The Value of Older Donors' Klotho Level in Predicting Recipients' Short-Term Renal Function.

BACKGROUND The present organ shortage has led to increased use of kidneys from expanded-criteria donors, but the prognosis is disappointing due to poor graft quality. As a promising kidney protector, the Klotho gene's role in predicting short-term prognosis has not been assessed. MATERIAL AND METHODS We retrospectively analyzed data from 41 recipients and 25 donors. Multiple clinical variables were compared between different subgroups of donors or their corresponding recipients. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the distinguishing ability. Dynamic changes in serum Klotho, FGF-23, and urinary NGAL were assessed. RESULTS Serum Klotho level was significantly lower in donors age ≥50 years (p=0.017), and there was a moderate negative correlation between serum Klotho expression and age (r=-0.464, p=0.019). Moreover, detection of Klotho mRNA and immunohistochemical analysis in kidneys revealed the same trend as in serum. Furthermore, for older donors (age ≥50 years), serum Klotho level had a strong negative correlation with recipient eGFR 1 month post-transplant (r=-0.686, p=0.007), which was proved to be a good predictor for estimating graft function by ROC analysis. Additionally, during the post-transplant follow-up, serum Klotho levels increased slightly after a temporary decline, while serum FGF-23 and urinary NGAL decreased significantly and then stayed low thereafter. CONCLUSIONS Klotho level, which decreases with age, may be a potential predictor of short-term renal function, especially for grafts from older donors.

LGALS3BP is a novel and potential biomarker in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common solid renal tumor. Therefore, it is necessary to explore the related tumor markers. LGALS3BP (galectin 3 binding protein) is a multifunctional glycoprotein implicated in immunity and cancer. Some studies have shown that LGALS3BP promotes the occurrence and development of tumors. However, their exact role in renal tumorigenesis remains unclear. Our study used a webserver to explore the mRNA expression and clinical features of LGALS3BP in ccRCC. Survival analysis showed that patients with high LGALS3BP expression had significantly worse OS and DFS than those with low LGALS3BP expression. LGALS3BP expression is significantly related to B cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. Furthermore, we determined that LGALS3BP is significantly associated with angiogenesis, stemness and proliferation in renal cancer. Three phenotypes may be associated with a poor prognosis. Genes related to proliferation, angiogenesis and stemness were derived from a Venn diagram of FGF2. FGF2 is negatively correlated with proliferation and positively correlated with angiogenesis. Finally, we screened for drugs that may have potential therapeutic value for ccRCC. The PCR results showed that the expression of LGALS3BP in the normal cell line was lower than that in the tumor cell lines. After LGALS3BP knockdown, the proliferation of 769-P and 786-O cells decreased. The present findings show that LGALS3BP is critical for ccRCC cell proliferation and may be a potential target and biomarker for ccRCC.

Predicting response of immunotherapy and targeted therapy and prognosis characteristics for renal clear cell carcinoma based on m1A methylation regulators.

In recent years, RNA methylation modification has been found to be related to a variety of tumor mechanisms, such as rectal cancer. Clear cell renal cell carcinoma (ccRCC) is most common in renal cell carcinoma. In this study, we get the RNA profiles of ccRCC patients from ArrayExpress and TCGA databases. The prognosis model of ccRCC was developed by the least absolute shrinkage and selection operator (LASSO) regression analysis, and the samples were stratified into low-high risk groups. In addition, our prognostic model was validated through the receiver operating characteristic curve (ROC). "pRRophetic" package screened five potential small molecule drugs. Protein interaction networks explore tumor driving factors and drug targeting factors. Finally, polymerase chain reaction (PCR) was used to verify the expression of the model in the ccRCC cell line. The mRNA matrix in ArrayExpress and TCGA databases was used to establish a prognostic model for ccRCC through LASSO regression analysis. Kaplan Meier analysis showed that the overall survival rate (OS) of the high-risk group was poor. ROC verifies the reliability of our model. Functional enrichment analysis showed that there was a obviously difference in immune status between the high-low risk groups. "pRRophetic" package screened five potential small molecule drugs (A.443654, A.770041, ABT.888, AG.014699, AMG.706). Protein interaction network shows that epidermal growth factor receptor [EGRF] and estrogen receptor 1 [ESR1] are tumor drivers and drug targeting factors. To further analyze the differential expression and pathway correlation of the prognosis risk model species. Finally, polymerase chain reaction (PCR) showed the expression of YTHN6-Methyladenosine RNA Binding Protein 1[YTHDF1], TRNA Methyltransferase 61B [TRMT61B], TRNA Methyltransferase 10C [TRMT10C] and AlkB Homolog 1[ALKBH1] in ccRCC cell lines. To sum up, the prognosis risk model we created not only has good predictive value, but also can provide guidance for accurately predicting the prognosis of ccRCC.

The protective effects of ischemic preconditioning on rats with renal ischemia-reperfusion injury and the effects on the expression of Bcl-2 and Bax.

The aim of the present study was to investigate the protective effects of ischemic preconditioning on rats with renal ischemia-reperfusion injury and the effects on the expression of Bcl-2 and Bax. Thirty-six SD rats were randomly divided into three groups (n=12) including sham operation (S) group, ischemia-reperfusion group (I/R) group and ischemic preconditioning (IP) group. After anesthesia with intraperitoneal injection of chloral hydrate, bilateral renal pedicles were clipped for 45 min, followed by perfusion for 6 h to establish the I/R model. Both kidneys in rats of S group were separated and exposed for 45 min, but renal pedicles were not clipped. In IP group, bilateral renal pedicles were clipped for 5 min, followed by perfusion for 5 min, this procedure was repeated 3 times. Then bilateral renal pedicles were clipped for 45 min, followed by perfusion for 6 h. Blood samples were collected and rats were sacrificed to collect renal tissue. Levels of serum creatinine (Cr) and blood urea nitrogen (BUN) were measured. Activity of superoxide dismutase (SOD) was measured by xanthine oxidase assay. Degree of renal injury was evaluated by H&E staining. TUNEL kit was used to detect the number of apoptotic cells in renal tissue. Expression levels of Bcl-2 and Bax were detected by semi-quantitative PCR and western blot analysis at mRNA and protein levels, respectively. Results showed that levels of Cr and BUN in I/R and IP groups were significantly higher than those in S group, and levels of Cr and BUN in I/R group were significantly higher than that in IP group (P<0.05). Activity of SOD in I/R group and IP group were significantly lower than those in S group, and activity of SOD in I/R group were significantly lower than those in IP group (P<0.05). H&E staining showed that, compared with S group, renal injury in the I/R and IP groups was more serious than that in the S group, and I/R group was more serious than the IP group (P<0.05). TUNEL apoptosis assay showed that number of apoptotic cells in IP and I/R groups were significantly higher than that in the S group (P<0.01). Semi-quantitative PCR and western blot analysis showed that, compared with the S group, expression levels of Bcl-2 mRNA and protein were significantly decreased, expression levels of Bax mRNA and protein were significantly increased, and the ratio of Bcl-2/Bax was significantly decreased in the IP and I/R groups (P<0.01). Compared with the I/R group, expression level of Bcl-2 was significantly increased, the level of Bax was significantly deceased, and the ratio of Bcl-2/Bax was significantly increased in the IP group (P<0.01). As a result, ischemic preconditioning can protect rats with renal ischemia-reperfusion injury possibly by increasing the expression level of Bcl-2 and decreasing the expression level of Bax.

Persistent Muellerian duct syndrome with transverse testicular ectopia.

Persistent Muellerian duct syndrome (PMDS) is a rare form of male pseudohermaphrodism without the feature of ambiguous genitalia. We present a case of PMDS with transverse testicular ectopia (TTE).

[CD4(+) T lymphocyte detection in renal transplant recipients and its clinical value for cytomegalovirus pneumonia treatment].

OBJECTIVE: To explore the clinical value of CD4(+)T lymphocyte detection in the treatment of cytomegalovirus(CMV) pneumonia following kidney transplantation. METHODS: From January 2005 to May 2008, 133 recipients of kidney transplantation were enrolled in this study. The number of CD4(+)T cells in peripheral blood was examined. According to the changes of CD4(+)T cell, immunosuppressive agents (CsA/FK506+MMF+Pred) were adjusted, and the effects of CMV pneumonia occurring were investigated. RESULTS: In the period of 45-72 day after renal transplantation, 36 cases were found to have significantly lower number of CD4(+)T cells than that before operation. Of the 133 recipients, 12(9.0%, 12/133) had severe pneumonia, during 58-118 days after operation, including 7 with acute respiratory distress syndrome(ARDS); 4 patients(33.3%, 4/12) died and 8(66.7%, 8/12) were cured. The incidence of CMV pneumonia(27.8%, 10/36) in the low- CD4(+)T cell recipients was significantly higher than that(2.1%, 2/97) in patients with normal T cell level(P<0.01). During the withdrawal of immunosuppressive agents, 34 patients had normal kidney function(serum creatinine 71-126 micromol/L), except 2 cases underwent mild acute rejection. In 24 non-pneumonia recipients, the number of CD4(+)T cell kept growing as the withdrawal, on 14, 21 day after the withdrawal increased markedly compared with that on 0 day. In 8 survival patients with CMV pneumonia, the number of CD4(+)T cell rose slowly,on 21 day after the withdrawal increased to the normal level. But in 4 non-survival patients, the number of CD4(+)T cell kept continuously in lower level. CONCLUSION: CMV pneumonia is associated with lower CD4(+)T cell level in kidney transplant recipients. Determination of CD4(+) T cell could reflect the status of cellular immunity and give directions of the withdrawal. Discontinuance of immunosuppressive agents in severe CMV pneumonia patients was safe. However, it may be helpful to guide the clinical treatment.