Analgesic use and the risk of renal cell carcinoma – Findings from the Consortium for the Investigation of Renal Malignancies (CONFIRM) study

PurposeThe incidence of renal cell carcinoma (RCC) is rising. Use of analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol may affect renal function. The aim of this study was to assess associations between analgesic use and risk of RCC.MethodsA population-based case-control family design was used. Cases were recruited via two Australian state cancer registries. Controls were siblings or partners of cases. Analgesic use was captured by self-completed questionnaire. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for RCC risk associated with regular analgesic use (at least 5 times per month for 6 months or more) and duration and frequency of use.ResultsThe analysis included 1064 cases and 724 controls. Regular use of paracetamol was associated with an increased risk of RCC (OR 1.41, 95%CI 1.13–1.77). Regular use of NSAIDs was associated with increased risk of RCC for women (OR 1.71, 95% CI 1.23–2.39) but not men (OR 0.83, 95% CI 0.58–1.18; p-interaction=0.003). There was no evidence of a dose-response for duration of use of paracetamol (linear trend p = 0.77) and weak evidence for non- aspirin NSAID use by women (linear trend p = 0.054).ConclusionThis study found that regular use of paracetamol was associated with increased risk of RCC. NSAID use was associated with increased risk only for women.     

Effects of dibutyryl cyclic amp on the transport of α-methyl-d-glucoside and α-aminoisobutyric acid in separated tubules and brush border membranes from rabbit kidney

The effect of dibutyryl cyclic AMP on the transport of α-methyl-d-glucoside and α-aminoisobutyric acid in separated tubules and purified brush border membranes from rabbit kidney was investigated using a rapid filtration procedure. Dibutyryl cyclic AMP stimulated the uptake of α-methyl-d-glucoside and α-aminoisobutyric acid by separated renal tubules in agreement with prior studies utilizing renal slices (Rea, C. and Segal, S. (1973) Biochim. Biophys. Acta 311, 615–624; Weiss, I.W., Morgan, K. and Phang, J.M. (1972) J. Biol. Chem. 247, 760–764). However, in contrast to previous reports, no preincubation of the tissue with dibutyryl cyclic AMP was required for stimulation of transport to be manifest. Dibutyryl cyclic AMP stimulated oxygen consumption by separated tubules suggesting that stimulation of transport may occur by a linkage with renal oxidative metabolism. Dibutyryl cyclic AMP increased the uptake of α-aminoisobutyric acid into purified renal brush border membranes. However the uptakes of α-methyl-d-glucoside, proline, leucine and phosphate into brush border membranes were significantly inhibited.     

Sulfur-containing amino acids that increase renal glutathione protect the kidney against papillary necrosis induced by 2-bromoethylamine

Papillary necrosis was observed in the kidneys of rats, 72 h after receiving a single injection of bromoethylamine (BEA). This effect was associated with renal glutathione (GSH) depletion 1 h after the administration of BEA. Stimulation of renal GSH synthesis by pretreatment of the animals either with glutamine + glycine + cystine or N-acetyl-L-cysteine was attempted. Low doses of these precursors administered previously to BEA, respectively, decreased or abolished the GSH depletion. Nevertheless, both pretreatments failed to modify the magnitude of renal papillary necrosis. High doses of these precursors did not modify the BEA-induced GSH depletion, but they significantly increased GSH levels 24 h after BEA administration. At this time, although a smaller intensity of renal papillary necrosis was observed with the amino acid mixture pretreatment, N-acetyl-L-cysteine pretreated rats showed no papillary necrosis. It is suggested that the observed protective effects against BEA-induced renal papillary injury may be ascribed in some measure, to a mechanism independent of GSH.     

Effects of naloxone on renal responses to noxious stimuli in the cynomolgus monkey

Behavioral influences on excretion of Na⁺ and H₂O were studied during saline diuresis in three unanesthetized adult female cynomolgus monkeys. During control infusions of isotonic saline, the average rates of urine and Na⁺ excretion were 210μl/kg/min and 36.1μl/kg/min, respectively, and the average rate of inulin clearance was 4.6 ml/kg/min. Intermittent exposure to an electrical stimulus applied to the monkey's tail for a 30-min period modestly reduced rates of excretion of Na⁺ and H₂O; these reductions were 58% and 56% of baseline values respectively during the first 10 min, but excretion rates returned to baseline values or exceeded them by the end of the 30-min period. The effects of naloxone hydrochloride (10 mg/kg), an opiate antagonist, were studied by administering the drug immediately before the period of electrical-stimulus delivery. After naloxone, the electrical-stimulus markedly reduced the rates of Na⁺ and H₂O excretion to 29% and 31% of baseline values during the first 10 min, and delayed the return to baseline values. Inulin clearance was not altered significantly by the electrical stimulus in the absence of naloxone, but was decreased to 32% of the baseline rate during the first 10 min of exposure to the electric stimulus in the presence of naloxone. Naloxone had similar effects on rates of Na⁺ and urine excretion in response to 30 min of 108 dBA noise. These results show that renal responses to noxious environmental stimuli (electrical stimulus or noise) can be altered by naloxone.     

Functional Expression and Purification of Histidine-Tagged Rat Renal Na/Phosphate (NaPi-2) and Na/Sulfate (NaSi-1) Cotransporters

Two mammalian sodium-dependent anion-cotransporters (NaPi-2 for phosphate and NaSi-1 for sulfate) have been expressed in Sf9 insect cells using the baculovirus expression system. A histidine tag was introduced at the C-termini in order to facilitate purification by metal-affinity chromatography. Sf9 cells infected with the histidine-tagged Ni/P _i -cotransporter exhibited more than 60-fold higher sodium-dependent transport of phosphate compared to noninfected cells. Expressed Na/P _i -cotransport exhibited a K _m of P _i of 0.21 mm and an apparent K _m of sodium of 92 mm. Infected cells expressed a 65 kDa polypeptide as detected by Western blotting and immunoprecipitation. Sf9 cells infected with the histidine-tagged NaSi-1 or untagged NaSi-1 protein expressed sodium-dependent sulfate cotransport up to 60-fold higher compared to noninfected cells. Transport of sulfate was highly dependent on sodium exhibiting a K _m of SO²⁻ ₄ of about 0.3–0.4 mm and a K _m of sodium of 55 mm. By Western blotting and immunoprecipitation expressed NaS _i -1 proteins were detected at 55–60 kDa. These studies demonstrate that histidine tagged proximal tubular Na-dependent cotransporters for phosphate and sulfate can be expressed functionally in Sf9 cells and that the kinetic characteristics were not altered by the introduction of a histidine tag at the C-termini. Furthermore, it is demonstrated that after solubilization under denaturing conditions histidine-tagged cotransporter proteins can be purified by metal-chelate affinity chromatography. Received: 24 March 1997/Revised: 8 July 1997     

The emerging role of small non-coding RNA in renal cell carcinoma

Noncoding RNAs are transcribed in the most regions of the human genome, divided into small noncoding RNAs (less than 200 nt) and long noncoding RNAs (more than 200 nt) according to their size. Compelling evidences suggest that small noncoding RNAs play critical roles in tumorigenesis and tumor progression, especially in renal cell carcinoma. MiRNA, the most famous small noncoding RNA, has been comprehensively explored for its fundamental role in cancer. And several miRNA-based therapeutic strategies have been applied to several ongoing clinical trials. However, piRNAs and tsRNAs, have not received as much research attention, because of several technological limitations. Nevertheless, some studies have revealed the presence of aberration of piRNAs and tsRNAs in renal cell carcinoma, highlighting a potentially novel mechanism for tumor onset and progression. In this review, we provide an overview of three classes of small noncoding RNA: miRNAs, piRNAs and tsRNAs, that have been reported dysregulation in renal cell carcinoma and have the potential for advancing diagnosis, prognosis and therapeutic applications of this disease.     

甲基强的松龙对体外循环下心脏瓣膜置换患者肾功能的影响

背景与目的:有研究表明甲基强的松龙可减轻体外循环所致的肺损伤,但其对体外循环患者术后肾功能损害的作用尚不十分清楚。本文探讨甲基强的松龙是否有效抑制体外循环心内直视术中的炎症反应,并对肾脏有保护作用。方法:随机选取40例体外循环下择期行心脏瓣膜置换手术的患者,年龄30～55岁,心功能Ⅱ～Ⅲ级,随机分为甲基强的松龙组和对照组,每组20例。甲基强的松龙(MPS)组于体外循环前以甲基强的松龙10mg/kg预冲,对照组(NS)以等量的生理盐水代替。于CPB前(T1),CPB结束后2h(T2)、CPB结束后12h(T3),CPB结束后24h(T4),等时点留取中心静脉血和尿液,以酶联免疫吸附实验(ELISA)法检测炎性介质(IL-6、TNF-α、IL-10);取尿上清液检测反映肾功能的早期敏感指标:尿-N-乙酰氨基-葡萄糖苷酶(NAG)、尿α1-微球蛋白(α1-MG)、尿视黄醇结合蛋白(RBP)的水平。结果:CPB前两组炎性介质和肾功检测指标,差异均无统计学意义(P>0.05),而CPB结束后,两组炎性介质的水平和肾功各项指标均较术前增高。与NS相比,MP组T2~T4时点IL-6水平明显降低(P<0.05)。在T2~T3时点TNF-α的水平明显低于对照组(P<0.05)。两组IL-10的水平在CPB后均增加,但在T2~T3时点MP组升高幅度明显高于NS组(P<0.05)。与NS比较,MP组在CPB后各时点尿NAG、α1-MG、RBP的水平均明显降低(P<0.05)。结论:CPB可导致全身炎性反应及肾功能损伤;甲基强的松龙可减轻炎性反应,同时对肾功能有一定的保护作用。     

Protective effect of Acorus calamus on kidney and liver functions in healthy mice

Acorus calamus (AC), is an herbal medicine commonly used as traditional practice in pharmacological applications. Present study initiated was evident to proof the hepatoprotective and nephroprotective activity with supporting histopathological status of kidneys and liver. Investigation done with the 5% (w/v) of AC dissolved in tap water (50 g/l) given for 15 days compared with control tap water to 5-7 week old C57Bl/6 mice both sexes. Renal function, liver function, biochemical and complete blood count was evaluated. AC significantly reduced food intake, body weight, also plasma concentration of electrolytes such as Na⁺, K⁺, Ca²⁺, were reduced as the excretion of electrolytes were increased in urine, significantly increased Fluid Intake, with Urinary urea, Urinary creatinine, Glomerular Filtration Rate, creatinine clearance, High-density lipoproteins, Mean Corpuscular Volume. The biochemical findings showed the hepatoprotective and histopathological changes showed the nephroprotective nature of AC by normal structure with no necrosis.