Hyperactivation of p53 contributes to mitotic catastrophe in podocytes through regulation of the Wee1/CDK1/cyclin B1 axis.

Podocyte loss in glomeruli is a fundamental event in the pathogenesis of chronic kidney diseases. Currently, mitotic catastrophe (MC) has emerged as the main cause of podocyte loss. However, the regulation of MC in podocytes has yet to be elucidated. The current work aimed to study the role and mechanism of p53 in regulating the MC of podocytes using adriamycin (ADR)-induced nephropathy. In vitro podocyte stimulation with ADR triggered the occurrence of MC, which was accompanied by hyperactivation of p53 and cyclin-dependent kinase (CDK1)/cyclin B1. The inhibition of p53 reversed ADR-evoked MC in podocytes and protected against podocyte injury and loss. Further investigation showed that p53 mediated the activation of CDK1/cyclin B1 by regulating the expression of Wee1. Restraining Wee1 abolished the regulatory effect of p53 inhibition on CDK1/cyclin B1 and rebooted MC in ADR-stimulated podocytes via p53 inhibition. In a mouse model of ADR nephropathy, the inhibition of p53 ameliorated proteinuria and podocyte injury. Moreover, the inhibition of p53 blocked the progression of MC in podocytes in ADR nephropathy mice through the regulation of the Wee1/CDK1/cyclin B1 axis. Our findings confirm that p53 contributes to MC in podocytes through regulation of the Wee1/CDK1/Cyclin B1 axis, which may represent a novel mechanism underlying podocyte injury and loss during the progression of chronic kidney disorder.

Factors Associated with Dialysis Initiation in Patients with Predialysis Arteriovenous Fistula.

INTRODUCTION: A large proportion of patients initiated hemodialysis with a central vein catheter rather than a permanent vascular access which was recommended by guidelines. One major barrier was the paucity of evidence regarding the optimal timing of vascular access creation in predialysis patients. METHODS: Our study prospectively enrolled 300 patients undergoing predialysis arteriovenous fistula (AVF) creation in our center from 2015 to 2018. Cox proportional hazard regression was performed to identify which demographic and clinical factors were associated with the initiation of hemodialysis after AVF surgery. A receiver operating characteristic area under the curve (AUC) was used to assess the predictive power of preoperative factors for the likelihood of hemodialysis initiation. RESULTS: Overall, 163 (54.3%), 214 (71.3%), and 275 (91.7%) patients initiated hemodialysis within 3 months, 6 months, and 1 year, respectively, after AVF creation. The median time between AVF creation and hemodialysis start was 71.5 days. Using multivariate Cox regression analysis, three factors were associated with hemodialysis initiation within 1 year: serum phosphorus (HR = 1.407, p = 0.021), diabetic kidney disease (DKD) (HR = 1.429, p = 0.039), and cystatin C (HR = 1.179, p = 0.009). Cystatin C alone had a moderate predictive value for dialysis initiation (AUC = 0.746; p < 0.001), whereas the full model had a higher predictive value (AUC = 0.800; p < 0.001). CONCLUSION: DKD, serum cystatin C, and phosphorus at access surgery were associated with hemodialysis initiation within 1 year of the predialysis AVF creation. Our findings provide a basis for a more customized approach to planning AVF placement in patients with chronic kidney disease.

Serum Phosphorus Might Be a Predictor of Kidney Disease Progression in IgA Nephropathy.

INTRODUCTION: High serum phosphorus level has been reported to be a risk factor for disease progression in patients with chronic kidney disease, whereas, its role in IgA nephropathy (IgAN) still remains uncertain. This study aimed to investigate the association between serum phosphorus and progression of IgAN. METHODS: A total of 247 patients diagnosed with IgAN from 2016.11 to 2019.12 at the First Affiliated Hospital of Xi'an Jiaotong University were retrospectively enrolled in this study. The association between serum phosphorus and kidney disease progression events, defined as 30% estimated glomerular filtration rate (eGFR) decline or kidney failure, was evaluated using Cox models. RESULTS: Serum phosphorus was an independent risk factor for poor renal outcome after adjusting for age, gender, urine protein, MAP, eGFR, hemoglobin, Oxford S and T scores (HR, 2.586; 95% CI, 1.238-5.400, p = 0.011). The addition of serum phosphorus to the reference model containing clinical and pathological variables significantly improved the risk prediction of IgAN progression (C statistic, 0.836; 95% CI, 0.783-0.889) as compared with the reference model (C statistic, 0.821; 95% CI, 0.756-0.886). The ability of serum phosphorus level to predict progression was much stronger in IgAN patients without use of immunosuppression (HR 5.173; 95% CI, 1.791-14.944; p = 0.002). CONCLUSION: Higher serum phosphorus levels were independently associated with kidney disease progression in patients with IgAN, especially in those without immunosuppression. The addition of serum phosphorus to clinical and pathological data at the time of biopsy significantly improved risk prediction of IgAN progression.

Microbacterium spp. peritonitis in patients undergoing peritoneal dialysis: a single-center experience and literature review.

Introduction: Peritoneal dialysis-related peritonitis (PDRP) caused by Microbacterium spp. is very rare, with only 9 cases reported to date. In this study, we report the treatment experiences of 7 patients at our peritoneal dialysis center. Methods: We retrospectively collected clinical characteristics and antibiotic management of all 7 episodes of PDRP caused by Microbacterium spp. in 7 patients from at our center over 4 years, and reviewed the documented Microbacterium spp. PDRP in the literature. Results: Empiric antibiotic therapy was initiated as soon as possible, and consisted of intraperitoneal (IP) gentamicin in combination with vancomycin. After up to 5 days, gentamicin was changed to meropenem if the treatment was not effective. The intended course of antibiotic treatment was 21-day. Totally, 6 episodes were cured (85.7%), which was higher than reported. Conclusion: The 21-day antibiotic therapy program by combining vancomycin and meropenem may benefit the management of Microbacterium spp. PDRP.

The association of serum anti-PLA2R antibody and glomerular PLA2R antigen staining with clinical manifestations and outcomes in membranous nephropathy.

BACKGROUND: Phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN) was manifested as seropositive for PLA2R antibodies (SAb) and/or glomerular PLA2R antigens' (GAg) deposits. According to the test of SAb and GAg, PLA2R-associated MN can be divided into SAb + /GAg-, SAb-/GAg + , and SAb + /GAg + groups. The clinical characteristics and outcomes of the three groups need to be further evaluated. METHODS: 184 PLA2R-associated MN patients were enrolled. SAb was measured by enzyme-linked immunosorbent assay with a cut-off value of 14 RU/mL. GAg was detected by immunofluorescence using a paraffin section of renal biopsy samples. Clinical characteristics and the decline of eGFR were compared among the 3 groups. RESULTS: There were 33 SAb + /GAg-, 46 SAb-/GAg +, and 105 SAb + /GAg + PLA2R-associated MN patients reviewed. Clinical characteristics, such as the level of proteinuria, serum albumin, as well as eGFR, were comparable between the SAb + /GAg- and SAb + /GAg + patients. While SAb-/GAg + patients exhibited mild clinical manifestations as evidenced by higher serum albumin (P < 0.001) and lower proteinuria (p = 0.049) compared with SAb + /GAg + patients. After 21.96 ± 7.39 month follow-up, the eGFR decrease was no difference between the SAb + /GAg- and SAb + /GAg + patients. SAb-/GAg + patients had a lower rate of the > 20% eGFR decline as well as a 50% eGFR decline compared with the SAb + /GAg + patients (10.87% vs 30.48%, p = 0.013; 0.00% vs 4.76%, p = 0.324). CONCLUSIONS: Our study showed that the clinical manifestations of SAb + /Gag- patients were the same as those of double-positive patients, while SAb-/GAg + patients exhibited mild clinical manifestations and slower eGFR decline compared to the double-positive patients.

Clinical features and outcomes of patients with antineutrophil cytoplasmic antibody-positive systemic lupus erythematosus.

Purpose: To investigate the clinical characteristics, pathological features, and outcomes of patients with antineutrophil cytoplasmic antibody (ANCA)-positive systemic lupus erythematosus (SLE) in northwest China.Methods: This retrospective study included 491 patients with SLE tested for ANCA antibodies and 171 patients with ANCA-associated vasculitis (AAV) as controls. Subgroup analysis limited to those with renal involvement, and by ANCA antibody subtype (PR3 vs MPO). To compare the proteinuria remission rates between ANCA-positive and ANCA-negative lupus nephritis (LN) groups, a logistic regression model was used for propensity score matching based on age, hemoglobin, and baseline estimated glomerular filtration rate (eGFR).Results: Compared to ANCA-negative SLE (n = 442), ANCA-positive SLE (n = 46) occur in older patients; however, these patients were younger than those with AAV (n = 167). The eGFR of patients with ANCA-positive LN (n = 25) was higher than that of patients having AAV with renal involvement (n = 56) but lower than that of patients with ANCA-negative LN (n = 163). Patients with SLE who had MPO-ANCA (n = 16) had higher levels of serum creatinine compared to those with PR3-ANCA (n = 30) (156.5 µmol/L vs. 45.5 µmol/L, p = 0.005). During the follow-up period, the remission rate of proteinuria in patients with ANCA-positive LN was lower than that of patients with ANCA-negative LN (50% vs. 75%, p = 0.008).Conclusion: Patients with ANCA-positive LN may have worse baseline renal function and lower protein remission rates compared to patients with ANCA-negative LN. ANCA titers should be regularly monitored throughout the follow-up period in patients with SLE, especially in cases of renal involvement.

Efficacy and Safety of Sevelamer Carbonate in Chinese Nondialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized, Double-Blind, Parallel-Group Study.

Introduction: Previous studies suggested that sevelamer carbonate is well tolerated with a favorable efficacy and safety profile in both dialysis and nondialysis patients in Europe; however, the efficacy remains controversial, and few studies have examined sevelamer carbonate therapy in other ethnic nondialysis CKD patients. This study assessed the efficacy and safety of sevelamer carbonate in Chinese nondialysis CKD patients with hyperphosphatemia. Methods: The multicenter, randomized, double-blind, parallel-group, placebo-controlled, and phase 3 clinical trial enrolled 202 Chinese nondialysis CKD patients with serum phosphorus ≥1.78 mmol/L. Patients were randomly assigned 1:1 to receive sevelamer carbonate (2.4-12 g per day) or placebo for 8 weeks. The primary outcome was the change in serum phosphorous between baseline and week 8. Results: Totally 482 Chinese patients were screened and 202 were randomized (sevelamer carbonate, n = 101; placebo, n = 101). The mean serum phosphorous decreased significantly in patients treated with sevelamer carbonate compared with placebo (-0.22 ± 0.47 vs. 0.05 ± 0.44 mmol/L, p < 0.0001). Significantly (p < 0.0001), decreases of serum total cholesterol, low-density lipoprotein cholesterol, and calcium-phosphorus (Ca × P) product levels from baseline to week 8 were shown in sevelamer carbonate group compared with placebo group. Serum intact parathyroid hormone was not significantly changed in the sevelamer carbonate group (p = 0.83). Patients in the sevelamer carbonate group experienced similar adverse events as the placebo group. Conclusion: Sevelamer carbonate is an effective and well-tolerated phosphate binder in advanced nondialysis CKD Chinese patients with hyperphosphatemia.

Bone marrow mesenchymal stem cell-derived exosomal miR-30e-5p ameliorates high-glucose induced renal proximal tubular cell pyroptosis by inhibiting ELAVL1.

BACKGROUND: The rapid increase in the prevalence of diabetes has resulted in more cases of diabetic kidney disease (DKD). Treatment with bone marrow mesenchymal stem cells (BMSCs) may represent an alternative strategy to manage DKD. METHODS: HK-2 cells were treated with 30 mM high glucose (HG). Bone marrow MSC-derived exosomes (BMSC-exos) were isolated and internalized into HK-2 cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) and lactate dehydrogenase (LDH) assays were used to measure viability and cytotoxicity. The secretion of IL-1ß and IL-18 was measured by ELISA. Pyroptosis was assessed by flow cytometry. Quantitative RT-PCR was used to measure the levels of miR-30e-5p, ELAV like RNA binding protein 1 (ELAVL1), IL-1ß, and IL-18. The expression of ELAVL1 and pyroptosis-associated cytokine proteins was determined by western blot analysis. A dual-luciferase reporter gene assay was conducted to confirm the relationship between miR-30e-5p and ELAVL1. RESULTS: BMSC-exos decreased LDH, IL-1ß, and IL-18 secretion and inhibited the expression of the pyroptosis-related factors (IL-1ß, caspase-1, GSDMD-N, and NLRP3) in HG-induced HK-2 cells. Moreover, miR-30e-5p depletion derived from BMSC-exos promoted HK-2 cell pyroptosis. Besides, miR-30e-5p over-expression or ELVAL1 knockdown could directly inhibit pyroptosis. ELAVL1 was a target of miR-30e-5p and knocking down ELAVL1 reversed the effect of miR-30e-5p inhibition in BMSC-exos-treated HK-2 cells. CONCLUSIONS: BMSC-derived exosomal miR-30e-5p inhibits caspase-1-mediated pyroptosis by targeting ELAVL1 in HG-induced HK-2 cells, which might provide a new strategy for treating DKD.

Serum vancomycin levels predict the short-term adverse outcomes of peritoneal dialysis-associated peritonitis.

BACKGROUND: The role of monitoring serum vancomycin levels during treatment of peritoneal dialysis (PD)-associated peritonitis is controversial. Substantial inter-individual variability may result in suboptimal serum levels despite similar dosing of vancomycin. The published predictors of suboptimal serum vancomycin levels remain limited. METHODS: Data were retrospectively collected from 541 patients on continuous ambulatory peritoneal dialysis between 1 January 2018 and 31 December 312019. For gram-positive cocci and culture-negative peritonitis, we adopted a vancomycin administration and monitoring protocol. Short-term adverse outcomes of PD-associated peritonitis, including transfer to haemodialysis, death, persistent infection beyond planned therapy duration and relapse, were observed. The association between trough serum vancomycin levels and short-term adverse outcomes was evaluated. RESULTS: Intraperitoneal vancomycin was used in 61 gram-positive cocci or culture-negative peritonitis episodes in 56 patients. Fourteen episodes of short-term adverse outcomes occurred in 12 patients, whose average trough serum vancomycin levels on day 5 of treatment were significantly lower than those who didn't experience any adverse outcomes (8.4 ± 1.7 vs 12.5 ± 4.3 mg/L, p = 0.003). In gram-positive cocci or culture-negative peritonitis patients, those with higher day 5 trough serum vancomycin levels had a lower risk of short-term adverse outcomes (odds ratio: 0.6, 95% confidence interval: 0.4 to 0.9, p = 0.011). Receiver operating charecteristic curve (ROC) analyses showed that the day 5 trough serum vancomycin levels diagnostic threshold value for short-term adverse outcomes was 10.1 mg/L. After adjustments for gender, exchange volume and residual kidney function (RKF), baseline higher peritoneal transport was associated with a suboptimal (<10.1 mg/L) day 5 serum vancomycin level. CONCLUSIONS: Serum vancomycin levels are correlated with short-term adverse outcomes of PD-associated peritonitis, and higher peritoneal solute transport status is associated with suboptimal trough serum vancomycin levels on day 5.

Population structure and genetic diversity in Eucalyptus pellita based on SNP markers.

Eucalyptus pellita has the characteristics of rapid growth and high resistance. However, there is little research on molecular breeding of E. pellita, which is essential to shortening breeding life and selecting quality varieties. Therefore, a crucial step before selective breeding can be carried out to increase the wood quality of E. pellita is identifying genetic diversity and population structure using single nucleotide polymorphism (SNP) markers. In this study, the genetic diversity of 1st generation 196 E. pellita families from 23 geographically defined was assessed using 1,677,732 SNP markers identified by whole genome resequencing. SNP annotation showed that the ratio of non-synonymous to synonymous coding mutations was 0.83. Principal component analysis (PCA), phylogenetic tree, and population structure analysis permitted the families to be categorized into three groups, one of which (G2) contains most of the Indonesian (IDN) and Papua New Guinea (PNG) families. Genetic relationship analysis showed that IDN was closely related to PNG. Genetic diversity analysis showed that He, PIC, I, and H mean values were 0.2502, 0.2027, 0.3815, and 0.2680, respectively. PCA analysis classified various provenances in QLD into two categories (G1 and G3). The genetic diversity of G3 was higher than that of G2. The results of genetic differentiation (Fst) showed that PNG region was divided into two groups (PNG1 and PNG2), the Fst (0.172) between QLD and PNG2 region was higher than QLD and PNG1, and the Fst (0.024) between IDN and PNG1 is smaller than IDN and PNG2. A Mantel test revealed a positive correlation between the genetic and geographic distance of E. pellita. This study has a certain reference value for genetic identification, germplasm preservation, and breeding of E. pellita. Also, it provides a basis for subsequent association analysis to explore excellent alleles and introduction.

Genome-wide identification and expression analysis of GDP-D-mannose pyrophosphorylase and KATANIN in Corymbia citriodora.

The GDP-D-mannose pyrophosphorylase (GMP) and microtubule severing enzyme KATANIN (KTN) are crucial for wood formation. Although functional identification has been performed in Arabidopsis, few comprehensive studies have been conducted in forest trees. In this study, we discovered 8 CcGMP and 4 CcKTN genes by analyzing the whole genome sequence of Corymbia citriodora. The chromosomal location, genome synteny, phylogenetic relationship, protein domain, motif identification, gene structure, cis-acting regulatory elements, and protein-interaction of CcGMP and CcKTN were all investigated. KTN has just one pair of segmentally duplicated genes, while GMP has no duplication events. According to gene structure, two 5' UTRs were identified in CcGMP4. Furthermore, there is no protein-interaction between KTN and GMP. Based on real-time PCR, the expression of most genes showed a positive connection with DBH diameters. In addition, the expression of CcGMP4 and CcKTN4 genes were greater in different size tree, indicating that these genes are important in secondary xylem production. Overall, this findings will enhance our comprehension of the intricacy of CcGMP&CcKTN across diverse DBHs and furnish valuable insights for future functional characterization of specific genes in C. citriodora.

Influence of dietary protein on serum phosphorous levels in peritoneal dialysis patients with different initial transport function.

INTRODUCTION: This cross-sectional study investigated the influence of dietary protein intake (DPI) on serum phosphate levels in peritoneal dialysis (PD) patients and determined the DPI cutoff required to prevent hyperphosphatemia. METHODS: A total of 504 PD patients were categorized into fast (4 h dialysate/plasma [D/P] creatinine clearance ≥0.65) or slow (<0.65) peritoneal transporters. Serum phosphorus and peritoneal solute clearance were compared between the groups with different DPI. RESULTS: The fast peritoneal transporters (n = 233) were older, had lower serum albumin and phosphorus levels, and had higher peritoneal phosphorus clearance (all p < 0.001). Among the slow transporters (n = 271), serum phosphorus levels were significantly higher among patients with DPI > 1.0 g/kg/d (p < 0.001). High DPI only increased the hyperphosphatemia risk in slow transporters (not in high transporters). DPI ≥1.026 g increased the hyperphosphatemia risk in those patients (area under the curve: 0.66, p = 0.001). CONCLUSION: High DPI increases the hyperphosphatemia risk in PD patients with slower peritoneal transport function.

Epidemiological characteristics and pathological changes of primary glomerular diseases.

OBJECTIVE: By analyzing the pathological characteristics and clinical data of renal biopsy in our hospital in the past 20 years, to further understand the epidemic characteristics and pathological changes of primary glomerular disease, and to provide regional data for the big data of kidney disease in my country. METHODS: A retrospective analysis of 9448 patients with primary glomerular disease who were hospitalized in our hospital from January 1, 2000 to December 31, 2019, aged 18 years or older, and undergoing renal biopsy. Divided every 5 years into a group, a total of 4 groups (first group 2000.1.1-2004.12.31, second groups 2005.1.1-2009.12.31; third groups 2010.1.1-2014.12.31, fourth groups 2015.1.1-2019.12.31). RESULTS: ① There were more males than females, and male: female vs 1.53:1. The proportion of men in the past five years has increased compared with the previous 15 years. ② Mostly middle-aged, with a median age of 41.39 years old. The age is increasing over time. There are differences between the four groups, P <0.001; ③ The most common clinical manifestations are nephrotic syndrome, followed by chronic glomerulonephritis. Occult glomerulonephritis, the proportion of patients with nephrotic syndrome increases over time, first to fourth group (40.08%< 42.64% < 47.08%< 53.69%); ④ The most common pathology type from 2000 to 2009 was mesangial proliferative glomerulonephritis. IgA nephropathy was the most common type from 2010 to 2014, but the proportion of membranous nephropathy increased year by year, and it became the most common pathological type from 2015 to 2019; ⑤ The clinical and pathological manifestations of different genders are different, but there is no statistical difference. CONCLUSION: In the past 20 years, the primary glomerular disease is mainly middle-aged. There are more men than women. The most common type of clinical manifestation is nephrotic syndrome. The pathological type is mesangial proliferative glomerulonephritis. Over time, the average age is increasing, and the proportion of patients with renal syndrome is increasing. IgA nephropathy is the most common pathological type from 2010 to 2014, and membranous nephropathy has become the main pathological type in the past 5 years.

Early life body mass index trajectories and albuminuria in midlife: A 30-year prospective cohort study.

Background: Albuminuria is a marker of vascular dysfunction and is associated with chronic renal and cardiovascular diseases. Data on the association between the longitudinal patterns of weight change early in life and albuminuria later in life are limited. We aimed to identify the body mass index (BMI) trajectory across a 30-year span and evaluate its association with middle-age albuminuria. Methods: Of the 4623 participants aged 6-18-year-old recruited by Hanzhong Adolescent Hypertension Study cohort in northern China from March 10, 1987 to June 3, 2017, a total of 1,825 participants followed up with 6 visits over 30 years were enrolled. Group-based trajectory modeling was used to identify distinct BMI trajectories in longitudinal analyses. Albuminuria was defined as a urinary albumin-to-creatinine ratio (uACR) ≥ 30 mg/g. Findings: Three distinct BMI trajectories were identified: low-increasing (n = 671, 36.8%), moderate-increasing (n = 940, 51.5%), and high-increasing (n = 214, 11.7%); male participants exhibited a steeper increase in BMI than females. The uACR was increased linearly from the low- to high-increasing group. A total of 201 individuals developed albuminuria, with an incidence of 11.0%. Compared with the low-increasing group, the odds ratio (OR) of albuminuria in middle age was 2.13(95% confidence interval [CI]: 1.26 to 3.61) for the high-increasing group after full adjustment for age, sex, smoking, alcohol consumption, marital status, systolic blood pressure, diabetes, and hyperlipidemia. The unadjusted ORs of the high-increasing BMI group were 5.08 (2.76-9.37) for males and 3.45 (1.78-6.69) for females, and the association remained significant in males in the fully adjusted models. Interpretation: Higher BMI trajectories are associated with higher uACR and an increased risk of albuminuria in middle age, especially in males. Identifying long-term BMI trajectories from an early age may assist in predicting the risk of renal diseases and cardiovascular disease later in life. Funding: This work was supported by the National Natural Science Foundation of China (81600327, 82070437, 81870319, 82070549, and 82170437), Natural Science Basic Research Program of Shaanxi Province (2021JM-257 and 2021JM-588), Institutional Foundation of the First Affiliated Hospital of Xi'an Jiaotong University (2019QN-06 and 2021ZXY-14), the Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University of China (XJTU1AF-CRF-2019-004, XJTU1AF2021CRF-021, and XJTU1AFCRF-2017-021), Research Incubation Fund of Xi'an People's Hospital (FZ-61), Grants from the Major Chronic Non-communicable Disease Prevention and Control Research Key Project of the Ministry of Science and Technology of China (2017YFC1307604 and 2016YFC1300104).

Associations of Long-Term Visit-to-Visit Blood Pressure Variability With Subclinical Kidney Damage and Albuminuria in Adulthood: a 30-Year Prospective Cohort Study.

BACKGROUND: Recent evidence indicates that long-term visit-to-visit blood pressure variability (BPV) may be associated with risk of cardiovascular disease. We, therefore, aimed to determine the potential associations of long-term BPV from childhood to middle age with subclinical kidney damage (SKD) and albuminuria in adulthood. METHODS: Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, which recruited children and adolescents aged 6 to 18 years at baseline, we assessed BPV by SD and average real variability (ARV) for 30 years (6 visits). Presence of SKD was defined as estimated glomerular filtration rate between 30 and 60 mL/min per 1.73 m2 or elevated urinary albumin-to creatinine ratio at least 30 mg/g. Albuminuria was defined as urinary albumin-to creatinine ratio ≥30 mg/g. RESULTS: During 30 years of follow-up, of the 1771 participants, 204 SKD events occurred. After adjustment for demographic, clinical characteristics, and mean BP during 30 years, higher SDSBP , ARVSBP , SDDBP , ARVDBP , SDMAP , ARVMAP , and ARVPP were significantly associated with higher risk of SKD. When we used cumulative exposure to BP from childhood to adulthood instead of mean BP as adjustment factors, results were similar. In addition, greater long-term BPV was also associated with the risk of albuminuria. Long-term BPV from childhood to middle age was associated with higher risk of SKD and albuminuria in adulthood, independent of mean BP or cumulative exposure to BP during follow-up. CONCLUSIONS: Identifying long-term BPV from early age may assist in predicting kidney disease and cardiovascular disease in later life.

Peritoneal dialysis first policy in Hong Kong for 35 years: Global impact.

Peritoneal dialysis (PD) first policy has been established in Hong Kong since 1985. After 35 years of practice, the PD first policy in Hong Kong has influenced many countries around the world including governments, health ministries, nephrologists and renal nurses on the overall health policy structure and clinical practice in treating kidney failure patients using PD as an important dialysis modality. In 2021, the International Association of Chinese Nephrologists and the Hong Kong Society of Nephrology jointly held a symposium celebrating the 35 years of PD first policy in Hong Kong. In that symposium, experts and opinion leaders from around the world have shared their perspectives on how the PD first policy has grown and how it has affected PD and home dialysis practice globally. The advantages of PD during COVID-19 pandemic were highlighted and the use of telemedicine as an important adjunct was discussed in treating kidney failure patients to improve the overall quality of care. Barriers to PD and the need for sustainability of PD first policy were also emphasized. Overall, the knowledge awareness of PD as a home dialysis for patients, families, care providers and learners is a prerequisite for the success of PD first. A critical mass of PD regional hubs is needed for training and mentorship. Importantly, the alignment of policy and clinical goals are enablers of PD first program.

Spectrum of biopsy-proven kidney diseases in northwest China: a review of 30 years of experiences.

PURPOSE: Large-scale, contemporary studies assessing the spectrum of kidney diseases in northwest China are lacking. Therefore, we aimed to assess the profile of 30-year temporal changes in biopsy-proven kidney diseases in northwest China. METHODS: This cross-sectional study included all patients with a native kidney biopsy specimen in the First Affiliated Hospital of Xi'an Jiaotong University between 1989 and 2018. Data on demographic characteristics and pathological diagnosis were extracted from medical records and pathological reports. Changing patterns of kidney diseases over the study period and disease distributions in different gender and age groups were examined. RESULTS: This study included 13,620 patients with a mean age of 38.5 ± 16.5 years and included 58.2% of men. Primary glomerulonephritis (PGN), second glomerulonephritis (SGN), tubulointerstitial disease, and other renal diseases accounted for 79.1, 18.3, 2.4, and 0.2% of all kidney diseases, respectively. In PGN, IgA nephropathy (IgAN) (25.1%) was the most common type, followed by non-IgA mesangial proliferative glomerulonephritis (MsPGN) (24.9%) and membranous nephropathy (MN) (17.4%). The frequency of MN dramatically increased (p < 0.001) over the course of the study. Lupus nephritis (6.2%) and Henoch-Schönlein purpura nephritis (HSPN) (4.9%) were leading SGN diagnosis. The frequencies of IgAN, non-IgA MsPGN, and HSPN declined, while those of ANCA/pauci-immune glomerulonephritis and diabetic nephropathy significantly increased. CONCLUSION: PGN continues to be the predominant kidney disease in northwest China, and IgAN is the most common type. The frequencies of MN and diabetic nephropathy significantly increased. These findings might be explained by behavioral and environmental exposures and provide implications on future hypothesis-driven research.

Associations of Renalase With Blood Pressure and Hypertension in Chinese Adults.

Objective: Renalase, a novel secretory flavoprotein with amine oxidase activity, is secreted into the blood by the kidneys and is hypothesized to participate in blood pressure (BP) regulation. We investigated the associations of renalase with BP and the risk of hypertension by examining renalase single nucleopeptide polymorphism (SNPs), serum renalase levels, and renal expression of renalase in humans. Methods: ① Subjects (n = 514) from the original Baoji Salt-Sensitive Study cohort were genotyped to investigate the association of renalase SNPs with longitudinal BP changes and the risk of hypertension during 14 years of follow-up. ② Two thousand three hundred and ninety two participants from the Hanzhong Adolescent Hypertension Study cohort were used to examine the association of serum renalase levels with hypertension. Renalase expression in renal biopsy specimens from 193 patients were measured by immunohistochemistry. ③ Renalase expression was compared in hypertensive vs. normotensive patients. Results: ① SNP rs7922058 was associated with 14-year change in systolic BP, and rs10887800, rs796945, rs1935582, rs2296545, and rs2576178 were significantly associated with 14-year change in diastolic BP while rs1935582 and rs2576178 were associated with mean arterial pressure change over 14 years. In addition, SNPs rs796945, rs1935582, and rs2576178 were significantly associated with hypertension incidence. Gene-based analysis found that renalase gene was significantly associated with hypertension incidence over 14-year follow-up after adjustment for multiple measurements. ② Hypertensive subjects had higher serum renalase levels than normotensive subjects (27.2 ± 0.4 vs. 25.1 ± 0.2 µg/mL). Serum renalase levels and BPs showed a linear correlation. In addition, serum renalase was significantly associated with the risk of hypertension [OR = 1.018 (1.006-1.030)]. ③ The expression of renalase in human renal biopsy specimens significantly decreased in hypertensive patients compared to non-hypertensive patients (0.030 ± 0.001 vs. 0.038 ± 0.004). Conclusions: These findings indicate that renalase may play an important role in BP progression and development of hypertension.