氯沙坦和帕立骨化醇联合治疗对尿毒症鼠肾脏的保护作用

目的：观察氯沙坦和维生素D类似物——帕立骨化醇联用对尿毒症鼠肾脏的保护作用。方法：尿毒症鼠分组如下：尿毒症组（uc）、氯沙坦组（UL）、帕立骨化醇组（UP）、氯沙坦＋帕立骨化醇组（ULP）。正常鼠为对照组（NC）。给药10周后检测大鼠血压（BP）,血清中的肌酐（Cr）、钙（ca）、磷（P）、甲状旁腺素（PTH）,24h尿蛋白、尿足细胞（UPC）。免疫组化染色计数肾组织浸润的巨噬细胞（ED-1）。蛋白印迹分析转化生长因子-β1（TGF-β1）、肝细胞生长因子（HGF）的表达。结果：UC、uP组BP较NC组显著升高,较UL、ULP组亦显著升高（P〈0．01）。与NC组相比,UC组Cr、P、PTH明显升高（P〈0．01）,Ca降低（P〈0．05）。与UC组相比,UL组cr明显降低,uP组Cr、P、唧也显著降低（P〈0．01）,且血钙水平明显升高（P〈0．05）。UC组24h尿蛋白、UPC排泄较NC组增加,但可被氯沙坦、帕立骨化醇所改善。UL、uP组肾组织ED．1阳性细胞浸润较UC组显著减少,ULP组较UL、uP组明显减少。TGF-β1蛋白在UC组表达明显增加,UL、UP组明显减少,ULP组减少更为显著。UL、uP和ULP组HGF的表达明显增加（P〈0．01）。结论：氯沙坦和帕立骨化醇均有肾保护作用,两者联用较单用肾保护作用更加明显。     

辛伐他汀对一氧化氮缺乏性高血压大鼠心脏局部肾素血管紧张素系统的影响

目的：观察辛伐他汀对一氧化氮（NO）缺乏性高血压大鼠心脏局部肾素－血管紧张素系统（RAS）的影响。方法：24只Wistar大鼠随机分为正常对照组（C组）、硝基精氨酸甲酯（L－NAME）组（L组）和L－NAME＋辛伐他汀组（L＋S组）。每2wk尾袖法测定动脉收缩压，8wk后测定血清甘油三酯（TG）、总胆固醇（TC）及血清和心肌组织血管紧张素Ⅱ（AngⅡ）水平、血管紧张素转移酶（ACE）活性。结果：L组大鼠血压与同期C组血压相比有极显性差异（P＜0．01），辛伐他汀干预未对增高的血压产生明显影响（P＞0．05）；各组大鼠血清TG和TC水平比较也无显性差别（P＞0．05）。与C组相比，L组大鼠血清ACE活性明显降低（P＜0．01），L组和L＋S组大鼠血浆AngⅡ水平与C组比较无显性差异（P＞0．05），心肌组织中AngⅡ水平和ACE活性则较C组明显增高（P＜0．01）；辛伐他汀干预后L＋S组大鼠血清ACE活性升高，但与L组无显性差异（P＞0．05），心肌ACE活性和AngⅡ水平则均比L组明显降低（P＜0．05）。结论：辛伐他汀可能通过降低局部心肌组织ACE活性抑制NO缺乏性高血压大鼠心脏局部RAS活性，减少AngⅡ生成，这种作用独立于调脂和降压作用之外。     

吡格列酮调节糖尿病鼠肾小球肝素酶的表达

目的：观察胰岛素增敏剂吡格列酮对糖尿病大鼠肾小球肝素酶的表达,探讨其肾脏的保护作用及其机制。方法：将雌性SD大鼠分为3组：正常对照组（NC,n=10）、糖尿病组（DM,n=12）和吡格列酮组（DP,n=12）。链脲菌素腹腔注射诱导糖尿病大鼠模型。实验第6周,测定血糖（BG）、糖化血红蛋白（GHb）,血尿素氮（BUN）、血肌酐（Scr）,24h尿蛋白（24hUP）、尿足细胞（UPC）排泄水平。RT-PCR检测肾小球肝素酶mRNA的表达,肾小球间接免疫荧光分析肝素酶的表达分布。结果：与DM组相比,DP组BG、GHb、BUN、Scr水平显著降低（P〈0．01）;24hUP、UPC排泄量亦明显减少（P〈0．05）;肝素酶mRNA的表达及平均吸光度值显著降低（P〈0．05）。结论：吡格列酮可抑制肝素酶的表达,减轻蛋白尿,对糖尿病肾脏病变有保护作用。     

1,25-(OH)2D3增加多柔比星肾病大鼠肾小球的nephrin表达

目的：观察1，25-（OH）2D3对多柔比星肾病大鼠肾小球nephrin表达的影响。方法：雄性Wistar大鼠随机分为对照组和多柔比星肾病模型组；后者经尾静脉注射多柔比星诱导肾病模型，再随机分模型组和1，25-（OH）2D3组。实验5周末测定大鼠尿红细胞、尿蛋白、血清白蛋白、总胆固醇、甘油三酯。肾小球nephrin荧光染色定量分析检测肾小球nephrin蛋白的表达。结果：与对照组相比，模型组大鼠尿红细胞、尿蛋白、总胆固醇（TC）、甘油三酯（TG）明显升高（P〈0．01），血清白蛋白明显降低（P〈0．01），nephrin蛋白表达明显下调（P〈0．01）。与模型组相比，1，25-（OH）2D3组尿红细胞、尿蛋白、总胆固醇、甘油三酯下降（P〈0．05或P〈0．01），而血清白蛋白明显增加（P〈0．01），nephrin蛋白表达明显增加（P〈0．01）。结论：1，25-（OH）2D3可恢复多柔比星肾病大鼠nephrin蛋白的表达而有肾保护作用。     

miR-34a改变自噬通路AMPK/mTOR的活性在心肌细胞肥大中的作用

目的 研究 miR-34a 与自噬通路磷酸腺苷蛋白激酶（AMPK）/哺乳动物雷帕霉素靶点（mTOR）在血管紧张素（Ang）Ⅱ 诱导的原代大鼠心肌细胞肥大中的作用。 方法 体外培养原代大鼠心肌细胞, 分成 3 组： 阴性对照慢病毒（NC）组、AngⅡ 刺激+阴性对照慢病毒（AngⅡ +NC）组、AngⅡ 刺激+miR-34a 过表达慢病毒（AngⅡ +miR-34a）组。激光共聚焦检测心肌细胞肥大变化; 利用荧光定量聚合酶链反应（qRT-PCR）检测 miR-34a、心房钠尿肽（ANP）和 β- 肌球蛋白重链（β-MHC）表达; 利用蛋白印迹（Western blot）测定 AMPK/mTOR 信号通路的活性变化。 结果 与 NC 组比较, AngⅡ +NC 组心肌细胞表面积明显增大（P＜ 0.05）; 与 AngⅡ +NC 组比较, AngⅡ +miR-34a 组心肌细胞表面积减少（P＜ 0.05）。 与 NC 组比较, AngⅡ +NC 组的 miR-34a 表达下调, ANP 和 β-MHC 表达上调（均 P＜ 0.05）; 而与 AngⅡ +NC 组比较, AngⅡ +miR-34a 组的 miR-34a 表达上调, ANP 和 β-MHC 表达下调（均 P＜ 0.05）。 与 NC 组比较, AngⅡ +NC 组 p-AMPK/AMPK 增加, p-mTOR/mTOR 减少（均 P＜ 0.05）; 与 AngⅡ +NC 组比较, AngⅡ +miR-34a 组 p-AMPK/AMPK 减少, p-mTOR/mTOR 增加（均 P＜ 0.05）。 结论 miR-34a 能抑制 AngⅡ 诱导的心肌细胞肥大, 其作用部分是通过改变 AMPK/mTOR 的活性来实现的。     

来氟米特对血管紧张素Ⅱ诱导的大鼠足细胞Nephrin表达的影响

目的 观察来氟米特对血管紧张素Ⅱ诱导的大鼠足细胞相关蛋白nephrin表达的影响及机制.方法 体外培养大鼠足细胞,间接免疫荧光法鉴定nephrin、WT-1表达阳性的细胞为足细胞,建立AngⅡ足细胞损伤,RT-PCR法检测来氟米特治疗后nephrin mRNA表达变化.结果 Nephrin沿胞膜、细胞骨架、胞核分布,WT-1位于细胞核,ANGⅡ刺激足细胞后nephrin表达呈剂量及时间依赖性降低,来氟米特纠正这一下调作用,呈剂量依赖性.结论 AngⅡ下调大鼠足细胞nephrin表达导致足细胞损害,来氟米特阻断这一损害.     

非选择性内皮素受体拮抗剂对肥厚心肌局部血管紧张素系统的影响

目的：探讨内皮素受体拮抗剂对肥厚心肌局部血管紧张素系统的影响及可能作用机制。方法：24只大鼠随机分为对照组、心肌肥厚组和内皮素受体拮抗剂组。测定左室指数,采用免疫组化法测定心肌组织中血管紧张素受体-1（AT1R）,放射免疫法测定心肌组织血管紧张素Ⅱ（AngⅡ）含量,分光光度法测心肌组织血管紧张素转化酶（ACE）活性,部分心肌组织进行HE、VG染色。结果：与对照组相比,心肌肥厚组左室指数、左室全心比、ACE活性、AngⅡ浓度及AT1R阳性表达率增加均有统计学意义（P〈0.05）。与心肌肥厚组相比,内皮素受体拮抗剂组左室指数、左室全心比、ACE活性、AngⅡ浓度及AT1R阳性表达灰度值降低均有统计学意义（P〈0.05）,但ACE活性、AT1R阳性表达灰度值仍高于对照组（P〈0.05）,而其他指标差异无统计学意义。结论：去甲肾上腺素诱导的心肌肥厚大鼠心肌组织局部血管紧张素系统活化,导致心肌细胞肥大,胶原增生。PD142893可以部分抑制这一作用,内皮素可能参与了血管紧张素系统活化过程。     

益肾平肝方对SHR血压及RAS系统表达的影响

目的1．观察益肾平肝方对血压的影响;2．观察益肾平肝方对自发性高血压大鼠（SHR）肾素血管紧张素系统（RAS）的影响。方法以同龄雄性SHR和正常血压大鼠（Wistar—Kyotorats,WKY）为研究对象,在10周龄时,SHR随机分为模型组（蒸馏水）、中药组（益肾平肝方）和西药组（洛汀新）,WKY作为正常对照组（蒸馏水）,每组8只,用药12周,检测实验第0、6、12周大鼠血压,实验12周末,检测大鼠血清及肾脏血管紧张素转换酶2（ACE2）和血管紧张素Ⅱ（AngⅡ）含量,所得结果进行统计分析。结果12周时,与模型组比较发现,中药组、西药组大鼠血压明显降低（P〈0．01）,中药组大鼠血清ACE2较WKY对照组及西药组明显减少（P〈0．05）,AngⅡ明显增加（P〈0．05）,与模型组无统计学差异（P〉0．05）,而二者在肾脏中的表达却不同,中药组大鼠肾脏ACE2较模型组明显增加（P〈0．05）,与西药组、WKY对照组无统计学差异（P〉0．05）,AngⅡ则明显减少（P〈0．05）,与WKY组无统计学差异（P〉0．05）。结论益肾平肝方能降低SHR血压从而减轻。肾脏损害,其作用可能与调节肾脏局部RAS的表达有关。     

缬沙坦与贝那普利联合应用对糖尿病肾病大鼠nephrin蛋白表达的影响

目的观察缬沙坦与贝那普利联合应用对糖尿病肾病大鼠nephrin蛋白表达的影响。方法将雄性SD大鼠随机分为正常对照组(NC组)和实验组。实验组通过单侧肾切除+腹腔注射链脲佐菌(STZ)建立糖尿病肾病大鼠模型,随机将鼠模分为糖尿病(DN组)、缬沙坦和贝那普利联合干预组(CT组)。8周后采用免疫组织化学方法检测各组大鼠肾组织nephrin表达指数及形态学观察,同时电镜观察肾小球足细胞病理情况。结果与NC组比较,DN组大鼠肾组织nephrin表达明显下调(t=13.40,P<0.01),CT组轻度下调(t=2.53,P<0.05),CT与DN比较差异有统计学意义(t=10.60,P<0.01);NC组与CT组nephrin免疫组化形态及肾小球足细胞病理大致相同,而DN组形态学及肾小球足细胞病理改变明显。结论缬沙坦与贝那普利联合应用能提高nephrin的表达,促进足细胞损伤修复,延缓糖尿病肾病的进展。     

骨形态发生蛋白-7对尿毒症大鼠肾脏的保护作用

目的:观察骨形态发生蛋白-7对尿毒症大鼠肾脏Klotho表达及氧化应激的影响,探讨其对肾损伤的保护作用机制.方法:雄性SD大鼠切除右肾并结扎左肾动脉前支诱导尿毒症模型.将20只尿毒症鼠随机分为尿毒症组(UC组)、UC+骨形态发生蛋白-7治疗组(UB组).另设正常SD大鼠为对照组(NC组).第12周检测大鼠血清钙(Ca)、磷(P)、成纤维细胞生长因子23( FGF23)、白蛋白、尿素氮(BUN)、血肌酐(Cr)、24h尿蛋白(24 h UP).并检测肾脏总抗氧化能力(TAOC)、丙二醛(MDA)、铜锌超氧化物歧化酶(Cu/Zn SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平.RT-PCR检测肾组织Klotho、肿瘤坏死因子-α(TNF-α)、单核细胞趋化蛋白-1 mRNA的表达.结果:与NC组相比,UC组P、FGF23、BUN、Cr、24hUP较NC组显著升高(P＜0.01),Ca、Alb降低(P＜0.05或0.01);T-AOC、Cu/zn SOD、GSH-Px显著降低(P＜0.01),MDA明显升高(P＜0.01);肾组织Klotho mRNA的表达显著降低,而TNF-α及MCP-1 mRNA的表达则显著升高.BMP-7改善尿毒症鼠肾病理损伤和矿物质代谢,减少尿蛋白的排泄;降低氧化应激反应,恢复Klotho的表达,抑制TNF-oα、MCP-1的表达.结论:BMP-7通过上调Klotho的表达,抑制氧化应激反应而具有保护肾脏作用.     

Inhibitor effect of paricalcitol in rat model of pentylenetetrazol-induced seizures

Vitamin D has various systemic effects on bone metabolism, modulation of the immune system, stabilization of the cell membrane, oxidative stress, inflammation, apoptosis, and various other hormones. Differing from active vitamin D, paricalcitol is a relatively safe VDR agonist due to its relatively few side effects. This study has investigated the anticonvulsant effect of paricalcitol in convulsions induced by pentylenetetrazole (PTZ). 36 male Sprague-Dawley rats were divided randomly into two groups: 18 for EEG recording (PTZ 35 mg/kg) and 18 for behavioral studies (PTZ 70 mg/kg). Forty-five minutes before the PTZ injection, both groups of rats were given 5 and 10 μg/kg of paricalcitol i.p., respectively. Racine convulsion scores, first myoclonic jerk time, spike percentages, and antioxidant status were evaluated in the groups. Our results showed that the Racine’s Convulsion Scale (RCS) score significantly dropped in the paricalcitol-treated group, analysis of the first myoclonic jerk (FMJ) latencies demonstrated a significantly longer latency in the paricalcitol-applied group, and spike percentages at EEG recordings significantly decreased with paricalcitol. Moreover, MDA levels were lower and SOD activity were higher in the 5 μg/kg paricalcitol group compared to the saline group; these results were more prominent in 10 μg/kg paricalcitol group. Our study has demonstrated that paricalcitol has protective effects on PTZ-induced convulsions. Based on the SOD and MDA levels in our study, these effects may result from the antioxidant characteristics of paricalcitol.     

Antiapoptotic Effect of Paricalcitol in Gentamicin-induced Kidney Injury

While the anti-apoptotic effect of paricalcitol has been demonstrated in various animal models, it is not yet clear whether paricalcitol attenuates the apoptosis in gentamicin (GM)-induced kidney injury. We investigated the effect of paricalcitol on apoptotic pathways in rat kidneys damaged by GM. Rats were randomly divided into three groups: 1) Control group (n=8), where only vehicle was delivered, 2) GM group (n=10), where rats were treated with GM (150 mg/kg/day) for 7 days, 3) PARI group (n=10), where rats were co-treated with paricalcitol (0.2 µg/kg/day) and GM for 7 days. Paricalcitol attenuated renal dysfunction by GM administration in biochemical profiles. In terminal deoxynucleotidyl transferase dUTP nick end labeling staining, increased apoptosis was observed in GM group, which was reversed by paricalcitol co-treatment. Immunoblotting using protein samples from rat cortex/outer stripe of outer medulla showed increased Bax/Bcl-2 ratio and cleaved form of caspase-3 in GM group, both of which were reversed by paricalcitol. The phosphorylated Jun-N-terminal kinase (JNK) expression was increase in GM, which was counteracted by paricalcitol. The protein expression of p-Akt and nitro-tyrosine was also enhanced in GM-treated rats compared with control rats, which was reversed by paricalcitol co-treatment. Paricalcitol protects GM-induced renal injury by antiapoptotic mechanisms, including inhibition of intrinsic apoptosis pathway and JNK.     

Paricalcitol prevents cisplatin-induced renal injury by suppressing apoptosis and proliferation

The present study was performed to examine whether paricalcitol may prevent the cisplatin-induced kidney injury. Furthermore, potential molecular mechanisms underlying the protective effect of paricalcitol were explored. Male Sprague-Dawley rats were treated with vehicle (n=12), cisplatin (n=12, 6 mg/kg/day, i.p.), or cisplatin+paricalcitol (n=12, 0.2 μg/kg/day, s.c.) for 4 days. In another series of experiment, HK-2 cells were treated with cisplatin (50 μM), with or without paricalcitol (0.2 ng/ml). Paricalcitol counteracted the cisplatin-induced decline in renal function. Paricalcitol also suppressed the expression of TGF-β1, Smad signaling, and the subsequent epithelial-to-mesenchymal process in cisplatin-treated rats. The expression of P-p53 and p21 was increased in cisplatin-induced nephropathy. These changes were completely prevented or significantly attenuated with paricalcitol co-treatment. The expression of p27(kip1) was increased in cisplatin-treated rats, which was, however, further augmented by the paricalcitol co-treatment. In HK-2 cells, cisplatin increased the expression of p-ERK1/2 and P-p38. Cisplatin also increased the expression of fibronectin and CTGF. Cisplatin increased the expression of pro-apoptotic markers. The expression of CDK2 and Cyclin E as well as that of PCNA was increased. These changes were completely prevented or significantly attenuated by the paricalcitol pretreatment. In contrast, cisplatin increased the expression of p27(kip1), which was further augmented by the paricalcitol-pretreatment. These results suggest that paricalcitol may ameliorate cisplatin-induced renal injury by suppressing the fibrotic, apoptotic and proliferative factors. Its underlying mechanisms may include inhibition of TGF-β1, mitogen-activated protein kinase signaling, p53-induced apoptosis, and augmentation of p27(kip1).     

Effects of combination of cyclosporine with losartan or enalapril on kidney function in uremic rats

Long-term treatment with cyclosporine in solid organ transplantation has been shown to be associated with the development of hypertension and nephrotoxicity. Angiotensin-converting enzyme inhibitors have well-known nephroprotective properties and may prevent cyclosporine A (CYA)-induced hypertension. Angiotensin receptor 1 antagonists have similar properties. The purpose of this study was to investigate if losartan or enalapril could be administered with CYA to reduce its nephrotoxic effect in uremic rats. The studies were performed on the following groups of rats: group I--control; group II--control rats + losartan; group III--control rats + CYA; group IV uremic rats; group V--uremic rats + losartan; group VI--uremic rats + CYA; group VII--uremic rats + losartan + CYA, group VIII--control rats + enalapril; group IX--control rats + enalapril + CYA; group X - uremic rats + enalapril; group XI--uremic rats + enalapril + CYA. Pretreatment with CYA, losartan or enalapril in uremic rats resulted in a significant increase in urea and creatinine levels and a decrease in hematocrit. The same effect was observed when uremic rats were given CYA + losartan or CYA + enalapril. Pretreatment with losartan was associated with the increase in the level of CYA much higher than with CYA treatment alone. Similarly, pretreatment with enalapril resulted in a significant increase in CYA concentration in both groups of rats given CYA: uremic and non-uremic. Results of our study show that the treatment with cyclosporine and a combination of losartan or enalapril results in an increase in creatinine and urea levels and a decrease in hematocrit. Therefore, physicians should exercise caution, when they give losartan and enalapril to kidney allograft recipients treated with cyclosporine, particularly with impaired allograft function.     

Clearance of prednisone in isolated perfused livers of normal and uremic rats. Effects of acute and chronic cyclosporin A administration

The influence of cyclosporin A (CsA) on the hepatic clearance of prednisone (HCP) was studied in isolated perfused livers of normal and chronic uremic rats perfused with a hemoglobin-free medium containing prednisone at an initial concentration of 635 +/- 129 micrograms/liter. Prednisone concentration was measured by a normal phase HPLC technique. Addition of CsA to the perfusate in livers of normal rats resulted in an increase of HCP by 38% from 10.8 +/- 2.4 to 14.9 +/- 3.4 ml/min/liver (p less than 0.01). In livers of uremic rats no effect was observed. Acute pretreatment with a large dose (120 mg) of CsA/kg/day ip for 1 day resulted in a 41% increase of HCP in livers of normal rats from 10.8 +/- 2.4 to 15.2 +/- 3.2 ml/min/liver (p less than 0.01). No effect was observed in livers of uremic rats. Chronic pretreatment with a CsA dose of 16 mg/kg/day ip continuously infused for 1 week reduced the HCP by 26% in livers obtained from normal rats and by 29% in livers of uremic rats, 10.8 +/- 2.4 to 8.0 +/- 1.7 ml/min/liver (p less than 0.01) and 14.7 +/- 1.1 to 10.4 +/- 1.2 ml/min/liver (p less than 0.01), respectively, whereas pretreatment with 7 mg/kg/day sc of CsA for 4 weeks resulting in blood CsA concentrations below 350 ng/ml had no influence.(ABSTRACT TRUNCATED AT 250 WORDS)     

活性维生素D类似物对内毒素感染小鼠肾脏细胞因子的影响

目的研究活性维生素D类似物对内毒素感染小鼠肾脏细胞因子的影响。方法将C57 BL/6源性野生小鼠(20只)随机分为正常对照组(CON组)、帕立骨化醇组(P组)、脂多糖组(LPS组)、帕立骨化醇+脂多糖组(P+LPS组)。比较各组小鼠一般状态,应用ELISA试剂盒检测小鼠血清肌酐含量,实时定量PCR法测定小鼠肾脏中细胞因子水平。结果一般状态比较,P+LPS组小鼠较LPS组小鼠不良反应减轻。各组小鼠肾脏形态学及血清肌酐水平未见明显差异。P+LPS组肾脏组织细胞因子IL-1β、ICAM、TNF-α、INF-γ表达比LPS组明显下降(P<0.05)。结论活性维生素D类似物能显著减少内毒素感染小鼠肾脏组织中IL-1β、ICAM、TNF-α、INF-γ的含量,减轻炎性细胞因子介导的肾脏损伤,从而起到对肾脏的保护作用。     

石榴皮鞣质降低尿毒素作用的研究

目的:研究石榴皮鞣质降低尿毒症毒素的作用。方法:用200mg.kg-1腺嘌呤溶液连续灌胃致Wistar大鼠产生类似慢性肾衰的症状。2wk后,分别用石榴皮鞣质(30、20、10mg.kg-1.d-1)灌胃,4wk后处死大鼠,取血、留取肾组织,测定血肌酐(Scr)、尿素氮(BUN)、甲基胍(MG)、胍基琥珀酸(GSA)、钙离子(Ca2+)和磷离子(P3+),进行统计学处理,并进行形态学观察。结果:石榴皮鞣质可降低慢性肾衰竭大鼠的血Scr、BUN、MG、GSA和P3+水平,升高Ca2+水平,疗效显著优于模型组,且石榴皮鞣质可使慢性肾衰竭大鼠肾结构基本恢复正常。结论:石榴皮鞣质有一定的降低尿毒症毒素作用。     

Chronic kidney disease Markov model comparing paricalcitol to calcitriol for secondary hyperparathyroidism: a US perspective

ABSTRACT

Objective: The objective of this study was to determine the cost effectiveness of paricalcitol versus calcitriol for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease in the United States setting.

Methods: A Markov process model was developed employing data sources from the published literature, paricalcitol clinical trials and observational studies, official US price/tariff lists and national population statistics. The comparator was calcitriol, a non-selective vitamin D receptor activator (VDRA) medication. The primary perspective of the study was that of the third-party payer in the US. The efficacy outcomes (reduction in secondary hyperparathyroidism (SHPT), reduction in proteinuria, complications and mortality) were extrapolated to: number of life-years gained (LYG) and number of quality-adjusted life-years (QALYs). Clinical and economic outcomes were discounted at 3.5%.

Results: The reference case analysis was a 10-year time horizon based on a comparison of paricalcitol with calcitriol, which is started in chronic kidney disease (CKD) stage?3 and continued in CKD stage?4 and CKD stage?5. The use of paricalcitol leads to a cost saving of US$1941. The inclusion of indirect costs leads to a cost saving of US$2528. The use of paricalcitol leads to an increase in life-years gained (0.47 years) and a gain in QALYs (0.43). The use of paricalcitol results in a dominant outcome from the perspective of the third-party payer, as well as from the societal perspective. One-way sensitivity analyses and probabilistic sensitivity analyses confirmed the robustness of the model.

Conclusion: This model showed that the favorable clinical benefit of paricalcitol results in positive short and long-term health economic benefits. This study suggests that the use of paricalcitol in patients with early chronic kidney disease may be cost-effective from the third-party payer perspective in the US versus calcitriol. Additional comparative studies are necessary to validate these results.