Tanner G A, Tanner J A
Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Kidney Int. 2000 Nov;58(5):1859-69. doi: 10.1111/j.1523-1755.2000.00357.x.
Few treatments are available to slow the progression to renal failure in autosomal dominant polycystic kidney disease (PKD). In an animal model of PKD, the male heterozygous Han:SPRD rat, intake of a solution of potassium citrate plus citric acid (KCitr) from age one to three months prevented a decline in glomerular filtration rate (GFR). The present study tested whether this beneficial effect is sustained and explored handling of citrate and ammonia in normal and cystic kidneys.
Rats were provided with tap water or citrate solutions to drink, and clearance and survival studies were performed.
The GFRs of rats with PKD that consumed KCitr from one month of age were normal at six months of age, while those of their counterparts on water were about one third of normal. Long-term KCitr treatment extended the average life span of rats with PKD from 10 to 17 months. Compared with normal rats, water-drinking rats with PKD had higher plasma [citrate], renal cortical [citrate], and fractional excretion of citrate, and lower rates of renal citrate consumption, ammonia synthesis, and ammonia excretion. Cortical PNH3 was not elevated in cystic kidneys. Intake of Na3 citrate/citric acid solution or K3 citrate solution, but not ammonium citrate/citric acid solution, prevented a decline in GFR in three-month-old rats with PKD.
Rats with PKD show abnormal renal handling of citrate and ammonia. Citrate salts that have an alkalinizing effect preserve GFR and extend survival.
在常染色体显性多囊肾病（PKD）中，几乎没有可用的治疗方法来减缓肾衰竭的进展。在PKD的动物模型——雄性杂合子Han:SPRD大鼠中，从1月龄到3月龄摄入柠檬酸钾加柠檬酸（KCitr）溶液可防止肾小球滤过率（GFR）下降。本研究测试了这种有益作用是否持续，并探讨了正常肾脏和囊性肾脏中柠檬酸盐和氨的处理情况。
给大鼠提供自来水或柠檬酸盐溶液饮用，并进行清除率和存活研究。
1月龄开始摄入KCitr的PKD大鼠在6月龄时GFR正常，而饮用自来水的大鼠的GFR约为正常水平的三分之一。长期KCitr治疗将PKD大鼠的平均寿命从10个月延长至17个月。与正常大鼠相比，饮用自来水的PKD大鼠血浆[柠檬酸盐]、肾皮质[柠檬酸盐]和柠檬酸盐分数排泄较高，而肾柠檬酸盐消耗、氨合成和氨排泄率较低。囊性肾脏中的皮质PNH3没有升高。摄入柠檬酸钠/柠檬酸溶液或柠檬酸钾溶液，但不摄入柠檬酸铵/柠檬酸溶液，可防止3月龄PKD大鼠的GFR下降。
PKD大鼠的肾脏对柠檬酸盐和氨的处理存在异常。具有碱化作用的柠檬酸盐可维持GFR并延长生存期。
