Objective To access the clinical efficacy and safety of hydroxychloroquine (HCQ) in treatment of IgA nephropathy (IgAN). Methods The data of IgAN patients who were diagnosed by renal biopsy in the First Affiliated Hospital, College of Medicine, Zhejiang University from May 2016 to August 2020 and had been treated with HCQ for more than 6 months without other immunosuppressants were retrospectively analyzed. The efficacy and side effects were compared between groups according to the baseline urine protein/creatinine ratio (UPCR) or whether combined with renin-angiotensin-aldosterone system inhibitor (RAASi). Results A total of 121 patients were enrolled, including 45 males (37.19%). At baseline, the median UPCR was 0.69(0.45, 1.00) g/g; the median estimated glomerular filtration rate (eGFR) was 93.46(73.14, 115.67) ml·min^-1·(1.73 m²)^-1; the median serum creatinine was 80.00(61.00, 98.00) μmol/L, and the serum albumin was (44.39±3.36) g/L. After HCQ treatment, UPCR and red blood cells were significantly decreased compared with baseline (all P<0.05). Triglyceride, total cholesterol and low-density lipoprotein cholesterol were also significantly decreased during the follow-up period. Serum creatinine, eGFR, serum albumin and serum uric acid remained stable. After 6 months of follow-up, the total remission rate was 56.88%, including 15.60% of partial remission and 41.28% of complete remission; at the end of follow-up, the median follow-up time was 280.00(214.00, 411.00) days and the total remission rate was 56.20%, including 9.92% of partial remission and 46.28% of complete remission. Group analysis showed that the remission rate was 60.53% (n=76) and 48.48% (n=33) at 6 months (Mann-Whitney U test, Z=-2.331, P=0.020) and 57.65% (n=85) and 52.78% (n=36) at the end of follow-up (Mann-Whitney U test, Z=-1.673, P=0.094) between patients with baseline UPCR<1 g/g and patients with baseline UPCR≥1 g/g; and the remission rate was 66.67% (n=30) and 53.16% (n=79) at 6 months (Mann-Whitney U test, Z=1.062, P=0.288) and 61.29% (n=31) and 54.44% (n=90) at the end of follow-up (Mann-Whitney U test, Z=0.930, P=0.352) between patients with single HCQ and patients with HCQ+RAASi. For side effects, the eGFR of 2 patients decreased by more than 30% compared with baseline, 1 patient relapsed and 1 patient developed blurred vision. Conclusions HCQ is safe and effective for the treatment of IgAN.

Objective To study the structure and diversity of intestinal flora in IgA nephropathy (IgAN) patients, and to explore the correlation of intestinal microorganisms with clinical indicators and renal pathology. Methods Fifteen IgAN patients in the First Affiliated Hospital of Baotou Medical College from May 2020 to September 2020 were retrospectively enrolled as IgAN group, and 8 healthy families and 7 health checkups were enrolled as healthy control group. Illumina high-throughput sequencing technology was performed for DNA sequencing in the 16S rDNA-V4 region of all bacteria in the feces sample. QIIME 2 was used to process and analyze original sequence, compared with Greengenes (V138) database. The DADA2 software was called to denoise the data, which was equivalent to a 100% similarity cluster (OTU was a 97% similarity cluster). PCoA was used to analyze the structure and diversity of intestinal flora. Spearman correlation or Pearson correlation analysis was used to analyze the correlation of differential flora with renal pathology and clinical indicators. Results (1) The intestinal microbial β diversity in IgAN patients was significantly different from that in healthy controls (P=0.010). (2) Compared with the healthy control group, the numbers of intestinal flora species in IgAN group were significantly increased in 1 phylum, 3 families and 22 genus. At the levels from phylum to family, the species numbers of Firmicutes and Ruminococcaceae in IgAN patients reduced than those in healthy controls and the species numbers of Chloroflexi, Gaiellaceae, Staphylococcaceae and Family-XⅢ in IgAN patients increased than those in healthy controls (all P<0.05). At the genus level, compared with the healthy controls, the species number of Subdoligranulum in IgAN patients was significantly reduced (P=0.020), and the species number of Ruminococcus-gnavus-group was significantly increased (P=0.004). (3) At the phylum level of the species number, Firmicutes in IgAN patients was positively correlated to albumin (ALB) (r=0.637, P=0.037) and IgG (r=0.452, P=0.046), Gemmatimonadetes was negatively correlated to serum creatinine (r=-0.453, P=0.045), Verrucomicrobia was negatively correlated to IgM (r=-0.450, P=0.046), and Patescibacteria was positively correlated to IgA (r=0.469, P=0.037). At the genus level of the species number, Ruminococcus-gnavus-group (r=-0.614, P=0.004) and Megamonas (r=-0.451, P=0.042) were negatively correlated to ALB; Subdoligranulum was positively correlated to ALB (r=0.563, P=0.009); Dialister was negatively correlated to C3 (r=-0.427, P=0.041) and was positively correlated to IgA (r=0.434, P=0.035); Veillonella was positively correlated to estimated glomerular filtration rate (r=0.452, P=0.043). The species numbers of Eisenbergiella (r=-0.850, P=0.007), Holdemania (r=-0.845, P=0.008), Flavonifractor (r=-0.845, P=0.008), and Ruminiclostridium-9 (r=-0.845, P=0.008) were negatively correlated to glomerulosclerosis or adhesion (S) of Oxford classification; the species number of Fusicatenibacter was negatively correlated to mesangial hypercellularity (r=-0.845, P=0.008); the number of Coprococcus-2 was positively correlated to S (r=0.738, P=0.037) and tubular atrophy or interstitial fibrosis (r=0.756, P=0.030). (4) Random forest model was built with Ruminococcus-gnavus-group and Subdoligranulum, after fitting the area under the receiver operating characteristic curve was 0.927. Conclusions The intestinal flora of IgAN patients is different from that in healthy subjects. Changes of intestinal flora in IgAN patients are related to clinical indicators and renal pathology. In particular, Ruminococcus-gnavus-group and Subdoligranulum may play an important role in IgAN.

Objective To investigate the effect of usage of transthoracic echocardiography (TTE) on the prognosis of patients after acute kidney injury (AKI) in intensive care unit (ICU). Methods The clinical data of patients with AKI in the Medical Information Mart for Intensive Care (MIMIC-Ⅲ v1.4) database was collected retrospectively, and the patients were divided into TTE group (with TTE within 24 hours of AKI diagnosis) and No-TTE group (without TTE examination or first TTE examination was more than 24 hours after AKI diagnosis). Propensity score matching (PSM) was utilized to balance the baseline variables between the two groups and Cox regression analysis was used to evaluate the independent risk factors for 28-day all-cause mortality (the primary outcome). Moreover, after PSM, the effects of TTE usage on the second outcomes (including the volumes of intravenous fluid and urine output in the first, second and third 24-hour after the diagnosis of AKI; the total number of mechanical ventilation-free days, renal replacement therapy-free days and vasopressor-free days within 28 days after ICU admission; use of diuretics after the diagnosis of AKI; reduction in serum creatinine within 48 hours after the diagnosis of AKI; and the length of ICU stay and hospital stay) were also evaluated. Results Among 23 945 eligible AKI patients, 3 365 patients (14.1%) patients received TTE within 24 hours after the diagnosis of AKI and finally there were 3 361 patients in TTE group and No-TTE group included in this study after PSM based on the ratio of 1∶1. After PSM, all variables in the two groups were well balanced (standardized mean difference<0.1, respectively). Before and after PSM, patients in TTE group had lower 28-day all-cause mortality compared with patients in No-TTE group (10.76% vs 13.04%, χ²=13.535, P<0.001; 10.65% vs 18.80%, χ²=88.932, P<0.001), and Kaplan-Meier survival curves also revealed that patients in the TTE group had higher cumulative survival rate compared with patients in No-TTE group (Log-rank χ²=15.438, P<0.001; Log-rank χ²=75.360, P<0.001, respectively). Multivariate Cox regression analysis showed that TTE was an independent influencing factor for 28-day all-cause mortality before and after PSM (HR=0.80, 95%CI 0.73-0.89, P<0.001; HR=0.58, 95%CI 0.51-0.65, P<0.001). And all subgroup analyses showed the similar results. Compared with patients in the No-TTE group, patients in the TTE group had higher volume of intravenous fluid on the first day and the second day after the diagnosis of AKI (both P<0.01). Patients in the TTE group had higher volume of urine output on the first day and the third day after the diagnosis of AKI (both P<0.01). The patients in the TTE group had a significantly lower duration of vasopressor-free and mechanical ventilation-free (both P<0.01). The usage of diuretic was significantly higher in the TTE group compared with that in the No-TTE group (54.1% vs 44.2%, χ²=65.609, P<0.001). With respect to serum creatinine, the reduction in serum creatinine within 48 hours after the diagnosis of AKI was higher in the TTE group than that in the No-TTE group [36.6(23.0, 97.2) μmol/L vs 30.1(14.2, 61.9) μmol/L, Z=-9.549, P<0.001]. Moreover, TTE group had shorter ICU stay than that in the No-TTE group [5.03(3.40, 8.90) d vs 5.37(3.77, 10.00) d, Z=-6.589, P<0.001]. There were no significant difference between the two groups in other secondary outcomes (all P>0.05). Conclusions Timely TTE utilization after AKI incident is associated with better clinical outcomes for ICU patients.

Objective To investigate the incidence of acute kidney injury (AKI) following pancreaticoduodenectomy and related risk factors in elderly patients. Methods The clinical data of elderly patients who underwent pancreaticoduodenectomy in Henan Provincial People′s Hospital from January 2017 to June 2020 were collected retrospectively. According to the changes of serum creatinine within 48 h or 7 days after operation, the patients were divided into AKI group and non-AKI group. The basic clinical characteristics of the two groups were compared, and the incidence of AKI was calculated. Multivariate logistic regression model was used to analyze the risk factors of postoperative AKI. Results A total of 322 elderly patients were enrolled, with age of (67.1±5.2) years old (60-85 years old) and 186 males (57.76%). Among 322 elderly patients, there were 41 patients (12.73%) suffering from AKI following pancreaticoduodenectomy. Compared with the non-AKI group, the level of bilirubin in AKI group was higher (Z=-2.012, P=0.044), and the level of hemoglobin in AKI group was lower (Z=-2.111, P=0.035). Multivariate logistic regression analysis showed that increased preoperative total bilirubin (OR=1.003, 95%CI 1.000-1.006, P=0.027) and postoperative exploratory laparotomy (OR=3.936, 95%CI 1.071-14.460, P=0.039) were the independent influencing factors for AKI after pancreaticoduodenectomy in elderly patients. Conclusions The incidence of AKI after pancreaticoduodenectomy in elderly patients is 12.73%. Preoperative high bilirubin and postoperative exploratory laparotomy may be the independent risk factors for AKI after pancreaticoduodenectomy in elderly patients.

Objective To investigate the role of complement activation in the pathogenesis of primary malignant hypertension (MHT) with nephrosclerosis complicated with severe cardiorenal injury. Methods Data of MHT patients with nephrosclerosis proven by biopsy from January 2010 to December 2020 in the Beijing Anzhen Hospital, Capital Medical University were retrospectively analyzed. The expressions of complement-related component C4d, C1q, complement factor H-related protein 5, C3c and C5b-9 were detected by immunohistochemical staining. According to whether the patients were complicated with acute heart failure (AHF) and/or acute kidney injury (AKI), they were divided into severe cardiorenal injury group and non-severe cardiorenal injury group. The differences of clinicopathological data between the two groups were compared. According to the degree of C4d deposition in renal tissues, patients were divided into C4d diffused deposition group and non-C4d diffused deposition group. The severity of cardiorenal injury and the pathological characteristics of thrombotic microangiopathy in renal tissues were compared between the two groups. Results A total of 33 patients were enrolled in this study, of which 17 cases (51.5%) were complicated with severe cardiorenal injury; AHF occurred in 16 patients (48.5%), AKI occurred in 8 patients (26.7%), and AHF and AKI were combined in 7 patients (21.2%). Compared with non-severe cardiorenal injury group, patients in severe cardiorenal injury group had higher levels of baseline lactate dehydrogenase[326.0 (217.0, 366.0) IU/L vs 197.0 (165.0, 220.0) IU/L, Z=37.000, P=0.002] and hemoglobin [(143.6±24.0) g/L vs (106.4±24.7) g/L, t=38.500, P<0.001], lower levels of 12 h urinary incontinence osmolality [400.0 (342.5, 504.0) mmol/L vs 476.0 (432.3, 616.5) mmol/L, Z=72.000, P=0.021] and serum albumin [(36.2±9.4) g/L vs (43.2±6.2) g/L, t=6.423, P=0.017], and thicker left ventricular posterior wall [(14.0±2.1) mm vs (12.1±1.1) mm, t=6.552, P=0.018]. The immunohistochemical results of kidney tissue showed that the proportions of C4d and C5b-9 diffused deposition in severe cardiorenal injury group were significantly higher than those in non-severe cardiorenal injury group (5/16 vs 0/15, P=0.043; 12/16 vs 5/15, P=0.032). Compared with non-C4d diffused deposition group, C4d diffused deposition group had higher incidence of AHF (5/5 vs 10/26, P=0.018), poorer heart function, more severe ventricular remodeling, and shorter history of hypertension [2.0 (0, 12.0) months vs 48.0 (9.5, 84.0) months, Z=22.500, P=0.022]. Conclusions The incidence of severe cardiorenal injury in MHT patients with nephrosclerosis is about 51.5%. The proportion of diffuse deposition of complement activated components in renal tissues in patients with severe cardiorenal injury is higher than that in patients with non-severe cardiorenal injury. Overactivation of complement may be involved in the pathogenic process of severe heart and kidney injury caused by MHT.

Objective To evaluate perirenal adipose tissue inflammation in obesity-related glomerulopathy induced by a high-fat diet in C57BL/6J mice and further explore its probable mechanism. Methods Twelve 8-10-week-old male C57BL/6J mice were divided into normal diet group (ND, n=6) and high-fat diet group (HFD, n=6) using simple random sampling method. After 14 weeks, the blood and kidney tissue were sampled, and the pathological change in the kidney and perirenal adipose tissue was observed by hematoxylin-eosin, periodic acid-Schiff, and Masson staining. The mRNA expression of tumor necrosis factor -α (TNF-α), M1-type macrophage marker CD11c, interleukin (IL)-1β, monocyte chemotactic protein-1 (MCP-1), IL-10, transforming growth factor -β1, M2-type macrophage marker CD206 and fibronectin 1 in perirenal fat was detected by real-time fluorescence quantitative PCR. The expression of macrophages marker F4/80, CD68 and leukocyte common antigen (LCA) in the kidney and perirenal adipose tissue was detected by immunohistochemistry. Results After 14 weeks of feeding, compared with mice in the ND group, the weight of mice in the HFD group was significantly higher [(35.83±1.19) g vs (24.06±0.37) g, P<0.05]. In the HFD group, perirenal adipocyte hyperplasia, accompanied by glomerular hyperplasia, mesangial matrix hyperplasia and renal interstitial fibrosis, and other pathological changes was observed (all P<0.05). The level of blood glucose, blood lipid, serum creatinine and blood urea nitrogen was also significantly higher (all P<0.05). The mRNA expression of TNF-α, CD11c, IL-1β and MCP-1 related to M1 macrophages in the perirenal adipose tissue was higher (all P<0.05), and immunohistochemistry showed that the expression of F4/80, CD68 and LCA in the perirenal adipose tissue was higher in HFD group (all P<0.05). The above results showed that the number of macrophages and inflammatory cells in the perirenal adipose tissue was significantly greater in the HFD group than those in the ND group. Pearson linear correlation analysis showed that the average perirenal fat area was positively correlated with macrophages number in perirenal adipose tissue, several morphological indexes such as glomerular cross-sectional area and renal function injury indexes such as blood urea nitrogen (all P<0.05). Conclusion The C57BL/6J mice model of obesity-related glomerulopathy induced by a high-fat diet is successfully established, and the perirenal adipose tissue shows an obvious inflammatory response, with the macrophages significantly polarized mainly in the pro-inflammatory direction towards the M1-type macrophages.