成纤维细胞生长因子23与慢性肾脏病矿物质代谢

目的:观察慢性肾脏病(CKD)不同阶段血成纤维细胞生长因子23(FGF23)水平变化及其与甲状旁腺素(PTH)等生化指标的相关性,初步探讨FGF23在CKD进展中与矿物质代谢相互关系及对机体的影响。方法:选择78例估算的肾小球滤过率(eGFR)波动在4～96ml/(min·1.73m2)CKD住院患者及20例健康志愿者,测定外周血FGF23及其他生化指标,分析它们之间的相关性。结果:(1)各组CKD患者血FGF23水平均高于健康对照组,LogPTH各组间差异性显著(P<0.05),LogFGF23及血磷在CKD4,5期组中存在显著性差异(P<0.01),而CKD1～2期组与CKD3期组之间无明显差异(P>0.05);(2)四组间血磷(r=0.54,P<0.01)、LogPTH(r=0.61,P<0.01)及1,25羟维生素D3[1,25(OH)2D3](r=0.32,P<0.01)与LogFGF23均呈显著正相关,而eGFR(r=-0.64,P<0.01)与LogFGF23呈显著负相关;(3)FGF23甲旁亢组值(4372.25±1996.66pg/ml)较非甲旁亢组值(2943.99±1981.21pg/ml)明显升高(P<0.01),LogFGF23与LogPTH仅在甲旁亢组中显著正相关(r=0.569,P<0.01),而LogFGF23与1,25(OH)2D3仅在非甲旁亢组中显示正相关(r=0.437,P<0.05);两组中LogFGF23与eGFR均显著负相关,但与血磷间均有正相关性;(4)多元线性回归分析显示多因素(年龄、血清白蛋白、活性维生素D3、eGFR及"有甲旁亢")与LogFGF23有相关性(P<0.05)。结论:(1)血FGF23水平在CKD早期已高出正常,并随着肾功能减退不断升高,在终末期异常升高。(2)慢性肾脏病终末期血磷水平显著升高并刺激FGF23生成增加,高FGF23水平与继发性甲旁亢发生相关。(3)年龄、活性维生素D3、肾功能状态、营养状况及有无"甲旁亢"均能影响血FGF23水平。     

慢性肾脏病患者钙磷代谢及调节因子的变化

目的观察慢性肾脏病（CKD）患者钙磷代谢的特点、影响因素及可能的作用机制。方法测定94例CKD患者及20例对照组血清1,25-二羟维生素D[1,25-（OH）2VitD]、成纤维细胞生长因子-23（FGF-23）、全段PTH（iPTH）、血清肌酐（Scr）、钙（Ca）和磷（P）等指标。结果CKD3、4期、血液透析（HD）及腹膜透析（PD）患者血磷、肌酐水平高于对照组及CKD1-2期患者（P〈0.01）,iPHT也明显升高（P〈0.05）。CKD3、4期、HD及PD患者血清1,25-（OH）2VitD3水平明显低于对照组及CKD1、2期（P〈0.01）,且HD组低于PD组（P〈0.05）。血清FGF-23水平CKD3期（75.18 ng/L&#177;25.03 ng/L）、4期（78.43 ng/L&#177;20.81 ng/L）、HD（88.51 ng/L&#177;35.01 ng/L）及PD（87.85 ng/L&#177;33.65 ng/L）患者均明显高于对照组（11.76&#177;3.63 ng/L）及CKD1-2期（26.78 ng/L&#177;6.69 ng/L）,P〈0.01。Pearson相关性分析显示血清FGF-23水平与血清肌酐、iPTH、磷呈正相关,与1,25-（OH）2VitD负相关。血清1,25-（OH）2VitD与血清肌酐、iPTH、血磷呈负相关,与白蛋白呈正相关。结论CKD3期起即存在活性维生素D缺乏、FGF-23及iPTH升高。CKD患者钙磷代谢紊乱与1,25-（OH）2VitD、FGF-23、iPTH等调节因子的变化相辅相成,提示多种因子共同参与其调节及病理生理过程。     

慢性肾脏病患者动脉僵硬度的相关因素研究

背景动脉僵硬是慢性肾脏病(CKD)患者的重要心血管危险因素,明确CKD患者动脉僵硬度相关因素有助于寻找预防CKD患者心血管疾病的靶点。目的分析CKD患者动脉僵硬度的相关因素。方法选取2016年1月—2018年6月江苏省中医院肾内科病房收治的CKD患者70例,收集其一般资料〔包括年龄、体质指数(BMI)及血压〕及实验室检查指标{包括血肌酐(Scr)、尿素氮(BUN)、血红蛋白、血钙、血磷、血清1,25-二羟维生素D3〔1,25-(OH)2D3〕水平、甲状旁腺激素、估算肾小球滤过率(eGFR)及稳态模型胰岛素抵抗指数(HOMA-IR)},采用超极速超声成像脉搏波(uf-PWV)技术定量评定脉搏波传导速度(PWV)。CKD患者PWV相关因素分析采用Pearson相关分析及多元线性回归分析。结果 (1)Pearson相关分析结果显示,CKD患者PWV与年龄(r=0.481)、收缩压(r=0.257)、HOMA-IR(r=0.286)呈正相关(P0.05),与血清1,25-(OH)2D3水平(r=-0.467)、eGFR(r=-0.272)呈负相关(P0.05)。(2)多元线性回归分析结果显示,年龄(β=0.316)和血清1,25-(OH)2D3水平(β=-0.366)与CKD患者PWV独立相关(P0.05)。结论高龄及血清1,25-(OH)2D3水平较低的CKD患者动脉僵硬度增高,应引起临床重视。     

骨代谢标志物在慢性肾病患者中的表达

目的分析慢性肾病(CKD)1～5期患者的骨钙素、Ⅰ型胶原N端前肽(PⅠNP)、β-胶原特殊序列(CTX)、25羟维生素D3[25(OH)D3]、血钙、血磷、血甲状旁腺激素(iPTH)之间的相关性。方法 157例CKD患者作为研究对象,收集临床资料,检测骨钙素、PⅠNP、β-CTX、25(OH)D3、血钙、血磷、血iPTH、血肌酐(Scr),使用流行病学合作(EPI)公式计算肾小球滤过率(eGFR)后将其分成CKD1～5期共5组,同时进行相关性分析,再将CKD5期的腹透患者根据iPTH水平及是否行腹膜透析分成iPTH正常+腹透组、iPTH正常+非腹透组、iPTH升高+腹透组、iPTH升高+非腹透组4组。结果男性CKD患者25(OH)D3水平显著高于女性(P0.05),骨钙素、PⅠNP、β-CTX、血磷、血钙、血iPTH水平无性别差异(P0.05)。CKD1～4期患者PⅠNP、β-CTX、骨钙素、血磷、血iPTH水平差异无统计学意义(P0.05),CKD5期患者以上各指标显著高于其他4期(P0.05);同时血钙及25(OH)D3在5组间差异无统计学意义(P0.05),其中25(OH)D3水平在各组间均呈现缺乏或不足状态。EPI-eGFR与骨钙素、PⅠNP、β-CTX、血磷、血iPTH呈明显负相关(P0.01),而与血钙及25(OH)D3无相关性(P0.05);CKD5期患者中iPTH升高+腹透组患者与iPTH正常+腹透组患者比较,血磷、骨钙素、PⅠNP、β-CTX、iPTH水平均明显升高(P0.05)。结论 CKD患者普遍存在25(OH)D3的缺乏,且在CKD早期即存在,女性较男性更容易出现25(OH)D3缺乏。不同CKD分期患者中,CKD5期患者表现出较前4期患者更活跃的骨代谢状态,骨形成加快,骨降解活跃,这种骨代谢状态和eGFR的变化呈显著负相关。在腹膜透析患者中高iPTH水平及低eGFR水平更容易导致骨代谢的异常。     

老年慢性肾脏病患者铁调素与骨形态发生蛋白-2关系

目的老年慢性肾脏病(CKD)患者铁调素(hepcidin)与骨代谢指标骨形态发生蛋白-2(BMP-2)关系探讨。方法随机选择在本科门诊随访的30例非透析CKD 1~3A期患者,30例非透析CKD 4~5期患者及健康体检者30例作为对照。检测参试者血红细胞计数(RBC)、血红蛋白(Hb)、红细胞比容(Hct)、血清铁调素、血钙(Ca)、血磷(P)、全段甲状旁腺激素(i PTH)、超敏C反应蛋白(hs-CRP)、血清铁蛋白(SF)、BMP-2水平,并比较组间差异。采用多元回归分析铁调素的影响因素。结果 CKD患者血清铁调素水平显著高于健康对照组(P0.01)。与CKD 1~3A期相比,CKD患者CKD 4~5期血清铁调素水平升高(P0.05)。Pearson相关分析显示CKD患者血清铁调素水平与估算肾小球滤过率(e GFR)呈负相关(r=-0.484,P0.05),血清铁调素水平与尿素氮(BUN)、血肌酐(Scr)、Ca、P、BMP-2呈正相关(r=0.45、0.377、0.582、0.514、0.947,P均0.05)。多元逐步回归分析显示,CKD患者血清Scr、SF、BMP-2与铁调素水平密切相关。结论铁调素与e GFR相关,随e GFR下降,CKD进展、BUN、Scr水平上升,铁调素水平逐渐上升。铁调素与BMP-2水平密切相关,铁调素可能通过调节BMP-2,参与CKD患者骨代谢调节。     

糖尿病肾病患者血清胱抑素C、β2-微球蛋白水平及其与eGFR的相关性

目的探讨糖尿病肾病所致慢性肾脏病(CKD)患者不同时期血清胱抑素(Cys)C、β2-微球蛋白(β2-MG)的变化特点及临床意义。方法应用免疫比浊法分别检测各受试对象血清Cys C、β2-MG浓度,采用苦味酸法检测血清肌酐(Scr)。根据Scr水平推算肾小球滤过率(e GFR),按NKF-K/DOQI分期分为5期。结果Ⅰ期患者血清Cys C、β2-MG及Scr水平与健康对照组相比均无统计学意义;Ⅱ期患者血清Cys C、β2-MG与健康对照组相比差异有统计学意义(P0.01),Scr水平差异无统计学意义(P0.05),Cys C与CKDⅠ期相比差异有统计学意义(P0.01)。自Ⅲ期开始,各检测指标与健康对照组及CKDⅠ期相比均有统计学意义(P0.01)。患者血清Cys C、β2-MG与e GFR均呈负相关(r=-0.712、-0.692)。结论血清Cys C与β2-MG不仅可作为DN患者早期评价GFR的敏感指标,且血清Cys C与β2-MG的血液浓度水平对初步估计CKD患者肾损害的程度、指导临床分期有一定临床意义。     

慢性肾脏病5期患者血清铁调素表达水平及与维生素D的相关性研究

目的探讨血清铁调素(Hepcidin)在慢性肾脏病(chronic kidney disease,CKD)5期患者中的表达水平及与血清25羟维生素D[25(OH)D]的关系。方法入选CKD 5期患者85例,其中维持性血液透析(MHD组)55例,非透析组30例;健康体检者30名为对照组。检测三组血清Hepcidin、25(OH)D水平;MHD组、非透析组同时测定血红蛋白、钙、磷、甲状旁腺素(PTH)、血清铁蛋白(SF)、血清铁(SI)、转铁蛋白饱和度(TSAT)、C反应蛋白(CRP)、血肌酐(Scr)等临床指标,分析Hepcidin与25(OH)D等指标的相互关系。结果MHD组、非透析组、对照组Hepcidin水平分别是(91.8±11.3)μg/L、(58.9±5.27)μg/L、(46.9±5.95)μg/L;25(OH)D水平分别是(25.9±3.25)μg/L、(29.2±4.21)μg/L、(36.9±3.65)μg/L,组间比较,差异有统计学意义(P0.05)。85例患者中,28例25(OH)D缺乏,32例25(OH)D不足,25例25(OH)D正常。与25(OH)D正常组相比,缺乏组血清Hepcidin、CRP及不足组的PTH明显升高,两组血红蛋白明显降低,差异有统计学意义(P0.05)。相关性分析结果显示,CKD 5期患者血清Hepcidin水平与血红蛋白、SI、25(OH)D呈负相关(r=-0.436,P0.01;r=-0.337,P0.05;r=-0.578,P0.05),与SF、CRP呈正相关(r=0.406,P0.05;r=0.366,P0.05),与血钙、磷、PTH、SCr、白蛋白无相关性(P0.05)。多元线性回归分析Hepcidin与血红蛋白、CRP、SF相关(P0.05)。结论 CKD 5期患者Hepcidin表达水平升高,尤以MHD组明显;Hepcidin的表达水平与贫血、炎症及铁负荷状态密切相关;25(OH)D缺乏或不足在CKD 5期患者较为常见,25(OH)D缺乏患者血Hepcidin升高,但多元线性回归分析并未显示与Hepcidin具有相关性。     

慢阻肺患者血清1,25(OH)_2D_3、钙水平与肺功能关系的研究

目的分析探讨慢性阻塞性肺疾病急性加重期患者血清1,25-二羟维生素D3[1,25(OH)2D3]、钙(Ca2+)水平与其肺功能关系的相关性。方法选取2013年12月至2014年4月在我院住院的慢阻肺患者60例,分别在其慢阻肺急性加重期和稳定期,抽取静脉血,检测患者血清1,25(OH)2D3、Ca2+、磷(P)的水平,并同时检测其动脉血气分析及肺功能。结果急性加重期的血清1,25(OH)2D3、Ca2+、P以及FEV1/FVC等指标与稳定期相比,明显降低;急性加重期患者血清中1,25(OH)2D3、Ca2+与FEV1(%)呈正相关(r=0.341,0.454,P均0.01)。结论慢阻肺急性加重期患者的血清1,25(OH)2D3、Ca2+水平与FEV1(%)有相关性,在一定程度上反映了慢阻肺患者疾病严重程度。     

血清25羟维生素D3或1,25二羟维生素D3水平与慢性阻塞性肺疾病关系的Meta分析

目的：系统评价血清25(OH)D3或1,25(OH)2 D3与 COPD 相关病例对照研究,进一步明确血清维生素 D 水平与 COPD 之间的关系。方法计算机检索 PubMed、EMBASE、The Cochrane Library、中国生物医学文献数据库(CBM)、中国知网(CNKI)数据库、万方数据库、维普数据库,并辅以文献追溯的方法,收集国内外发表的相关病例对照研究,检索时间均从建库至2015年11月。2位研究者按纳入排除标准筛选文献并评价纳入研究质量,应用 RevMan 5.2软件进行 Meta 分析。结果共纳入15篇病例对照研究,包含1948例 COPD患者及1549例健康对照者。25(OH)D3浓度水平结果：Meta分析结果表明无论是急性加重期 COPD还是稳定期 COPD,与健康对照组相比,其25(OH)D3浓度水平差异均有统计学意义,COPD组25(OH)D3浓度低于健康对照组。急性加重期组vs对照组,WMD=-14.28,95%CI =(-23.82~-4.73),Z=2.93,P <0.01;稳定期组vs对照组 WMD=-4.46,95%CI =(-7.36~-1.57),Z=3.02,P <0.01;急性加重期与稳定期相比,25(OH)D3浓度水平差异亦有统计学意义[WMD=-2.66,95%CI =(-4.19~-1.12), Z=3.38,P<0.01,见图2];1,25(OH)2 D3浓度水平结果：Meta分析结果表明无论是急性加重期COPD还是稳定期 COPD,与健康对照组相比,其1,25(OH)2 D3浓度水平差异均有统计学意义, COPD组1,25(OH)2 D3浓度低于健康对照组。急性加重期组vs对照组,WMD=-15.09,95%CI =(-17.97~-12.22),Z =10.3,P <0.01;稳定期组 vs 对照组,WMD=-9.62,95%CI =(-12.55~-6.70),Z=3.02,P<0.01。结论 COPD患者体内25(OH)D3与1,25(OH)2 D3浓度水平均显著降低,维生素D缺乏可能参与COPD的发生、发展,并影响COPD患者的预后。     

25-羟维生素D与糖尿病慢性肾脏疾病患者血糖控制的相关性研究

目的探讨25-羟维生素D[25(OH)D]与糖尿病慢性肾脏疾病(CKD)患者血糖控制的相关性。方法收集CKD患者130例和健康体检(NC)者45名,根据eGFR分为CKD1期、CKD2期和CKD3~5期组,测定各组血清25(OH)D和HbA1c。结果 CKD各组25(OH)D水平低于NC组(P0.05);CKD1期、CKD2期和CKD3~5期组25(OH)D水平依次降低(P0.05),HbA1c依次升高(P0.05)。25(OH)D与HbA1c呈负相关(r=-0.511,P=0.002)。多元线性回归分析结果显示,HbA1c、年龄、病程和BMI是25(OH)D的影响因素。结论 CKD患者血糖控制情况与25(OH)D水平密切相关。     

Analysis of the biochemical mechanisms for the endocrine actions of fibroblast growth factor-23

Fibroblast growth factor (FGF)-23 has emerged as an endocrine regulator of phosphate and of vitamin D metabolism. It is produced in bone and, unlike other FGFs, circulates in the bloodstream to ultimately regulate phosphate handling and vitamin D production in the kidney. Presently, it is unknown which of the seven principal FGF receptors (FGFRs) transmits FGF23 biological activity. Furthermore, the molecular basis for the endocrine mode of FGF23 action is unclear. Herein, we performed surface plasmon resonance and mitogenesis experiments to comprehensively characterize receptor binding specificity. Our data demonstrate that FGF23 binds and activates the c splice isoforms of FGFR1-3, as well as FGFR4, but not the b splice isoforms of FGFR1-3. Interestingly, highly sulfated and longer glycosaminoglycan (GAG) species were capable of promoting FGF23 mitogenic activity. We also show that FGF23 induces tyrosine phosphorylation and inhibits sodium-phosphate cotransporter Npt2a mRNA expression using opossum kidney cells, a model kidney proximal tubule cell line. Removal of cell surface GAGs abolishes the effects of FGF23, and exogenous highly sulfated GAG is capable of restoring FGF23 activity, suggesting that proximal tubule cells naturally express GAGs that are permissive for FGF23 action. We propose that FGF23 signals through multiple FGFRs and that the unique endocrine actions of FGF23 involve escape from FGF23-producing cells and circulation to the kidney, where highly sulfated GAGs most likely act as cofactors for FGF23 activity. Our biochemical findings provide important insights into the molecular mechanisms by which dysregulated FGF23 signaling leads to disorders of hyper- and hypophosphatemia.     

Calcium and Phosphorus Regulatory Hormones and Risk of Incident Symptomatic Kidney Stones

Background and objectives

Calcium and phosphorus regulatory hormones may contribute to the pathogenesis of calcium nephrolithiasis. However, there has been no prospective study to date of plasma hormone levels and risk of kidney stones. This study aimed to examine independent associations between plasma levels of 1,25-dihydroxyvitamin D (1,25[OH]₂D), 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, fibroblast growth factor 23 (FGF23), parathyroid hormone, calcium, phosphate, and creatinine and the subsequent risk of incident kidney stones.

Design, setting, participants, & measurements

This study was a prospective, nested case-control study of men in the Health Professionals Follow-Up Study who were free of diagnosed nephrolithiasis at blood draw. During 12 years of follow-up, 356 men developed an incident symptomatic kidney stone. Using risk set sampling, controls were selected in a 2:1 ratio (n=712 controls) and matched for age, race, and year, month, and time of day of blood collection.

Results

Baseline plasma levels of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, parathyroid hormone, calcium, phosphate, and creatinine were similar in cases and controls. Mean 1,25(OH)₂D and median FGF23 levels were higher in cases than controls but differences were small and statistically nonsignificant (45.7 versus 44.2 pg/ml, P=0.07 for 1,25[OH]₂D; 47.6 versus 45.1 pg/ml, P=0.08 for FGF23). However, after adjusting for body mass index, diet, plasma factors, and other covariates, the odds ratios of incident symptomatic kidney stones in the highest compared with lowest quartiles were 1.73 (95% confidence interval, 1.11 to 2.71; P for trend 0.01) for 1,25(OH)₂D and 1.45 (95% confidence interval, 0.96 to 2.19; P for trend 0.03) for FGF23. There were no significant associations between other plasma factors and kidney stone risk.

Conclusions

Higher plasma 1,25(OH)₂D, even in ranges considered normal, is independently associated with higher risk of symptomatic kidney stones. Although of borderline statistical significance, these findings also suggest that higher FGF23 may be associated with risk.     

Long-term renal outcome in patients with malignant hypertension: a retrospective cohort study

Background

In patients with chronic kidney disease studies focusing on platelet function and properties often are non-conclusive whereas only few studies use functional platelet tests. In this study we evaluated a recently developed functional flow cytometry based assay for the analysis of platelet function in chronic kidney disease.

Methods

Platelet reactivity was measured using flow cytometric analysis. Platelets in whole blood were triggered with different concentrations of agonists (TRAP, ADP, CRP). Platelet activation was quantified with staining for P-selectin, measuring the mean fluorescence intensity. Area under the curve and the concentration of half-maximal response were determined.

Results

We studied 23 patients with chronic kidney disease (9 patients with cardiorenal failure and 14 patients with end stage renal disease) and 19 healthy controls. Expression of P-selectin on the platelet surface measured as mean fluorescence intensity was significantly less in chronic kidney disease patients compared to controls after maximal stimulation with TRAP (9.7 (7.9-10.8) vs. 11.4 (9.2-12.2), P?=?0.032), ADP (1.6 (1.2-2.1) vs. 2.6 (1.9-3.5), P?=?0.002) and CRP (9.2 (8.5-10.8) vs. 11.5 (9.5-12.9), P?=?0.004). Also the area under the curve was significantly different. There was no significant difference in half-maximal response between both groups.

Conclusion

In this study we found that patients with chronic kidney disease show reduced platelet reactivity in response of ADP, TRAP and CRP compared to controls. These results contribute to our understanding of the aberrant platelet function observed in patients with chronic kidney disease and emphasize the significance of using functional whole blood platelet activation assays.     

Massive proteinuria and acute renal failure in a patient with acute silicoproteinosis.

Acute pulmonary silicoproteinosis, massive proteinuria and fatal renal failure developed in a 23 year old male sandblaster. Examination of the kidney by immunofluorescence revealed granular deposits of immunoglobulin M (IgM) and the third component of complement (C3) along the glomerular basement membrane. Light microscopy disclosed mild proliferative glomerulonephritis with loss of colloidal iron staining for sialoprotein, and electron microscopy disclosed an increased density of epithelial cytoplasm, altered lysosomes and endothelial cell microtubular structures. The silicon content of the kidney was 264 parts per million (ppm), but particles of silicon were not demonstrated by electron microscopy. No primary or systemic causes of renal diseases were elucidated. The renal dysfunction apparently resulted from acute renal silicon toxicity, a new complication of acute pulmonary silicoproteinosis.     

A pilot study comparing furosemide and hydrochlorothiazide in patients with hypertension and stage 4 or 5 chronic kidney disease

Furosemide is the diuretic of choice for the treatment of hypertension in chronic kidney disease but the adaptative changes in the distal nephron may decrease its efficacy. Hydrochlorothiazide is not believed to be efficient in this setting. In a randomized, double-blind, cross-over trial, 23 patients with hypertension and stage 4 or 5 chronic kidney disease received long-acting furosemide (60 mg) and hydrochlorothiazide (25 mg) for 3 months and then both diuretics for 3 months. Sodium and chloride fractional excretions were measured after 3 months of each diuretic and then after their association. A trend towards an increase in the fractional excretion of sodium and chloride was observed with furosemide and hydrochlorothiazide (P=not significant). The association of the two diuretics increased the fractional excretions of sodium and chloride from 3.4±1.8 to 4.9±2.8 and from 3.8±2.0 to 6.0±3.1, respectively (P<.05). Furosemide and hydrochlorothiazide decreased mean blood pressure by the same extent. The association of the two diuretics was more efficient on blood pressure. There were no differences between furosemide and hydrochlorothiazide with respect to natriuresis and blood pressure control in patients with hypertension and chronic kidney disease.     

Erythrocytosis Associated with Diffuse Parenchymal Lesions of the Kidney

Thirteen patients with diffuse parenchymal disease of the kidney and erythrocytosis are reported. In five the haematocrit was only minimally elevated because of an associated increase in plasma volume. The erythrocytosis in three patients was of particular interest: (1) transient appearance in a 23-year-old man with glomerulonephritis; (2) persistence despite the partial remission of nephrotic state in a 19-year-old man; (3) appearance following removal of a nephrosclerotic kidney from a 54-year-old woman. Because an associated expansion of plasma volume is not uncommon with parenchymal renal disease, it is suggested that the only reliable screening method for renal erythrocytosis is direct measurement of red cell volume.     

Chagas' disease in patients with kidney transplants: 7 years of experience 1989-1996.

Chagas' disease was present in 17.22% of persons undergoing kidney transplantation in an Argentine Hospital. The criterion for attributing reactivation of chronic Chagas' disease and transmission of Trypanosoma cruzi to grafts was detection of parasites in blood (patent parasitemia) or tissues. Reactivation was diagnosed in 5 (21.7%) of 23 recipients. Ten (43.4%) of 23 chagasic recipients without reactivation of chronic Chagas' disease had abrogation of serological reactivity. T. cruzi infection was transmitted to 3 (18.7%) of 16 non-chagasic recipients. Reactivation and infection were diagnosed by patent parasitemia or cutaneous panniculitis. For diagnosis, detection of parasites in blood and tissues had more relevance than serology. Sequential monitoring detected early reactivation and infection, permitting application of preemptive or therapeutic therapy with benznidazole, thus inhibiting, in all patients, severe clinical disease produced by a progressive and systemic replication of the parasite.     

Effect of TSH on conversion of T4 to T3 in perfused rat kidney

This study was undertaken to elucidate the effect of thyrotropin (TSH) on the conversion of thyroxine (T4) to 3,5,3'-triiodothyronine (T3) in the isolated perfused rat kidney. The kidney was perfused with a synthetic medium containing 20 micrograms/dL T4 and the effect of constant infusion of bovine TSH (125 or 250 microU/mL) on the conversion of T4 to T3 was investigated. T4 uptake in the perfused kidney was not changed by the addition of TSH. However, the release of T3 (89 +/- 11 ng/g/30 min, mean +/- SD), tissue T3 (190 +/- 23 ng/g/30 min), net T3 production (227 +/- 37 ng/g/30 min), and the conversion rate of T4 to T3 (9.5 +/- 1.6%) in the kidney perfused with 250 microU/mL TSH were significantly (P less than 0.005) greater than those in controls (63 +/- 9, 143 +/- 15, 152 +/- 36 ng/g/30 min, and 6.3 +/- 1.9%), respectively. Degradation rate of T3 in perfused rat kidney was not changed by the addition of 250 microU/mL TSH. These results suggest that TSH may directly affect renal iodothyronine-monodeiodinating activity in rats in vitro.     

Lamivudine therapy of chronic hepatitis B in three groups of patients: non transplanted patients, liver recipients, and kidney recipients

OBJECTIVE: As conflicting results have been observed by some authors in liver recipients, the aim of the study was to evaluate lamivudine therapy in 3 groups of patients with chronic hepatitis B: non-transplanted patients, liver and kidney recipients.METHODS: All patients were studied for clinical symptoms, hepatic enzymes, hepatitis B virus (HBV) serology, serum HBV DNA load, and HBV polymerase genotype (mutations associated with lamivudine resistance).RESULTS: During the 48-144 week-long follow-up (mean: 75 weeks), 23 non-transplanted patients, 5 liver and 6 kidney recipients were studied. A sustained biochemical and virological response was obtained in 19 out of the 23 non-transplanted patients and in 4 of 6 kidney recipients, while the 5 liver recipients did not respond. After the development of lamivudine resistance, mutations rtM204V and rtL180M were detected in all studied patients, mutation rtM207I in one, with similar results from traditional nucleotide sequencing and a commercial line probe assay.CONCLUSION: The poor response to lamivudine in liver recipients requires further studies.