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.

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.

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.

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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Implication of combined urinary biomarkers in early diagnosis of acute kidney injury following percutaneous coronary intervention.

BACKGROUND: Kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and interleukin 18 (IL-18) are three of the most promising biomarkers for the early detection of acute kidney injury. In the present study, to determine whether a combination of the three biomarkers enhances their predictive value, representing an ideal indicator for the early detection of Acute Kidney Injury (AKI) we examined 118 adults undergoing elective percutaneous coronary intervention (PCI). METHODS: We performed a single center, nested case-control study. Urinary KIM-1, NGAL and IL-18 were measured by enzyme-linked immunosorbent assay before and 6 h, 24 h, 48 h postcontrast. Serum creatinine was measured before and 24 h, 48 h postcontrast. RESULTS: 12 patients (10.1%) were identified with AKI. 30 patients were selected as controls, matched with cases at an attempted 2.5 : 1 ratio. Compared to the non-AKI group, urinary NGAL were significantly higher at all the time-points. Urinary KIM-1 and IL-18 levels were significantly higher at 24 h and 48 h postcontrast. In the AKI group, Urinary NGAL peaked at 6 h postcontrast, and then decreased. Both KIM-1 and IL-18 peaked at 24 hours postcontrast, remained markedly elevated up to 48 h. By applying area under the receiver operator characteristic curve, the combination of KIM-1, NGAL and IL-18 had the most powerful diagnostic power (AUC = 0.99, (95%CI: 0.90 - 1.00), p = 0.0001) for diagnosis of AKI at 24 h postcontrast, superior to that for single detection and serum creatinine. CONCLUSIONS: KIM-1, NGAL and IL-18 were increased in tandem after PCI. The combination of urinary biomarkers may allow for early detection of AKI following PCI, better than serum creatinine, and the individual biomarkers.