Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Prospective Randomized Study on the Efficacy and Safety of the Prophylactic Use of Rituximab, Added to Standard Immunosuppressive Treatment in Comparison With Standard Immunosuppressive Treatment Alone in Renal Transplantation
Brief Summary: Our standard immunosuppressive treatment after renal transplantation is a combination of tacrolimus, mycophenolate mofetil, and prednisolone. With this regimen the incidence of acute rejection within the first six months after transplantation has dropped to about 20%. The main challenge at present remains to improve long-term outcome by preventing chronic allograft nephropathy (CAN). Since acute rejection is a strong predictor of CAN, a further decrease in the incidence of acute rejection can improve the long-term graft survival. Current strategies to prevent rejection are mainly directed at alloreactive T cells. Recently, the attention for the role of antibodies in the pathogenesis of acute rejection has increased. In addition, anti-B cell therapy was shown to be effective in diseases that were considered to be mainly T cell driven, like rheumatoid arthritis. In the latter case it has been suggested that anti-B cell antibodies may impair the antigen presenting function of B cells. We therefore decided to investigate the effectiveness and safety of the anti-B cell monoclonal antibody rituximab for prophylaxis of acute rejection after renal transplantation.

Study design: Double-blind, placebo controlled intervention study. One group receives a single dose of rituximab of 375 mg/m2 intravenously at the time of transplantation, and the other group receives a placebo infusion.

Primary Objective:

To determine the incidence and severity of biopsy-confirmed acute rejection within the first six months after transplantation.

Secondary Outcomes:

* Renal function as estimated by the endogenous creatinine clearance at 6 months
* Occurrence of chronic allograft nephropathy at 6 months
* Cumulative incidence of infections and malignancies at 6 months
* Medical costs during the first 6 months after transplantation
* Patient and graft survival


Options:
A: Inclusion Criteria:

1. Patient has been fully informed and has signed a dated IRB approval informed consent form and is willing to follow study procedures for the extent of the study (36 months). Parent or legal guardian must provide written consent for patients \<18 years of age.
2. Age 16-65 years
3. Weight \> 40 kg
4. Primary renal allograft: living related (non HLA identical) and unrelated donor
5. Negative standard cross-match for T-cells. All donor-recipient pairs matched for a minimum of 1 HLA DR antigen. (Standard at our center)
6. Women of childbearing potential will be required to have a negative qualitative serum pregnancy test and agree to use an adequate method of contraception for 3 months following discontinuation of Thymoglobulin or Campath-1H
7. Males and females are to be studied equivalently as they become available for transplantation using these criteria.

Exclusion Criteria:

1. Patient has previously received or is receiving an organ transplant other than a kidney.
2. Patient is receiving an ABO incompatible donor kidney.
3. Recipient or donor is seropositive for human immunodeficiency virus (HIV), Hepatitis C viruses, or Hepatitis B virus antigenemia.
4. Patient has a current malignancy or a history of malignancy (within the past 5 years), except non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully or carcinoma in situ of the cervix that has been treated successfully.
5. Patients with significant liver disease, defined as having during the past 28 days continuously elevated AST (SGOT) and/or ALT (SGPT) levels greater than 3 times the upper value of the normal range of this center.
6. Patient has uncontrolled concomitant infections and/or severe diarrhea, vomiting, active upper gastro-intestinal tract malabsorption or an active peptic ulcer or any other unstable medical condition that could interfere with study objectives.
7. Patient is currently participating in another clinical trial of an investigational drug in the 30 days prior to transplant.
8. Patient will be receiving any immunosuppressive agent other that those prescribed in the study.
9. Patient is unable to take medications orally or via nasogastric tube by the morning of the second day following completion of the transplant procedure (i.e. skin closure).
10. Patient is receiving or may require warfarin, fluvastatin or herbal supplements during the study.
11. Concurrent use of astemizole, pimozide, cisapride, terfenadine, or ketoconazole.
12. Patient has a known hypersensitivity to Tacrolimus, Campath-1H, Thymoglobulin, Daclizumab (Zenapax®), Sirolimus, MMF or corticosteroids.
13. Patient is pregnant or lactating.
14. Patients with a screening/baseline (or within 96 hours of transplant) total white blood cell count \<4000/mm3; platelet count \<100,000/mm3; fasting triglycerides \>400 mg/dl (\>4.6 mmol/L); fasting total cholesterol \>300 mg/dl (\>7.8 mmol/L); fasting HDL-cholesterol \<30 mg/dl; fasting LDL-cholesterol \>200mg/dl.
15. Patient is unlikely to comply with the visits scheduled in the protocol.
16. Patient has any form of substance abuse, psychiatric disorder or a condition that, in opinion of the investigator, may invalidate communication with the investigator.
17. If tacrolimus cannot be instituted for longer than 5 days postoperatively.
B: Inclusion Criteria:

* Subject capable of giving written informed consent, with end-stage kidney disease, who is a suitable candidate for primary kidney transplantation
* Male or female subject who has reached legal age in the state where they reside and is at least 18 years of age
* Deceased or living donors
* Compatible ABO blood type
* Expanded-criteria donor (ECD) kidneys with a donor grade score of ≤ 25 (as developed by Nyberg, et al.)
* If Kidneys are pumped, they must meet the following pumping parameters: resistance \<0.35 with a flow rate of \>60 ml/min.

Exclusion Criteria:

* Recipient age \>65 years
* PRA \>50%, or donor-specific antibody
* CIT \>30 hours
* Re-transplant patients
* Multi-organ transplant recipients (example: kidney/pancreas or kidney/liver)
* Renal transplant recipients planned for future pancreas transplantation
* Current unstable cardiovascular disease or history of myocardial infarction within the previous 6 months
* Current malignancy or history or malignancy (within the previous 5 years) with the exception of non-metastatic basal or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix that has been treated successfully.
* Hepatitis B and C recipients or active liver disease
* HIV positive recipients
* Primary disease requiring treatment with steroids after transplantation
* Expanded-criteria donor kidneys (current UNOS criteria) with a donor grade score of \> 25
* Donation after cardiac death (DCD) donors
* Dual adult kidneys
* Recipients of pediatric (age \<12 years) unilateral or en-bloc kidneys
* Previous treatment with rATG
* Known hypersensitivity, extensive exposure, or allergy to rabbits
* Pregnant
* Any condition that in the investigator's opinion may compromise study participation (e.g., history or likelihood of non-compliance with immunosuppression regimen, protocol visits, tests, and studies)

Relative Exclusion Criteria:

* Patients with a BMI \> 37 should be considered on an individual basis based on overall health and body habitus.
C: Inclusion Criteria:

* Renal transplant recipients
* Signed, dated, and witnessed IRB approved informed consent

Exclusion Criteria:

* Pregnancy
* Living donor, who is HLA identical.
* Hemolytic uremic syndrome as original kidney disease.
* Focal segmental glomerulosclerosis that had recurred in a previous graft.
* More than two previously failed grafts and/or PRA \> 85%.
* Previous treatment with anti-CD20 antibodies.
* Diabetes mellitus that is currently not treated with insulin.
* Total white blood cell count \<3,000/mm3 or platelet count \<75,000/mm3.
* Active infection with hepatitis B, hepatitis C, or HIV.
* History of tuberculosis
D: Inclusion Criteria:

* Age \>14 years
* Weight \> 40 kg
* Primary renal allograft: cadaveric or mismatched living donor
* Negative standard cross match for T-cells
* Women of childbearing potential will be required to have a negative qualitative serum pregnancy test and agree to use an adequate method of contraception throughout the study period and for 3 months after discontinuation of study medication (3yrs, 3 mos.)
* Signed and dated informed consent (Parent or legal guardian must provide written consent for patients \<18 years of age)

Exclusion Criteria:

* Evidence of systemic infection
* History of malignancy within 10 years (with the exception of localized skin cancer)
* Use of any investigational drug or treatment up to 4 weeks prior to enrolling in the study and during the 12-month treatment phase
* Concurrent use of astemizole, pimozide, cisapride, terfenadine, or ketoconazole
* Known hypersensitivity to sirolimus and its derivatives
* Patients with a screening/baseline (or within 96 hours of transplant)

  * total white blood cell count \< 4000/mm3;
  * platelet count \< 100,000/mm3;
  * fasting triglycerides \> 400 mg/dl (\> 4.6 mmol/L);
  * fasting total cholesterol \> 300 mg/dl (\> 7.8 mmol/L);
  * fasting HDL-cholesterol \< 30 mg/dl;
  * fasting LDL-cholesterol \> 200mg/dl

Answer: C