Paradoxical body and kidney growth in potassium deficiency

In the growing animal, K deficiency (KD) retards body growth, but paradoxic ally stimulates renal growth. If KD persists, interstitial infiltrates appe ar and eventually tubulointerstitial fibrosis develops: In patients with ch ronic KD, renal cysts may form and with time tubulointerstitial disease wit h renal failure develops. Since early in KD, kidney IGF-I levels increase a nd may be a cause of the renal hypertrophy, and as TGF-3 promotes hypertrop hy and fibrosis; we examined the expression of these growth factors in chro nic KD. Rats were given a KD diet or pair or ad-lib fed a normal K diet. Af ter 21 days, KD rats weighed less than pair fed controls, while the kidneys were 49% larger Serum IGF-I and kidney IGF-I protein levels were depressed , as were IGF-I mRNA levels, and is largely attributable to decreased food intake. Kidney IGFBP-1 and TGF-beta mRNA levels were increased (p < 0.05). There was marked hypertrophy and adenomatous hyperplasia of outer medullary collecting ducts, hypertrophy of thick ascending limbs of Henle (TALH) and interstitial infiltrates. Both nephron segments stained strongly for IGF-I and IGFBP-1. Only the non-hyperplastic TALH was strongly TGF-beta positive . Interstitial infiltrates containing monocytes/macrophages were prominent. These findings are consistent with a sustained role for IGF-I in promoting the renal hypertrophy of KD and appear to be caused by local trapping of I GF-I by the over-expressed IGFBP-1. Localization of TGF-beta to the hypertr ophied non-hypoplastic tubules containing IGF-I, suggests that TGF-beta may be acting to convert the proliferative action of IGF-I into a hypertrophic response. TGF-beta may also contribute to the genesis of the tubulointerst itial infiltrate. Finally, the reduced levels of serum IGF-1 levels may be a cause of the blunted body growth.