Tanner G A
Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis 46202, USA.
J Am Soc Nephrol. 1998 Jul;9(7):1242-8. doi: 10.1681/ASN.V971242.
Polycystic kidney disease (PKD) has been shown to be exacerbated by acidosis or a low potassium intake, and there is evidence that administration of alkali might have a beneficial effect. This study determined whether ingestion of potassium citrate and citric acid would ameliorate PKD. Healthy normal and heterozygous littermate Han:SPRD rats with autosomal dominant PKD were provided with either tap water or 55 mM K3citrate/67 mM citric acid solution (KCitr) to drink starting at the age of 1 mo. Renal clearance measurements and histologic assessments were performed when the rats were 3 mo old. KCitr intake did not affect body weight or urine flow, but completely prevented the decline in GFR found in untreated rats with PKD. In rats that drank tap water, left kidney GFR averaged (in microliter/min per 100 g body wt) 503 +/- 78 (n = 9) in normal animals and 242 +/- 56 (n = 6) in rats with PKD. In rats that drank KCitr, GFR averaged 562 +/- 123 (n = 7) in normal animals and 534 +/- 103 (n = 7) in rats with PKD. Kidneys of rats with PKD were approximately double normal size. KCitr treatment did not affect kidney size, but led to fewer interstitial abnormalities and smaller cysts in cystic kidneys. KCitr ingestion led to a significantly lower (P < 0.001) plasma [K+] in rats with PKD (3.3 +/- 0.2 versus 4.1 +/- 0.2 mEq/L in rats on tap water). Chronic KCitr intake in the young heterozygous Han:SPRD rat with PKD yields a modest improvement of kidney histology and a dramatic improvement in GFR. The mechanism of action of KCitr and the long-term effects of this treatment on renal structure and function in PKD deserve further study.
多囊肾病（PKD）已被证明会因酸中毒或低钾摄入而加重，并且有证据表明给予碱可能具有有益作用。本研究确定摄入柠檬酸钾和柠檬酸是否会改善PKD。从1月龄开始，为健康的正常和杂合子同窝出生的患有常染色体显性PKD的Han:SPRD大鼠提供自来水或55 mM K3柠檬酸盐/67 mM柠檬酸溶液（KCitr）饮用。当大鼠3月龄时进行肾清除率测量和组织学评估。摄入KCitr不影响体重或尿流，但完全防止了未治疗的PKD大鼠中出现的肾小球滤过率（GFR）下降。在饮用自来水的大鼠中，正常动物的左肾GFR平均为（每100 g体重微升/分钟）503±78（n = 9），PKD大鼠为242±56（n = 6）。在饮用KCitr的大鼠中，正常动物的GFR平均为562±123（n = 7），PKD大鼠为534±103（n = 7）。PKD大鼠的肾脏大小约为正常大小的两倍。KCitr治疗不影响肾脏大小，但导致囊性肾脏中的间质异常减少且囊肿变小。摄入KCitr导致PKD大鼠的血浆[K+]显著降低（P < 0.001）（饮用自来水的大鼠中为3.3±0.2与4.1±0.2 mEq/L）。在年轻的杂合子Han:SPRD PKD大鼠中慢性摄入KCitr可使肾脏组织学有适度改善，GFR有显著改善。KCitr的作用机制以及这种治疗对PKD肾脏结构和功能的长期影响值得进一步研究。
