Study of serum activin a and follistatin in post renal transplant patients: correlation with renal hemodynamics, graft function and survival

Chronic allograft nephropathy [CAN] is a devasting long-term complication of kidney transplantation that is responsible for a significant proportion of graft loss. Activin A, a member of the transforming growth factor-beta [TGF- beta] superfamily of proteins, has a pro-fibrotic activity. The biologic effects of activin A are countered by follistatin, which is a high affinity extracellular binding protein for activin A. To study serum activin A and follistatin levels in the post-renal transplant patients and their correlation to renal hemodynamics, graft function and survival. The study included 20 post-renal transplant patients [Group I] and 20 age and sex matched healthy subjects [Group II] as controls. Serum activin A and serum follistatin were measured by enzyme linked immunosorbent assay [ELISA]. Serum C-reactive protein [S.CRP] was measured by turbidimetry. Serum and urinary alkaline phosphatase [S.ALP, U.ALP] were measured by spectrophotometry. Renal henwdynamics were evaluated by duplex Doppler ultrasonography; resistive and pulsatility indices [RI, PI] were calculated. Ten patients were categorized as chronic allograft nephropathy [CAN; group Ia]. The other ten patients had a stable renal function [non-CAN; group Ib]. There was a statistically significant increase in serum activin A [S.activin A], S.ALP, S.CRP, RI and PI and a statistically significant decrease in U.ALP and follistarin/activin ratio in patients with CAN than healthy controls, versus a statistically significant difference only in S. activin A and follistatin/activin ratio between non-CAN and controls. There was no statistically significant differences in S. follistatin between the studied groups. In post-renal transplant patients, S.activin A showed a statistically significant positive correlation with S. creatinine, S.CRP, RI and PI versus a statistically significant negative correlation with creatinine clearance, U.ALP and follistatin/Activin ratio. U.ALP showed a statistically significant positive correlation with creatinine clearance versus a statistically significant negative correlation with S. creatinine, S. activin A, S.CRP, RI and PI. Enhanced activin A activity together with normal follistatin level and the decrease in follistatin/activin ratio in post-renal transplant patients, showed that there is a dysregulation of activin-follistatin axis with the increase of the unbound biologically active activin A with deterioration of renal function. Also, there is an increased activity of ongoing inflammation accompanied by impaired renal function among renal allograft recipients that led to enhanced renal fibrosis and a degree of tubular dysfunction

Effect of melatonin on some bone turnover markers in ovarectomized rats

This study was carried out to evaluate the effect and the mechanism of action of melatonin on some bone markers in ovarectomized bone loss in rats. 32 female albino rats underwent either bilateral laparotomy [sham, n=8] or bilateral ovarectomy [Ovx, n=24]. The Ovx rats were divided into 3 groups, each of 8 rats; Vehicle-treated [Ovx], estrogen-treated [E2] and melatonin-treated [Mlt] group. After 14 weeks treatment, blood and urine were collected. Serum osteoprotegerin [OPG], inhibin, follistatin, and alkaline phosphatase [ALPase] were determined as bone markers. In addition, urinary Deoxypyridinoline [uDPD] was assayed. Serum OPG, inhibin and follistatin levels significantly decreased upon Ovx. They increased upon either treatment with E2 or Mlt with non- significant difference in between as compared to Ovx group. In addition, serum ALPase and uDPD significantly increased on Ovx and decreased with either therapy as compared to Ovx one with non- significant difference between both therapies. The results revealed that administration of Mlt inhibited high bone turnover and prevented calcium loss in ovarectomized rats. This may be through increasing OPG, inhibin and/or follistatin levels. Mlt could be a candidate for the treatment of postmenopausal osteoporosis