Hong Kong Journal of Nephrology最新文献

Background/Purpose

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by numerous epithelium-lined cysts in the kidney and is the leading genetic cause of end-stage renal disease worldwide. Endothelin-1 is a potent vasoactive peptide implicated in the regulation of basal vascular tone. Endothelin (ET)-converting enzyme 1 (ECE1) is well known for its critical role in the process of ET.

Methods

We investigated ECE1 gene variants to unravel ECE1 modifier effects associated with renal disease progression in ADPKD. Three ECE1 functional polymorphisms [rs213046 (−839 A>C), rs213045 (−338 G>T), and rs1076669 (Thr338Ile)] were genotyped using a fluorescence resonance energy transfer-based KASPar method in 106 ADPKD patients and 112 healthy participants. A Chi-square test was used to determine the relationship between ADPKD and ECE1 variants, and multivariate logistic regression analysis was performed to assess the effect of ECE1 variants on chronic kidney disease (CKD) progression. Mantel-Haenszel stratified analysis was performed to assess relationships between different CKD stages, hypertension, and their interaction.

Results

All loci are polymorphic and followed a Hardy-Weinberg equilibrium. Distribution of ECE1 genotypes in controls and ADPKD groups was not statistically significant, and linkage disequilibrium was not strong between pairs of single-nucleotide polymorphisms. The rs213046 variant genotypes were overrepresented in advanced CKD stages (p = 0.031).

Conclusion

Significant confounding effects of hypertension on CKD progression in ADPKD were observed. These results suggested that the ECE1 gene variant is a modifier of CKD advancement among ADPKD patients.

背景

自體顯性多囊性腎病 (ADPKD) 的特點，是腎臟呈現相當多由上皮構成的囊腫，在全球是導致末期腎病 (ESRD) 的主要遺傳性原因。Endothelin-1 (ET-1) 是一種具有高度血管活性的胜肽，被認為與基礎血管張力的調節有關。眾所周知，endothelin (ET) 轉化酵素 1 (ECE1) 則在 ET 代謝上佔有重要的角色。

方法

在本研究中，我們調查了在 ADPKD 患者間，ECE1 基因變體與 CKD 病情發展的可能關聯。我們採用以 FRET 為基礎的 KASPar 方法，對 106 位 ADPKD 患者及 112 位健康人士，作出 3 種 ECE1 功能性多態性 [rs213046 (-839 A>C)、rs213045 (-338 G>T) 及 rs1076669 (Thr338Ile)] 的基因型辨識。對於 ADPKD 與 ECE1 基因變體的關聯，我們採取卡方檢驗；ECE1 基因變體與 CKD 病情發展的關聯，以多變項邏輯迴歸進行分析；CKD 分期與高血壓的關聯及兩者的交互作用，則採用 Mantel-Haenszel 分層分析。

結果

所有基因座 (loci) 均呈現多態性，且遵循 Hardy-Weinberg 平衡。ADPKD 患者與對照組間的 ECE1 基因型分佈並無明顯差別。單核苷酸多態性鹼基對 (SNP pairs) 之間，並未呈現出明顯的連鎖不平衡 (LD)。在晚期 CKD 患者間，rs213046 變體基因型呈現過度的表達 (p = 0.031)。

結論

我們觀察到，在 ADPKD 患者間，高血壓是 CKD 病情發展的一個明顯的干擾因素。以上結果意味著，在 ADPKD 患者間，ECE1 基因變體可影響 CKD 的病情發展。

A peritoneal dialysis patient with cirrhosis presented with drowsiness, vomiting, and mild hyponatremia. Despite no active correction of hyponatremia, she developed convulsion and quadriplegia. Magnetic resonance imaging of the brain showed changes of osmotic demyelination syndrome. This case illustrates that osmotic demyelination syndrome may occur in peritoneal dialysis without rapid correction of hyponatremia.

With the increase in epidemic proportions of diabetes worldwide, the number of patients who will require renal replacement therapy (RRT) will be a great challenge to the health infrastructures of developing countries such as Nigeria. Because those mostly affected are in the economically productive age group, a vicious circle is established whereby those who keep the economy going are the same people affected. Secondary and tertiary care of chronic kidney disease involving RRT would exact disproportionate toll on the income of patients in the developing world where patients pay out of pocket for their own care. Whilst there is an increase in the number of facilities offering RRT, there is no commensurate sustainability of care either by the patients themselves or even by the government. The level of unemployment is increasing. Kidney transplantation is out of reach in addition to the cost of post-transplant care, which includes hospitalization and immunosuppressive medications. Most of the end-stage kidney disease patients who enlisted in our dialysis program were unable to get or sustain adequate hemodialysis. The data also showed that more men were dialyzed at our facilities over the period under review and the age distribution has not changed much over the decade. From this dismal picture in the last decade emerges a series of questions as to why this is so and what must be done to increase access to RRT. Prudent fund management and cost containment, local manufacture of dialysis materials and nongovernmental sources of funding are means of driving down the cost of dialysis. In countries where drugs and equipment for health services are locally manufactured, such as India and other countries, the cost of health care is more affordable than in countries such as Nigeria where these are imported.

在全世界，糖尿病的盛行率與日俱增，然而對於發展中國家如尼日利亞，基礎醫療架構並不足以應付患者對腎置換療法 (RRT) 的需求。本地民眾必須自費支付自身的醫療費用，但其收入水平遠不足以負擔慢性腎病二級與三級照護所需的 RRT。即使目前 RRT 設施已有所增加，但無論是患者或政府均難以維持治療的長期實施。此外，腎臟移植所需的資源在本地更是相當之有限。在被我們納入透析計劃的末期腎病 (ESKD) 患者間，大多數並未能接受足夠或持續的透析治療。過去十年間，在我們設施內接受透析的病人中，年齡分佈大致穩定，且男性佔較多數。目前，我們正研究如何能促進 RRT 普及實施的方案。透過謹慎的理財與成本控制、透析物料的本土生產、及非政府資金的運用，透析的相關費用可望得以降低。目前，發展中國家如尼日利亞的藥物與醫療器材大多仰賴進口，因此相關物資的本土生產是降低醫療成本的可行方案。