Fluck S, McKane W, Cairns T, Fairchild V, Lawrence A, Lee J, Murray D, Polpitiye M, Palmer A, Taube D
The Brent Laboratory, St. Mary's Hospital, London, UK.
Nephrol Dial Transplant. 1999 Jul;14(7):1687-91. doi: 10.1093/ndt/14.7.1687.
In December 1996 we identified an outbreak of erythropoietin (rHuEpo) resistance requiring a substantial increase in rHuEpo dosage in one of our four haemodialysis (HD) units. The dialysate chloramine levels in this unit had risen from <0.1 p.p.m. in 1996 to 0.25-0.3 p.p.m. in 1997. In the other three HD units levels remained <0.1 p.p.m. Other parameters of water quality were within accepted standards.
Monthly records of haemoglobin level and rHuEpo dose were available for 148 patients between January 1996 and May 1998. Seventy-two patients, with no recognized cause of rHuEpo resistance, were analysed in detail (August 1997 to April 1998). A subgroup of 15 patients was examined for evidence of haemolysis during HD (methaemoglobin and haptoglobin levels, reticulocyte counts and Heinz bodies). Larger carbon columns were installed in December 1997 to effect chloramine removal.
There was an increase in mean methaemoglobinaemia of 23% (P<0.01) and a 21% fall in mean haptoglobin (P<0.01) across HD, although no patient had a reticulocytosis and only one patient with G6PD deficiency had Heinz bodies. Following installation of larger carbon columns there was an 18.6% rise (P<0.001) in mean haemoglobin level and a subsequent 25.0% reduction (P<0.001) in mean rHuEpo dose. Intradialytic changes in methaemoglobin and haptoglobin were abolished. The dialysate chloramine levels fell to < 0.1 p.p.m. Water company records subsequently revealed a sustained twofold increase in mains water chloramine from November 1996.
This is the first report linking chloramine exposure and rHuEpo resistance, with only subtle signs of haemolysis. Unheralded changes in mains water constituents can directly affect dialysate water quality and clinical outcomes.
1996年12月，我们发现我们四个血液透析（HD）单元中的一个出现了促红细胞生成素（rHuEpo）抵抗的爆发，需要大幅增加rHuEpo剂量。该单元的透析液氯胺水平已从1996年的<0.1 ppm升至1997年的0.25 - 0.3 ppm。在其他三个HD单元中，水平仍<0.1 ppm。水质的其他参数在可接受标准范围内。
1996年1月至1998年5月期间，有148名患者的血红蛋白水平和rHuEpo剂量的月度记录。对72名无公认rHuEpo抵抗原因的患者进行了详细分析（1997年8月至1998年4月）。对15名患者的亚组进行了HD期间溶血证据的检查（高铁血红蛋白和触珠蛋白水平、网织红细胞计数和海因茨小体）。1997年12月安装了更大的碳柱以去除氯胺。
尽管没有患者出现网织红细胞增多，只有一名葡萄糖-6-磷酸脱氢酶（G6PD）缺乏患者有海因茨小体，但整个HD过程中平均高铁血红蛋白血症增加了23%（P<0.01），平均触珠蛋白下降了21%（P<0.01）。安装更大的碳柱后，平均血红蛋白水平上升了18.6%（P<0.001），随后平均rHuEpo剂量降低了25.0%（P<0.001）。透析期间高铁血红蛋白和触珠蛋白的变化消失。透析液氯胺水平降至<0.1 ppm。自来水公司记录随后显示，自1996年11月以来，自来水氯胺持续增加了两倍。
这是第一份将氯胺暴露与rHuEpo抵抗联系起来的报告，仅有轻微的溶血迹象。自来水中成分的意外变化可直接影响透析液水质和临床结果。
