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Role of atypical TGF in the response of subtotal nephrectomy to ischemia
Author(s) -
Singh Prabhleen,
Kashkouli Ali,
Blantz R,
Thomson Scott C.
Publication year - 2010
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.24.1_supplement.1059.33
Subject(s) - nephrectomy , medicine , ischemia , hemodynamics , renal function , kidney , urology , cardiology , endocrinology
Subtotal nephrectomy (STN) leads to atypical and highly variable tubuloglomerular feedback (TGF) behavior in the residual nephrons in which the mean TGF response is zero ( Singh P. AJP, 2009 ). Since TGF is a major hemodynamic mechanism causing fall in GFR after ischemia reperfusion (IR) injury, we examined the response of STN to IR. STN and unilateral nephrectomy (UN) rats underwent IR 1 week after surgery. GFR (inulin clearance) was measured at 24 hours post IR. GFR fell by 75% in UN after IR and only 28% in STN, p=0.0001. Losartan, which paradoxically normalizes TGF in STN ( Singh P, 2009 ) made STN susceptible to IR (p=0.001). Micropuncture experiments examined the magnitude and heterogeneity of individual nephron responses to IR. Mean SNGFR dropped from 52 to 40 nl/min in UN post IR, but did not change in STN (60 to 66 nl/min). The variance in SNGFR differed among groups (p=0.000), with STN+IR being most variable ( Fig. 2). The F max test for raw variances in SNGFR was significant between UN+IR and STN+IR groups (172 vs. 1107), p<0.01. Early STN kidneys are largely resistant to IR and we propose that the atypical TGF in STN contributes to this resistance. The effect of IR on SNGFR in STN parallels the effect of STN on TGF (fixed mean with high variability). Whether the high variance in SNGFR in STN+IR reflects the heterogeneous TGF responses prior to ischemia or the variable tubular injury after IR will need to be determined. 12