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result sql = Effects of everolimus as an antiproliferative agent on regression of encapsulating peritoneal sclerosis in a rat model.
Effects of everolimus as an antiproliferative agent on regression of encapsulating peritoneal sclerosis in a rat model.
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char = p;code = 112
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = z;code = 122
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = m;code = 109
char = u;code = 117
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = T;code = 84
char = O;code = 79
char = R;code = 82
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = u;code = 117
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = o;code = 111
char = p;code = 112
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = E;code = 69
char = P;code = 80
char = S;code = 83
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = 3;code = 51
char = 2;code = 50
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = n;code = 110
char = -;code = 45
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = b;code = 98
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = ;code = 32
char = W;code = 87
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = 4;code = 52
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = p;code = 112
char = s;code = 115
char = :;code = 58
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = p;code = 112
char = ,;code = 44
char = ;code = 32
char = 2;code = 50
char = ;code = 32
char = m;code = 109
char = L;code = 76
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = s;code = 115
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = j;code = 106
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = (;code = 40
char = I;code = 73
char = P;code = 80
char = );code = 41
char = ;code = 32
char = d;code = 100
char = a;code = 97
char = i;code = 105
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = 3;code = 51
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = k;code = 107
char = s;code = 115
char = ;;code = 59
char = ;code = 32
char = C;code = 67
char = G;code = 71
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = p;code = 112
char = ,;code = 44
char = ;code = 32
char = 2;code = 50
char = ;code = 32
char = m;code = 109
char = L;code = 76
char = /;code = 47
char = 2;code = 50
char = 0;code = 48
char = 0;code = 48
char = ;code = 32
char = g;code = 103
char = ;code = 32
char = (;code = 40
char = 0;code = 48
char = .;code = 46
char = 1;code = 49
char = %;code = 37
char = );code = 41
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = l;code = 108
char = o;code = 111
char = r;code = 114
char = h;code = 104
char = e;code = 101
char = x;code = 120
char = i;code = 105
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = g;code = 103
char = l;code = 108
char = u;code = 117
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = C;code = 67
char = G;code = 71
char = );code = 41
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = j;code = 106
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = I;code = 73
char = P;code = 80
char = ;code = 32
char = d;code = 100
char = a;code = 97
char = i;code = 105
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = (;code = 40
char = 1;code = 49
char = 5;code = 53
char = %;code = 37
char = );code = 41
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = s;code = 115
char = o;code = 111
char = l;code = 108
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = s;code = 115
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = 3;code = 51
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = k;code = 107
char = s;code = 115
char = ;;code = 59
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = p;code = 112
char = ,;code = 44
char = ;code = 32
char = C;code = 67
char = G;code = 71
char = ;code = 32
char = (;code = 40
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = k;code = 107
char = s;code = 115
char = ;code = 32
char = 0;code = 48
char = ;code = 32
char = -;code = 45
char = ;code = 32
char = 3;code = 51
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = p;code = 112
char = l;code = 108
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = (;code = 40
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = k;code = 107
char = s;code = 115
char = ;code = 32
char = 3;code = 51
char = ;code = 32
char = -;code = 45
char = ;code = 32
char = 6;code = 54
char = );code = 41
char = ;;code = 59
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = E;code = 69
char = v;code = 118
char = o;code = 111
char = -;code = 45
char = R;code = 82
char = ,;code = 44
char = ;code = 32
char = C;code = 67
char = G;code = 71
char = ;code = 32
char = (;code = 40
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = k;code = 107
char = s;code = 115
char = ;code = 32
char = 0;code = 48
char = ;code = 32
char = -;code = 45
char = ;code = 32
char = 3;code = 51
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = p;code = 112
char = l;code = 108
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 3;code = 51
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = /;code = 47
char = L;code = 76
char = ;code = 32
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = m;code = 109
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = (;code = 40
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = k;code = 107
char = s;code = 115
char = ;code = 32
char = 3;code = 51
char = ;code = 32
char = -;code = 45
char = ;code = 32
char = 6;code = 54
char = );code = 41
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = u;code = 117
char = d;code = 100
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = 1;code = 49
char = -;code = 45
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = b;code = 98
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = 2;code = 50
char = 5;code = 53
char = ;code = 32
char = m;code = 109
char = L;code = 76
char = ;code = 32
char = 3;code = 51
char = .;code = 46
char = 8;code = 56
char = 6;code = 54
char = %;code = 37
char = ;code = 32
char = P;code = 80
char = D;code = 68
char = ;code = 32
char = s;code = 115
char = o;code = 111
char = l;code = 108
char = u;code = 117
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = -;code = 45
char = t;code = 116
char = o;code = 111
char = -;code = 45
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = m;code = 109
char = a;code = 97
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = ;code = 32
char = (;code = 40
char = D;code = 68
char = /;code = 47
char = P;code = 80
char = ;code = 32
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = o;code = 111
char = o;code = 111
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = f;code = 102
char = i;code = 105
char = l;code = 108
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = (;code = 40
char = U;code = 85
char = F;code = 70
char = );code = 41
char = ;code = 32
char = v;code = 118
char = o;code = 111
char = l;code = 108
char = u;code = 117
char = m;code = 109
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = u;code = 117
char = m;code = 109
char = .;code = 46
char = ;code = 32
char = E;code = 69
char = x;code = 120
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = C;code = 67
char = G;code = 71
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = 3;code = 51
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = k;code = 107
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = ;code = 32
char = (;code = 40
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = D;code = 68
char = /;code = 47
char = P;code = 80
char = ;code = 32
char = u;code = 117
char = r;code = 114
char = e;code = 101
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char = l;code = 108
char = ;code = 32
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char = f;code = 102
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char = ;code = 32
char = f;code = 102
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char = i;code = 105
char = l;code = 108
char = u;code = 117
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char = l;code = 108
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char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = o;code = 111
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char = ;code = 32
char = (;code = 40
char = p;code = 112
char = ;code = 32
char = <;code = 60
char = ;code = 32
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char = 0;code = 48
char = 5;code = 53
char = );code = 41
char = .;code = 46
char = ;code = 32
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char = o;code = 111
char = w;code = 119
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char = e;code = 101
char = r;code = 114
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char = ;code = 32
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char = e;code = 101
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char = l;code = 108
char = i;code = 105
char = m;code = 109
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = e;code = 101
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char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = p;code = 112
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char = i;code = 105
char = t;code = 116
char = o;code = 111
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char = a;code = 97
char = l;code = 108
char = ;code = 32
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char = e;code = 101
char = s;code = 115
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char = ;code = 32
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char = t;code = 116
char = h;code = 104
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char = r;code = 114
char = e;code = 101
char = g;code = 103
char = a;code = 97
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char = d;code = 100
char = ;code = 32
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char = v;code = 118
char = a;code = 97
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char = u;code = 117
char = l;code = 108
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char = t;code = 116
char = y;code = 121
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char = e;code = 101
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char = ;code = 32
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char = h;code = 104
char = i;code = 105
char = c;code = 99
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char = n;code = 110
char = e;code = 101
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char = s;code = 115
char = ;code = 32
char = (;code = 40
char = p;code = 112
char = ;code = 32
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char = ;code = 32
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char = e;code = 101
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char = ;code = 32
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char = f;code = 102
char = e;code = 101
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char = u;code = 117
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char = b;code = 98
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char = .;code = 46
char = ;code = 32
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char = e;code = 101
char = r;code = 114
char = o;code = 111
char = l;code = 108
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char = m;code = 109
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = y;code = 121
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = e;code = 101
char = u;code = 117
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = u;code = 117
char = e;code = 101
char = ;code = 32
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char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = E;code = 69
char = P;code = 80
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result sql = The most serious complication of peritoneal dialysis is encapsulating peritoneal sclerosis (EPS). The prolonged inflammatory stimuli, fibrogenic cytokine overexpression, and angiogenesis that underlie EPS ultimately result in increased production of fibrous tissue, encapsulating the bowel loops. In recent years, inhibitors of mammalian target of rapamycin (mTOR) as an alternative agent for calcineurin inhibitor toxicity have been widely used in organ transplantation. These agents have also been used since the 1990s in endovascular medicine for drug-eluting stents because of antiproliferative effects on vascular smooth muscle cells and potent anti-inflammatory properties by direct action on human immune cells. Because of the shared characteristics of EPS and other fibrotic processes, we hypothesized that everolimus, an mTOR inhibitor can reverse the process responsible for the eventual development of EPS. We allocated 32 non-uremic albino Wistar rats to 4 groups: control group, 2 mL isotonic saline injected intraperitoneally (IP) daily for 3 weeks; CG group, 2 mL/200 g (0.1%) chlorhexidine gluconate (CG) injected IP daily and ethanol (15%) dissolved in saline, for 3 weeks; resting group, CG (weeks 0 - 3), plus peritoneal rest (weeks 3 - 6); and Evo-R, CG (weeks 0 - 3), plus 0.3 mg/L everolimus in drinking water (weeks 3 - 6). At the end of the study, we performed a 1-hour peritoneal equilibration test with 25 mL 3.86% PD solution, and examined the dialysate-to-plasma ratio of urea (D/P urea), dialysate white blood cell count, ultrafiltration (UF) volume, and morphologic change in the parietal peritoneum. Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased UF volume, p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness, p < 0.05). Peritoneal rest has some beneficial effect only on UF failure and dialysate cell count (p < 0.05). However; everolimus was more effective than peritoneal rest with regard to vascularity and peritoneal thickness (p < 0.05). Everolimus has beneficial effects on UF failure, inflammation, and fibrosis. Everolimus may have therapeutic value in the management of EPS.

Publication: Adv Perit Dial 2008 ;24:104-10.
Publication Date: 2008
Study Author(s): Duman, Soner;Bozkurt, Devrim;Sipahi, Savas;Sezak, Murat;Ozkan, Sultan;Ertilav, Muhittin;Sen, Sait;Ok, Ercan;
Institution: Department of Nephrology, Ege University, Izmir, Turkey. [email protected]
Shortcut link to this study:
The most serious complication of peritoneal dialysis is encapsulating peritoneal sclerosis (EPS). The prolonged inflammatory stimuli, fibrogenic cytokine overexpression, and angiogenesis that underlie EPS ultimately result in increased production of fibrous tissue, encapsulating the bowel loops. In recent years, inhibitors of mammalian target of rapamycin (mTOR) as an alternative agent for calcineurin inhibitor toxicity have been widely used in organ transplantation. These agents have also been used since the 1990s in endovascular medicine for drug-eluting stents because of antiproliferative effects on vascular smooth muscle cells and potent anti-inflammatory properties by direct action on human immune cells. Because of the shared characteristics of EPS and other fibrotic processes, we hypothesized that everolimus, an mTOR inhibitor can reverse the process responsible for the eventual development of EPS. We allocated 32 non-uremic albino Wistar rats to 4 groups: control group, 2 mL isotonic saline injected intraperitoneally (IP) daily for 3 weeks; CG group, 2 mL/200 g (0.1%) chlorhexidine gluconate (CG) injected IP daily and ethanol (15%) dissolved in saline, for 3 weeks; resting group, CG (weeks 0 - 3), plus peritoneal rest (weeks 3 - 6); and Evo-R, CG (weeks 0 - 3), plus 0.3 mg/L everolimus in drinking water (weeks 3 - 6). At the end of the study, we performed a 1-hour peritoneal equilibration test with 25 mL 3.86% PD solution, and examined the dialysate-to-plasma ratio of urea (D/P urea), dialysate white blood cell count, ultrafiltration (UF) volume, and morphologic change in the parietal peritoneum. Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased UF volume, p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness, p < 0.05). Peritoneal rest has some beneficial effect only on UF failure and dialysate cell count (p < 0.05). However; everolimus was more effective than peritoneal rest with regard to vascularity and peritoneal thickness (p < 0.05). Everolimus has beneficial effects on UF failure, inflammation, and fibrosis. Everolimus may have therapeutic value in the management of EPS.
PMID: 18986012

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