SOCRATES: Steroid or Cyclosporine Removal After Transplantation Using Everolimus

The glomerular filtration rate (GFR) was calculated by the Nankivell formula: GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)^ 2 + C where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kg, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients.

The glomerular filtration rate (GFR) was calculated by the Nankivell formula: GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)^ 2 + C where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kg, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients.

A biopsy-proven acute rejection is defined as a biopsy graded IA, IB, IIA, IIB, or III as per Banff 97 classification.

A biopsy-proven acute rejection is defined as a biopsy graded IA, IB, IIA, IIB, or III as per Banff 97 classification.

Composite endpoint of treatment failure includes biopsy-proven acute rejection (BPAR), graft loss, death and loss-to-follow-up. A BPAR is defined as a biopsy graded IA, IB, IIA, IIB, or III as per Banff 97 classification.

The allograft was presumed to be lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis. If the patient underwent a graft nephrectomy, then the day of nephrectomy was the day of graft loss.

Composite endpoint of treatment failure includes biopsy-proven acute rejection (BPAR), graft loss, death and loss-to-follow-up. A BPAR is defined as a biopsy graded IA, IB, IIA, IIB, or III as per Banff 97 classification.

The allograft was presumed to be lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis. If the patient underwent a graft nephrectomy, then the day of nephrectomy was the day of graft loss.

A per-protocol biopsy was performed at Baseline and Month 12 and read by an independent blinded pathologist in order to assess chronic allograft nephropathy. Chronic rejection is characterized by a slow progressive decline in renal function and is typically preceded by the histological picture of chronic allograft nephropathy. The presence of biopsy confirmed Grade I, II or III chronic allograft nephropathy by Banff 97 criteria was assessed on all optional biopsies obtained for clinical suspicion of chronic rejection.

Data summarized by 3 categories. "Yes" - Patients with histological evidence of CAN ; "No" - Patients with histological evidence of CAN and "Not Done" - Central protocol defined kidney allograft biopsies were not done.

Chronic rejection is characterized by a slow progressive decline in renal function and is typically preceded by the histological picture of chronic allograft nephropathy. The presence of biopsy confirmed Grade I, II or III chronic allograft nephropathy by Banff 97 criteria was assessed on all optional biopsies obtained for clinical suspicion of chronic rejection.

Data summarized by 3 categories. "Yes" - Patients with histological evidence of CAN ; "No" - Patients with histological evidence of CAN and "Not Done" - Central protocol defined kidney allograft biopsies were not done.

Based on Banff 97 criteria, sub clinical acute rejection can be:

GRADE IA - Cases with significant interstitial infiltration (>25% of parenchyma affected) and foci of moderate tubulitis (>4 mononuclear cells/tubular cross section or group of 10 tubular cells).

GRADE IB - Cases with significant interstitial infiltration (>25% of parenchyma affected) and foci of moderate tubulitis (>10 mononuclear cells/tubular cross section or group of 10 tubular cells).

GRADE IIA - Cases with significant interstitial infiltration and mild to moderate intimal arteritis (v1).

GRADE IIB - Cases with moderate to severe intimal arteritis comprising >25% of the luminal area (v2).

GRADE III - Cases with "transmural" arteritis or fibrinoid change and necrosis of medial smooth muscle cells (v3).

"Borderline" category is used when no intimal arteritis is present, but there are foci of mild tubulitis (1 to 4 mononuclear cells/tubular cross section).

Based on Banff 97 criteria, sub clinical acute rejection can be:

GRADE IA - Cases with significant interstitial infiltration (>25% of parenchyma affected) and foci of moderate tubulitis (>4 mononuclear cells/tubular cross section or group of 10 tubular cells).

GRADE IB - Cases with significant interstitial infiltration (>25% of parenchyma affected) and foci of moderate tubulitis (>10 mononuclear cells/tubular cross section or group of 10 tubular cells).

GRADE IIA - Cases with significant interstitial infiltration and mild to moderate intimal arteritis (v1).

GRADE IIB - Cases with moderate to severe intimal arteritis comprising >25% of the luminal area (v2).

GRADE III - Cases with "transmural" arteritis or fibrinoid change and necrosis of medial smooth muscle cells (v3).

"Borderline' category is used when no intimal arteritis is present, but there are foci of mild tubulitis (1 to 4 mononuclear cells/tubular cross section).

Creatinine clearance were calculated according to the Cockcroft-Gault formula:

CrCl (males) = (140-A) × BW/(72 × Cr) CrCl (females) = CrCl (males) × 0.85 where A is age [years], BW is body weight [kg], and Cr is the serum concentration of creatinine [mg/dL].

The Cockcroft-Gault formula estimates creatinine clearance based on serum creatinine level, body weight, and age.

Creatinine clearance were calculated according to the Cockcroft-Gault formula:

CrCl (males) = (140-A) × BW/(72 × Cr) CrCl (females) = CrCl (males) × 0.85 where A is age [years], BW is body weight [kg], and Cr is the serum concentration of creatinine [mg/dL].

The Cockcroft-Gault formula estimates creatinine clearance based on serum creatinine level, body weight, and age.

Proteinuria is measured by spot morning urine Albumin/Creatinine Ratio [ACR]. When the ACR is more than or equal to 30 mg/mmol then it is known as proteinuria.

Proteinuria is measured by spot morning urine Albumin/Creatinine Ratio [ACR]. When the ACR is more than or equal to 30 mg/mmol then it is known as proteinuria.

The symptoms of post transplant diabetes mellitus (PTDM) and impaired fasting glucose are defined as any of the following conditions:

• Patients receiving glucose lowering treatment
• Fasting plasma glucose (FPG) >= 126 mg/dL on 2 separate occasions
• Hemoglobin subtype A1c (HbA1c) > 6.5%
• Diabetes reported as treatment emergent AE with end date > Day 15

The symptoms of new onset diabetes mellitus after transplantation (NODAT) and impaired fasting glucose are defined as any of the following conditions:

• Patients receiving glucose lowering treatment
• 2 fasting plasma glucose (FPG) values >= 126 mg/dL or 2 random plasma glucose (RPG) values >= 200 mg/dL or FPG value >= 126 mg/dL and 1 RPG value >= 200 mg/dL
• Diabetes reported as treatment emergent AE with end date > Day 15

Notable abnormal systolic blood pressure is defined as :

• Either an increase of >=30 that results in >=180 or >200 (mm/Hg)
• OR a decrease of >=30 that results in <=90 or <75 (mm/Hg)from baseline

Notable abnormal diastolic blood pressure is defined as :

• Either an increase of >=20 that results in >=105 or >115 (mm/Hg)
• OR a decrease of >=20 that results in <=50 or <40 (mm/Hg) from baseline

Notable abnormal systolic blood pressure is defined as :

• Either an increase of >=30 that results in >=180 or >200 (mm/Hg)
• OR a decrease of >=30 that results in <=90 or <75 (mm/Hg) from baseline

Notable abnormal diastolic blood pressure is defined as :

• Either an increase of >=20 that results in >=105 or >115 (mm/Hg)
• OR a decrease of >=20 that results in <=50 or <40 (mm/Hg) from baseline

SF-36 measures impact of disease on overall quality of life (QoL). 36-item survey has 8 subscales. The 8 subscales are: Physical functioning (PF), Role-physical (RP), Bodily pain (BP), General health (GH), Vitality (VT), Social functioning (SF), Role-emotional (RE) and Mental health (MH).

Score for eash sub-scale has been standardized with the use of norm-based methods based on assessment of the general U.S. population free of chronic conditions. Scores range from 1-100 with a mean=50 and a standard deviation=10. A higher score indicates less impact on QoL.

SF-36 measures impact of disease on overall quality of life (QoL). 36-item survey has 8 subscales. The 8 subscales are : Physical functioning (PF), Role-physical (RP), Bodily pain (BP), General health (GH), Vitality (VT), Social functioning (SF), Role-emotional (RE) and Mental health (MH).

Score for each sub-scale has been standardized with the use of norm-based methods based on assessment of the general U.S. population free of chronic conditions. Scores range from 1-100 with a mean=50 and a standard deviation=10. A higher score indicates less impact on QoL.

This analysis is reporting number of participants hospitalized for reasons (such as acute rejection, infection, gastrointestinal (GI) events, cardiovascular event, metabolic disorder and Other) other than primary transplantation.

This analysis is reporting number of participants hospitalized for reasons (such as acute rejection, infection, gastrointestinal (GI) events, cardiovascular event, metabolic disorder and Other) other than primary transplantation.

The various employment status reported are:

• Employed/self employed full time
• Employed part time
• Unemployed
• Homemaker
• Volunteer
• Permanently disabled
• Non-permanently disable
• Retired
• Other

The various employment status reported are:

• Employed/self employed full time
• Employed part time
• Unemployed
• Homemaker
• Volunteer
• Permanently disabled
• Non-permanently disable
• Retired
• Other

Patients with any wound healing problem such as infection related to kidney surgery, dehiscence, lymphocele, hernia, seroma, hematoma, ureteral anastomotic complication and other were reported in this analysis.

Patients with any wound healing problem such as infection related to kidney surgery, dehiscence, lymphocele, hernia, seroma, hematoma, ureteral anastomotic complication and other were reported in this analysis.

Notable abnormal total cholesterol is defined as : High: >= 9.1 mmol/L , normal range is 0.00 - 5.17 mmol/L

Notable abnormal triglycerides is defined as : High: >= 8.5 mmol/L, normal range is 0.30 - 2.00 mmol/L

Notable abnormal total cholesterol is defined as : High: >= 9.1 mmol/L , normal range is 0.00 - 5.17 mmol/L

Notable abnormal triglycerides is defined as : High: >= 8.5 mmol/L, normal range is 0.30 - 2.00 mmol/L

The influence of demographic characteristics and comorbidities on incidence of BPAR were analyzed in the following way: Demographic characteristics were age (<55 years, ≥55 years), Expanded criteria Donor (ECD) organ (donor age >60 years or donor non heart-beating and donor age >50), gender, living vs. deceased donor, Body Mass Index (BMI) classes (underweight <18.5, normal 18.5 - <25.0, overweight 25.0 - <30.0, obesity 30.0 and above), years on dialysis before transplantation (<1, 1-5, >5 years). Comorbidities were diabetes, hypertension, cardiovascular diseases/events, nephrosclerosis, glomerulonephritis/glomerular disease, polycystic disease, and Cytomegalovirus status.

The influence of demographic characteristics and comorbidities on incidence of BPAR were analyzed in the following way: Demographic characteristics were age (<55 years, ≥55 years), Expanded Criteria Donor [ECD] organ (donor age >60 years or donor non heart-beating and donor age >50), gender, living vs. deceased donor, Body Mass Index (BMI) classes (underweight <18.5, normal 18.5 - <25.0, overweight 25.0 - <30.0, obesity 30.0 and above), years on dialysis before transplantation (<1, 1-5, >5 years). Comorbidities were diabetes, hypertension, cardiovascular diseases/events, nephrosclerosis, glomerulonephritis/glomerular disease, polycystic disease, and Cytomegalovirus status.

Measurements of bone mineral density (BMD) by Dual Energy X-ray Absorptiometry (DEXA) were done at Week 2 and Month 24. Change in BMD between week 2 and Month 24 were done for neck of femur and lumbar spine.