脂联素及其受体对糖尿病肾病大鼠的保护作用

目的 探讨脂联素（ADPN）及其受体（AdipoR）对糖尿病肾病的保护作用及其可能机制。 方法 （1）64只雌性SD大鼠被随机均分入对照组和实验组：实验组一次性空腹腹腔注射链脲菌素（STZ) 60 mg/kg,诱导糖尿病大鼠模型;对照组腹腔注射等体积的枸橼酸缓冲液。于糖尿病大鼠成模后第2、6、10、12周两组分别测体质量、肾质量、空腹血糖、24 h尿白蛋白排泄量;心内采血检测空腹血清胰岛素;ELISA法检测血、尿脂联素浓度;取肾脏常规制作PAS染色,免疫组化SP法检测肾脏脂联素受体1和2（AdipoR1和AdipoR2）的表达。（2）将NRK-52E细胞分别用含5 mmol/L葡萄糖（正常对照组）、30 mmol/L葡萄糖（高糖组）、30 mmol/L葡萄糖+不同浓度ADPN（终浓度分别为1 mg/L、5 mg/L、10 mg/L）培养,12 h后RT-PCR法检测单核细胞趋化蛋白1（MCP-1） mRNA表达。 结果 （1）造模成功后6、10、12周实验组血清和尿ADPN水平均高于对照组（P < 0.01）,并随着肾脏病变进展而逐渐升高。（2）实验组各时期AdipoR1和AdipoR2在肾脏的表达高于对照组,并随时间逐渐增强,其与血清脂联素水平呈正相关（r = 0.666,P < 0.01;r = 0.684,P < 0.01）。（3）MCP-1 mRNA在高糖组表达较高,加入脂联素以后MCP-1 mRNA表达显著减少（P < 0.05）。 结论 血和尿脂联素水平随糖尿病肾病病程进展而升高,与AdipoR1和AdipoR2的表达亦呈正相关,推测脂联素通过AdipoR直接作用于肾小管,通过减少MCP-1的表达对肾脏起保护作用。     

Post-fertilization effects of chronic renal failure in male rats

We evaluated the potential for growth and intrauterine development of embryos generated from the fertilization of oocytes with spermatozoa recovered from animals with chronic renal failure (CRF). Group A included sham-operated rats ( n  = 28), group B1 involved CRF rats that had undergone erythropoietin plus bromocryptine treatment ( n  = 28), and group B2 included CRF rats that had received normal saline. Embryos derived from the in vitro fertilization of oocytes with spermatozoa recovered from rats of group A or group B1 or group B2 were transferred to female recipients. We induced CRF in a group of rats (group B; n  = 56; the total kidney volume was reduced to one-sixth with two operations). One week after the second operation, the rats of group B were randomly divided into group B1 (they subsequently received bromocryptine plus erythropoietin) and group B2 (they received injections of saline). Nine weeks after the second operation, the fertility of each male rat was assessed by mating tests and in vitro fertilization of oocytes. The mean litter size was significantly smaller in the subpopulation of fertile animals in group B2 than in the fertile rats of group B1 and in the fertile rats of group B1 than in the fertile rats of group A. Per cent of transferred blastocysts that developed into alive offspring were significantly lower in group B2 than in group B1 and in group B1 than in group A. Epididymal spermatozoa demonstrated a significantly larger DNA-oxidative damage in group B2 than in group B1 and in group B1 than in group A. These findings demonstrate that sperm-DNA damage because of CRF development is accompanied by a defect in the development of embryos generated in vitro. We may suggest that bromocryptine and erythropoietin protecting sperm DNA from oxidative damage improve reproductive potential in rats with CRF.     

Endothelin in chronic renal failure.

The aims of the present study were to determine plasma endothelin (ET) in chronically uraemic patients, the renal clearance of endogenous ET in normal dog and man, and the effect of acute volaemic expansion on ET. The mean plasma ET concentration in haemodialysis patients was 57.5 +/- 5 pg/ml before haemodialysis and remained unchanged at 52.5 +/- 5 pg/ml after haemodialysis. They were thus significantly elevated both before and after haemodialysis (P less than 0.01) compared with plasma ET in normal subjects of 20.8 +/- 0.8 pg/ml. There was no evidence of ET clearance across the cuprophane membrane of the dialyser. Resting plasma ET values in the 15 non-dialysed uraemic patients ranged between 20 and 52.5 pg/ml (mean 38.2 +/- 2.3 pg/ml), significantly greater than those observed in controls (P less than 0.01). In CAPD patients, plasma ET was also significantly (P less than 0.01), elevated (63 +/- 10 pg/ml) when compared to controls, and similar to those observed in patients before haemodialysis. In dogs, mean ET did not diminish between the aorta and the renal vein (28.1 +/- 1 versus 28.4 +/- 2 pg/ml). In man mean ET did not significantly decline between the renal artery and the renal vein (17 +/- 3 to 13 +/- 0.8 pg/ml). In the seven healthy subjects who received 2000 ml of isotonic saline intravenously ET remained unchanged (24 +/- 2; 23 +/- 1 and 23 +/- 2 pg/ml before and 1 and 2 h after starting hydration respectively). We have thus shown that plasma ET is elevated in patients with chronic renal failure especially those on dialysis and CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Back pain in chronic renal failure.

Back pain in chronic renal failure Patient SK, a 40-yr-old female, resident of Bhagalpur villagein Bihar, India, was operated for gallstones 3 years previously.On pre-operative checkup, mild renal dysfunction was detected.She was asymptomatic for renal disease with serum creatinineof 159 µmol/l (1.8 mg/dl), bland urinary sediment     

Up-regulation of adiponectin, its isoforms and receptors in end-stage kidney disease.

BACKGROUND: Despite the favourable effects of adiponectin on the vasculature and insulin resistance (IR), levels are increased in patients with end-stage kidney disease (ESKD), in whom both IR and atherosclerosis are prevalent. METHODS: To investigate this paradox, we examined the distribution of adiponectin isoforms, the expression of adiponectin receptor (AdipoR) mRNA on peripheral blood mononuclear cells (PBMC) in 41 patients with ESKD on haemodialysis and 41 matched controls, and its function by adenosine monophosphate-activated protein kinase (AMPK) phosphorylation of AdipoR on PBMC. We also compared the expression of AdipoR on PBMC with that on muscle and subcutaneous and visceral fat in 10 patients undergoing elective cholecystectomy. RESULTS: The proportion of the high molecular weight (HMW) isoform of adiponectin was increased in the dialysis group (P = 0.001), even though these patients were significantly insulin resistant compared with controls (P = 0.006). AdipoR1 and AdipoR2 on PBMC were also increased in patients with ESKD (P < 0.05 and P = 0.007, respectively), but levels did not correlate with IR, the HMW isoform or other anthropometric measurements. There was a strong correlation between AdipoR1 and AdipoR2 on PBMC in ESKD and in subcutaneous and visceral fat in controls. However, there was no relationship between AdipoR in PBMC, muscle or visceral fat. Phosphorylation of AMPK by recombinant adiponectin showed that AdipoR on PBMC, from controls and ESKD patients, were equally functional. CONCLUSIONS: IR in ESKD is not explained by the change in isoformic distribution, or by AdipoR down-regulation or dysfunction. Rather, this receptor-ligand axis is up-regulated and may be a beneficial response to the inflammatory milieu of ESKD.     

Adiponectin, leptin and thyroid hormones in patients with chronic renal failure and on renal replacement therapy: are they related?

BACKGROUND: Renal function affects thyroid function and adipocytokines in many ways. We aimed to assess the adipocytokines adiponectin and leptin in relation to thyroid function in patients with chronic renal failure treated conservatively, in haemodialysed patients and in kidney allograft recipients. METHODS: The study was performed on 33 patients with chronic renal failure, 64 haemodialysed patients, 54 kidney allograft recipients and 38 healthy volunteers. Thyroid volume was estimated sonographically, thyroid hormones were determined by Micropartide Enzyme Immunoassay (MEIA), and serum adiponectin and leptin were assessed by radioimmunoassay. RESULTS: Serum thyroid-stimulating hormone (TSH), free T4 and free T3 were within the normal range. Adiponectin correlated significantly with free T3, haematocrit, haemoglobin, platelet count, body mass index (BMI) and urea in kidney allograft recipients. In haemodialysed patients, adiponectin correlated with free T4 and TSH, whereas leptin correlated with free T3. Multiple regression analysis showed that adiponectin was independently related only to the serum concentration of free T3 and urea in kidney transplant recipients and to free T4 and adequacy of dialysis in haemodialysed patients. In univariate analysis in patients with chronic renal failure, adiponectin correlated with free T3 and platelet count, and in healthy volunteers adiponectin correlated only with free T3 and triglycerides, and leptin correlated with BMI. CONCLUSIONS: We described novel relationships between adiponectin and thyroid hormones in patients with kidney diseases. However, possible pre-existing thyroid dysfunction prior to transplantation (during dialysis therapy) and immunosuppression after transplantation make all these findings relatively complex. Therefore, the relationships between adiponectin and the thyroid axis in patients with chronic renal failure, in haemodialysed subjects or in kidney transplant recipients merit additional studies.     

Somatic and renal effects of growth hormone in rats with chronic renal failure

Recombinant human growth hormone (rhGH) has been widely used to improve growth in children with chronic renal failure (CRF). However, there has been great concern that GH may aggravate renal disease and hasten the progression to end-stage renal failure. We therefore investigated the effect of prolonged administration of rhGH at various doses on somatic growth and renal function and structure in rats with CRF, divided into four groups based on rhGH dose (vehicle, 0.4, 2.0, and 10.0 IU/day). rhGH was administered subcutaneously daily for 8 weeks. The mean growth was significantly greater in rats treated with high-dose rhGH (10.0 IU) than those treated with low-dose rhGH (P = 0.0089) or vehicle (P = 0.0011). Body weight gain increased in parallel with body length (Creatinine clearance at the end of the experiment was significantly lower in rats on high or medium-dose rhGH than those on low-dose rhGH and controls (P <0.05). The glomerular sclerosing index was greater in rats treated with higher doses of rhGH. There were significant differences between rats treated with high-dose rhGH and controls (P = 0.0144) and also between rats on medium-dose rhGH and controls (P = 0.0065). Although there was no significant difference, rats treated with higher doses of rhGH tended to excrete more protein. Renal insulin-like growth factor-I (IGF-I) content and circulating IGF-I and IGF-II levels did not significantly differ among groups. We conclude that: (1) GH improves somatic growth failure in rats with CRF, but prolonged administration of GH dose-dependently induces deterioration in renal function and structure and (2) this effect was induced neither via circulating IGF-I and IGF-II nor by local production of IGF-I, but seems to be direct. Received June 7, 1996; received in revised form and accepted November 19, 1996     

Effects of erythropoietin, bromocryptine and hydralazine on testicular function in rats with chronic renal failure

Summary. We evaluated the effects of chronic renal failure (CRF) on testicular function and semen physiology. A CRF model was created in 48 male rats by performance of five-sixths nephrec-tomies in two-stage procedures, and a control (group A) by two-stage sham operation on six male rats. Seven weeks later, serum urea and creatinine concentrations were assessed, and the nephrectomized rats were then equally divided into four groups, B, C, D and E, and treated with saline, erythropoietin, bromocryptine and hydralazine, respectively. Seventeen weeks after the first surgical procedure, the number of fertile rats, the mean values of epididymal sperm content and motility, the outcome of in vitro fertilization, and peripheral serum testosterone concentrations and responses to human chorionic gonadotropin were significantly higher ( P <0.05) in groups A, G and D than in groups B and E. Serum prolactin concentration was significantly higher ( P <0.05) in all groups of nephrectomized rats than in group A. Our results indicate that bromocryptine and erythropoetin improve Leydig cell function, sper-matogenesis, epididymal sperm maturation, and sperm fertilizing capacity in rats with CRF.     

Whole body and regional body composition in patients with chronic renal failure

BACKGROUND.: Nutritional state is a powerful prognostic factor in chronicrenal failure (CRF). Techniques for the assessment of nutritionhave limitations which are often most marked in the presenceof renal disease. We have used techniques of body compositionanalysis to assess the nutritional state of groups of patientswith CRF. METHODS.: Body composition was measured in groups of patients with advancedCRF on conservative treatment, peritoneal dialysis, and haemodialysisand the results compared with a healthy control group. The selectioncriteria for the CRF patients ensured that they were ‘stable’with no recent intercurrent illness, and dialysis adequacy wassatisfactory according to currently accepted targets. RESULTS.: Whole body dual energy X-ray absorptiometry (DEXA) found significantreduction in lean tissue in haemodialysis patients and femaleperitoneal dialysis patients. Regional analysis with DEXA showedreduction in limb (especially arm), lean tissue in CRF patients,with arm lean tissue being reduced in all three CRF groups forfemales and both dialysis groups for males. Limb/trunk leantissue ratios were significantly reduced for all CRF groups.Bioelectrical impedance showed reductions of fat-free mass inthe same groups who had reduced whole body lean tissue withDEXA, but skinfold anthropometry failed to detect any significantreduction in fat-free mass. CONCLUSIONS.: We conclude that even in ‘healthy’ groups of CRFpatients receiving adequate dialytic and dietary management,lean tissue depletion is a common problem. Regional analysisby DEXA, with measurement of limb lean tissue mass is a moresensitive method for the detection of lean tissue depletionthan measurement of whole body lean tissue in patients withCRF.     

Colchicine myoneuropathy in chronic renal failure patients with gout

Colchicine myoneuropathy is a rare and often underdiagnosed disease. It often presents as painless subacute muscle weakness. We present a case of painful colchicine myoneuropathy in a 76-year-old man with chronic renal failure and gout. Published work about clinical presentations of colchicine myoneuropathy in gouty arthritis patients are reviewed. During the previous year, the patient had a drug regimen of colchicine 0.5 mg three times per day for a 3 day course each month. He developed bilateral lower leg weakness and severe myalgia. His serum creatinine level was 680.7 micromol/L and creatinine kinase was 959 IU/L on admission. Laboratory findings included decreasing amplitude of motor and sensory nerve conduction velocity and an electromyogram showed small amplitude, short duration polyphasic waves over the right biceps. A muscle biopsy disclosed vacuolar changes in the cytoplasm. These results all supported a diagnosis of colchicine myoneuropathy. After cessation of colchicine, the creatinine kinase level decreased approximately 50% in 6 days, myalgia subsided and his muscle weakness improved gradually over the next 2 weeks.     

腺嘌呤致雄性不育和慢性肾衰大鼠模型的相关性研究

目的　探讨腺嘌呤致雄性不育大鼠模型的机制。方法　用含 0 .75 %的腺嘌呤饲料饲喂大鼠 15天 ,在实验第 30天、第 6 0天检测血中FSH、LH、T、黄嘌呤氧化酶 (XOD)、尿素氮 (BUN)、肌酐 (Scr)的含量。结果　FSH在第 6 0天显著性升高 ,与对照组相比 (P <0 .0 1) ;T进行性下降 (P <0 .0 1) ;XOD在第 6 0天较第 30天显著性升高 (P<0 .0 1) ;BUN、Scr进行性升高 (P <0 .0 1)。第 30天XOD的升高与T的下降呈直线负相关 (r=- 0 .98,P <0 .0 1) ;在第 6 0天 ,Scr的升高与FSH的升高呈直线正相关 (r=0 .91,P <0 .0 1) ,Scr的升高与T的下降呈直线负相关 (r=- 0 .96 ,P <0 .0 1)。结论　在慢性肾衰早期 ,T的下降可能与XOD反应产生氧自由基的损害有关 ;而在慢性肾衰晚期 ,进展性的肾功能不全则引起FSH的升高 ,T的下降。     

The epidemiology of chronic renal failure and provision of renal services in Albania

Tirana, the only dialysis facility in Albania (pop 4 million),has a stock of 12 patients and three haemodialysis machines.To determine the need for renal services in Albania we studiedthe incidence and outcome of patients with chronic renal failure(CRF) referred to the renal service in Tirana (pop 300000) over1 year. Case-notes of all patients with a serum creatinine concentration300 µmol/l during the study period (1992) were examinedand outcome at 2 years recorded for each patient. In all, 84 patients (mean age 41.6±17.5 years, 56% male)were referred to nephrologists of whom 35 (42%) came from Tirana,giving an annual incidence of 116 per million pop. 77% wereunder 40 and had no co-morbid illness. Glomerulonephritis, themost common renal diagnosis, affected 26% patients. 22% patients(mean age 38±18.1) died within 2 years and only 5% receiveddialysis. The mean age of those who received dialysis was 29±8.3compared with those who were not dialysed (42±18.0).The 59 patients (24 from Tirana i.e. 80 per million) who werealive with advanced CRF (creatinine > 500) had a mean creatinineof 623±93 µmol/l and would be candidates for dialysis.Patients with progressive renal failure in Albania are regularlyfollowed and treated with antihy-pertensives and dietary modification.The need for RRT, however, is not being met even for young patientswith no co-morbidity.     

A study of erythropoiesis inhibitory factors in chronic renal failure sera

Summary: Three separate high molecular weight fractions, designated as FI, FII and FIII, were isolated from sera of chronic renal failure (CRF) patients by precipitate with ammonium sulfate of different concentrations and DEAE celluose. All fractions had obvious suppressive effect on red blood cell growth, both erythroid colony (CFU-E) and BFU-E in vitro , but the maximal inhibitory rate that may be found in Fl or in FII and FIII depends entirely on individuals. the study also showed that none of these fractions was a homogeneous substance in SDS-PAGE electrophoresis. As well, a close correlationship between serum erythropoietin level and the inhibitory rate of the isolated fractions was observed. It is suggested that the inhibitory factors might exist in CRF sera and play a role in triggering the anaemia of CFR.     

肾组织移植对慢性肾功能衰竭大鼠促红细胞生成素的调节作用

目的研究鼠婴肾组织移植于肾包膜下对促红细胞生成素的调节作用,为临床应用治疗肾性贫血提供理论依据。方法以Wistar雄性大鼠建立慢性肾功能衰竭动物模型为受体,将鼠婴肾组织块多点植入受体肾包膜下。治疗期间用EPO酶联免疫(ELISA)试剂盒测定血清EPO水平;观察肾组织病理改变,用免疫组化方法检测EPO在移植物中的表达。结果①60d时D组血清促红细胞生成素(1.768±0.140)mu/mL高于B组(1.160±0.324)mu/mL(P<0.01),与C组(2.329±0.125)mu/mL也有差异(P<0.05)。②移植后60d,移植物的体积由1mm3增至3-4mm3大小,表面血管网丰富,光镜下见肾小球、肾小管结构正常;③移植物EPO免疫组化,发现移植物EPO着色颗粒主要分布于肾皮质的肾小管,明显多于病例对照组大鼠肾组织(P<0.05)。结论通过对移植物的形态观察和功能测定,证明肾组织移植是一种有效的治疗手段,有可能为慢性肾性贫血提供一种新的途径。     

肾衰康延缓慢性肾衰竭进展的实验研究

目的：探讨肾衰康延缓慢性肾衰竭（CRF）进展的疗效及机理。方法：采用5／6肾切除大鼠CRF模型,随机分为模型组、洛汀新组及肾衰康组治疗,观察各组Scr、BUN及尿中细胞外基质成分（ECM）排泄量。结果：洛汀新组及肾衰康组Scr及BUN均显低于模型组（P＜0．01及P＜0．05）,而肾衰康组Scr又低于洛汀新组（P＜0．05）,肾衰康组尿中Ⅳ型胶原（Col-Ⅳ）、纤维连接蛋白（FN）及层粘连蛋白（LN）含量均明显比模型组高（P＜0．01）。结论：肾衰康有延缓CRF进展的作用,其机理可能与促进ECM成分从尿中排泄,从而减轻肾小球内ECM的聚集有关。但肾衰康对ECM是抑制合成还是促进降解尚需进一步探讨。     

Effectiveness of low-dose erythropoietin in predialysis chronic renal failure patients

Recombinant human erythropoietin (rHuEpo) has been shown tobe both effective and usually safe in patients with chronicrenal failure who have not yet reached the stage requiring dialysis.There are, however, disturbing reports on the possibility ofdeterioration of the reserve renal function in association withrHuEpo therapy. Most of the published studies have used rHuEpoin doses of 50–150 U/kg three times weekly subcutaneously.An open-label trial of rHuEpo therapy was conducted on 21 patientswith chronic renal failure treated sequentially at a referralhospital, rHuEpo was used in doses of 50 U/kg twice weekly for4 weeks followed by 25 U/kg twice weekly for 8 weeks subcutaneously,a regimen substantially lower than current recommendations.This was associated with a gentle but significant increase inhaematocrit (P<0.05) and haemoglobin (P<0.05), while theserum creatinine and the reciprocal of the creatinine remainedstable, with a tendency to improve rather than worsen (P=0.06).We conclude that there is no need to aim at a rapid increasein haematocrit and haemoglobin by rHuEpo therapy; rather a gentleincrease using modest doses is both effective and safe.