Geriatric nutritional risk index is associated with mortality in peritoneal dialysis patients.

BACKGROUND: Malnutrition is one of the most common complications among dialysis patients. The Geriatric Nutritional Risk Index (GNRI) is rarely used in dialysis patients, especially peritoneal dialysis (PD). AIM: To use the GNRI to evaluate the initial nutritional state of PD patients and to examine the association between the GNRI and mortality in chronic PD patients. METHODS: We retrospectively examined the medical records at our centre to identify all adults (≥18 years) who had undergone PD for over 3 months before recruitment from January 2005 to December 2017. The correlation between the GNRI and mortality was examined by Kaplan-Meier and Cox proportional hazards analyses. RESULTS: A total of 1804 patients was enrolled in the study. Significant correlations were noted between the initial GNRI and Charlson index, uric acid, blood calcium, potassium, triglycerides, low-density lipoprotein cholesterol, haemoglobin and so on. Multivariate Cox proportional hazards analyses demonstrated that the GNRI was associated with all-cause mortality (hazard ratio = 0.96, P < 0.001, 95% confidence interval: 0.95-0.98) after adjustment. Compared with the lowest GNRI group, all-cause mortality decreased significantly for each level of GNRI after adjusting for various influencing factors, and the mortality risk of the highest GNRI grade decreased by 66%. The Kaplan-Meier analysis survival rate was significantly different among the four groups in terms of all-cause mortality and cardiovascular and cerebrovascular mortality (log-rank test, P < 0.05). CONCLUSIONS: These results demonstrated that the GNRI is significantly associated with mortality and can be a simple, clinically useful marker for the assessment of nutritional status in PD patients.

A Fast Decline of Residual Renal Function in the First Year is a Predictor for Early Withdrawal from Peritoneal Dialysis in Non-Diabetic Patients.

BACKGROUND/AIMS: Little is known about the relationship between residual renal function (RRF) decline in early period and survival in non-diabetic peritoneal dialysis (PD) patients. METHODS: A total of 567 non-diabetic patients who began PD from January 1, 2005 to June 30, 2013 was investigated. The rate of RRF decline was determined by the "slope of the trend equation" of serial RRFs. A composite end-point of all-cause mortality and conversion to hemodialysis (HD) was used, survival status was censored on June 30, 2016. RESULTS: The median of "the slope of RRF decline equation" was 0.308 (0.001-2.111) ml/min/1.73 m2/ month. In the median follow-up period of 43 months (range 12 to 120 months), 65 (11.5%) patients died, 90 (15.9%) patients converted to HD and 171 (30.2%) patients received kidney transplantation. Multivariate linear regression showed male, high baseline RRF, high baseline peritoneal Kt/V urea, low serum albumin and low uric acid were independently associated with the rate of RRF decline in the first year of PD. Multivariate Cox models revealed that RRF decline in the first year remained a predictor for composite end-point (HR, 2.74, 95% CI, 1.53 to 4.90, P=0.001). The patients were divided into high RRF decline group (> 0.308ml/ min/1.73m2/month) and low RRF decline group (≤0.308 ml/min/1.73m2/month). In the first three years of PD, the rate of end-point events was higher in high RRF decline group (23.2%) than that in low RRF decline group (11.0%) (P< 0.001). There were 189 patients in low RRF decline group and 171 patients in high RRF decline group maintaining PD for more than 3 years, in a median follow-up of 54 months (range 37 to 120 months), the survival rate was 30.9% in high RRF decline group and 46.4% in low RRF decline group (P=0.883). In high RRF decline group, there were 92 patients reaching composited end-point and 112 patients maintaining PD; multivariate Cox model showed high peritoneal Kt/V urea after 1 year of PD and high albumin level were protective factors (HR, 0.29, 95% CI, 0.13 to 0.61, P= 0.001; HR, 0.94, 95% CI, 0.90-0.99, P=0.022, respectively), while fast RRF decline remained risk factor for composite end-point (HR, 3.28, 95% CI,1.48-7.31, P=0.004). CONCLUSION: A faster RRF decline in the first year was a predictor for all-cause mortality and conversion to HD in non-diabetic PD patients, mainly in the first three year. For patients with faster RRF decline, increasing PD dose was effective to improve survival.

Dialysate cell-free mitochondrial DNA fragments as a marker of intraperitoneal inflammation and peritoneal solute transport rate in peritoneal dialysis.

BACKGROUND: Mitochondrial DNA (mtDNA) released into extracellular subsequent to cell injury and death can promote inflammation in patients and animal models. However, the effects of peritoneal dialysate cell-free mtDNA on intraperitoneal inflammation and peritoneal solute transport rate (PSTR) in peritoneal dialysis (PD) patients remain unclear. METHODS: We select the incident patients who began PD therapy between January 1, 2009, and December 30, 2010. Peritoneal dialysate was collected at the time of peritoneal equilibration test. The cell-free mtDNA, IL-6, IL-17A, TNF-α and IFN-γ were measured. All patients were followed till December 2017. The results were compared with PSTR and patient survival. RESULTS: One hundred and eighty-nine patients were included in the study. The average age was 47.1 ± 13.5 years, 55.6% of the patients were males. The average PSTR was 0.66 ± 0.12, the median dialysate mtDNA levels were 4325 copies/ul. The median concentrations of IL-6, IL-17A, TNF-α and IFN-γ were 25.9, 10.8, 25.8 and 17.9 pg/ml, respectively. We found that dialysate mtDNA was significantly correlated with PSTR (r = 0.461, P < 0.001), IL-6 (r = 0.568, P < 0.001), TNF-α (r = 0.454, P < 0.001) and IFN-γ (r = 0.203, P = 0.005). After adjustment for multiple covariates, dialysate mtDNA levels were independently correlated with IL-6 and PSTR. Dialysate mtDNA levels were not associated with patient survival. CONCLUSIONS: We found that dialysate mtDNA levels correlated with the degree of intraperitoneal inflammatory status in PD patients. Peritoneal effluent mtDNA was an independent determinant of PSTR but did not affect patient survival.

[Associations of mean arterial pressure levels with mortality in patients with peritoneal dialysis].

OBJECTIVE: To investigate the associations between mean arterial pressure (MAP) and mortality in patients with peritoneal dialysis (PD). METHODS: A total of 1737 patients with terminal renal diseases under PD in the First Affiliated Hospital of Zhejiang University from 2008 to 2016 were enrolled. Patients were followed up for 33.0(19.3, 52.4) months. The mean arterial pressure over the first 3 months of PD therapy were calculated. All-cause death and cardiovascular death were assessed using Cox regression models adjusted for demographics, laboratory measurements, comorbid conditions and antihypertensive medications. RESULTS: During the follow-up, 208 patients died, among which 95(45.7%) patients died of cardiovascular causes. Compared with patients with MAP >95-<120 mmHg, patients with MAP ≤ 95 mmHg were associated with significantly higher risk of all-cause death (HR=1.40,95%CI:1.01-1.93,P<0.05); patients with MAP ≥ 120 mmHg were associated with significantly higher risk of all-cause (HR=2.12,95%CI:1.32-3.40, P<0.01) and cardiovascular morality (HR=2.55, 95%CI:1.38-4.70, P<0.01). MAP presents a U-shaped association with all-cause mortality and a J-shaped association with cardiovascular mortality. CONCLUSIONS: Both high MAP and low MAP are associated with higher risk of mortality in PD patients.

Changes in the diagnosis of glomerular diseases in east China: a 15-year renal biopsy study.

BACKGROUND: There have been some gradual changes in the distribution of renal biopsy pathological diagnoses during recent years. This study aimed to show changes in renal disease prevalence in China by investigating 10 patients diagnosed at our Kidney Disease Centre during the last 15 years. METHODS AND RESULTS: All patients aged 15-year-old or older who underwent renal biopsy at the First Affiliated Hospital, Zhejiang University, from 2001 to 2015 were enrolled. There were 5 common types of primary glomerulonephritis: IgA nephropathy (IgA N), membranous nephropathy (MN), mesangial progressive glomerulonephritis (MsPGN), minimal change disease (MCD), and focal segmental glomerulosclerosis (FSGS), which represented 50%, 16.8%, 15.9%, 8.1% and 2.5% of total cases, respectively. IgA nephropathy was the most common type of primary glomerulonephritis (PGN). CONCLUSIONS: Our results mostly showed a new trend that the diagnosis of IgA nephropathy was not increasing and the prevalence of membranous nephropathy had increased, becoming the second most common type of primary glomerulonephritis. Key POINTS Distinguished with other domestic studies, IgA nephropathy did not show a trend of continuous growth although it still had about the half proportion of PGN, whereas membranous nephropathy kept rising and became the second common PGN. Concerning SGN, LN peaked in the younger-age and middle-age groups with a significant female prevalence, DN, BANS and SV had a male predominance peaking in the middle-age and old-age groups.

Simple Cysts in Donor Kidney Contribute to Reduced Allograft Function.

BACKGROUND: Simple renal cysts may be an early marker of renal disease. We investigated whether simple cysts in donor kidney are associated with the decline of allograft function in living donor kidney transplantation. METHODS: We retrospectively reviewed records of donors and recipients from 716 living donor kidney transplants performed between April 2007 and April 2015 in our hospital. Ninety-one donors with renal cysts and 64 recipients with cysts in donor kidney were noted. We compared these 64 cases to 128 no cyst-bearing controls matched for the donor gender, recipient gender, donor baseline serum creatinine (sCr), donor/recipient body surface area ratio, donor age, recipient age and the date of kidney transplantation in turn. RESULTS: The presence of cysts was interrelated with age, gender and renal function independently in donors. Pathological findings of time-zero biopsy revealed that donor kidney harboring cysts existed more glomerular sclerosis compared with no cyst-bearing controls (p = 0.040). The estimating glomerular filtration rate levels of recipients were 80.82 ± 26.61 vs. 88.21 ± 23.12, 66.95 ± 17.42 vs. 72.15 ± 16.42 and 60.92 ± 22.17 vs. 68.72 ± 14.43 ml/min· 1.73 m2 in cyst-bearing and no cyst-bearing group on day 7, month 6 and year 5, respectively, after surgery (p < 0.05). The mean sCr were 112.14 ± 48.32 vs. 98.75 ± 29.71 and 126.28 ± 42.32 vs. 115.05 ± 26.35 µmol/l on the 7th day and a half year after transplant, respectively (p < 0.05). The 2 groups did not significantly differ in terms of the other characteristics. CONCLUSION: Simple cysts in donor kidney can influence the early and long-term allograft function. In living donor transplantation, kidney presenting cysts should be considered carefully at the time of donor selection.

Association Between Comprehensive Nutritional Scoring System (CNSS) and Outcomes of Continuous Ambulatory Peritoneal Dialysis Patients.

BACKGROUND/AIMS: The presence of protein-energy wasting (PEW) among dialysis patients is a crucial risk factor for outcomes. The complicated pathogenesis of PEW makes it difficult to assess and treat. This single-center retrospective study focuses on the association between nutritional markers and the outcomes of continuous ambulatory peritoneal dialysis(CAPD) patients, aiming to establish a practical comprehensive nutritional scoring system for CAPD patients. METHODS: 924 patients who initiated peritoneal dialysis in our center from January 1st,2005 to December 31st,2015 were enrolled. Comprehensive nutritional scoring system(CNSS) was based on items including SGA, BMI, ALB, TC, MAC and TSF. We divide patients into 3 groups according to their CNSS score. Outcomes including mortality, hospitalization days and hospitalization frequency were compared between 3 grades. RESULTS: The CNSS grade correlated significantly with hospitalization days (P<0.05). Both categorized CNSS grade (HR:0.56; 95% CI:0.41-0.78; P = 0.001) and continuous CNSS score (HR:0.87; 95% CI: 0.80-0.94; P = 0.001) independently protect PD patients from all-cause mortality. CONCLUSION: CNSS provides an integrated scoring system with significant associations with hospitalization and mortality in PD patients. The CNSS grade differentiates patients with malnutritional risk and independently predicts high risk of morbidity and mortality.

Risk Factors and Outcomes of Early-Onset Peritonitis in Chinese Peritoneal Dialysis Patients.

BACKGROUND/AIMS: Studies on the risk factors and outcomes of peritonitis within the first 6 months in peritoneal dialysis patients are sparse. This study aims to investigate the risk factors associated with early-onset peritonitis (EOP) and its influence on patients' technique survival and mortality. METHODS: This is a retrospective observational cohort study. A total of 483 patients who had at least one episode of peritonitis were enrolled and followed from March 1, 2002, to August 31, 2016, at our center. According to the time to first peritonitis, we divided patients into two groups: EOP (≤ 6 months, n=167) and late-onset peritonitis (LOP, >6 months, n=316). Logistic regression was used to analyze the factors associated with EOP. A Cox proportional hazards model was constructed to examine the influence of EOP on clinical outcomes. RESULTS: Of the 483 patients, 167 (34.6%) patients developed their first episode of peritonitis within the first 6 months. The EOP patient group had more male patients, a shorter time on peritoneal dialysis (PD), lower serum albumin levels at the time of PD initiation and a higher peritonitis rate (P<0.05). The EOP patient group had fewer infections with Gram-negative organisms (P=0.013) and more culture-negative peritonitis (P=0.014) than the LOP patient group for the first episode of peritonitis. The multivariate logistic regression analysis showed that factors associated with EOP included male gender (odds ratio (OR) 1.920, 95% confidence interval (CI) 1.272-2.897, P=0.002) and a low serum albumin level at the start of PD (OR 0.950, 95% CI 0.914-0.986, P=0.007). In the Cox proportional hazards model, EOP was a significant predictor of all-cause mortality (hazard ratio (HR) 2.766, 95% CI 1.561-4.900, P<0.001). There were no differences between EOP and LOP for technique failure. However, in continuous analyses, a negative correlation was observed between the time to first peritonitis and technique failure (HR 0.988, 95% CI 0.980-0.997, P=0.006). In the Spearman analysis, the time to first peritonitis was negatively correlated with the peritonitis rate (r=-0.573, P<0.001). CONCLUSION: Male gender and a low serum albumin level before PD were strongly associated with EOP. Additionally, EOP patients had a higher risk of poor clinical outcomes. More importantly, an early peritonitis onset was associated with a high peritonitis rate.

Association of very Low-density Lipoprotein Cholesterol with All-cause and Cardiovascular Mortality in Peritoneal Dialysis.

BACKGROUND/AIMS: Cardiovascular disease (CVD) is the leading cause of death in dialysis patients. Little is known about the relationship between very low-density lipoprotein cholesterol (VLDL-C) and cardiovascular mortality in these patients. METHODS: A total of 1324 incident patients who began continuous ambulatory peritoneal dialysis (CAPD) therapy at our hospital between January 1, 2005, and September 30, 2014, with baseline serum VLDL-C values were investigated. The associations of the VLDL-C levels with all-cause and cardiovascular mortality were assessed. RESULTS: The mean age of the cohort was 50.2 ± 14.8 years, and the mean VLDL-C level was 33.6 ± 18.0 mg/dl. One hundred sixty-five (12.5%) patients died during the study period. Multivariable models revealed that the high VLDL-C group was associated with significantly higher all-cause (HR, 2.08, 95% CI, 1.13 to 3.29, P = 0.002) and cardiovascular mortality (HR, 1.92, 95% CI, 1.18 to 4.29, P = 0.013) compared with the low VLDL-C group even after adjusting for various covariates. Using the VLDL-C level as a continuous variable, the hazard ratios (HRs) of all-cause and cardiovascular mortality associated with a 10-mg/dl increase in VLDL-C level were 1.12 (95% CI, 1.02 to 1.26, P = 0.025) and 1.11 (95% CI, 1.02 to 1.22, P = 0.029), respectively. VLDL-C was associated more strongly to all-cause (e.g., Akaike information criteria of 1990.205 vs. 1994.451) and cardiovascular (e.g., Akaike information criteria of 984.146 vs. 985.634) mortality than triglyceride (TG) levels. CONCLUSIONS: An elevated VLDL-C level is an independent risk factor for all-cause and cardiovascular mortality in peritoneal dialysis (PD) patients.

The efficacy and safety of tacrolimus monotherapy in adult-onset nephrotic syndrome caused by idiopathic membranous nephropathy.

INTRODUCTION: The purpose of the study is to evaluate the efficiency and safety of tacrolimus (TAC) monotherapy in the treatment of nephrotic idiopathic membranous nephropathy (IMN) compared with the protocol of cyclophosphamide (CTX) combined with corticosteroids. METHODS: In total, 58 patients with nephrotic syndrome and biopsy-proven IMN were included in this study. 30 patients received TAC monotherapy with an initial dose of 0.05-0.1 mg/kg/day. 28 patients received transvenous CTX at a dose of 0.5-0.75 g/m2 once in every month initially for 6 months and once in every 2 or 3 months for the later period, and the regimen was combined with corticosteroids (prednisone 1 mg/kg/d). All patients were observed for the treatment effects, recurrence and side effects. RESULTS: Twelve months after the initial treatment, a total of 24 (80%) patients in the TAC group and 23 (82.1%) patients in the CTX group achieved remission (either partial or complete remission). The survival curve of the probability of remission and complete remission were similar between the two groups (p > .05). Proteinuria (based on 24 h urinary protein excretion) was significantly decreased, and serum albumin was significantly increased after immunosuppressive treatment in both the groups. Estimated glomerular filtration rate (eGFR) was comparable between before and after treatment. The main adverse effects in TAC treatment were glucose intolerance, diabetes and abnormal aminotransferase. CONCLUSIONS: TAC monotherapy is an alternative therapeutic regimen for patients with nephrotic IMN. Its short-term efficiency and patient tolerance are both acceptable.

[Effects of interim hemodialysis on survival and clinical outcomes in patients with maintenance peritoneal dialysis].

OBJECTIVE: To investigate the effects of interim hemodialysis (HD) on survival and clinical outcomes in patients with maintenance peritoneal dialysis (PD). METHODS: The clinical data of 908 patients undergoing maintenance PD from January 2010 to December 2014 registered in Zhejiang Dialysis Regisration System were retrospectively analyzed. Among all PD patients, 176 cases received interim HD for less than 3 months, and then transferred to PD (transfer group) and 732 cases had initial PD (non-transfer group). The demographic parameters, biochemical data, comorbidity, details of peritonitis and transplantation were documented. Survival curves were made by the Kaplan-Meier method; univariate and multivariate analyses were performed with Cox proportional hazard regression model to identify risk factors of mortality. RESULTS: Compared with patients in transfer group, patients in non-transfer group had significantly higher serum albumin and total Kt/V levels. The survival rate was significantly higher in non-transfer group, but there was no significant difference in technique survival between two groups. After multivariable adjustment, initial dialysis modality (HR=1.60, 95% CI: 1.01~2.56), age (HR=1.07, 95% CI:1.05~1.09) and serum albumin (HR=0.96, 95% CI: 0.93~0.99) and Charslon comorbidity index (HR=2.54, 95% CI:1.63~3.94) were independent factors for long-term survival. CONCLUSION: Patients who transfer to PD after interim HD have lower survival rate than patients who start with and are maintained on PD. HD is an independent risk factor for PD patients, therefore, patients with PD should be well informed and educated with dialysis protocols.

mTOR inhibitor versus mycophenolic acid as the primary immunosuppression regime combined with calcineurin inhibitor for kidney transplant recipients: a meta-analysis.

BACKGROUND: A number of studies have provided information regarding the risks and benefits of mammalian target of rapamycin inhibitors (mTOR-I) combined with calcineurin inhibitors (CNI) versus mycophenolic acid (MPA). METHODS: Medline, Embase and the Cochrane Central Register of Controlled Trials were searched. Randomized controlled trials comparing mTOR-I to MPA as the primary immunosuppressive regimen in combination with CNI were selected and meta-analyzed. RESULTS: Eleven randomized controlled trials consisting of 4930 patients in total were included. No significant difference was observed in the risk of biopsy-proven acute rejection and patient death between the two groups. However, an increased risk of graft loss (relative risk (RR) = 1.20) and inferior graft function (creatinine clearance, weighted mean difference (WMD) = -2.41 µmol/L) were demonstrated in mTOR-I-treated patients. Patients treated with mTOR-I had a higher risk of new-onset diabetes mellitus (RR = 1.32), dyslipidemia, proteinuria (RR = 1.79), peripheral edema (RR = 1.34), thrombocytopenia (RR = 1.97) and lymphocoele (RR = 1.80), but a lower risk of cytomegalovirus infection (RR = 0.40), malignancy (RR = 0.64) and leucopenia (RR = 0.43). There was no difference in diarrhea, anemia, urinary tract infection, polyoma virus infection and impaired wound healing when mTOR-I was compared with MPA. CONCLUSIONS: mTOR-I showed no particular superiority to MPA. Notably, mTOR-I had an increased risk of graft loss when combined with CNI, even when combined with a reduced dose of CNI. Therefore, the optimal dosage strategies for mTOR-I and CNI need to be further explored.

Clinical characteristics and outcomes of hospitalized kidney transplant recipients with COVID-19 infection in China during the Omicron wave: a single-center cohort study. / 在2019å† çŠ¶ç— æ¯’ç— æš´å‘æµè¡ŒæœŸé—´æ„ŸæŸ“å¹¶ä½é™¢æ²»ç–—çš„è‚¾ç§»æ¤å—è€ çš„ä¸´åºŠç‰¹å¾ä¸Žé¢„åŽï¼š ä¸€é¡¹ä¸­å›½å•ä¸­å¿ƒé˜Ÿåˆ—ç ”ç©¶.

BACKGROUND: Following the short-term outbreak of coronavirus disease 2019 (COVID-19) in December 2022 in China, clinical data on kidney transplant recipients (KTRs) with COVID-19 are lacking. METHODS: We conducted a single-center retrospective study to describe the clinical features, complications, and mortality rates of hospitalized KTRs infected with COVID-19 between Dec. 16, 2022 and Jan. 31, 2023. The patients were followed up until Mar. 31, 2023. RESULTS: A total of 324 KTRs with COVID-19 were included. The median age was 49 years. The median time between the onset of symptoms and admission was 13 d. Molnupiravir, azvudine, and nirmatrelvir/ritonavir were administered to 67 (20.7%), 11 (3.4%), and 148 (45.7%) patients, respectively. Twenty-nine (9.0%) patients were treated with more than one antiviral agent. Forty-eight (14.8%) patients were treated with tocilizumab and 53 (16.4%) patients received baricitinib therapy. The acute kidney injury (AKI) occurred in 81 (25.0%) patients and 39 (12.0%) patients were admitted to intensive care units. Fungal infections were observed in 55 (17.0%) patients. Fifty (15.4%) patients lost their graft. The 28-d mortality rate of patients was 9.0% and 42 (13.0%) patients died by the end of follow-up. Multivariate Cox regression analysis identified that cerebrovascular disease, AKI incidence, interleukin (IL)|-6 level of >6.8 pg/mL, daily dose of corticosteroids of >50 mg, and fungal infection were all associated with an increased risk of death for hospitalized patients. CONCLUSIONS: Our findings demonstrate that hospitalized KTRs with COVID-19 are at high risk of mortality. The administration of immunomodulators or the late application of antiviral drugs does not improve patient survival, while higher doses of corticosteroids may increase the death risk.

Wide-spectrum antibiotic prophylaxis guarantees optimal outcomes in drowned donor kidney transplantation.

BACKGROUND: Drowned victims possibly obtain various pathogens from drowning sites. Using drowned renal donors to expand the donor pool still lacks consensus due to the potential risk of disease transmission. RESEARCH DESIGN AND METHODS: This retrospective study enrolled 38 drowned donor renal recipients in a large clinical center from August 2012 to February 2021. A 1:2 matched cohort was generated with donor demographics, including age, gender, BMI, and ICU durations. Donor microbiological results, recipient perioperative infections, and early post-transplant and first-year clinical outcomes were analyzed. RESULTS: Compared to the control group, drowned donors had significantly increased positive fungal cultures (36.84% vs.13.15%, p = 0.039). Recipients in the drowned group had significantly higher rates of gram-negative bacteria (GNB) and multidrug-resistant GNB infections (23.68% vs.5.26%, 18.42% vs. 3.95%, both p < 0.05). Other colonization and infections were also numerically more frequent in the drowned group. Drowned donor recipients receiving inadequate antibiotic prophylaxis had more perioperative bloodstream infections, higher DGF incidences, and more first-year respiratory tract infections and recipient loss than those receiving adequate prophylaxis (all p < 0.05). Clinical outcomes were similar between the adequate group and the control group. CONCLUSIONS: Drowned donors could be suitable options under wide-spectrum and adequate antimicrobial prophylaxis.

Impaired Amino Acid Metabolism and Its Correlation with Diabetic Kidney Disease Progression in Type 2 Diabetes Mellitus.

BACKGROUND: Metabolomics is useful in elucidating the progression of diabetes; however, the follow-up changes in metabolomics among health, diabetes mellitus, and diabetic kidney disease (DKD) have not been reported. This study was aimed to reveal metabolomic signatures in diabetes development and progression. METHODS: In this cross-sectional study, we compared healthy (n = 30), type 2 diabetes mellitus (T2DM) (n = 30), and DKD (n = 30) subjects with the goal of identifying gradual altering metabolites. Then, a prospective study was performed in T2DM patients to evaluate these altered metabolites in the onset of DKD. Logistic regression was conducted to predict rapid eGFR decline in T2DM subjects using altered metabolites. The prospective association of metabolites with the risk of developing DKD was examined using logistic regression and restricted cubic spline regression models. RESULTS: In this cross-sectional study, impaired amino acid metabolism was the main metabolic signature in the onset and development of diabetes, which was characterized by increased N-acetylaspartic acid, L-valine, isoleucine, asparagine, betaine, and L-methionine levels in both the T2DM and DKD groups. These candidate metabolites could distinguish the DKD group from the T2DM group. In the follow-up study, higher baseline levels of L-valine and isoleucine were significantly associated with an increased risk of rapid eGFR decline in T2DM patients. Of these, L-valine and isoleucine were independent risk factors for the development of DKD. Notably, nonlinear associations were also observed for higher baseline levels of L-valine and isoleucine, with an increased risk of DKD among patients with T2DM. CONCLUSION: Amino acid metabolism was disturbed in diabetes, and N-acetylaspartic acid, L-valine, isoleucine, asparagine, betaine, and L-methionine could be biomarkers for the onset and progression of diabetes. Furthermore, high levels of L-valine and isoleucine may be risk factors for DKD development.

Maternal and neonatal outcomes of pregnancy complicated by urolithiasis: a systematic review and meta-analysis.

BACKGROUND: The effect of urolithiasis on pregnancy-related outcomes remains unknown. The aim of this study was to determine the risk of adverse maternal and neonatal outcomes. METHODS: We searched PubMed, Embase, and the Cochrane Library through December 2020 for studies reporting on adverse maternal and neonatal outcomes in patients with urolithiasis. Risk ratios (ORs) with 95% confidence intervals (CIs) were calculated for these outcomes in pregnant mothers with urolithiasis and compared to healthy controls. RESULTS: Eight studies comprising 26,577 mothers with urolithiasis were included in our analysis. Preterm birth (OR = 1.63; 95% CI 1.37-1.95, p < 0.001) or very preterm birth risk (OR = 1.49, 95% CI 1.06-2.11, p = 0.02) was more common in patients with urolithiasis compared to healthy controls. Mothers with urolithiasis had an increased incidence of preeclampsia (OR = 1.75, 95% CI 1.33-2.3, p < 0.001), hypertension (OR = 2.97, 95% CI 1.31-6.71, p = 0.009), caesarean section (OR 1.31, 95% CI 1.11-1.55, p = 0.001), and gestational diabetes mellitus (OR 1.84, 95% CI 1.37-2.46, p < 0.001). CONCLUSION: Patients with urolithiasis may be at increased risk of developing adverse maternal or neonatal outcomes.

High alkaline phosphatase and low intact parathyroid hormone associate with worse clinical outcome in peritoneal dialysis patients.

OBJECTIVE: Alkaline phosphatase (ALP) is used as a biomarker to monitor the chronic kidney disease-mineral bone disorder (CKD-MBD) and high levels of parathyroid hormone (PTH) that were reported to be related to increased mortality in CKD patients. Therefore, we conducted this longitudinal cohort study to evaluate the relations between ALP and intact PTH (iPTH) and the associations with all-cause and cardiovascular mortality in peritoneal dialysis (PD) patients. METHODS: In 1276 incident PD patients (median age 50 years, 56% males), baseline serum ALP, iPTH, and metabolic biomarkers potentially linked to CKD-MBD were analyzed in relation to mortality during follow-up period of up to 60 months. All-cause and cardiovascular mortality risk of ALP and iPTH were analyzed with competing-risks regression models with transplantation as competing risk adjusting for all covariates. RESULTS: After adjustments for confounders by logistic regression model, older age, higher change level to levels of iPTH, S-albumin, calcium, alanine transaminase (ALT), and lower level of phosphorus were associated with higher ALP level (>79 U/L), and female gender, non-diabetes mellitus, younger age, lower calcium, higher ALT, total bilirubin, phosphorus, and ALP were associated with higher iPTH level (>300 pg/mL). During 60 months (median 44 months) of follow-up, the all-cause mortality rate was 16%, and 91 (46%) of the 199 deaths were caused by cardiovascular disease. In competing-risks regression analysis, "high ALP + low iPTH" was independently associated with all-cause and cardiovascular mortality after adjustment for age, gender, presence of diabetes, and cardiovascular disease, the calendar year of recruitment and vitamin D therapy in PD patients. The subhazard ratio (sHR) of group "high ALP + low iPTH" was 1.96 times and 3.35 times higher than sHR of group "low ALP + high iPTH" for all-cause mortality and cardiovascular mortality, respectively. CONCLUSIONS: The combination of high ALP and low iPTH was independently associated with increased all-cause and cardiovascular mortality in PD patients, suggesting that ALP and iPTH have the potential to predict clinical outcomes and might be useful risk assessment tools in PD patients. Further studies exploring the observed association between combination of ALP with iPTH and mortality are warranted.

DNA demethylase Tet2 suppresses cisplatin-induced acute kidney injury.

Demethylase Tet2 plays a vital role in the immune response. Acute kidney injury (AKI) initiation and maintenance phases are marked by inflammatory responses and leukocyte recruitment in endothelial and tubular cell injury processes. However, the role of Tet2 in AKI is poorly defined. Our study determined the degree of renal tissue damage associated with Tet2 gene expression levels in a cisplatin-induced AKI mice model. Tet2-knockout (KO) mice with cisplatin treatment experienced severe tubular necrosis and dilatation, inflammation, and AKI markers' expression levels than the wild-type mice. In addition, the administration of Tet2 plasmid protected Tet2-KO mice from cisplatin-induced nephrotoxicity, but not Tet2-catalytic-dead mutant. Tet2 KO was associated with a change in metabolic pathways like retinol, arachidonic acid, linolenic acid metabolism, and PPAR signaling pathway in the cisplatin-induced mice model. Tet2 expression is also downregulated in other AKI mice models and clinical samples. Thus, our results indicate that Tet2 has a renal protective effect during AKI by regulating metabolic and inflammatory responses through the PPAR signaling pathway.

MicroRNA-874-3p/ADAM (A Disintegrin and Metalloprotease) 19 Mediates Macrophage Activation and Renal Fibrosis After Acute Kidney Injury.

[Figure: see text].

The associations of blood pressure parameters with all-cause and cardiovascular mortality in peritoneal dialysis patients: a cohort study in China.

BACKGROUND: It remains controversial to claim blood pressure (BP) as a leading risk factor for high risk of death in peritoneal dialysis patients, and less is known about the relationship between BP and mortality in Chinese peritoneal dialysis patients. METHODS: From Zhejiang Renal Data System in China, we collected data on patients treated and followed up at 98 peritoneal dialysis centres from 2008 to 2016. The associations of BP parameters [SBP, DBP, mean arterial pressure (MAP) and pulse pressure (PP)] with all-cause and cardiovascular mortality were examined. We fitted Cox models for mortality with penalized splines using nonparametric smoothers. Several sensitivity analyses were performed to confirm the robustness of our primary findings. RESULTS: A total of 7335 Chinese peritoneal dialysis patients were included. During a median follow-up of 35.8 months, 1281 (17.5%) patients died. SBP, DBP, MAP follow a U-shaped pattern of both all-cause and cardiovascular mortality. PP presents a reverse L-shaped association with all-cause mortality. Either a higher (SBP >141, DBP >85 or MAP >102 mmHg) or lower (SBP <119, DBP <67 or MAP <88 mmHg) BP tends to have a significantly higher all-cause and cardiovascular mortality risk. Higher PP (>60 mmHg) is related to a higher risk of all-cause mortality, but not cardiovascular mortality. These associations remain the same in our competing risk analysis and subgroup analyses. CONCLUSION: These data indicate U-shaped associations of SBP, DBP and MAP with all-cause mortality and cardiovascular mortality, respectively, and a reverse L-shaped association of PP with all-cause mortality. Further studies are needed to reliably establish the optimal BP targets for better hypertension control in peritoneal dialysis patients.