PATIENT AND DONOR CHARACTERISTICS
We enrolled 150 patients in the study from November 2003 through June 2009. Survivors were followed for a median of 1.7 years (interquartile range [IQR], 0.7 to 3.0). One patient withdrew consent at 6 months. At the time of analysis, 53 patients had completed at least 3 years of follow-up. Recipient and donor characteristics, pretransplantation HAART regimens, and initial induction and maintenance immunosuppressive regimens are presented in . Antiretroviral therapy was withheld immediately after transplantation in 54 patients (36%). HAART was restarted within a week after transplantation in 46 patients and between 1 and 3 weeks after transplantation in the remaining 8 patients.
PATIENT AND GRAFT SURVIVAL
Patient survival rates (±SD) at 1 year and 3 years were 94.6±2.0% and 88.2±3.8%, respectively (). The 1-year and 3-year graft-survival rates were 90.4% and 73.7%, respectively. Patient- and graft-survival rates were generally between those reported in the SRTR database for older kidney-transplant recipients (≥65 years) and for all kidney-transplant recipients during a similar time frame ( and ).
Kaplan–Meier Estimates of Patient and Graft Survival and First Acute Kidney-Allograft Rejection
Rates of Patient Survival and Graft Survival at 1 Year and 3 Years among HIV-Infected Kidney-Transplant Recipients (Study Patients) and Patients in the SRTR Database.*
A total of 11 patients died: 3 from cardiac causes, 2 each from sepsis and pulmonary infection, 2 from renal-cell carcinoma in the native kidneys, and 2 from unknown causes. The graft was still functioning at the time of death in 8 patients. An additional 13 grafts failed owing to chronic rejection or chronic allograft nephropathy (5 grafts), vascular thrombosis (3 grafts), acute rejection (3 grafts), technical reasons (1 graft), and nonadherence to medical therapy (1 graft).
Univariate proportional-hazards models showed that an increased risk of graft loss was potentially associated with treated rejection (hazard ratio, 3.0; 95% confidence interval [CI], 1.3 to 7.1; P = 0.01), antithymocyte globulin induction (hazard ratio, 2.1; 95% CI, 0.9 to 4.6; P = 0.08), and delayed graft function (hazard ratio, 2.1; 95% CI, 1.0 to 4.8; P=0.07); the use of a graft from a living donor was protective (hazard ratio, 0.2; 95% CI, 0.04 to 0.70; P = 0.02). In the multivariate proportional-hazards model, an increased risk of graft loss was associated with treated rejection (hazard ratio, 2.8; 95% CI, 1.2 to 6.6; P = 0.02), and antithymocyte globulin induction (hazard ratio, 2.5; 95% CI, 1.1 to 5.6; P = 0.03). The use of a graft from a living donor was protective (hazard ratio, 0.2; 95% CI, 0.04 to 0.80; P = 0.02).
shows the patient- and graft-survival curves according to whether the patient was infected with HCV. The risks of death and of graft loss were marginally higher for patients who received antithymocyte globulin induction therapy than for those who did not (P = 0.06 and P = 0.07, respectively, by the log-rank test). When patients with a baseline diagnosis of HIV-associated nephropathy were compared with those who had ESRD from other causes, there were no significant differences in the 1-year patient survival rates (96.8% and 93.9%, respectively; P = 0.63 by the log-rank test) or in the 1-year graft survival rates (87.3% and 91.3%, respectively; P = 0.24 by the log-rank test).
Kaplan–Meier Estimates of Patient and Graft Survival and First Acute Kidney-Allograft Rejection According to Presence or Absence of Hepatitis C Virus (HCV) Infection
Among the kidney-allograft recipients, 49 (33%) had 67 acute rejection episodes. The cumulative incidence of rejection was 31% (95% CI, 24 to 40) at 1 year and 41% (95% CI, 32 to 52) at 3 years. The 1-year SRTR rejection rate was 12.3% (95% CI, 11.9 to 12.7) (). shows the time to a first acute rejection episode according to HCV infection status. There were 42 acute cellular rejection episodes (63%), 4 acute vascular rejection episodes (6%), 7 acute cellular and vascular rejection episodes combined (10%), and 4 chronic and acute rejection episodes (6%). There were 23 rejection diagnoses in patients taking cyclosporine (34%) and 38 in those taking tacrolimus (57%); 32 rejection episodes (48%) responded to glucocorticoid therapy.
For cyclosporine, the median trough level at 1 month was 171 ng per milliliter (IQR, 129 to 209) for patients who entered the study during the first half of the enrollment period and 234 ng per milliliter (IQR, 93 to 358) for those who entered during the second half. For tacrolimus, the corresponding median trough levels at 1 month were 8.6 ng per milliliter (IQR, 6.0 to 12.5) and 9.4 ng per milliliter (IQR, 6.0 to 11.8). Because HAART inhibits the cytochrome P-450 system, 28% of the patients (15% of the cyclosporine group and 31% of the tacrolimus group) received less frequent doses of these drugs (i.e., every other day or every third day).
A higher tacrolimus trough level was associated with a decreased risk of a first acute allograft rejection in the unadjusted model (hazard ratio, 0.90; 95% CI, 0.81 to 1.00; P = 0.04). In the multivariate proportional-hazards model, the only variables associated with an increased risk of graft rejection were the use of a kidney from a deceased donor (hazard ratio, 2.3; 95% CI, 1.1 to 4.8; P = 0.03) and cyclosporine use (hazard ratio, 2.1; 95% CI, 1.1 to 3.9; P = 0.02). A higher post-transplantation CD4+ T-cell count was marginally protective (hazard ratio per increase of 50 cells per cubic millimeter, 0.9; 95% CI, 0.9 to 1.0; P = 0.07).
Delayed graft function, defined as the need for dialysis during the first week after transplantation, occurred in 15% of patients with transplants from living donors and in 46% of patients with transplants from deceased donors. The median change in the estimated GFR at years 1 and 3, as compared with the value 3 months after transplantation, was 0.0 ml per minute per 1.73 m2 of body-surface area (IQR, −12.1 to 8.4; P = 0.23) and −11.8 ml per minute (IQR, −26.8 to 7.2; P = 0.04), respectively. Patients with rejection episodes had a significantly lower median estimated GFR than did those without such episodes at 1 year (51.8 vs. 60.5 ml per minute, P = 0.05) and at 3 years (38.8 vs. 64.0 ml per minute, P = 0.01).
PROGRESSION OF HIV DISEASE
There were two cases of newly diagnosed cutaneous Kaposi’s sarcoma and one case each of candidal esophagitis, presumptive P. jiroveci pneumonia, and cryptosporidiosis. Two patients had biopsy-proven, newly diagnosed HIV-associated nephropathy in the absence of detectable virus. One of the two patients, a white recipient of a kidney from a white, related living donor, had a CD4+ T-cell count of 770 per cubic millimeter at the time of diagnosis, and the patient has continued to have excellent kidney function. The other patient was a black recipient of a kidney from a black deceased donor. At the time of diagnosis, his CD4+ T-cell count was 0, but it increased to 274 cells per cubic millimeter by 9 months. Unfortunately, kidney function continued to deteriorate in this patient.
The median change in the CD4+ T-cell count from baseline to 1 year after transplantation was significantly greater in patients who received early induction therapy with antithymocyte globulin than in those who did not (−238 vs. −135 cells per cubic millimeter, P<0.001) (). The corresponding median changes from baseline to 3 years after transplantation were −57 cells per cubic millimeter (IQR, −237 to 61; P=0.31) and −52 cells per cubic millimeter (IQR, −258 to 34; P = 0.05), respectively. Of the 48 patients (32%) who had a detectable plasma HIV-1 RNA level at any time after transplantation, 29 had a detectable level on a single occasion; the HIV-1 RNA level was subsequently undetectable in 26 of these patients and was detectable at the time of graft loss in the other 3. Among the remaining 19 patients, there were 36 episodes of transient viremia (median peak HIV-1 RNA level, 604 copies per milliliter [IQR, 153 to 3270]). Only 1 patient had a detectable plasma HIV-1 RNA at year 3.
Changes in CD4+ T-Cell Count and Percentage of CD4+ T Cells after Transplantation, According to Antithymocyte Globulin Induction Status
INFECTIONS AND HOSPITALIZATIONS
Of the 150 kidney recipients, 57 (38%) had a total of 140 reported infections that required hospitalization. Of these infections, 69% were bacterial, 9% fungal, 6% viral, and 1% protozoal. Culture was not performed or was negative for the remaining 15%. The most common organisms isolated were Escherichia coli (in 21 patients), enterococcus (in 17), Staphylococcus aureus (in 12), S. epidermidis (in 11), and klebsiella (in 8). The three most common sites of infection were the genitourinary tract (in 26% of cases), the respiratory tract (in 20%), and the blood (in 19%). About 60% of the serious infections occurred within the first 6 months after transplantation.
Patients who tested positive for HCV infection had a higher average rate of serious infections per follow-up year than did those who tested negative (0.8 vs. 0.5, P = 0.02). The patients who received antithymocyte globulin therapy in the first week had about twice as many serious infections per follow-up year as patients who did not receive such therapy (0.9 vs. 0.4, P = 0.002). Five cases of polyomavirus nephropathy were reported. In addition, 212 hospitalizations were reported for reasons other than infection, about half of which were for the purpose of biopsy and diagnosis of rejection.
Nine neoplasms were reported. In addition to the two cases of renal-cell carcinoma and two cases of Kaposi’s sarcoma, there were two cases of oral squamous-cell carcinoma and one case each of squamous-cell skin cancer, basal-cell skin cancer, and cancer of the thyroid gland.