SOLUBLE ALPHA-KLOTHO SERUM LEVELS IN RENAL TRANSPLANTATION (Tx)

INTRODUCTION

• α-Klotho is a transmembrane protein expressed in renal distal tubules where it is a  co-factor for the  phosphaturic hormone FGF23 (Figura 1). Thus a decrease in α-Klotho may prevent the actions of FGF23.

• Soluble, circulating α-Klotho (s-Klotho), resulting from shedding of the α-Klotho transmembrane extracellular domain, acts as a humoral factor regulating phosphaturia, calciuria and other cell functions (Figura 1). Circulating levels of s-Klotho could reflect possible changes of membrane   α-Klotho  expression (Figura 1).

• CKD is a clinical condition with low α-Klotho and with a possible tubular resistance to FGF23 (Figura 1).

• Clinical significance of s-Klotho in CKD is still a matter of debate.

AIM OF THE STUDY

• To evaluate, in CKD-5T (or Tx), the circulating levels of s-Klotho.

• To consider its potential clinical and pathophysiological significance.

METHODS

• We assayed circulating s-Klotho, FGF23, vitamin D and standard parameters of mineral metabolism in 80 Tx pts with CKD stage 2 to 4.

• 10 normal subjects (34±12 y.o.; eGFR 95± 19 ml/min) were the control for s-Klotho and FGF23.

RESULTS

• The 80 enrolled Tx patients (55±10 y.o.) were transplanted since 6,7±5,1 years, had eGFR 47±16 ml/min and were in therapy with: calcineurin inhibitors (100%), corticosteroid (67,5%), mycophenolate mofetil (68,7%) and  mtor inhibitors (3,7%).

• With mild vitamin D insufficiency (25D: 26±11, ng/ml), patients had normal levels of 1,25D, mild increment of PTH,  normal values of serum P, Alkaline phosphatase (F.A.) and mild increment of serum Ca (Cas). (Figura 2)

• Circulating levels of s-Klotho were on average significantly lower in Tx than in normal (Figura 3).  This  difference was evident since CKD stage 2 (Figura 4), but values were not different in the different CKD stages•s-Klotho didn’t correlate with eGFR, age and other parameters of mineral metabolism

• Serum levels of FGF23 were increased on average as compared to normal (Figura 3), however, if we examined mean values in each of the CKD stages, values were still higher than control but did not reach a statistically significant difference (Figura 4).

DISCUSSIONS AND CONCLUSIONS

• According to our dates, a reduction of circulating Klotho occurs in renal Tx  be referred, as first instance, to reduced eGFR.

• The absence of correlation between s-Klotho and the examined parameters of mineral metabolism suggest that s-Klotho is not strictly correlated with mineral and bone disorders.

• Absence of progressive increments in serum FGF23 along with reduction of GFR, could be explained by the presence of hypophosphatemia.

• As a whole, it seems that reduction in soluble Klotho in renal Tx should be referred, as first instance, to reduced eGFR .

• Alternatively, other factors such as immunosuppressive drugs, inflammation, etc, could be involved.