Objective    To investigate the prevalence and related risk factors of hyperuricemia in patients with lupus nephritis (LN) in Southern China.    Methods    A single center retrospective study, 959 adult LN patients diagnosed with biopsy-proven, who admitted to The First Affiliated Hospital, Sun Yat-sen University from 1998.01 to 2010.12 were recruited.    Results    Among this cohort, the prevalence of hyperuricemia was 57.7%. The prevalence of hyperuricemia for CKD stage 1, 2, 3, 4, 5 was 44.1%, 65.7%, 74.7%, 77.6%, 73.9%, respectively. Logistic regression analysis showed that increased serum triglyceride level and endothelial proliferation (≥50%) were independent risk factors of hyperuricemia in LN patients; Also, increased serum triglyceride level was an independent risk factor of hyperuricemia in LN patients of CKD stage 1-2; Positive dsDNA and positive anticardiolipin antibody were independent risk factors of hyperuricemia in LN patients of CKD stage 3-5.  Conclusion    The prevalence of hyperuricemia in LN patients from this cohort is 57.7%. Increased level of serum triglyceride is an independent risk factor associated with hyperuricemia in both overall LN patients and those of CKD stages 1-2. Therefore, the present study indicates that metabolic factors may influence each other, and should be paid more attention in the clinical practice of LN care.

Objective    To analyze the clinical features and prognostic factors of patients with malignant tumor complicated by acute kidney injury (AKI), and provide the basis for preventing AKI and improving the prognosis.    Methods    Malignant tumor patients complicated by AKI were screened with the electronic medical records system from January 2001 to December 2012 at the Affiliated Hospital of Qingdao University. The clinical characteristics in the 12 years were analyzed by statistical analysis and compared. The risk factors of the hospital mortality in malignancies tumor complicated by AKI were analyzed by Logistic regression analysis.    Results    A total of 100 patients with malignant tumor complicated by AKI were collected, accounting for 24.94% of AKI patients and 1.66‰ of malignant tumor patients at the same period. Malignancies were consist of hematologic malignancies(11%), non-metastatic solid tumor (47%), metastatic solid tumor (42%). The most common factor leading to AKI for malignancies was post-renal obstruction (64%), followed by nephrotoxic drugs or contrast agents (24%), hypovolemia (18%). There was no significant change of the etiologies for AKI between the first six-year and the second six-year (P＞0.05). The hospital mortality of patients with malignant tumor complicated by AKI was 25%, and multivariate Logistic regression analysis showed that multiple etiologies (OR=13.356), multiple organ failure (OR=222.256), and metastatic solid tumors (OR=8.497) were the independent risk factors for hospital mortality.    Conclusions    AKI is a common complication in patients with malignant tumors, and the most common factor leading to AKI is post-renal obstruction. The hospital mortality in malignancies with AKI is high, which should get the attention of clinicians.

Objective    To investigate whether RAS inhibitors can improve renal function in  the treatment of lupus nephritis (LN) with thrombotic microangiopathy (TMA).    Methods    A total of 15 LN patients with TMA proven by renal pathology, from January 2000 to December 2013 in PUMCH, were included. The serum creatinine (Scr) and blood pressure (BP) before and after using RAS inhibitors were analyzed.    Results    (1)Male/female ratio was 1∶14. All of the patients had renal dysfunction, and median peak value of Scr was 396 μmol/L (160～643 μmol/L). 5 cases (33.3%) required acute dialysis during hospitalization. Hypertension occurred in 15 patients, while 6 cases (40.0%) were diagnosed malignant hypertension. (2) Anemia and thrombocytopenia occurred in 15 and 14 cases, respectively. Three cases (20.0%) were diagnosed MAHA definitely and 5 cases (33.3%) were diagnosed MAHA probably. (3) Renal biopsy showed class Ⅱ in 1 case, Ⅲ in 4 cases, Ⅳ-(G) in 2 cases, IV(S) in 5 cases and IV+V in 3 cases. Active lesions were predominant in both glomeruli and renal vasculopathy. (4) All the patients received steroid and immunosuppressive therapy, of whom 9 cases were given steroid pulse therapy. Thirteen cases received cyclophosphamide, and the rest 2 cases  received cyclophosphamide and mycophenolate. After steroid pulse therapy, there were only 5 patients (55.6%) who got decreased Scr. In 13 patients (86.7%), hypertension was ameliorated and Scr decreased within one week after implementing RAS inhibitors, which fell medianly 15.8% and 17.0%, respectively. (5) Eleven of the 15 patients were followed from 8 to 135 months (median 32 months), and the other 4 patients were lost. Five cases who was on dialysis during hospitalization became independent of renal replacement therapy, while the other cases also got improved renal function.    Conclusions    Patients of LN with TMA who develop AKI and refractory hypertension should be treated with RAS inhibitors. Improved renal survival and successful discontinuation of dialysis are possible benefits when RAS inhibitors are used to treat LN with TMA.

Objective    To evaluate the relationship of insulin resistance (IR) and carotid artery intima-media thickness (CA-IMT), plaque status in non-diabetic non-dialysis chronic kidney disease (CKD) patients with different stages.    Methods    One hundred and seventeen non-diabetes non-dialysis CKD patients were enrolled into this cross-sectional observational study. Insulin resistance index (HOME-IR) was assessed by the homeostasis model assessment. Patients with HOME-IR≥1.73 were defined as insulin resistance. And patients with CA-IMT≥0.9 mm were defined as thickening. The blood pressure measurement, heart Doppler ultrasound, bilateral carotid artery ultrasound examination, blood biochemistry and urine protein test were performed, eGFR was calculated by EPI formula.    Results    The prevalence of IR was 47.01% in 117 non-diabetic non-dialysis CKD patients, and it was 35.71%, 50.00% and 54.55% in eGFR≥60 ml•min^-1•(1.73 m²)^-1 group, 30≤eGFR＜60 ml•min^-1•(1.73 m²)^-1 group, and eGFR＜30 ml•min^-1•(1.73 m²)^-1 group separately. In eGFR＜30 ml•min^-1•(1.73 m²)^-1 group, cystain C, homocysteine, parathyroid hormone, Scr, BUN, uric acid, interventricular septal thickness, left ventricular dimension, left ventricular posterior wall thickness were significantly higher than that in the other two groups (P＜0.01), while the level of hemoglobin was significantly lower (P＜0.01); then the levels of serum albumin and systolic pressure were higher than that in the eGFR≥60 ml•min^-1•(1.73 m²)^-1 group, however, the levels of total cholesterol and low-density lipoprotein-cholesterol were lower than that in the eGFR≥60 ml•min^-1•(1.73 m²)^-1 group. Correlation analysis showed that insulin resistance index was significantly correlated with CA-IMT (r=0.444, P=0.006）in the eGFR＜30 ml•min^-1•(1.73 m²)^-1 group, however, there wasn’t correlation in other two groups. And although insulin resistance wasn’t correlated with soft plaque, it was significantly correlated with hard plaque (χ²=6.476, P=0.011) in the eGFR＜30 ml•min^-1•(1.73 m²)^-1 group. The Logistic regression analysis results displayed aging increase was the independent risk factor of the CA-IMT thickening for non-diabetes non-dialysis CKD patients but not insulin resistance.    Conclusions    HOMA-IR is correlated with CA-IMT and hard plaque when eGFR＜30 ml•min^-1•(1.73 m²)^-1 in non-diabetes non-dialysis CKD patients. However, the insulin resistance isn’t the independent risk factor of the CA-IMT thickening for non-diabetes non-dialysis CKD patients.

Object    To investigate the maturity status of the cephalic vein when the native arteriovenous fistula matures and set up indicators of a matured native arteriovenous fistula.    Methods The diameter, flow rate and wall thickness of the cephalic vein were prospectively measured by Doppler ultrasound after the native fistula was created. Mature judgment was done by skilled nurses depending on their experience before the fistula was punctured. The ultrasound data was marked as proposed mature at the same time. After three times dialysis, if blood flow was fluent and complications such as prolonged bleeding time and hematoma were absent, fistula mature was confirmed.    Results    Thirty-one patients were admitted to the study, then fistula were matured. The average age of those patients was (52.93±3.21) years old. Thirteen patients were female. Twenty two fistula located on the left arm. Thirteen of the patients were diabetic nephropathy. The average diameter of cephalic vein was increased from (3.10±0.11) mm before surgery to (4.74±0.16) mm when the fistula was matured, though it was still smaller than 6 mm which K/DOQI guideline had recommended (P＜0.05). The average mature period was (57.10±3.21) days. The matured fistula had an average high flow rate of (569.76±48.34) ml/min and wall thickness of (0.95±0.04) mm. The one-side 95% credibility interval of the diameter, flow rate and wall thickness of cephalic vein was 4.44 mm, 486.37 ml/min and 0.67 mm, respectively.    Conclusions    The diameter of cephalic vein in a matured native arteriovenous fistula in our study was significantly smaller than 6 mm which K/DOQI guideline had recommended. The indicators of native arteriovenous fistula mature in our country may different from abroad.

Objective    To observe the influence of adrenocorticotropic hormone (ACTH_4-10) in the changes of podocyte proliferation, apoptosis and expression of nephrin and podocin on adriamycin(ADR) -induced podocyte injury and investigate the protective effect of ACTH_4-10.    Methods    All podocytes were randomly divided into following groups: normal control, ADR-induced group and ACTH_4-10 intervention group (low, middle and high concentration). Normal control group was not treated, ADR-induced group was induced to set the model of podocyte injury by ADR (1 μmol/L) for 24 hours and ACTH_4-10 intervention groups were intervened by 1 μg/L, 10 μg/L and 100 μg/L ACTH_4-10 for 1 hours respectively, prior to setting the model of podocyte injury. Cell counting kit (CCK-8) was used to detect the multiplication of podocytes and TUNEL apoptosis detection kit was used to detect podocyte apoptosis. Real-time PCR and Western blotting were used to examine the expression of nephrin and podocin.    Results    Compared with control group, podocyte proliferation and expression of nephrin and podocin was decreased significantly in ADR-induced group (P＜0.05), meanwhile podocyte apoptosis was increased obviously (38.14% vs 5.12%). Compared with ADR-induced group, podocyte proliferation and expression of nephrin and podocin was increased generally with concentration of ACTH_4-10. Although podocyte apoptosis rates (20.45%, 17.39%, 11.02%) were increased in ACTH_4-10 intervention group (low, middle and high concentration) while comparing with normal control group, podocyte apoptosis decreased obviously while comparing with ADR-induced group.    Conclusions    ACTH_4-10 can stabilize the expression of nephrin and podocin on slid diaphragm, and has the protective effect on podocyte injury induced by ADR, while the effect depends on the concentration of ACTH_4-10.

Objective    To observe the expression of stromal cell-derived factor 1 (SDF-1) in the kidney after ischemic reperfusion injury (IRI), and explore its relationship with macrophage during the IRI kidney.    Methods    A total of 28 healthy C57BL/6 male mice were used to establish renal IRI model by clamping both pedicles for 35 min followed by reperfusion. Kidney tissue samples were collected at indicated time points. Renal histological changes were estimated. The expression of SDF-1 was determined by immunohistochemistry, ELISA and real-time PCR. After the liposomal clodronate was  injected intraperitoneally, the location of CD68 was observed by immunofluorescence. Renal histology and protein expression of SDF-1 were also detected.    Results    Compared with sham-operated group, classical tubular damage was found in IRI group, accompanied by a large number of inflammatory cells. The expression of total renal SDF-1 peaked on day 1 and decreased to control levels in the following days. SDF-1 in healthy kidney was localized at cortex, but spread to the corticomedullary area of the kidney during IRI. Compared with IRI groups, elimination of macrophage by injection of liposomal clodronate alleviated renal IRI and down-regulated the expressions of CD68 while up-regulating SDF-1.    Conclusions    SDF-1 expression is up-regulated in IRI kidney and is associated with macrophage. SDF-1 may play a role in the early phase of acute kidney injury and it may be a new marker in diagnosis of AKI.

Objective    To investigate the effects and underlying mechanism of secondary hyperparathyroidism (SHPT) patients’serum and klotho protein on the apoptosis of human umbilical vein endothelial cells (HUVECs).    Methods    Three types of mixed serum from 15 patients with SHPT (serum S), 10 CKD stage 5 patients without SHPT (serum C) and 15 healthy volunteers (serum H) were collected. HUVECs were incubated with 10% serum H，10% serum C, 10% serum S and 10% serum S plus klotho respectively. The apoptosis rate of endothelial cells was evaluated by flow cytometry. The activity of Caspase-3 was measured by spectrophotometry. The levels of AKT and phosphorylated forms of AKT (p- AKT) were detected by Western blotting (with or without PI3K/AKT inhibitor LY294002).    Results    The apoptosis of HUVECs was both induced by the serum  S and serum C. The apoptosis rate was greater in serum S group than that in serum C group (P＜0.05). The apoptosis was partly inhibited when klotho protein (50-100 μg/L) was added (P＜0.05), accompanying the up-regulation of p-AKT. The above effects could be blocked by LY294002. The activity of Caspase-3 was up-regulated in SHPT group compared to healthy control group (P＜0.05) and the up-regulation could also be inhibited by klotho  protein (P＜0.05).    Conclusions    The apoptosis of HUVECs is induced by the serum from CKD stage 5 patients without SHPT and SHPT patients. Klotho protein can protect the HUVECs from apoptosis  by up-regulating p-AKT and inhibiting Caspase-3.

Objective    To observe the effect of contrast media on autophagy and apoptosis of renal tubular epithelial cells, evaluate the role of autophagy in contrast media-induced renal tubular epithelial cells injury.    Methods    NRK-52E cells were exposed to iopromide at different concentration for 1 hour or at 50 gI/L for variable incubation time. Rapamycin (1 μg/L) and 3-methyadenine (2 mmol/L) were further introduced to investigate the role of autophagy in the process. The formation of autophagy was observed by acridine orange staining and Green fluorescent protein tagged LC3 (GFP-LC3). The expression of autophagy protein LC3 and Beclin-1 was examined by Western blotting, and the apoptosis level was examined by flow cytometry and Hoechst 33342-staining.    Results    (1) Autophagy could be enhanced by contrast media in renal tubular epithelial cells. (2) The expression of LC3-Ⅱ/LC3-I in renal tubular epithelial cells rose at first and then dropped with the increase of iopromide stimulation time and concentration (P＜0.05). (3) Iopromide promoted renal tubular epithelial cell apoptosis in dose-and time-dependent manner (P＜0.05). (4) Co-culture with rapamycin further increased LC3-Ⅱ/LC3-I, Beclin-1 and GFP-LC3 expression, but obviously prevented iopromide-induced apoptosis of renal tubular epithelial cells (P＜0.05). On the contrary, Co-culture with 3-methyadenine reduced iopromide-induced LC3-II/LC3-I, Beclin-1 and GFP-LC3 overexpression, but aggravated the apoptosis induced by iopromide (P＜0.05).    Conclusions    Contrast media can induce renal tubular epithelial cells apoptosis as well as autophagy. Enhancing autophagy appropriately has a protective effect on iopromide-induced renal tubular epithelial cells apoptosis, which conforms that autophagy plays an important role in antagonizing iopromide-induced renal tubular epithelial cells injury.