[Application progress of machine learning in kidney disease].

Kidney disease affects a large number of people around the world, imposing a significant burden to people's health and life. If early prediction, rapid diagnosis and prognosis prediction of kidney disease can be carried out, the health of patients will be better protected. Machine learning belongs to the category of artificial intelligence, which can be divided into supervised learning, unsupervised learning and reinforcement learning. With the increasing requirements for the processing and analyzing large-scale and high-dimensional data, machine learning is playing an increasingly important role in the medical domain, and the field of kidney disease is no exception. This article presents a comprehensive overview of the application progress of machine learning in kidney disease, aiming to make medical staff's decision-making in kidney disease more early, accurate and rapid, and better escort the life and health of patients.

Gut microbial products valerate and caproate predict renal outcome among the patients with biopsy-confirmed diabetic nephropathy.

AIMS: Valerate and caproate are two subtypes of short-chain fatty acids produced by gut microbiota. We aimed to measure the serum valerate and caproate levels and analyze the associations between them and renal prognosis of diabetic nephropathy (DN). METHODS: The serum samples of patients with biopsy-confirmed diagnosis of DN were collected in the First Affiliated Hospital of Zhejiang University, from April 1, 2013, to March 31, 2018. One hundred patients were included and divided into an early DN group (eGFR ≥ 60 ml/min, n = 42) and an advanced DN group (eGFR < 60 ml/min, n = 58). The valerate and caproate were measured using gas chromatography-mass spectrometry. Participants were followed up until the cutoff date of August 31, 2018, or if they met the primary endpoint of end-stage renal disease (ESRD). RESULTS: There were 71 males and 29 females in this study, and 29 patients developed ESRD. We observed a significant lower concentration of valerate and caproate in the advanced DN group. There were negative correlations between valerate and glomerular classification (r = - 0.20, P = 0.03) and between caproate and interstitial fibrosis and tubular atrophy (IFTA) (r = - 0.24, P = 0.01). And there were positive correlations between valerate or caproate and eGFR (r = 0.22, P = 0.02; r = 0.38, P < 0.01). Multivariate Cox analysis revealed higher levels of valerate and caproate were negatively related to progression to ESRD (HR = 0.024, P = 0.016; HR = 0.543, P = 0.030). The area under the curve values of valerate and caproate levels were 0.66 and 0.63, respectively, in predicting progression to ESRD. CONCLUSION: This study showed alterations in serum valerate and caproate in DN and demonstrates lower valerate and caproate levels with progression of DN to ESRD.

Changes of gut microbiota in diabetic nephropathy and its effect on the progression of kidney injury.

PURPOSE: We aimed to illustrate gut microbiota and short chain fatty acid (SCFA) levels in diabetic nephropathy (DN) patients, and investigate the mechanism of sodium butyrate in diabetic mellitus (DM) rats. METHODS: Gut microbiota and serum SCFA levels were measured by 16S rDNA and GC-MS. After being built by streptozotocin (DM rats), the DM rats were administered 300 mg/kg sodium butyrate for 12 weeks (DM + BU rats). Gut microbiota, serum and fecal butyrate level were measured. RT-PCR, WB and transmission electron microscopy were performed to explore LC3mRNA or LC3B protein expression, and autophagosomes in kidney tissues. AMPK/mTOR protein expression in renal tissue were also measured. RESULTS: The gut microbial dysbiosis was found in DM and DN groups, and some SCFAs-producing bacteria were decreased in DN group. The serum butyrate concentrations were lower in SCFA-DN group compared with SCFA-HC group and SCFA-DM group in the other cohort. Serum butyrate level was positively correlated with eGFR. Sodium butyrate increased serum and fecal butyrate levels, and improved the enlargement of glomerular area and fibronectin and collagen IV expressions in renal tissues in DM + BU rats. The LC3 mRNA, LC3BII/I ratio and number of autophagosomes were increased in renal tissue of DM + BU rats. Higher p-AMPK/AMPK ratio and lower p-mTOR/ mTOR ratio were shown in renal tissue of DM + BU rats compared with DM rats. CONCLUSIONS: We found the decrease in SCFAs-producing bacteria and low SCFAs concentrations in DN patients. Oral butyrate supplementation may improve kidney injury in DM rats, possibly by increasing autophagy via activating AMPK/mTOR pathway.

Mannose-binding lectin activates the nuclear factor-κB and renal inflammation in the progression of diabetic nephropathy.

Increased serum mannose-binding lectin (MBL) level has been proven to correlate with the development of diabetic nephropathy (DN). Here, we aim to find the role and mechanism of MBL involved in the progression of DN. Patients with DN were recruited and divided into two groups according to different rs1800450 genotypes of the MBL2 gene, and inflammatory profiles in monocytes/macrophages were compared between the two groups. MBL was given to treat macrophages, HK2, and HMC, and a co-culture transwell system was then employed. Renal inflammation and fibrosis parameters were measured after knocking down or overexpressing MBL genes in mice. Proinflammatory profile, manifesting as enhanced IL-1ß production and M1 polarization, was found in monocytes/macrophages from DN with a rs1800450 GG genotype of MBL2 gene who had higher MBL level, compared with those with a rs1800450 GA genotype. In mechanism, MBL directly induced inflammatory responses in macrophages, which promoted inflammatory and fibrotic markers in HK2 and HMCs during co-culture. Further experiments showed that MBL can promote macrophages transforming to the M1 subset mainly by activating the nuclear factor-κB pathway. After downregulation of MBL, the blood glucose, triglyceride, urine protein, injuries of glomerulus and tubules, and the degree of renal inflammation and fibrosis were ameliorated in db/db mice treated with AAV-MBL1/2-shRNA. Overexpression of MBL promoted macrophage infiltration in the kidney. In conclusion, MBL is a crucial mediator in the progression of DN via activating the nuclear factor-κB pathway in macrophages. This will serve as a genetic base for some patients with DN who have poor outcomes and provide a direction for the screening.

The change of gut microbiota-derived short-chain fatty acids in diabetic kidney disease.

BACKGROUND: Previous studies found the dysbiosis of intestinal microbiota in diabetic kidney disease (DKD), especially the decreased SCFA-producing bacteria. We aimed to investigate the concentration of the stool and serum short-chain fatty acids (SCFAs), gut microbiota-derived metabolites, in individuals with DKD and reveal the correlations between SCFAs and renal function. METHODS: A total of 30 participants with DKD, 30 participants with type 2 diabetes mellitus (DM), and 30 normal controls (NC) in HwaMei Hospital were recruited from 1/1/2018 to 12/31/2019. Participants with DKD were divided into low estimated glomerular filtration rate (eGFR)(eGFR<60ml/min, n=14) and high eGFR (eGFR≥60ml/min, n=16) subgroups. Stool and serum were measured for SCFAs with gas chromatograph-mass spectrometry. RESULTS: The DKD group showed markedly lower levels of fecal acetate, propionate, and butyrate versus NC (p<0.001, p<0.001, p=0.018, respectively) [1027.32(784.21-1357.90)]vs[2064.59(1561.82-2637.44)]µg/g,[929.53(493.65-1344.26)]vs[1684.57(1110.54-2324.69)]µg/g,[851.39(409.57-1611.65)] vs[1440.74(1004.15-2594.73)]µg/g, respectively, and the lowest fecal total SCFAs concentration among the groups. DKD group also had a lower serum caproate concentration than that with diabetes (p=0.020)[0.57(0.47-0.61)]vs[0.65(0.53-0.79)]µmol/L. In the univariate regression analysis, fecal and serum acetate correlated with eGFR (OR=1.013, p=0.072; OR=1.017, p=0.032). The correlation between serum total SCFAs and eGFR showed statistical significance (OR=1.019, p=0.024) unadjusted and a borderline significance (OR=1.024, p=0.063) when adjusted for Hb and LDL. The decrease in serum acetate and total SCFAs were found of borderline significant difference in both subgroups (p=0.055, p=0.050). CONCLUSION: This study provides evidence that in individuals with DKD, serum and fecal SCFAs levels (fecal level in particular) were lowered, and there was a negative correlation between SCFAs and renal function.

Predictive Value of Peripheral Blood Neutrophil-To-Lymphocyte Ratio and Platelet-To-Lymphocyte Ratio on Patient Survival with Peritoneal Dialysis.

BACKGROUND: This study is to explore the predictive value of peripheral blood neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) on the prognosis of patients with peritoneal dialysis (PD). METHODS: A total of 378 patients who underwent PD from July 2004 to November 2019 were selected as the research subjects. According to whether death occurred during the follow-up period, they were divided into death group (86 cases) and survival group (292 cases). The differences in clinical indicators between the two groups were compared, and the multivariate Cox regression model and receiver operating characteristic curve (ROC) were used to analyze and summarize the factors affecting the prognosis of PD patients. RESULTS: Compared with the survival group, there were significant differences in age, lymphocytes, NLR, PLR, and combined cerebrovascular disease between the death group and the survival group (p < 0.05). Multivariate Cox regression analysis showed that advanced age (HR = 1.055, 95% CI: 1.038 - 1.072), increased NLR (HR = 1.136, 95% CI: 1.067 - 1.210), and increased PLR (HR = 1.184, 95% CI: 1.018 - 3.026) were risk factors for all-cause death in PD patients. The results showed that the area under the ROC curve (AUC) of NLR and PLR for predicting all-cause death of PD patients were 0.698 and 0.659, respectively, the sensitivity was 69.77%, and the specificity was 66.78% and 58.56%, respectively. The optimal critical values were NLR ≥ 3.71 and PLR ≥ 149.28. Taking the best cutoff value of the ROC curve as the threshold, it showed that the cumulative survival rate of patients with NLR ≥ 3.71 was significantly lower than that of patients with NLR < 3.71 (Log rank 2 = 37.551, p = 0.000). It also showed that the cumulative survival rate of patients with PLR ≥ 149.28 was lower than that of patients with PLR < 149.28 (Log rank 2 =23.686, p = 0.000). CONCLUSIONS: NLR and PLR have a good predictive effect on the prognosis of PD patients.

The Correlation Between Low Serum T3 Levels and All-Cause and Cardiovascular Mortality in Peritoneal Dialysis Patients.

OBJECTIVE: This study is to investigate the correlation between serum triiodothyronine (T3) levels and all-cause and cardiovascular mortality in PD patients. METHODS: A total of 376 end-stage renal disease (ESRD) patients who started maintenance PD treatment in the Department of Nephrology in our hospital and stable treatment for ≥3 months were selected, and the total T3 (TT3) and free T3 (FT3) levels were determined. Among them, 168 cases with FT3 <3.5 pmol/L and/or TT3 <0.92 nmol/L were divided into the low serum T3 level group, and the remaining 208 cases were divided into normal serum T3 level group. The Cox survival analysis method was used to analyze the correlation between low serum T3 levels and all-cause and cardiovascular mortality in PD patient. RESULTS: Compared with the normal serum T3 level group, patients with low serum T3 levels had higher systolic blood pressure and a higher proportion of heart disease, and lower levels of total T4, free T4, hemoglobin, serum albumin, blood calcium, serum total bilirubin, alanine aminotransferase, and 24-h urine volume (all P < 0.05). Binary Logistic regression analysis showed that heart disease (P = 0.003, OR: 2.628, 95% CI: 1.382-4.997) and high TT4 level (P < 0.001, OR: 0.968, 95% CI: 0.956-0.979) were related to low serum T3 levels in PD patients. Multivariate Cox regression analysis showed that low serum FT3 level was an independent risk factor for all-cause death in PD patients (HR = 0.633, 95% CI = 0.431-0.930; P < 0.020). CONCLUSION: Low serum T3 levels in PD patients were associated with heart disease and TT4 levels. Low serum FT3 levels were associated with the risk of all-cause death in PD patients.

Reduced fecal short-chain fatty acids levels and the relationship with gut microbiota in IgA nephropathy.

BACKGROUND: IgA nephropathy(IgAN)) is the common pathological type of glomerular diseases. The role of gut microbiota in mediating "gut-IgA nephropathy" has not received sufficient attention in the previous studies. The purpose of this study was to investigate the changes of fecal short-chain fatty acids(SCFAs), a metabolite of the intestinal microbiota, in patients with IgAN and its correlation with intestinal flora and clinical indicators, and to further investigate the role of the gut-renal axis in IgAN. METHODS: There were 29 patients with IgAN and 29 normal control subjects recruited from January 2018 to May 2018. The fresh feces were collected. The fecal SCFAs were measured by gas chromatography/mass spectrometry and gut microbiota was analysed by16S rDNA sequences, followed by estimation of α- and ß-diversity. Correlation analysis was performed using the spearman's correlation test between SCFAs and gut microbiota. RESULTS: The levels of acetic acid, propionic acid, butyric acid, isobutyric acid and caproic acid in the IgAN patients were significantly reduced compared with control group(P < 0.05). Butyric acid(r=-0.336, P = 0.010) and isobutyric acid(r=-0.298, P = 0.022) were negatively correlated with urea acid; butyric acid(r=-0.316, P = 0.016) was negatively correlated with urea nitrogen; caproic acid(r=-0.415,P = 0.025) showed negative correlation with 24-h urine protein level.Exemplified by the results of α-diversity and ß-diversity, the intestinal flora of IgAN patients was significantly different from that of the control group. Acetic acid was positively associated with c_Clostridia(r = 0.357, P = 0.008), o_Clostridiales(r = 0.357, P = 0.008) and g_Eubacterium_coprostanoligenes_group(r = 0.283, P = 0.036). Butyric acid was positively associated with g_Alistipes (r = 0.278, P = 0.040). The relative abundance of those were significantly decreased in IgAN group compared to control group. CONCLUSIONS: The levels of fecal SCFAs in the IgAN patients were reduced, and correlated with clinical parameters and gut microbiota, which may be involved in the pathogenesis of IgAN, and this finding may provide a new therapeutic approach.

Relationship between blood neutrophil-lymphocyte ratio and renal tubular atrophy/interstitial fibrosis in IgA nephropathy patients.

BACKGROUND: The study aimed to explore the relationship between neutrophil-lymphocyte ratio(NLR) in peripheral blood and renal tubular atrophy/interstitial fibrosis and to evaluate the clinical significance of NLR in IgA nephropathy (IgAN) patients. METHODS: A Total of 263 IgAN patients were included. The participants were categorized into four groups based on quartile of NLR. The clinical data, pathological features, and 2-year renal survival rates were compared among the four groups. The independent factors affecting renal tubular atrophy/interstitial fibrosis in IgAN were determined by multivariate linear regression analysis. RESULTS: The percentage of renal tubular atrophy/interstitial fibrosis increased with the increase of NLR level (p=0.003). The tubular atrophy/interstitial fibrosis score T1 and T2 in Group Q4 was 40%, which was higher than that of other groups, especially Group Q1 (22.73%, p=0.033) and Group Q3 (22.39%, p=0.029). NLR [ß=1.230, 95%CI (0.081, 2.379), p=0.036] might be an independent factor affecting renal tubular atrophy/interstitial fibrosis in IgAN. The area under curve predicted by NLR was 0.596 (95%CI 0.534~0.656, p=0.007) with the specificity 88.24% and the optimal critical value of NLR 3.25. Fourteen patients progressed to end-stage renal disease within 2 years, and the 2-year survival rate of kidney was 93.49%. The renal survival rate in Group Q4 was 87.04%, lower than that in other three groups, especially Group Q1 (98.11%, p=0.029). CONCLUSION: NLR was correlated with the level of renal tubular atrophy/interstitial fibrosis and might be a significant factor for predicting the prognosis in the IgAN. BACKGROUND: IgA nephropathy (IgAN) is an important cause of the end stage renal disease (ESRD). The study aimed to explore the relationship between neutrophil-lymphocyte ratio (NLR) in peripheral blood and renal tubular atrophy/interstitial fibrosis, and to evaluate the clinical significance of NLR in IgA nephropathy (IgAN) patients. METHODS: Total 263 IgAN patients confirmed by renal biopsy pathology were included from January 2013 to May 2018 in Ningbo Hwamei Hospital, University of Chinese Academy of Sciences. The peripheral blood samples were taken from these participants and the NLR was analyzed. The participants were categorized into four groups based on the median and upper and lower quartile of NLR, which were Group Q1 (NLR<1.64), Group Q2 (1.64≤NLR<2.19), Group Q3 (2.19≤NLR<3.00), and Group Q4 (NLR≥3.00), respectively. The clinical data and pathological features were compared among four groups. The independent factors affecting renal tubular atrophy/interstitial fibrosis in IgAN were determined by multivariate linear regression analysis. The diagnostic ability of NLR for renal tubular atrophy/interstitial fibrosis was evaluated by the area under receiver operating characteristic curve (AUC). The 2-year renal survival rates were compared among the four groups. RESULTS: The levels of white blood cell count, neutrophil count, highly sensitive C-reactive protein, and the percentage of renal tubular atrophy/interstitial fibrosis were increased while lymphocyte count and estimated glomerular filtration rate were decreased with the increase of NLR level (P < 0.05). The percentage of tubular atrophy/interstitial fibrosis 26%-50% (T1) and >50% (T2) in Group Q4 was 40%, which was higher than that of other groups, especially Group Q1 (22.73%) and Group Q3 (22.39%), with significant difference (P < 0.05). NLR [ß = 1.230, 95%CI (0.081, 2.379), P = 0.036] might be an independent factor affecting renal tubular atrophy/interstitial fibrosis in IgAN according to multivariate linear regression analysis results. The AUC predicted by NLR was 0.596 (95%CI 0.534~0.656, P = 0.007) with the specificity 88.24%, the sensitivity 30.00% and the optimal critical value of NLR 3.25. Fourteen patients progressed to end-stage renal disease within 2 years; and the 2-year survival rate of kidney was 93.49%. The renal survival rate in Group Q4 was 87.04%, lower than that in other three groups, especially Group Q1 (98.11%), with significant difference (P < 0.05). CONCLUSION: NLR was correlated with the level of renal tubular atrophy/interstitial fibrosis and might be an significant factor for predicting the prognosis in IgAN.

Successful application of roxadustat in the treatment of patients with anti-erythropoietin antibody-mediated renal anaemia: a case report and literature review.

Recombinant human erythropoietin (rHuEPO) has been used worldwide for treatment of renal anaemia due to its good curative effect. However, rHuEPO treatment is associated with a rare but severe complication because of the development of anti-EPO antibodies, which are difficult to treat. Currently, the main treatments for the anti-EPO antibodies include withdrawing the rHuEPO, providing blood transfusions and administrating steroid-based immunosuppressive agents. Although the above methods can alleviate anti-EPO-related anaemia, there are obvious side-effects such as decreased immunity and an increased risk of infection. Therefore, accurately identifying anti-EPO-related anaemia and effectively treating this complication is worth exploring. This current case report describes a 49-year-old female patient with chronic kidney disease that received rHuEPO subcutaneously and then developed anti-EPO antibody-mediated renal anaemia with her haemoglobin levels dropping to 37 g/l. The patient refused to be treated with steroids, so she received 120 mg roxadustat administered orally every 72 h and her Hb level increased to 110 g/l over a few months. This current case report demonstrates that roxadustat can be used to successfully treat anti-EPO antibody-mediated renal anaemia without the use of steroid-based immunosuppressants.

Mannose-binding lectin activation is associated with the progression of diabetic nephropathy in type 2 diabetes mellitus patients.

BACKGROUND: We aimed to investigate whether mannose-binding lectin (MBL) activation contributed to the progression of diabetic nephropathy (DN), and its role in predicting the renal prognosis of DN. METHODS: Seventy-seven patients who received renal biopsy in the First Affiliated Hospital, College of Medicine, Zhejiang University between August 2013 and September 2016 were enrolled in the study. These patients were followed up until the endpoint of end-stage renal disease (ESRD) or the last follow-up time of August 31, 2018. They were divided into ESRD group (33 patients) and non-ESRD group (44 patients). Their baseline characteristics and MBL levels (serum and urine) were compared between groups. The correlation between single nucleotide polymorphisms (SNPs) of the MBL2 gene and renal outcomes was also analyzed. RESULTS: The median (interquartile ranges) of serum and urine MBL levels were significantly higher in ESRD group than those in non-ESRD group [2,783.75 (1,244.28, 3,837.07) vs. 1,141.60 (652.67, 3,188.44) ng/mL, P=0.016; 1.02 (0.43, 2.05) vs. 0.27 (0.04, 0.58) ng/mg, P<0.01, respectively]. Both univariate and multivariate Cox analysis showed that serum MBL >1,108.75 ng/mL (stratified by maximum Youden index) was an independent predictor for ESRD [hazard ratio (HR) =4.164, 95% confidence interval (CI): 1.601-10.833, P=0.003; HR =4.644, 95% CI: 1.320-16.337, P=0.017; respectively]. For the patients with rs1800450 SNPs of MBL2 gene, patients with homozygous genotype (GG) had higher serum MBL level (median 2,963.52 ng/mL) compared with those with heterozygous genotype (GA) (median 665.38 ng/mL) (P<0.001). MBL2 rs1800450 GA genotype was an independent protective factor for ESRD with a HR of 0.485 (95% CI: 0.237-0.991; P=0.047). CONCLUSIONS: Activation of MBL contributed to the progression of DN. The rs1800450 SNP of the MBL2 gene may be of value in predicting the progression to ESRD in DN patients.

Perilipin2 inhibits diabetic nephropathy-induced podocyte apoptosis by activating the PPARγ signaling pathway.

Podocyte apoptosis plays a pivotal role in the pathogenesis of diabetic nephropathy (DN). The main purpose of this study was to investigate the effects of perilipin2 on high glucose (HG)-induced podocyte apoptosis and associated mechanisms. Differentially expressed genes (DEGs) in BTBR ob/ob mice vs. nondiabetic mice kidneys were obtained from GSE106841 dataset and picked out using the 'limma' package. The protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) and was visualized by Cytoscape. Perilipin2 was a hub gene using the cytoHubba plug-in from Cytoscape. Gene ontology (GO) analysis revealed that the 126 overlapping DEGs were mainly enriched in 'oxidation reduction' [biological process, (BP)], metal ion binding' [molecular function, (MF)] and 'extracellular region' [cellular component, (CC)]. KEGG pathway analysis revealed that perilipin2 was mainly involved in 'PPAR signaling pathway'. DN inhibited perilipin2 expression and PPARγ expression, as by both in vitro and in vivo studies. In vitro experiments demonstrated that perilipin2 inhibition could not only reduced PPARγ expression in podocytes, it could also promote the apoptosis, and inhibit the viability in HG treated podocytes using western blot, CCK8 and flow cytometry assays. Perilipin2 overexpression reversed the effects of HG on inhibiting podocalyxin, nephrin, precursor (pro)-caspase-3/-9 and PPARγ protein expression and increasing cleaved caspase-3/-9 protein expression. Furthermore, the functions of perilipin2 overexpression reversing HG-induced podocyte apoptosis were inhibited by PPARγ inhibitor. In conclusion, the functions of DN-induced podocyte apoptosis were inhibited by activation of the PPARγ signaling pathway caused by perilipin2 overexpression.

Association between coffee consumption and risk of bladder cancer in a meta-analysis of 16 prospective studies.

BACKGROUND: Current evidence remains equivocal as to whether and how consumption of coffee may be associated with risk of bladder cancer, and potential influence of confounding by smoking on this association is yet to be elucidated. We conducted an updated meta-analysis of prospective studies to address these issues. METHODS: Relevant studies were identified by searching PubMed and EMBASE databases from inception to April 2019. A random-effects model was used to estimate summary relative risk (RR) with corresponding 95% confidence interval (CI) of bladder cancer associated with coffee consumption. RESULTS: The final analysis included 16 prospective studies comprising 2,122,816 participants and 11,848 bladder cancer cases. Overall, coffee consumption was not associated with risk of bladder cancer (RR high-vs-low = 1.07, 95% CI: 0.96-1.20). The lack of association persisted in the strata defined by sex or participants' smoking status. Meta-regression analyses identified the number cases (P difference = 0.06) and the degree of adjustment for smoking (P difference = 0.04) as potential sources of heterogeneity. There was an increased risk of bladder cancer related to higher coffee consumption among studies with fewer cases (RR high-vs-low = 1.38, 95% CI: 1.05-1.81) and among those with poorer adjustment for smoking (RR high-vs-low = 1.48, 95% CI: 1.14-1.93). Results were similar in the dose-response analyses (RR 1 cup/d = 1.01, 95% CI: 0.98-1.03). CONCLUSION: Best evidence available to date does not support an independent association between coffee consumption and bladder cancer risk. Some direct associations observed in individual studies may be a result of residual confounding by smoking. SUPPLEMENTARY INFORMATION: Supplementary information accompanies this paper at 10.1186/s12986-019-0390-3.

Full age spectrum equation versus CKD-EPI and MDRD equations to estimate glomerular filtration rate in adults with obstructive nephropathy.

OBJECTIVE: To compare the full age spectrum (FAS) equation with the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in predicting glomerular filtration rate (GFR) in patients with obstructive nephropathy. METHODS: Adult patients with obstructive nephropathy who had undergone a GFR measurement using technetium-99m diethylenetriaminepentaacetic acid radioisotope renography were enrolled in the study. The measured GFR was taken as the reference value. Bias, precision and accuracy were compared between the three equations. Kappa test and the Bland-Altman method were used to evaluate the classification and the agreement. Receiver operating characteristic (ROC) curve analysis was used to describe the diagnostic accuracy of each equation. RESULTS: A total of 327 patients were enrolled. The P30 value for the FAS equation was 60.2% in the overall study cohort. The FAS equation had the highest diagnostic accuracy (ROCAUC = 0.87, 95% confidence interval [CI] 0.84, 0.91) compared with the MDRD equation (ROCAUC = 0.86, 95% CI 0.82, 0.89). The median bias of the FAS equation was significantly higher than that of the MDRD equation (8.7 versus 7.6 ml/min/1.73 m2, respectively). CONCLUSIONS: Despite the drawbacks associated with each equation, the FAS equation was probably closer to ideal to estimate GFR in patients with obstructive nephropathy.

Baseline Serum Magnesium Level and Its Variability in Maintenance Hemodialysis Patients: Associations with Mortality.

BACKGROUND/AIMS: The study aimed at investigating the impact of serum magnesium (Mg) baseline level and its variability on mortality in maintenance hemodialysis (MHD) patients. METHODS: Eligible patients receiving regular MHD at Ningbo No. 2 Hospital between January 2009 and August 2016 were enrolled and follow-ups were conducted afterwards until death or transplantation. General information, laboratory results, and outcomes of subjects were collected. The relationship between baseline serum Mg level, its coefficient of variation (CV), and all-cause mortality and cardiovascular disease mortality were assessed, respectively. Subjects were divided into groups in 2 manners: by serum Mg level (lower Mg group: serum Mg <1.00 mmol/L, higher Mg group: serum Mg ≥1.00 mmol/L) and by serum Mg CV (high variation group: CV ≥0.149 mmol/L, middle variation group: 0.114 mmol/L ≤ CV < 0.149 mmol/L, and low variation group: CV <0.114 mmol/L). RESULTS: 169 MHD patients were recruited in the study, with mean serum Mg 1.00 ± 0.18 mmol/L, average age 60.20 ± 15.64 years, and median dialysis duration 37.00 (18.30, 77.97) months. During the follow-up, 69 (40.83%) patients died, 24 (34.78%) of which died due to cardiovascular disease. Comparing the two groups, patients in the lower Mg group had a higher all-cause mortality (50.00 vs. 29.33%, p = 0.007). The multivariate Cox regression analysis suggested that lower Mg level was an independent factor for all-cause mortality as well as cardiovascular mortality (HR = 13.268, 95% CI 6.234-28.237, p < 0.001; HR = 12.702, 95% CI 3.737-43.174, p < 0.001, respectively). However, there were no significant statistical differences of all-cause and cardiovascular mortality among these three groups concerning Mg variation. And in the univariate and multivariate Cox regression analysis, serum magnesium CV was not the independent factor for all-cause mortality and cardiovascular mortality. CONCLUSIONS: The lower baseline serum magnesium level was associated with all-cause and cardiovascular mortality in MHD patients. However, the variability of magnesium level was not independently associated with the risk of death and further studies need to be conducted.

Full age spectrum equation may be an alternative method to estimate the glomerular filtration rate in Chinese patients with chronic kidney disease
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OBJECTIVE: To assess the performance of the full age spectrum (FAS) equation in comparison to other equations in subjects with chronic kidney disease (CKD) for the first time in China. MATERIALS AND METHODS: The measured glomerular filtration rate (mGFR) obtained by the 99mTc-diethylenetriamine pentaacetic acid renogram was used as the reference standard. Bias, precision, and accuracy were analyzed to identify which of these four equations performed better: FAS equation, the Modification of Diet in Renal Disease (MDRD) equation, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the Berlin Initiative Study-1 (BIS-1) equation. κ-test and the Bland-Altman method were applied to evaluate the classification and the agreement between the estimated glomerular filtration rate (eGFR) and mGFR, respectively. RESULTS: 396 subjects were enrolled in this study. The precision (root mean square error, RMSE) of the FAS equation was 19.49 (95% CI 17.98, 21.27) in adults (18 - 70 years) and 14.06 (95% CI 12.50, 16.07) in older adults (≥ 70 years), better than the corresponding values of MDRD equation 22.32 (95% CI 20.59, 24.36) and 20.76 (95% CI 18.46, 23.72)(p < 0.05), superior to 17.59 (15.64, 20.10) for CKD-EPI equation in older adults, respectively. The FAS equation showed the least bias (1.28 (95% CI -1.38, 4.03)) in older adults and the highest percentage (63.64%) of accuracy (30%) in all participants. The FAS correctly classified subjects into GFR categories. CONCLUSION: The FAS equation improved the precision and accuracy of eGFR, especially in older adults. It also decreased the bias of the estimated GFR. The FAS equation is applicable to adults and may be an alternative to measuring eGFR in China.
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Neutrophil-lymphocyte ratio is associated with arterial stiffness in patients with peritoneal dialysis.

BACKGROUND: Patients with peritoneal dialysis are in the persistent inflammation state and have elevated arterial stiffness. Neutrophil-lymphocyte ratio(NLR) is a new inflammatory marker in renal and cardiac disorders. Brachial-ankle pulse wave velocity (baPWV) is a non-invasive measurement, which is widely used as a surrogate marker of arterial stiffness. However, there is little evidence to show an association between NLR and baPWV in patients with peritoneal dialysis. The aim of this cross-section study was to investigate the relationship between NLR and arterial stiffness measured by baPWV in patients with peritoneal dialysis. METHODS: In this cross-section study, 101 patients with peritoneal dialysis were enrolled from January 2014 to June 2015. According to average baPWV level (1847.54 cm/s), the patients were categorized into two groups, low group and high group. baPWV, which reflects arterial stiffness, was calculated using the single-point method. Clinical data were collected in details. NLR was calculated using complete blood count. Associations between NLR and baPWV were assessed using Pearson's correlation and linear regression analysis. RESULTS: The NLR was significantly lower in the low baPWV group than in the high baPWV group (p = 0.03). There were positive correlations between baPWV and neutrophil count (r = 0.24, p = 0.01) and NRL(r = 0.43, P < 0.01), and there was a negative correlation between baPWV and lymphocyte count (r = -0.23, p = 0.01). In addition, albumin, phosphorous and intact parathyroid hormone showed negative correlations with baPWV (r = -0.32, p < 0.01; r = -0.28, p < 0.01; r = -0.25, p = 0.01, respectively). Age and hsCRP showed positive correlations with baPWV (r = 0.47, p < 0.01; r = 0.25, p = 0.01). In multivariate analysis, NLR independently correlated with baPWV in patients with peritoneal dialysis (ß = 0.33, p < 0.01), even after adjustment for various confounders. CONCLUSION: Our study suggests that NLR was an independently associated with arterial stiffness in patients with peritoneal dialysis. However, further prospective studies are needed to confirm cause-and-effect relationship between NLR and baPWV, and to investigate whether anti-inflammatory treatment could improve arterial stiffness in patients with peritoneal dialysis.

Hypomagnesemia Is Associated with Increased Mortality among Peritoneal Dialysis Patients.

OBJECTIVE: Hypomagnesemia has been associated with an increase in mortality among the general population as well as patients with chronic kidney disease or those on hemodialysis. However, this association has not been thoroughly studied in patients undergoing peritoneal dialysis. The aim of this study was to evaluate the association between serum magnesium concentrations and all-cause and cardiovascular mortalities in peritoneal dialysis patients. METHODS: This single-center retrospective study included 253 incident peritoneal dialysis patients enrolled between July 1, 2005 and December 31, 2014 and followed to June 30, 2015. Patient's demographic characteristics as well as clinical and laboratory measurements were collected. RESULTS: Of 253 patients evaluated, 36 patients (14.2%) suffered from hypomagnesemia. During a median follow-up of 29 months (range: 4-120 months), 60 patients (23.7%) died, and 35 (58.3%) of these deaths were attributed to cardiovascular causes. Low serum magnesium was positively associated with peritoneal dialysis duration (r = 0.303, p < 0.001) as well as serum concentrations of albumin (r = 0.220, p < 0.001), triglycerides (r = 0.160, p = 0.011), potassium (r = 0.156, p = 0.013), calcium(r = 0.299, p < 0.001)and phosphate (r = 0.191, p = 0.002). Patients in the hypomagnesemia group had a lower survival rate than those in the normal magnesium groups (p < 0.001). In a multivariate Cox proportional hazards regression analysis, serum magnesium was an independent negative predictor of all-cause mortality (hazard ratio [HR] = 0.075, p = 0.011) and cardiovascular mortality (HR = 0.003, p < 0.001), especially in female patients. However, in univariate and multivariate Cox analysis, △Mg(difference between 1-year magnesium and baseline magnesium) was not an independent predictor of all-cause mortality and cardiovascular mortality. CONCLUSION: Hypomagnesemia was common among peritoneal dialysis patients and was independently associated with all-cause mortality and cardiovascular mortality.