+CID group (all P>0.05). Compared with the UUO group, the protein expression levels of renal fibrosis-related factors fibronectin, collagen Ⅰ and vimentin, and the mRNA expression levels of fibronectin, collagen Ⅰ, collagen Ⅲ and α?SMA were lower in the UUO+CID group (all P<0.05). The degree of renal tubular dilation and interstitial collagen fiber deposition in the UUO+CID group was significantly reduced compared to the UUO group (all P<0.05). Conclusions CID16020046 can reduce serum creatinine in UUO mice, protect renal function, and simultaneously decrease the expression of fibrosis-related factors in renal fibroblasts and mouse kidney tissues, thereby alleviating renal fibrosis.

Objective To explore the risk factors of recent cardiovascular and cerebrovascular events and long-term all-cause mortality in hemodialysis (HD) patients. Methods The clinical data of two groups of retrospective cohort study, which included newly admitted HD (group A) and maintenance HD (group B) patients respectively, were sourced from the HD Center of Beijing Anzhen Hospital, Capital Medical University. The endpoint events were defined as occurrence of cardiovascular or cerebrovascular events or all-cause mortality at less than 12 mouths of dialysis age in group A, and all-cause mortality in group B. The patients were divided into event group and non-event group based on whether endpoint events occurred during the follow-up period. The baseline and follow-up clinical data within the two groups were compared. Cox regression model was used to analyze the risk factors of endpoint events in HD patients. Results A total of 104 HD patients were enrolled in group A, with 70 males (67.3%), aged (61.54±14.97) years old. The follow-up time was 12.0 (10.0,12.0) months, and 29 patients (27.9%) had endpoint events. In group A, the event group had a higher proportion of peripheral arterial disease (χ²=6.067, P=0.014), and lower low-density lipoprotein-cholesterol (t=-2.316, P=0.023) and body mass index (t=-2.245, P=0.028) than those in the non-event group. A total of 116 HD patients were enrolled in group B, with 86 males (74.1%), aged (65.89±10.06) years old. The follow-up time was 37.5 (21.0, 59.0) months, and 40 patients (34.5%) had endpoint events. In group B, the event group had lower serum albumin (t=-3.182, P=0.002) and potassium (t=-2.532, P=0.013) than those in the non-event group. Multivariate Cox regression analysis showed that high hemoglobin compliance rate (HR=0.977, 95%CI 0.957-0.998, P=0.031) and high serum albumin (HR=0.836, 95%CI 0.776-0.901, P<0.001) were protective factors of all-cause mortality in maintenance HD patients. Conclusions The presence of peripheral arterial disease, low low-density lipoprotein-cholesterol and low body mass index may increase the risk of recent cardiovascular and cerebrovascular events in newly HD patients. Substandard hemoglobin and serum albumin may increase the risk of long-term all-cause mortality in maintenance HD patients.

This article reports a rare case of proliferative glomerulonephritis with monoclonal immunoglobulin deposits. The patient, a middle-aged woman, exhibited clinical manifestations including nephrotic syndrome, microscopic hematuria, renal insufficiency, hyperglycemia, and bilateral diabetic retinopathy. Notably, monoclonal bands were absent in both blood and urine immunofixation electrophoresis. Renal biopsy revealed membranoproliferative glomerulonephritis, with immunofluorescence revealing exclusive petal-like deposition of IgG3 subtype along the capillary loop. Electron microscopy demonstrated segmental thickening of the glomerular basement membrane, along with electron dense deposits in the subendothelial and mesangial areas, lacking discernible substructure. The diagnosis comprised proliferative glomerulonephritis with monoclonal immunoglobulin deposition concurrent with diabetic nephropathy. Subsequent sequential treatment with daratumumab and cyclophosphamide over 6 months led to partial remission of nephrotic syndrome, normalization of renal function, and significant improvement of anemia. During the 24-month follow-up period, no serious adverse reactions occurred.

The paper reports a 68-year-old female patient admitted with "recurrent fever for 2 years" with a previous history of chronic kidney disease (stage 5) and receiving maintenance hemodialysis for 2 years. After 15 days of anti-infection treatment with vancomycin, the patient showed a steep drop in peripheral platelet count to <1×10⁹/L. Combined with the clinical manifestations and platelet antibody screening, considering vancomycin-induced thrombocytopenia (VIT), vancomycin was immediately stopped, and active plasma exchange was adopted. Finally, the peripheral blood platelet count of the patient returned to normal, supporting the diagnosis of VIT. Vancomycin is widely used in dialysis patients, and the clinicians should be aware of the rare but severe adverse effect of VIT. Once present, vancomycin should be stopped early and individualized treatment should be taken to avoid the risk of massive bleeding or death.

This article reports two cases of proteinuria caused by anti-vascular endothelial growth factor (VEGF) drugs in the treatment of liver cancer and ovarian cancer, respectively. Hypertension, massive albuminuria and renal insufficiency occurred in the patient with liver cancer during the use of toripalimab/camrelizumab combined with lenvatinib and regorafenib, and urinary protein was 4.02 g/24 h. The patient with ovarian cancer developed hypertension, proteinuria and 1.13 g/24 h urinary protein during the use of bevacizumab. Renal biopsy showed thrombotic microangiopathy in the glomeruli of both patients. Anti-VEGF drugs-associated glomerular microangiopathy was considered. The patient with liver cancer had no improvement after halving the dose of lenvatinib, and the effect was not good after treatment with low-dose corticosteroids combined with renin-angiotensin-aldosterone system inhibitors. After stopping anti-VEGF drugs, the proteinuria in both patients turned negative.

Autogenous arteriovenous fistula (AVF) is the preferred vascular access of hemodialysis in maintenance hemodialysis patients. However, due to the influence of various factors, new AVF may show immaturity, which will affect the use and dialysis effect of vascular access. AVF maturation is an important clinical concern. It is important to clarify the physiological and biochemical factors, and biological mechanisms of AVF immaturation. Based on the literature, this review focuses on the biological mechanisms of AVF maturation and the physiological and biochemical factors affecting AVF maturation, including vascular conditions, gender and age, and underlying diseases, to provide reference for improving the clinical maturation rate of AVF and the treatment effect in hemodialysis patients.

Henoch-Sch?nlein purpura is also known as IgA vasculitis. The kidney involvement, namely Henoch-Sch?nlein purpura nephritis (HSPN), is one of IgA vasculitis's main clinical manifestations. Galactose-deficient IgA1 plays an important role in the pathogenesis of HSPN, which not only is similar to the "four-hits hypothesis" of IgA nephropathy, leading to IgA1 deposit in the mesangial region of the kidney, but also is closely related to inflammation with more complicated compositions of its immune complex. Therefore, abnormal glycosylation of IgA1 is expected to be a biomarker for diagnosis and prediction of HSPN pathogenesis, disease activity determination and prognosis prediction. Here, the paper reviews the research progress on the pathogenesis and clinical application of abnormal glycosylation of IgA1 in HSPN.

The increasing focus and research on ectopic fat deposition, especially the locally impactful liver and cardiac fat, have been extensively studied. However, there has been relatively less research on renal sinus fat. The increased ectopic deposition of renal sinus fat has an independent effect on renal damage, but the underlying mechanism remains unclear. Therefore, this article will integrate current research to provide a comprehensive review of renal sinus ectopic fat deposition, covering its related imaging diagnosis, potential mechanisms influencing renal damage (mechanical pressure generated by renal sinus fat, lipotoxicity), and current interventions for renal sinus ectopic fat deposition. This is aimed at attracting more attention in clinical research to the role of renal sinus ectopic fat deposition in the occurrence and development of kidney-related diseases.