Hong Kong Journal of Nephrology

Global role of kidney transplantation

2012-04-01

Summary: World Kidney Day on March 8, 2012, provides a chance to reflect on the success of kidney transplantation as a therapy for end stage kidney disease that surpasses dialysis treatments both for the quality and quantity of life that it provides and for its cost effectiveness. Anything that is both cheaper and better, but is not actually the dominant therapy, must have other drawbacks that prevent replacement of all dialysis treatment by transplantation. The barriers to universal transplantation as the therapy for end stage kidney disease include the economic limitations, which, in some countries place transplantation, appropriately, at a lower priority than public health fundamentals such as clean water, sanitation and vaccination. Even in high income countries the technical challenges of surgery and the consequences of immunosuppression restrict the number of suitable recipients, but the major finite restrictions on kidney transplantation rates are the shortage of donated organs and the limited medical, surgical, and nursing workforces with the required expertise. These problems have solutions that involve the full range of societal, professional, governmental, and political environments. World Kidney Day is a call to deliver transplantation therapy to the 1 million people a year who have a right to benefit.在2012年3月8日舉行的世界腎臟日，讓我們再度檢視腎臟移植療法在治療末期腎病上所取得的成果，無論在患者死亡率、生活品質、或成本效益方面，腎臟移植療法均超越了透析療法。然而，基於多方面的原因，腎臟移植療法至今仍然未能全面取代透析療法的地位，例如某些國家基於經濟上的限制，使得腎臟移植的優先順序位列於潔淨水源、環境衛生、及疫苗接種等公衛基本環節之後。即使在較富裕的國家中，手術的技術需求及免疫抑制的後遺症，亦限制了適合接受移植的個案數目；但是腎臟移植普及化的主要限制性因素，仍然是捐贈器官來源的短缺及具經驗醫護人手的不足。為解決這些問題，必須依靠社會、專業團體、政府、及政治力量的共同努力。世界腎臟日提醒了我們，要致力為每年一百萬的合資格患者，提供他們所需的腎臟移植療法。

Patterns of matrix metalloproteinases and transforming growth factor-beta 1 expression during peritoneal repair in chlorhexidine induced peritoneal fibrosis mice

2012-04-01

Summary: Background/Purpose: Recovery from peritoneal fibrosis (PF) involves the digestion of accumulated collagens and remodeling. Matrix metalloproteinases (MMPs) may play an important role in repair. The role of MMP-13, an important component in the MMP cascade, in PF is still unclear. We examined the sequential expression of MMP synthesis during repair in a PF mouse.Methods: Forty-eight mice at 8 weeks of age were given an intraperitoneal injection of 0.1% chlorhexidine gluconate (CG) for 3 weeks. Control mice were injected with the same dosages of 15% ethanol dissolved in saline. These mice were sacrificed, and anterior abdominal walls were obtained on days 21, 28, 35, 42, 49, and 56. Gene expressions of MMP-2 and -13, tissue inhibition of metalloproteinase-1 (TIMP-1) and -2, MT1-MMP, transforming growth factor-beta 1, and collagen types I and III were analyzed by real-time polymerase chain reaction. MMP-13 enzyme activity was also measured. In immunohistological evaluation, MMP-13 expressing cells were examined.Results: Thickening of the peritoneum and marked infiltration of monocytes were induced by CG, and the alterations remained until 7 days after cessation of CG. Then tissue repair rapidly advanced. Synthesis of collagen types I and III, MMP-2, TIMP-1 and -2, and transforming growth factor-beta 1 in the injured peritoneum was significantly increased until day 28. These increments were preceded by an increase of MMP-13 synthesis and activity after cessation of CG. Some infiltrating macrophages in the thickened peritoneum showed MMP-13 expression early after cessation of CG.Conclusion: MMP-13 was synthesized by infiltrating monocytes early in the repair process in the CG-induced PF mouse. After cessation of stimulant, increase of MMP-13 synthesis may act as an inducer of an efficient degradation cascade in collagen-rich peritoneal tissue.背景: 腹膜纖維化的復原涉及膠原蛋白堆積的消化與其後的重塑，其中，基質金屬蛋白酶(MMPs)在組織修復期間可能佔有重要的角色。作為MMP級聯中的重要一環，MMP-13在腹膜纖維化上的角色仍然未明。本研究透過腹膜纖維化(PF)的小鼠，調查了在腹膜修復期間MMP生成的表現順序。方法: 研究材料為48隻年齡8週的小鼠，先接受每天共3週的0.1%葡萄糖酸氯己定(CG)腹膜內注射；另外對照組的注射則採用相同容量or劑量含15%乙醇的鹽水。其後陸續宰殺小鼠以取得第21、28、35、42、49及56天的前腹壁檢體，並採用實時PCR測量以下的基因表現：MMP-2-13、TIMP-1-2、MT1-MMP、TGF-β(1)、及I III型膠原蛋白。此外亦同時測量MMP-13之酵素活動，並對表現MMP-13的細胞作免疫組織學評估。結果: 在CG誘導下，可見腹膜增厚及單核球的明顯浸潤，直至停止CG後7天，其後可見組織修復的快速進行。在停止CG後的受損腹膜中，首先可見MMP-13生成與活動的增加，其後亦可見I III型膠原蛋白、MMP-2、TIMP-1-2、及TGF-β(1)生成的明顯增加，直至第28天。在停止CG後的早期，可見增厚腹膜中有若干巨噬細胞具MMP-13表現。結論: 在CG所致的PF小鼠中，腹膜修復早期已可見浸潤的單核球產生MMP-13。在停止刺激後，在富含膠原蛋白的腹膜環境中，MMP-13似乎可促使一個高效降解級聯的進行。

Beneficial effect of Astragalus membranaceus on estimated glomerular filtration rate in patients with progressive chronic kidney disease

2012-04-01

Summary: Background/Purpose: Several types of herbal preparations have been used as supplementary therapies for the treatment of progressive chronic kidney disease (CKD), but the scientific evidence for their use is scarce. The aim of the present study was to determine the effects of Astragalus membranaceus on renal outcome in patients with progressive CKD.Methods and Results: The study population consisted of 35 patients with CKD stages 4 and 5 whose estimated glomerular filtration rate (eGFR) decreased over a 3-month period before the start of A membranaceus treatment despite the use of conventional therapy (from 14.6±6.28mL/min/1.73m2 to 11.6±5.24; mean±SD, p<0.05). Similarly, the eGFR of 15 patients with CKD stage 4 decreased over the same period despite conventional therapy (from 20.8±4.59 to 16.7±4.17; r=−1.298; p<0.05), but increased after the initial period of 3 months of supplementary treatment with A membranaceus (to 18.6±5.67; r=0.973; p<0.05) and remained at that level at 6 months (17.8±5.60) and 12 months (16.3±5.89). However, in 20 patients with CKD stage 5, the beneficial effect of A membranaceus was limited to the first 3 months only (−3 months: 10.5±2.7, baseline: 8.0±2.75, 3 months: 8.4±2.96, 6 months: 6.8±2.45). A membranaceus had no significant effects on other laboratory parameters. Only seven patients (1 in stage 4 and 6 in stage 5) required dialysis within 12 months of A membranaceus treatment, whose eGFR at baseline was relatively low (7.4±1.06).Conclusion: The results suggest that A membranaceus can maintain stable levels of eGFR and delay the initiation of renal replacement therapy in patients with progressive CKD stage 4.至今已有數種草藥製劑被應用於進行性慢性腎病(CKD)的補充療法，然而此用途仍缺乏相關的科學理據。本研究旨在探討膜莢黃耆(Astragalus membranaceus)對進行性CKD患者的腎臟效應。研究對象為35位第4或5期CKD患者，即使在常規治療下(不包括A membranaceus)，其腎絲球過濾率估算值(eGFR)仍在3個月內明顯下降(從14.6±6.28mL/min/1.73m2至11.6±5.24; mean±SD, p<0.05)。其中15人為第4期CKD患者，eGFR於該段期間明顯下降(從20.8±4.59至16.7±4.17; r=−1.298; p<0.05)，但在膜莢黃耆補充療法開始後3個月回升(至18.6±5.67; r=0.973; p<0.05)，並維持穩定於6個月(17.8±5.60)及12個月(16.3±5.89)。另外20位為第5期CKD患者，膜莢黃耆對其效益僅可見於首3個月(−3個月: 10.5±2.7, 基線: 8.0±2.75, 3個月: 8.4±2.96, 6個月: 6.8±2.45)。至於其他實驗室項目，膜莢黃耆並不具明顯效應。在膜莢黃耆的12個月治療期間，僅7人(第4期：1人；第5期：6人)需接受透析治療，其基線eGFR均偏低(7.4±1.06)。因此，對於第4期進行性CKD患者，膜莢黃耆有助維持eGFR於穩定水平，並延遲腎臟替代療法的開始時間.

Relationship between human oxoguanine-DNA glycosylase-1 polymorphism and the outcome of Chinese peritoneal dialysis patients

2012-04-01

Summary: Background/Purpose: Human oxoguanine-DNA glycosylase 1 (hOGG1) is the enzyme that has DNA repairing capacity. C1245 G substitution of the hOGG1 gene results in reduced enzyme activity. Peritoneal dialysis (PD) is known to cause oxidative DNA damage. We investigated the effect of hOGG1 polymorphism on the clinical outcomes of PD patients.Methods: We studied the hOGG1 polymorphism in 441 new PD patients (232 men, age 56.6±13.5 years). The patients were followed for 41.4±18.2 months for cardiovascular events.Results: For the entire cohort, there was no significant difference in the 5-year event-free survival between the CC and CG/GG groups (42.9% vs. 33.2%; p=0.1). However, for patients with baseline serum C-reactive protein (CRP) levels ≤ 5.0mg/L, 5-year event-free survival of the CC group was significantly better than that of CG/GG group (50.3% vs. 31.9%, p=0.046). Multivariate analysis showed that hOGG1 polymorphism was an independent predictor of the survival (p=0.008). In contrast, for patients with baseline CRP > 5.0mg/L, there was no significant difference in 5-year event-free survival between the CC and CG/GG groups (26.7% vs. 30.2%, p=0.9).Conclusion: In PD patients with no systemic inflammation, hOGG1 1245CC genotype confers a survival benefit as compared to CG or GG genotype, but the protective effect disappears in patients with systemic inflammation. Our results suggest a complex interaction between hOGG1 and inflammation in the pathogenesis of cardiovascular disease in PD patients.背景: 人類oxoguanine-DNA glycosylase 1 (hOGG1)是一種具DNA修復能力的酵素，其酵素活動在hOGG1基因的C1245G替換後會有所下降。此外，腹膜透析(PD)已知會導致DNA的氧化性損害。本研究調查了hOGG1多態性對PD患者的影響。方法: 研究人員對441位剛開始接受PD的病人(男232人, 年齡56.6 ± 13.5歲)，作出hOGG1多態性的調查，並對心血管事件的發生進行共41.4 ± 18.2個月的追蹤。結果: 在整體病人中，CC與CG/GG組別之間在5年無事件存活率上無明顯差異(42.9% vs. 33.2%, p = 0.1)；然而，在基線血清C-反應蛋白(CRP)水平 ≤ 5.0 mg/L的病人中，CC組的5年無事件存活率明顯高於CG/GG組(50.3% vs. 31.9%, p = 0.046)。多變數分析顯示，hOGG1多態性是存活的獨立預測因子(p = 0.008)。相反，在基線CRP > 5.0 mg/L的病人中， CC與CG/GG組別之間在5年無事件存活率上並無明顯差異(26.7% vs. 30.2%, p = 0.9)。結論: 在不具系統性發炎的PD患者間，相比於CG或GG基因型，hOGG1 1245CC基因型具備若干的存活效益，但其效益並未出現於系統性發炎患者間。這些結果意味著，在PD患者的心血管致病過程中，hOGG1與發炎之間存在著複雜的交互關係。

Large utricle cyst misdiagnosed as rectovesical fistula on voiding cystogram

Keith K. Lau, Vladimir Belostotsky, Steve Arora, Luis H. Braga — 2012-04-01

An 8-year-old boy, who was born with a high imperforated anus that was corrected shortly after birth, presented with urinary incontinence after micturition. Renal ultrasound revealed normal kidneys and a small cystic structure posterior to the bladder that changed in size following micturition (). A voiding cystogram was performed (), and a utricle cyst in the prostatic urethra was diagnosed.