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    Clinical Study

  • Sun Ci, Song Kai, Jiang Shan, Lu Ying, Yin Peiran, Li Weiwei
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    Objective To evaluate the relationship between prognostic nutritional index (PNI) and risk of functional dependence in patients receiving maintenance hemodialysis (MHD). Methods It was a cross-sectional survey study. The clinical data of MHD patients in the Second Affiliated Hospital of Soochow University from June to December 2023 were collected. The Katz and Lawton?Brody questionnaires were used to assess the functional status. The patients were divided into normal functional status group and functional dependence group, and the differences of the clinical data between the two groups were compared. Serum albumin and lymphocytes were used to determine PNI, and the patients were divided into four subgroups: Q1 group (PNI≤44.3), Q2 group (44.3<PNI≤47.2), Q3 group (47.2<PNI≤49.8) and Q4 group (PNI>49.8) according to the quartile of PNI. Logistic regression analysis method was used to analyze the relationship between PNI and risk of functional dependence in MHD patients, and subgroup analysis was conducted. The receiver-operating characteristic (ROC) curve was used to assess the efficacy of PNI, serum albumin, and lymphocytes in predicting the risk of functional dependence in MHD patients. Results A total of 206 MHD patients were included in this study, with age of (58.35±0.98) years old, and 132 (64.1%) males. There were 58 (28.2%) patients with diabetes, 179 (86.9%) patients with hypertension, and 36 (17.5%) patients with cardiovascular diseases. There were 95 (46.1%) patients developing functional dependence. Compared with normal functional status group, functional dependence group had higher age (t=-6.87, P<0.001), proportion of diabetes (χ2=6.58, P=0.010), and pulse pressure (t=-3.17, P=0.002), and lower diastolic pressure (t=3.88, P<0.001), serum creatinine (t=3.44, P=0.001), serum albumin (t=4.09, P<0.001) and PNI (t=3.92, P<0.001). The incidence of functional dependence in PNI Q1 group (69.2%, 36/52) was significantly higher than those in Q2 group (49.0%, 25/51), Q3 group (34.0%, 18/53) and Q4 group (32.0%, 16/50), and the differences among groups were statistically significant (all P<0.05). Logistic regression analysis showed that after adjusting for confounding factors: age, diabetes, pulse pressure, and serum creatinine, the risk of functional dependence of PNI Q1 group was 3.217 folds higher than that in Q4 group (OR=3.217, 95%CI 1.229-8.422, P=0.017). The risk probability model of PNI predicting the occurrence of functional dependence in MHD patients: logit (odds)=5.854-0.128 3×PNI. The area under the ROC curve (AUC) for PNI predicting the risk of functional dependence in MHD patients was 0.66 (95%CI 0.58-0.73, P<0.001), slightly higher than that of serum albumin (AUC=0.64, 95%CI 0.54-0.73, P<0.001). The optimal cutoff value of PNI predicting the occurrence of functional dependence was 46.15, with sensitivity of 72.07% and specificity of 57.89%. Conclusion Low PNI is associated with high risk of functional dependence in MHD patients.

  • Jia Meng, Guo Yidan, Ye Pengpeng, Zhou Xiaoling, Luo Yang
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    Objective To analyze the clinical characteristics and risk factors of acute kidney injury (AKI) in portal venous hypertension patients undergoing transjugular intrahepatic portosystemic shunt (TIPS). Methods It was a retrospective observational study. In this study, the clinical data of portal venous hypertension patients undergoing TIPS at Beijing Shijitan Hospital, Capital Medical University from October 16, 2020 to March 30, 2022 were collected retrospectively. According to the Kidney Disease: Improving Global Outcomes (KDIGO) definition of AKI, patients were divided into AKI group and non-AKI group. The clinical characteristics of the patients were compared between the two groups, and multivariate logistic regression was used to analyze the risk factors of AKI. Results A total of 384 patients undergoing TIPS were included in this study, whose age was (53.17±13.35) years. Among them, 122 (31.8%) were female, and 32 patients (8.3%) had AKI. Compared to the non-AKI group, the proportion of patients with diabetes mellitus, baseline estimated glomerular filtration rate (eGFR) <60 ml·min-1·(1.73 m2)-1 and intraoperative hypotension, Child-Pugh score of liver function, preoperative serum creatinine, preoperative blood uric acid, and postoperative portal venous pressure gradient (PPG) were higher in AKI group (all P<0.05), while the levels of hemoglobin and serum albumin were lower (both P<0.05). Multivariate logistic regression results showed that combined diabetes (OR=3.728, 95% CI 1.262-11.013, P=0.017), baseline eGFR<60 ml·min-1·(1.73 m2)-1(OR=3.571, 95% CI 1.356-9.400, P=0.010), decreased serum albumin (OR=0.847, 95% CI 0.738-0.972, P=0.018), increased PPG after TIPS (OR=1.096, 95%CI 1.002-1.200, P=0.045) and intraoperative hypotension (OR=7.006, 95% CI 2.023-24.195, P=0.002) were independently associated with postoperative AKI in portal venous hypertension patients undergoing TIPS. Until discharge, 6 patients with AKI (18.8%) had complete renal function recovery, 24 patients (75.0%) partially recovered, and 2 patients (6.3%) did not recover. The length of hospital stay, hospitalization costs, and all-cause mortality in AKI patients were significantly higher than those in the non-AKI group (P<0.05, respectively). Conclusions AKI is not uncommon in patients receiving TIPS. The classical risk factors of AKI, such as diabetes and baseline renal dysfunction, and the factors affecting volumes like lower serum albumin level, hypotension during the operation, and higher PPG level are closely related to the incidence of AKI in these patients. AKI significantly increases the all-cause mortality and medical expenses, which is worth early prevention and treatment by clinicians.

  • Chen Si, Pan Ying, Lu Yifei, Qian Li, Li Qing, Xu Yili, Duan Suyan, Wu Lin, Zhang Bo, Xing Changying, Mao Huijuan, Yuan Yanggang
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    Objective To investigate the correlation between complement C3 and urine protein level and proteinuria remission status in patients with primary membranous nephropathy (PMN), and better guide individualized clinical treatment. Methods It was a single-center retrospective study. The clinical data of PMN patients who underwent renal biopsy in the First Affiliated Hospital of Nanjing Medical University from January 2017 to June 2022 were collected. Patients with 24 h urinary protein ≥ 3.5 g were followed up after receiving standard treatment, and the last outpatient or inpatient review was used as the end point of follow-up. 24 h urine protein was collected to evaluate the remission status of proteinuria. Kaplan-Meier method was used to analyze the correlation between serum and renal complements and proteinuria remission. Cox regression analysis method was used to analyze the correlation between serum C3 level and renal tissue C3 deposition and proteinuria remission. Results This study included 507 PMN patients with 312 (61.54%) males, aged 54 (43, 64) years old. Compared with 24 h urinary protein < 3.5 g group, proportion of males (χ2=22.479, P<0.001), age (Z=-2.521, P=0.012), systolic blood pressure (Z=-4.148, P<0.001), diastolic blood pressure (Z=-4.084, P<0.001), serum anti-phospholipase A2 receptor (PLA2R) antibody titer (Z=-7.019, P<0.001), total cholesterol (Z=-8.796, P<0.001), triglyceride (Z=-6.158, P<0.001), low density lipoprotein cholesterol (Z=-8.716, P<0.001), serum creatinine (Z=-7.368, P<0.001), serum C3 (Z=-3.663, P<0.001), serum C4 (Z=-6.560, P<0.001), proportion of glucocorticoid use (χ2=116.417, P<0.001) and proportion of immunosuppressant use (χ2=53.839, P<0.001) were all higher, while serum albumin (Z=12.518, P<0.001), estimated glomerular filtration rate (Z=6.345, P<0.001) and serum IgG (Z=7.321, P<0.001) were all lower in 24 h urinary protein ≥3.5 g group. There were 268 patients included in the follow-up cohort with baseline 24 h urinary protein of 7.15 (5.14, 10.24) g, serum anti-PLA2R antibody titer of 61.44 (14.35, 193.24) RU/ml, serum C3 of 1.005 (0.864, 1.150) g/L, and serum C4 of 0.260 (0.214, 0.317) g/L. Kaplan-Meier survival curve showed that the incomplete remission rate of proteinuria in serum C3 > 1.005 g/L group was lower than that in serum C3 ≤ 1.005 g/L group (log-rank χ2=4.757, P=0.029). There was no significant difference in the incomplete remission rate of proteinuria between serum C4 ≤ 0.260 g/L group and serum C4 > 0.260 g/L group (log-rank χ2=3.543, P=0.060). Renal C1q (log-rank χ2=0.167, P=0.683) and C4 (log-rank χ2=1.927, P=0.165) deposition had no significant effects on proteinuria remission in PMN patients. The incomplete remission rate of proteinuria in patients with renal C3 deposition was higher than that in patients without renal C3 deposition (log-rank χ2=7.018, P=0.008). Univariate Cox regression analysis showed that serum C3 level and C3 deposition in renal tissues were influencing factors of incomplete remission of proteinuria (both P<0.05), while adjusting for gender, age, mean arterial pressure, serum anti-PLA2R antibody, serum albumin and 24 h urinary protein, serum C3 ≤ 1.005 g/L (HR=1.374, 95% CI 1.021-1.849, P=0.036), C3 deposition in renal tissues (HR=1.949, 95% CI 1.098-3.460, P=0.023), and serum C3 ≤ 1.005 g/L combined with C3 deposition in renal tissues (HR=1.472, 95% CI 1.093-1.983, P=0.011) were independent influencing factors of incomplete remission of proteinuria. Conclusions The serum C3 level and C3 deposition in renal tissues are closely related to urinary protein level and proteinuria remission status in PMN patients. The patients with higher urinary protein have higher serum C3. For patients with massive proteinuria, serum C3 ≤ 1.005 g/L, C3 deposition in renal tissues, serum C3 ≤ 1.005 g/L combined with C3 deposition in renal tissues are independent risk factors of incomplete remission of proteinuria.

  • Zhang Xin, Yu Xiaojuan, Xu Jin, Zhao Minghui, Wang Suxia, Zhou Fude
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    Objective To analyze the clinical and pathological data of 15 patients with light chain amyloidosis initially diagnosed with other kidney diseases, and identify possible misdiagnosis reasons. Methods It was a retrospective observational study. The clinical and pathological data of 15 patients, whose initial kidney biopsies failed to diagnose light chain-amyloidosis but were confirmed by a subsequent kidney biopsy or pathology consultation at Peking University First Hospital from January 2010 to December 2022 were collected. The results of immunofluorescence, Congo red staining, and electron microscopy of two renal biopsies were analyzed. Results The median age of 15 patients was 56 years old, with a male-to-female ratio of 7∶8. The main clinical manifestation was massive proteinuria with normal kidney function, and there were 10 cases presenting as nephrotic syndrome. The initial diagnosis based on the first kidney biopsy included minimal change disease (8 cases), IgA nephropathy (3 cases), membranous nephropathy (3 cases), and type Ⅲ collagen glomerulonephritis (1 case). M proteinemia was not evaluated in 13 patients during the first kidney biopsy. Light chain immunofluorescence staining was not performed in 12 cases. Congo red staining was not performed in 13 cases. All fifteen patients received glucocorticoids combined with immunosuppressive therapy after their initial diagnosis, and 5 patients developed severe infection. After 12.0 (7.5, 20.0) months of treatment, none of them achieved clinical remission. Thirteen had evidences for M protein before the second kidney biopsy. The renal tissues of all patients underwent immunofluorescence light chain examination, Congo red staining, and immunoelectron microscopy examination when necessary. The repeat kidney biopsies of 14 cases and pathology consultation of one case consistently indicated light chain-amyloidosis. The kidney tissues in 13 cases were confirmed to be light chain restricted, 11 cases by immunofluorescence, and 2 cases by immune electron microscopy. After diagnosis of light chain-amyloidosis, all patients received targeted plasma cell therapy except for 1 patient lost to follow-up, 6 patients achieved hematologic remission, 5 patients achieved renal remission, 1 patient entered end-stage renal disease, and 3 patients died. Conclusions In middle and elderly-aged patients with nephrotic syndrome, if conventional immunosuppressive therapy yields unsatisfactory results, it is crucial to focus on identifying evidences of monoclonal immunoglobulinemia, if necessary, kidney biopsy should be actively repeated. Kidney biopsy pathology should include comprehensive examinations such as light chain immunofluorescence, Congo red staining, and electron microscopy to avoid misdiagnosis of light chain-amyloidosis.

  • Basic Study

  • Tang Tianfeng, Zhao Min, Xia Yangyang, Wang Lulu, Zhang Qingyan, Sun Cheng, Jiang Chunming
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    Objective To explore the mechanism of peritoneal dialysis solution (PDS)-induced peritoneal microinflammation through activation of ceramide (CER) in peritoneal dialysis model mice. Methods Thirty 5-week-old male C57BL/6 mice weighing about 22 g were used to set up peritoneal dialysis models, and then were randomly divided into 4 groups: sham operation group (1.5 ml sterilized water, n=7), high glucose-PDS group (1.5 ml 4.25% PDS, n=8), high glucose-PDS+ acid sphingomyelinase (ASMase) inhibitor desipramine (DES) group (1.5 ml sterilized water+10 mg/kg DES, n=8), high glucose-PDS+Src kinase inhibitor PP2 group (1.5 ml sterilized water +1 mg/kg PP2, n=7), with intraperitoneal injection once a day. After 28 days, the mice were sacrificed to retain peritoneal tissues. HE staining and Masson staining were used to observe the histological changes of peritoneum. Immunohistochemistry was used to detect the Toll-like receptor 4 (TLR4) and macrophages. High performance liquid chromatography, liquid chromatography/mass spectrometry and immunofluorescence were used to detect the expression of ASMase and CER. Real-time quantitative PCR was used to detect the mRNA levels of c?Src, p?Src, interleukin-6 (IL?6), and tumor necrosis factor-α (TNF?α). Western blotting was used to detect the protein levels of c?Src, and p?Src. Enzyme-linked immunosorbent assay was used to detect the serum C reactive protein (CRP), IL?6 and TNF?α. Results (1) High glucose-PDS led to peritoneal hyperplasia, collagen deposition and fibrosis in the peritoneal dialysis mice, indicating successful modeling. Compared with high glucose-PDS group, peritoneal hyperplasia, collagen deposition and fibrosis of mice treated with DES and PP2 were significantly improved (all P<0.05). (2) Compared with sham operation group, ASMase activation and CER level of peritoneal tissues were significantly higher in high glucose-PDS group, and DES could significantly inhibit activated ASMase and increased CER expression caused by high glucose-PDS (both P<0.05). PP2 had no significant effect on ASMase activation and CER level (both P>0.05). (3) Compared with sham operation group, there were more TLR4 and macrophage positive staining cells in peritoneal tissues in high glucose-PDS group, and the mRNA expression levels of IL?6 and TNF?α in peritoneal tissues and serum CRP, IL?6 and TNF?α were higher (all P<0.05). DES and PP2 could significantly inhibit the increased TLR4, macrophages and related inflammatory factors induced by high glucose-PDS (all P<0.05). (4) Compared with sham operation group, c?Src and p?Src mRNA and protein expression levels of peritoneal tissues in high glucose-PDS group were significantly higher (all P<0.05). PP2 significantly inhibited the increased p?Src mRNA and protein levels caused by high glucose-PDS (both P<0.05), but had no significant effect on the mRNA and protein expression levels of c?Src (both P>0.05). DES had no significant effect on the mRNA and protein expression levels of c?Src and p?Src (all P>0.05). Conclusions High glucose-PDS may enhance the expression of CER through stimulating the activity of ASMase, phosphorylate Src, activate TLR4 and induce inflammatory damage of peritoneum in peritoneal dialysis model mice.

  • Short Original Article

  • Chen Jiahui, Zhang Yanzi, Zhang Aisha, Sui Xiaolu, Xu Yunpeng, Xie Tingfei, Chen Jihong
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    This study aims to establish a rat model of renal ischemia reperfusion injury (RIRI) to observe the alterations in the expression of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway following various exosome treatments. Additionally, differential miRNA expression analysis will be conducted to elucidate the molecular mechanisms underlying the effects of exosomes derived from ischemic preconditioned (IPC) renal tubular cells in mitigating RIRI in rats. Initially, ten SD rats were subjected to bilateral nephrectomy under general anesthesia to prepare primary renal tubular cells. The second-generation renal tubular cells were then subjected to the following treatments for 12 hours: normoxia (38% O2, 5% CO2), hypoxia (1% O2, 5% CO2), and hypoxia plus inactivation (heated at 65 ℃ for 30 minutes). Following these treatments, exosomes were extracted, yielding normoxic exosomes, IPC exosomes, and inactivated exosomes, respectively. A subsequent cohort of 50 SD rats was randomly divided into five groups: Sham group, RIRI group, RIRI + normoxic exosome group (NC group), RIRI + IPC exosome group (IPC group), and RIRI + inactivated exosome group (INA group). RIRI model was established in the latter four groups. Twenty?four hours after RIRI modeling, the NC, IPC, and INA groups received intravenous injections of 200 μg of normoxic exosomes, IPC exosomes, and inactivated exosomes via the tail vein, respectively. Six days later, venous blood samples were collected, and both kidneys were excised to observe renal function, histopathological changes in kidney tissue, and alterations in the PI3K/AKT/mTOR signaling pathway among the five groups. Furthermore, differential miRNA expression analysis [P<0.05, |log2(Fold Change)|≥1] was conducted between the NC and IPC groups to investigate the changes in the miRNA expression profile. Subsequently, GO analysis and KEGG pathway enrichment analysis were performed. The results revealed that: (1) Compared with the Sham group, the RIRI and INA groups exhibited elevated levels of serum creatinine and urea nitrogen (all P<0.01). Histopathological examination of kidney tissues showed substantial inflammatory cell infiltration in the interstitium accompanied by varying degrees of edema, degenerative swelling of tubular structures, necrosis, and detachment of tubular epithelial cells. Notably, the number of TUNEL?positive cells was significantly increased, while the number of Ki67?stained positive cells was markedly decreased. Additionally, the mRNA and protein expression of PI3K/AKT/mTOR signaling pathway in RIRI group and INA group were down-regulated. (2) Compared to the NC group, the IPC group demonstrated lower levels of serum creatinine and urea nitrogen (both P<0.01). Notably, there was a significant decrease in the accumulation of inflammatory cells in the renal interstitium, and tissue edema was markedly improved. Moreover, the number of TUNEL?positive cells was reduced, while the number of Ki67?stained positive cells was significantly increased. Additionally, the mRNA and protein expressions of PI3K, PDK1, AKT, and mTOR were all up-regulated (all P<0.05). (3) Compared to the NC group, 56 miRNAs were up-regulated and 42 miRNAs were down-regulated in the IPC group. The target genes of GO enrichment analysis were PIK3C2A, PIK3CA, PIK3CB, PIK3CD, PIK3C2G, AKT1, mTOR, Rheb, and KEGG enrichment analysis revealed significant enrichment in PI3K/AKT signal pathway and mTOR signal pathway. In conclusion, this study reveals that during the course of RIRI, exosomes derived from IPC renal tubular cells induce differential miRNA expression in kidney tissues, resulting in enhanced expression of the PI3K/AKT/mTOR signaling pathway, which plays a pivotal role in mitigating RIRI in rats.

  • Case Report

  • Chen Na, Xu Tian, Liu Hong, Tian Na, Zhang Xiaoliang
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    Adynamic bone disease (ABD) is a common type of chronic kidney disease-mineral and bone disorder (CKD-MBD). It is characterized by decreased bone transport and bone remodeling. Clinically, low parathyroid hormone (PTH) is an important feature of ABD. Tumoral calcinosis (TC) is a rare benign lesion characterized by extensive calcification of soft tissue and periarticular structures, but its exact pathogenesis is still unclear. Although the incidence of uremic tumoral calcinosis (UTC) in dialysis patients is low, it has a serious adverse impact on the quality of life and prognosis of patients. This paper reports two patients with ABD complicated with UTC. One patient had TC involving both hands, both feet, both scapulae, sternoclavicular joint, ilium, femoral head and sacrococcygeal region, and the other patient had TC involving the left shoulder. After treatment with recombinant human PTH teriparatide injection, sodium thiosulfate, phosphorus reduction, and full dialysis, the patients' condition improved.

  • Huang Wenwen, Peng Yangpei, Zheng Yu, Zheng Shubei
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    Nephronophthisis (NPHP) is a rare autosomal recessive inheritance disease that is an important cause of renal failure in children and adolescents. The paper reports a 17-year-old male NPHP patient, admitted to the hospital with "vomiting and fatigue for 10 days, aggravated for 1 day", diagnosed with "kidney failure" after test results showed a significant increase in serum creatinine, anemia, hypocalcemia, hyperphosphatemia, hyperkalemia, and metabolic acidosis. Heterozygous variants in the ZNF423 gene c.1436T>C (p.Val479Ala), a novel mutation site, was identified in the patient by whole exome sequencing for renal failure-associated phenotypes, which provides a new direction for genetic and hereditary analysis of NPHP.

  • Zhu Huayan, Lei Xin, Chen Liangliang, Chen Jianghua, Han Fei
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    The paper reports a rare case of idiopathic multicentric Castleman's disease with nephrotic syndrome as the first presentation. The patient was a 68-year-old male, presented with edema at admission. His clinical manifestations included nephrotic syndrome, and multiple enlarged lymph nodes. Renal biopsy showed minimal change disease, and cervical lymph node biopsy showed Castleman's disease. The patient received treatment of glucocorticoid combined with tocilizumab, and then rituximab. After 14 months of follow-up, the patient achieved remission of nephrotic syndrome.

  • Experience Exchange

  • Meng Xianglong, Wang Junru, Ren Song, Liang Jing, Zhang Yaling, Zhang Tao, He Qiang
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    Long term retention of hemodialysis catheters in blood vessels can lead to the formation of fibrin sheath, which is one of the main reasons causing catheter dysfunction. This study aims to explore a new in situ tube replacement technique that breaks through the binding of fibrin sheath. The tunnel-cuffed catheters of right internal jugular vein due to dysfunction were reimplanted with a double guide wire combined with balloon catheter sheathing technique in seven patients. The surgery successfully broke through the fibrin sheath constraint, and postoperative catheter dialysis proceeded smoothly, and none had catheter dysfunction during 6 months of follow-up. The double guide wire combined with balloon catheter sheathing technique is a safe and effective method in situ catheterization.

  • Review

  • Zhang Ying, Wang Xiaoxu, Zhang Xiaoliang, Wang Bin
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    Common complications related to nutritional metabolism and somatic function in chronic kidney disease patients include protein-energy wasting, sarcopenia, and frailty. These three complications are different and closely related. This article reviews recent research progress on the definitions, epidemiology, diagnosis and evaluation, underlying causes, intervention measures and their differences and connections of chronic kidney disease in conjunction with protein-energy wasting, sarcopenia and frailty, to help clinicians identify them and personalize interventions.

  • Clinical Demand · Innovation · Transformation

  • CKIA Innovation Research Working Group, Society of Nephrology, Chinese Research Hospital Association
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    Peritoneal dialysis is becoming the preferred dialysis mode for more and more patients with end-stage renal disease. However, the current peritoneal dialysis products cannot meet the ideal peritoneal dialysis treatment needs. Based on the analysis of the incoPat patent database, the Innovation Research Working Group of the China Kidney Innovation Association (CKIA) summarized the peritoneal dialysis patent applications of the past ten years from 46 representative medical institutions in the field of nephrology in 19 provinces and 4 municipalities in China. A total of 271 patents related to peritoneal dialysis were screened, mainly utility model patents (80.1%), and the top three needs included peritoneal dialysis manual fluid exchange, peritoneal dialysis catheter or peritoneal dialysis transfer set, drainage fluid disposal and sampling. The subdivision of patent was summarized, which fully reflects the urgent need to improve the effectiveness, safety and convenience of peritoneal dialysis treatment, improve the achievement ratio of peritoneal dialysis-related surgery and reduce complications, and improve the whole chain of peritoneal dialysis related products to enhance the quality of treatment and meet the personalized needs of patients. At the same time, the report shows that the new diagnosis and treatment methods involved in the patent application for peritoneal dialysis are seriously insufficient, and there is still a considerable gap with the cutting-edge scientific and technological level in the field of kidney. By condensing the technological innovation needs of the whole chain of peritoneal dialysis related products, the working group provides track for the future innovation and transformation of peritoneal dialysis treatment, in order to promote the progress of peritoneal dialysis technology in China.