Objective To evaluate the efficacy and safety of sacubitril?valsartan (SV) in reducing blood pressure in patients with non-dialysis-dependent chronic kidney disease(NDD-CKD) stage 3-5 and concomitant hypertension. Methods It was a retrospective study. Adult NDD-CKD stage 3-5 patients with hypertension treated with SV alone or in combination with SV on the basis of 2 to 4 antihypertensive drugs having unsatisfactory effects from March 1, 2022 to June 30, 2023 in Zhongda Hospital Affiliated to Southeast University were included. SV doses ranged from 25 mg once daily to 200 mg twice daily. The primary outcome was blood pressure control. The changes of blood pressure and laboratory examination indexes between baseline and 1 to 2 months after SV treatment were compared, and adverse events were also recorded. Results A total of 37 NDD-CKD stages 3-5 patients with hypertension were included in the study, with age ranging from 29 to 85 years old, and 15 males (40.5%). The SV duration of medication was 1 (1, 1) month. At the study endpoint, there was a significant decrease in mean systolic blood pressure, diastolic blood pressure, and pulse pressure from baseline, with reduction of 20.4 (9.6, 28.8) mmHg (1 mmHg=0.133 kPa, Z=-5.243, P<0.001), (6.9±7.6) mmHg (t=5.532, P<0.001), and 13.0 (8.0, 18.8) mmHg (Z=-4.941, P<0.001), respectively. During the study period, 8 patients (21.6%) experienced worsening of renal function, and there were no statistically significant differences in the changes of serum creatinine and estimated glomerular filtration rate before and after treatment (Z=-0.487, P=0.626; Z=-0.110, P=0.912, respectively). No adverse drug reactions such as hyperkalemia, symptomatic hypotension, angioedema, hepatic impairment, and decreased hemoglobin level were observed during the study period. Conclusion SV effectively lowers blood pressure in NDD-CKD stage 3-5 patients with hypertension and exhibits good safety.

Objective To elucidate the prevalence of hyperphosphatemia and utilization rate of phosphorus-lowering drugs in adult non-dialysis chronic kidney disease (CKD) patients in China, and explore the relationship between hyperphosphatemia, phosphate-lowering therapy, and clinical outcomes. Methods It was a large retrospective and multicenter cohort study. The study subjects were sourced from the China Renal Data System. The first-time hospitalized patients aged 18 years old and above and diagnosed with CKD who did not enter dialysis and having serum phosphorus test results from 2013 to 2020 were included. Hyperphosphatemia was defined as an initial serum phosphorus level exceeding 1.45 mmol/L during hospitalization, and normal serum phosphorus was defined as 0.97 mmol/L ≤ serum phosphorus ≤ 1.45 mmol/L. Cox regression model was employed to assess the association of hyperphosphatemia with all-cause mortality, cardiovascular mortality, and CKD progression as well as the association of phosphorus-lowering therapy with all-cause mortality and cardiovascular mortality. Results A total of 157 987 adult non-dialysis CKD patients with serum phosphorus test results were included in the study, with age of 60 (47, 72) years old and 91 453 males (57.89%). The estimated glomerular filtration rate was 63.49 (39.12, 92.90) ml·min^-1·(1.73 m²)^-1. The common comorbidities included hyperlipidemia (53.48%, 84 497/157 987), hypertension (37.23%, 58 818/157 987) and heart failure (27.02%, 42 686/157 987). The prevalence of hyperphosphatemia was 14.83% (23 431/157 987). Among CKD stage 3-5 patients with hyperphosphatemia, the utilization rate of phosphate-lowering medications was 13.34% (3 962/29 705). Multivariate Cox regression analysis showed that among 64 662 patients with ≥ 90 days of follow-up [3.3 (1.5, 5.4) years], hyperphosphatemia was significantly correlated with an increased risk of all-cause mortality and cardiovascular mortality (hyperphosphatemia/normal serum phosphorus, HR=1.13, 95% CI 1.06-1.22, P=0.001; HR=1.28, 95% CI 1.04-1.56, P=0.018, respectively). Among 47 581 patients with ≥ 90 days of follow-up [1.8 (0.9, 3.2) years] and baseline estimated glomerular filtration rate > 30 ml · min^-1 ·(1.73 m²)^-1, hyperphosphatemia was significantly correlated with an increased risk of CKD progression (hyperphosphatemia/normal serum phosphorus, HR=1.08, 95% CI 1.00-1.17, P=0.038). Among 8 856 patients with follow-up data of death [3.3 (1.5, 5.4) years] and hyperphosphatemia,phosphate-lowering medication use was significantly correlated with a reduced risk of all-cause mortality (HR=0.88, 95% CI 0.82-0.95, P<0.001) and cardiovascular mortality (HR=0.84, 95% CI 0.72-0.97, P=0.022). Conclusions The prevalence of hyperphosphatemia is high among Chinese adult non-dialysis CKD patients, but the utilization rate of phosphate-lowering medications remains low. Hyperphosphatemia is an independent risk factor of all-cause mortality, cardiovascular mortality, and kidney function progression, while phosphate-lowering medications may mitigate these risks in non-dialysis CKD patients. Regular monitoring of serum phosphorus level for non-dialysis CKD patients, and initiating phosphate-lowering therapy for hyperphosphatemia patients may positively improve clinical outcomes.

Objective To investigate the extraglomerular deposition of C1q in patients with lupus nephritis (LN) and explore its clinicopathological significance, and to provide immunological evidence for the mechanism of renal tubulointerstitial injury in LN. Methods It was a cross-sectional study. The clinical data of patients with LN confirmed by renal biopsy in the First Affiliated Hospital of Henan University of Chinese Medicine from March 1, 2019 to June 30, 2023 were collected. Extraglomerular deposition of C1q, including tubular basement membranes (TBMs), peritubular capillaries and interstitial arterioles, was detected by direct immunofluorescence method in paraffin sections, and the relationship between C1q expression and corresponding tissue lesions was analyzed in successive sections. Pearson correlation coefficient or Spearman correlation coefficient was used to analyze the correlation between C1q expression level and renal histopathologic scores (active tubular interstitial index, active glomerular index, active index, chronic tubular interstitial index, chronic glomerular index, chronic index), clinical indexes(24-hour urinary protein, urinary alpha-1 microglobulin, urinary N-acetyl-β?D?glucosidase and serum creatinine). Results A total of 71 patients with LN were included in the study, including 14 males (19.72%) and 57 females (80.28%), with age of (20.83±11.77) years old (7-48 years old). The paraffin sections analysis showed that 60 patients (84.51%) had extraglomerular deposits of C1q. C1q deposits occurred in the TBMs and/or peritubular capillaries and/or interstitial arterioles, with the highest positive rate (50 patients, 70.42%) in TBMs. Forty-four patients (61.97%) had scattered or focal C1q deposition in the TBMs. Thirty-two patients (45.07%) had scattered or focal C1q deposition in peritubular capillaries. The positive proportion of C1q in TBMs was the highest in type Ⅳ of LN (15/18). The positive proportion of C1q in peritubular capillaries was the highest in type Ⅱ of LN (5/6). The continuous sections of kidney tissues showed that C1q was mainly expressed in the acute tubulointerstitial inflammation area, and no positive expression was found in the tubule atrophy area. The correlation analysis showed that C1q deposition level in TBMs was positively correlated with active tubular interstitial index (r=0.640, P<0.001), urinary alpha-1 microglobulin (r=0.573, P<0.001), urinary N?acetyl-β?D?glucosaminidase (r=0.404, P=0.008) and serum creatinine (r=0.399, P=0.001). There was no correlation between the positive percentage of C1q in peritubular capillaries and 24 h urinary protein, urinary alpha-1 microglobulin, urinary N-acetyl-β?D?glucosidase, serum creatinine and renal histological scores. Conclusion C1q deposition in TBMs may be one of the causes of tubulointerstitium injury, it is recommended to be marked in the routine renal pathological diagnosis.

Objective To explore the clinical features and genotypes of patients with nephronophthisis type 1 (NPH1) associated with NPHP1 gene defect. Methods It was a case series analysis. Clinical data and blood samples of patients who were suspected of NPH1 were collected retrospectively. Next generation sequencing (NGS) or microsatellite markers (MMS) were used to detect the variations and homozygous deletion of NPHP1. Results (1) In this study, a total of 20 patients from 16 families were diagnosed as NPH1 with NPHP1 variations and/or homozygous deletions. The median onset age of the patients was 9.5 years old (ranging from 3.0 to 21 years old), and the mean time from onset to diagnosis was 2.1 years (ranging from 0.1 to 6.5 years). The clinical manifestations of the first diagnosis were renal insufficiency in 7 cases (35.0%), polydipsia, polyuria or nocturia in 8 cases (40.0%), anemia in 4 cases (20.0%), and growth retardation in 7 cases (35.0%), of which 1 case was first diagnosed with growth retardation and thoracic malformation. In terms of renal manifestations, 10 patients (50.0%) exhibited negative urinary protein by urine routine test, while 10 patients (50.0%) presented with a small amount of proteinuria. Notably, none of the patients displayed hematuria. At first diagnosis, 18 patients (90.0%) exhibited varying degrees of renal impairment, and the median age of progression to stage 5 chronic kidney disease was 12 years (ranging from 9.1 to 16.5 years). Of the 17 patients who underwent urine protein composition analysis, 15 had elevated α1 microglobulin and β2 microglobulin, including 6 patients with negative urine routine test. The volume of the kidney was normal in 11 patients (55.0%) and decreased in 9 patients (45.0%), including 7 patients with both kidneys affected and 2 patients with a single kidney affected. B-ultrasonography and magnetic resonance hydrography showed that 12 patients (60.0%) presented with single or multiple renal cysts located at the cortical medullary junction and/or renal medulla, and 8 patients (40.0%) had no cyst. Renal biopsy performed on 9 patients consistently revealed tubular atrophy and lumen dilation, tubular basement membrane thickening or stratification, interstitial fibrosis and inflammatory cell infiltration. A total of 5 cases exhibited extrarenal manifestations, including Senior-Loken syndrome, amblyopia or ametropia, Cogan syndrome, liver cyst, etc. Among the 20 confirmed patients from 16 families, homozygous deletion of NPHP1 exon (exon 1-20) occurred in 10 patients from 8 families, heterozygous deletion accompanied by point mutation occurred in 7 patients from 5 families, and complex heterozygous point mutation occurred in 3 patients from 3 families. No statistically significant differences were found in clinical phenotypes (gender, kidney volume, cyst formation, urinary protein) among patients with different mutation types (all P>0.05). Of the 16 patients who underwent NGS (targeted exome sequencing and whole exome sequencing), 8 had pathogenic gene variants related to other ciliopathies. When compared to the 8 patients without other ciliopathy-related pathogenic gene variants, no significant differences were found in gender, age of onset, disease duration before treatment, kidney phenotype (including kidney size, cyst formation, urinary protein), and age of progression to stage 5 chronic kidney disease (all P>0.05). (2) In addition, 4 patients from 4 other families were found to have only a single heterozygous mutation in NPHP1, and lacked any other genetic variants that could explain cystic nephropathy and/or ciliopathy. Based on clinical findings, these patients were diagnosed as NPH. (3) Totally, 12 point mutations were found in this study, of which 8 novel point mutations (c.728+1G>A, c.1630delA, c.1122+1G>T, c.2081A>G, c.1333C>G, c.625-2A>T, c.1374G>T, c.968C>T) were identified. Conclusions The genotype of NPHP1 in this series of patients is significantly different from those reported abroad, with a higher proportion of novel mutation and greater genetic background diversity. There is no significant difference in clinical manifestation among patients with different genotypes.

Objective To understand the dynamic changes of genes and proteins in renal tissues of calcium oxalate crystal kidney injury, and to explore the possible mechanism of calcium oxalate crystal kidney injury. Methods Ten 8-week-old male C57BL/6J mice were adaptively fed for 1 week and divided into control group and calcium oxalate crystal kidney injury group (model group) according to random number table method. The calcium oxalate crystal kidney injury mice were established by intraperitoneal injection of glyoxylate (50%, 9 mmol/L, 100 mg·kg^-1·d^-1 for 5 days). Mice in control group were intraperitoneally injected with 0.9% sodium chloride solution of equal volume. HE staining, PAS staining, Masson staining, and Von Kossa staining were used to observe whether the model mice were successfully constructed. Transcriptome and proteome sequencing were performed on the kidneys of control mice and model mice. Genes and proteins related to calcium oxalate crystal kidney injury were screened according to the results of differential expressed genes (DEGs) and differential abundance proteins (DAPs), and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed based on the above results. Principal component analysis, heat map and volcano map were used to perform the transcriptomic and proteomic analysis of renal tissues. Venn diagram was used to analyze the overlap of differential genes and differential proteins. Results Von Kossa staining of the kidney showed a large amount of calcium salt deposition at the cuticer-pulp junction, and serum creatinine, blood urea nitrogen and other markers of kidney injury significantly increased in the model group, suggesting that calcium oxalate crystal kidney injury model was established successfully. Transcriptome and proteome sequencing showed that, compared with control group, 2 815 DEGs and 1 197 DAPs were obtained in the model group, respectively; 2 004 DEGs and 353 DAPs were significantly up-regulated; 811 DEGs and 844 DAPs were significantly down-regulated in the model group. A total of 338 DEGs corresponded with DAPs, 324 of which had the same trend with DAPs. The significantly different 10 molecules included serum amyloid A1 (SAA1), minichromosome maintenance 4 (MCM4), arginase 2 (ARG2), S100 calcium-binding protein A6 (S100A6), cluster of differentiation 14 (CD14), glucose-6-phosphatase catalytic subunit (G6PC), solute carrier family 22 member 6 (SLC22A6), solute carrier organic anion transporter family member 1A1 (SLCO1A1), phosphoenolpyruvate carboxykinase 1 (PEPCK1) and indolamine N-methyltransferase (INMT) in the up-regulated and down-regulated differential genes and proteins. GO analysis indicated that the commonly enriched pathways in the two groups of correlated differential molecules were primarily involved in mitochondrial dysfunction, energy metabolism pathways and immune disorder. KEGG enrichment analysis showed that the differentially expressed molecules were mainly enriched in transporter anomaly, mitochondrial dysfunction, neurodegenerative diseases, amino acid metabolism and abnormal energy metabolism pathways such as oxidative phosphorylation. Conclusions Abundant genes and proteins changes in kidneys of calcium oxalate crystal kidney injury mice. Mitochondrial dysfunction, multiple metabolic pathways abnormalities, and immune response may be important mechanisms involved in the pathogenesis of calcium oxalate crystal kidney injury.

It was a retrospective cohort study. Peritoneal dialysis exudate samples from patients diagnosed with peritoneal dialysis-associated peritonitis (PDAP) in the Nephrology Department of the Second Affiliated Hospital of Hainan Medical College from January 1, 2021 to December 31, 2022 were collected. Based on different time of peritonitis, the specimens were split into two groups: the traditional method group and the modified method group. Only the traditional method was used for pathogen culture in the traditional method group. Both the traditional method and modified method were used for pathogen culture in the modified method group. The rates of positive culture of pathogenic bacteria, duration required to obtain positive culture results, spectrum of pathogenic bacteria, and drug resistance were analyzed. The results showed that a total of 223 patients (324 cases) with PDAP were included in the study, including 115 patients (168 cases) in the traditional method group and 108 patients (156 cases) in the modified method group. The modified method group displayed a significantly higher rate of pathogenic bacteria than the traditional method group [84.62% (132/156) vs. 69.23% (108/156), χ² =18.903, P<0.001]. Additionally, the modified method group required less time to achieve a positive culture result of pathogenic bacteria than the traditional method group [69.0 (58.0, 90.9) h vs. 79.5 (65.6, 90.2) h, Z=2.061, P=0.039]. In this study, 120 culture-positive pathogens were identified in the traditional method group, of which, 69 (57.50%) were Gram-positive, 46 (38.33%) were Gram-negative, and 5 (4.17%) were fungi; The common strains of Gram-positive bacteria were staphylococcus epidermidis (17 strains, 14.17%) and streptococcus salivarius (10 strains, 8.33%). There were 134 culture-positive pathogens identified in the modified method group, of which 106 (79.10%) were Gram?positive, 24 (17.91%) were Gram?negative, and 4 (2.99%) were fungi; The common strains of Gram-positive bacteria were streptococcus salivarius (20 strains, 14.93%) and staphylococcus epidermidis (15 strains, 11.19%). Gram-positive bacteria had the highest resistance rate to oxacillin (50/85, 58.82%), Gram-negative bacteria had the highest resistance rate to ampicillin (21/35, 60.00%), and fungi was only resistant to fluconazole (1/9, 11.11%). The study suggests that the modified method can increase the positive rate of pathogen culture and shorten the culture time in peritoneal dialysate effluent. Gram?positive cocci are the main pathogenic bacteria of PDAP in this center. Oxacillin and ampicillin should not be the first choice for the treatment of PDAP in this center.

Primary hyperoxaluria is a rare autosomal recessive hereditary disease. Some patients are diagnosed with end-stage renal failure at their first visits, and require receiving maintenance renal replacement therapy. The paper reported a maintenance hemodialysis patient with primary hyperoxaluria characterized by severe anemia, intractable hypoalbuminemia and hypercoagulability. After intensively supportive treatment including increasing the frequency of hemodialysis, strengthening ultrafiltration, correcting anemia, iron supplementation, anticoagulation, albumin supplementation and correcting calcium/phosphorus metabolism disorder, and incombination with sodium thiosulfate treatment, the patient's condition improved significantly.

Metastatic pulmonary calcification (MPC), defined as abnormal deposition of calcium salts in the intact lung, is common in patients with chronic renal failure. The paper reported a case of rapidly progressing lung lesions in a maintenance peritoneal dialysis patient. The patient was finally diagnosed with MPC through ⁹⁹Tc^m-methylene diphosphonate bone scintigraphy and percutaneous lung puncture pathology. After treatment with intravenous infusion of sodium thiosulfate combined with a calcium-free phosphorus binding agents, the extent of pulmonary calcification decreased significantly compared to before. Pulmonary lesions did not progress after discontinuation of sodium thiosulfate. It suggests that sodium thiosulfate combined with calcium-free phosphorus binding agents is effective in treating MPC.

Dent disease is a rare X-linked recessive genetic disorder characterized by low molecular weight proteinuria (LMWP), hypercalcemia, and at least one other sign including nephrocalcinosis, nephrolithiasis, hematuria, hypophosphatemia, or renal insufficiency. Herein, a case of Dent diseases type 1 caused by CLCN5 gene deletion mutation confirmed by genetic testing is reported. This patient is a young male with clinical manifestations of LMWP, nephrolithiasis, hematuria, renal insufficiency, hypokalemia, and intermittent hypophosphatemia. The main manifestation of renal pathology is focal global glomerulosclerosis. By far, this deletion mutation of CLCN5 has not been reported previously. This case will raise the awareness of Dent disease among nephrologists.

As the most important component of renal parenchyma, tubular epithelial cells (TECs) play numerous regulatory roles in the occurrence and development of chronic kidney disease(CKD). Exosomes, double-membrane vesicles that are naturally secreted by cells, contain various bioactive molecules, including proteins, nucleic acids, and lipids, and serve as mediators for intercellular communications. This article reviewed the sources and characteristics of TECs-derived exosomes, the roles of TECs-derived exosomes affecting renal interstitial fibrosis in CKD, and the roles of TECs-derived exosomes in the diagnosis of CKD, to provide new ideas for the prevention and treatment in CKD.

Continuous renal replacement therapy (CRRT) is widely used in critically ill patients, and effective anticoagulation is a crucial step in this implementation. Regional citrate anticoagulation (RCA) has been widely used in clinical practice to reduce the risk of bleeding in patients. However, controversies persist regarding its application in CRRT patients with hyperlactatemia. Therefore, the author reviewed the progress in the application of RCA during CRRT in patients with hyperlactatemia of different etiologies by summarizing recent relevant literature, to provide a valuable reference and guide for its clinical implementation.

Anemia is a significant influencing factor of peritoneal dialysis (PD) patients to suffer from cardiovascular diseases, worse therapeutic effect and death. However, compared with hemodialysis patients, there are fewer clinical studies and epidemiological investigations concerning anemia in PD patients. The influencing factors of anemia in PD patients are numerous and complex, but there is a lack of strong evidence on the specific degree and direction of each factor. Further understanding of the influencing factors of anemia in PD patients is more conducive to the targeted correction of anemia status. This article reviewed the epidemiological status of anemia in PD patients, and the influencing factors of anemia from the aspects of physiological factors, therapeutic factors, nutritional factors and other factors, to provide references for the treatment and related studies of anemia in PD patients.