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LOWER GFR CAUSED BY REDUCTION OF FUNCTIONAL NEPHRONS IN ROMK TYPE II BARTTER’S MICE
Author(s) -
Yan Qingshang,
Zhang Junhui,
Hebert Steven,
Giebisch Gerhard,
Wang Tong
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a408
Subject(s) - endocrinology , medicine , nephron , bartter syndrome , reabsorption , chemistry , renal sodium reabsorption , furosemide , aldosterone , knockout mouse , renal function , kidney , receptor , biology , hypokalemia
We previously reported that ROMK null mice exhibit a similar phenotype to Type II Bartter’s syndrome including renal Na+ and K+ wasting due to reduced furosemide‐sensitive Na/2Cl/K‐cotransporter activity in the thick ascending limb. Compensating mechanisms of increasing Na+ and water absorption in distal nephron segments in ROMK null mice include increased renin expression, plasma aldosterone concentration and thiazide‐sensitive NaCl transport activity (JASN, 2004). Renal clearance experiments show a 3‐fold higher urine output (3.46 ± 0.58 vs. 1.00±0.10 ul/min, n=16), with a 43% lower glomerular filtration rate (GFR; 0.51±0.05 vs. 0.90±0.06ml/min/100 g BW; P<0.01), in ROMK null mice and wild‐type mice, respectively. Since no reduction in single nephron GFR was observed in ROMK knockout mice (Lorenz JN et al, JBC 2001), we assessed the number of glomeruli using the magnet bead method, and estimated hydronephrosis using liquid retention in kidneys of wild‐type and ROMK null mice. Liquid retention rates were significantly higher (18.86±2.32% vs. 4.61± 0.30%, n=24, P<0.001) and number of glomeruli significantly lower (10019.46±1299/2kidneys vs. 19183.33 ± 370.74/2kidneys, n=5, P<0.01) in ROMK knockout kidneys compared to the wild‐type. The 48% reduction in number of glomeruli is similar to the decreased total GFR in ROMK null mice. These results indicated that the lower GFR in ROMK Bartter’s mice was caused by a reduction of nephron number, possibly due to the high urine flow‐induced hydronephrosis.