Inhibition of Proprotein Convertase Subtilisin/Kexin-9 After Kidney Transplant: Single-Center Experience Among Patients With High Cardiovascular Risk.

OBJECTIVES: The benefits of reduction in low-density lipoprotein cholesterol by evolocumab by nearly 60% has not been evaluated among kidney transplant recipients to our knowledge. We assessed the efficacy and safety of evolocumab, a proprotein convertase subtilisin/kexin-9 inhibitor, in reducing lipids and cardiovascular events among kidney transplant recipients in a randomized controlled study. MATERIALS AND METHODS: Between June 2017 and June 2019, we enrolled 197 kidney transplant recipients with high cardiovascular risk score (>20). Patients who received evolocumab (140 mg/2 weeks) comprised group 1 (n = 98), and patients maintained on statin therapy comprised group 2 (n = 99). We followed patients clinically and with necessary laboratory investigations over 24 months. RESULTS: The 2 groups had comparable demographic characteristics (P > .05). Before enrollment in the study, smokers were significantly more prevalent in group 1, whereas posttransplant diabetes mellitus was more prevalent in group 2 (P = .033). Moreover, baseline serum creatinine was higher in group 1, whereas immunosuppression was equivalent in both groups (P > .05). We found no significant differences between the 2 groups concerning cardiovascular events, and both graft and patient outcomes were comparable (P > .05). The higher baseline cholesterol in group 1 (5.5 vs 4.7 mmol/L; P < .001) decreased significantly after 3 months and thereafter (P = .031) compared with levels in group 2 and baseline values (P < .001). We reported 2 cases of acute myocardial infarction and 1 atrial fibrillation in group 2. CONCLUSIONS: Proprotein convertase subtilisin/kexin-9 inhibitors, as an added therapy to statins, are safe and effective in treating hypercholesterolemia after kidney transplant. Evolocumab can minimize cardiovascular events after kidney transplant in patients with high events at baseline. Longer-term trials with larger number of patients are needed to confirm its beneficial effects on cardiovascular complications and patient and graft survival.

Kidney Transplant Recipient With Cerebral Paradoxical Embolism Following Recurrent Idiopathic Deep Vein Thrombosis and Pulmonary Embolism: Case Report and Review of the Literature.

Paradoxical embolism occurs when a thrombus crosses an intracardiac defect into the systemic circulation. Here, we present the case of a 35-yearold male kidney transplant recipient with a cerebral paradoxical embolism associated with a spontaneous venous thromboembolism. This patient had recurrent deep venous thrombosis and showering emboli to the lung and paradoxically to the brain through patent foramen ovale, and we treated him successfully. The role of bubble echocardiography was essential in diagnosis to avoid contrast-induced nephropathy. This is the first successfully managed case of a kidney transplant recipient with recurrent idiopathic deep vein thrombosis, pulmonary embolism, and cerebral paradoxical embolism. Bubble echocardiography was an excellent alternative to contrast angiography to avoid nephrotoxicity. Vitamin K antagonists are superior to direct oral anticoagulants, especially among nonadherent/noncompliant patients.

Effect of Structured Diabetes Education on Diabetic Angiopathies Among Kidney Transplant Recipients With Posttransplant Diabetes: Kuwait Experience.

OBJECTIVES: Diabetes knowledge among kidney transplant recipients with posttransplant diabetes has not been exhaustively assessed. Here, we evaluated the effects of structured diabetes education on development of diabetic micro- and macroangiopathies in kidney transplant patients with posttransplant diabetes. MATERIALS AND METHODS: This prospective randomized controlled study categorized 210 renal transplant patients with posttransplant diabetes mellitus into 2:1 groups according to type of diabetes education. Group 1 (n = 140) received structured education, and group 2 (n = 70) received conventional education. Patient data were collected through patient identification and metabolic control parameter forms. RESULTS: Most patients in groups 1 and 2, respectively, were Kuwaiti (60.7% vs 58.6%), men (57.9% vs 68.6%), and had high school-level education (43.6% vs 48.6%). Chronic glomerulonephritis was the original disease in 36.4% versus 35.4% of patients. Most patients (72.8% vs 78.6% in group 1 vs 2) received pretransplant hemodialysis. At study start, the rate of patients with diabetic neuropathy was comparable between groups (32.4% vs 27.9%). Moreover, after completion of 24 months of education, neurological evaluation by electromyograph and nerve conduction studies did not show any significant differences between the groups (P > .05). Similarly, the number of patients with fundus imaging showing retinopathy was comparable between groups at start and end of study (P > .05). Although macroangiopathic events were higher in group 1, this finding was not significant (P > .05). However, although the percentage of patients with nephropathy was comparable in both groups at start of study, the percentage decreased significantly in group 1 at 24 months after completion of education compared with group 2 and baseline value (P = .016). CONCLUSIONS: Structured diabetes education was associated with reduced diabetic nephropathy but had no significant effects on other micro- or macroangiopathies. However, we recommend education for all kidney transplant recipients with diabetes.

Fludrocortisone Among Adult Renal Transplant Recipients With Persistent Hyperkalemia: Single-Center Experience.

OBJECTIVES: Calcineurin inhibitors are the cornerstone of immunosuppression following solid-organ transplant. However, hyperkalemia may occur by multiple mechanisms affecting potassium in the distal tubule. Hyperkalemia is commonly observed in renal transplant recipients, and it is dose-dependent. Here, we evaluated the impact of fludrocortisone in the management of calcineurin inhibitor-induced hyperkalemia after renal transplant. MATERIALS AND METHODS: We evaluated newly transplanted patients who developed hyperkalemia or those with hyperkalemia who attended our outpatient renal transplant clinic (Hamed Al-Essa Organ Transplant Center, Kuwait). Clinical and laboratory parameters were collected before starting fludrocortisone (baseline values) and then at 1, 2, 4, and 8 weeks. Drug history was assessed, with any drugs that could induce hyperkalemia being discontinued (such as spironolactone); otherwise, essential drugs like prophylactic agents (sulfamethoxazole-trimethoprim) were maintained. Oral anti-hyperkalemic doses (bicarbonate, resonium calcium, fludrocortisone) were noted. RESULTS: Our study included 29 patients; most were men (aged 45.8 ± 15 years). Body weight did not significantly change after introduction of fludrocortisone (79.53 ± 24.31, 79.82 ± 23.85, 80.62 ± 24.24, 77.03 ± 20.7, and 79.21 ± 27.93 kg at baseline and at postdose week 1, 2, 4, and 8, respectively). Systolic and diastolic blood pressure levels were also similar at baseline versus postdose. Steroid doses (prednisolone) were significantly reduced over 1 month (15.7 ± 12.4, 14.1 ± 10.19, 12.6 ± 8.7, 9.5 ± 5.2, and 9.5 ± 5.2 mg/ day). Serum potassium levels significantly improved (5.18 ± 0.58, 4.9 ± 0.49, 4.8 ± 0.54, 4.8 ± 0.65, and 4.4 ± 0.72 mmol/L). Serum creatinine levels significantly improved by postdose week 8 (129.28 ± 48.9, 130.92 ± 52.2, 127.66 ± 50.9, 121.42 ± 41.7, and 124.1 ± 51.27 µmol/L). Serum bicarbonate levels remained similar. CONCLUSIONS: Fludrocortisone was a safe and effective option in management of calcineurin inhibitor-induced hyperkalemia among renal transplant recipients.

Disseminated Rhinocladiella mackenziei infection in a kidney transplant recipient: A case report and literature review.

Rhinocladiella mackenziei is a rare fungal pathogen which belongs to a large group of pigmented fungi causing phaeohyphomycosis. R. mackenziei primarily infects the brain and leads to high fatality rates among both immunocompetent and immunocompromised individuals. Among solid organ transplant recipients, the infection may disseminate to extra-neuronal sites, necessitating comprehensive radiologic imaging. Here we describe a new case of R. mackenziei infection in a renal transplant patient involving the brain and renal allograft. She received liposomal amphotericin B and voriconazole but no surgical intervention. Ultimately, the patient died after two months of hospital stay. A review of all reported cases of transplant patients infected with R. mackenziei is also presented.

Sleep Quality Among Healthcare Workers During the COVID-19 Pandemic and Its Impact on Medical Errors: Kuwait Experience.

OBJECTIVE: Millions of people suffer from sleep disturbances. In addition, the coronavirus disease 2019 (COVID-19) pandemic created several new challenges-particularly for frontline healthcare workers (HCWs). This study assessed the sleep quality (SQ) among HCWs. MATERIAL AND METHODS: A cross-sectional study was conducted using an English-language online survey. The participants were invited via a web link sent using social network platforms. It included sociodemographic- and profession-related characteristics. COVID-19-associated risks were assessed (e.g., being on the front line, doing swabs, satisfaction about protective equipment, and management protocols). Assessment of SQ was done using the Pittsburgh Sleep Quality Index (PSQI) and various medical errors were recorded. RESULTS: A total of 217 HCWs completed the survey with mean (±standard deviation) age of 35.8 (±7.3) years; 56.2% were male, 18.43% had comorbidities, and 61.75% experienced sleep difficulties before the COVID-19 crisis. This work reports a 78.8% prevalence of poor SQ, with the mean (standard deviation) global PSQI score of 9.36 (±4.4). HCWs with poor sleep experienced more positive comorbid profile (23.64% versus 6.52%, p=0.01). Working on the front lines of COVID-19 was associated with poor sleep (69.59% versus 47.83%, p=0.006). Among the participants, 77.42% performed medical errors, particularly not checking for drug allergies (17.97%), dispensing medication with incomplete instructions (20.74%), providing incorrect doses or overdosing (14.75%), incorrectly explaining the use of medication (9.22%), and prescribing a drug to the wrong patient (10.14%). CONCLUSION: This nationwide survey reported high prevalence of poor SQ among HCWs during the COVID-19 pandemic. Being an HCW on the front lines of COVID-19 and doing swabs with a positive comorbidity was associated with poor sleep.

Pretransplant donor-specific anti-human leukocyte antigen antibodies despite a negative complement-dependent lymphocytotoxicity crossmatch: Is it wise to desensitize before kidney transplant?

The significance of pretransplant donor-specific antibodies (DSAs) despite negative complement-dependent lymphocytotoxicity crossmatch (CDC-XM) would be useful for clinical decision-making. Hence, we aimed to determine the impact of pretransplant DSA despite negative crossmatch on the outcome of kidney transplantation. One hundred and eleven kidney recipients were prospectively enrolled in this study after being transplanted at Hamed Al-Essa Organ Transplant Center of Kuwait between January 2011 and December 2013. Of them, 50 recipients with positive DSA at the time of transplant were subjected to desensitization (Group 1). Three local protocols were utilized; first included plasma exchange, high-dose intravenous immunoglobulin (IVIG), and rituximab; second included immunoadsorption plus RTX, and the third included high-dose IVIG and rituximab. The second group included 61 recipients with negative DSA. All recipients had negative CDC-XM and flow cytometry crossmatch at the time of transplant. Panel-reactive antibody (±DSA) levels with mean fluorescence intensity and graft function were monitored along the first 24 months for all patients. There were no statistically significant differences between the two groups regarding early posttransplant graft function, patient and graft survivals. Pretransplant DSA with negative CXM carries a minimal clinical risk with optimized immunosuppression.

Conversion From Twice-Daily to Once-Daily Tacrolimus Among Egyptian Living-Donor Kidney Allograft Recipients: A Single-Center Experience.

OBJECTIVES: Adherence to immunosuppression and minimization of drug exposure are important con-siderations in preventing rejection and maximizing transplant outcomes. The once-daily tacrolimus protocol confers potential benefit by simplifying immunosuppressive regimens, thereby improving adherence among transplant recipients. Studies of stable transplant recipients have suggested that once-daily tacrolimus is bioequivalent to twice-daily tacrolimus and is noninferior to twice-daily tacrolimus with a concentration-dependent rejection risk. Our aim was to evaluate the safety and efficacy of conversion from twice-daily tacrolimus formulation to a once-daily formulation among a cohort of adult living related-donor renal transplant patients as a single-center experience. MATERIALS AND METHODS: This prospective, one arm, single-center study included 238 patients with at least 12 months posttransplant follow-up and no rejection episodes in the last 3 months. Conversion from twice-daily to once-daily formulation was based on a 1:1 ratio. RESULTS: The mean tacrolimus dose was 4.7 ± 2.7 mg/day preconversion versus 4.9 ± 3.2 mg/day postconversion (P = .8). The mean tacrolimus level was 7.4 ± 3.4 versus 6.1 ± 2.8 ng/mL (P = .75). Of total patients, 45% were maintained on a tacrolimus dose of less than 2 ng/dL. Renal function was comparable before and after conversion (mean serum creatinine was 1.25 ± 0.88 vs 1.23 ± 0.78 mg/dL; P = .9). The incidence of biopsy-proven acute rejection was 19.7% preconversion versus 4.2% postconversion. Graft and patient survival rates were comparable between the 2 tacrolimus formulations. Once-daily tacrolimus also had favorable effects on blood pressure, lipid profile, and glucose tolerance. CONCLUSIONS: Conversion from conventional tacrolimus (twice daily) to once-daily tacrolimus may be a valuable option with comparable patient and graft survival and may lead to improved adherence that may be reflective of better long-term results. It should be considered for de novo immunosuppression among living-donor renal allotransplant recipients.

Diabetic Nephropathy Following Posttransplant Diabetes Mellitus.

Diabetic nephropathy is one of the main long-term diabetic microangiopathies that can complicate type 1 and 2 and other secondary forms of diabetes mellitus, including posttransplant diabetes mellitus. Posttransplant diabetes mellitus was initially reported in the 1960s, with case reports of recurrent and de novo diabetic nephropathy after kidney transplant reported in the early 2000s, mostly as a result of same-risk and precipitating factors of diabetic nephropathy as in native kidneys. The disease may appear early in view of the hyperfiltration risk of being a single grafted kidney. Here, we discuss risk factors, early serologic and genetic biomarkers for early detection, and strategies to avoid and delay the progression of diabetic nephropathy after posttransplant diabetes mellitus. In this overview of published literatures, we searched PubMed and MEDLINE for all articles published in English language between January 1994 and July 2018. Included studies reported on the prevalence, incidence, or determinants of post-transplant diabetes among renal transplant recipients and studies reporting diabetic nephropathy in their cohorts. Our review showed that avoidance or good control of posttransplant diabetes is the cornerstone in management of posttransplant diabetes mellitus and hence diabetic nephropathy. Control and avoidance can be commenced in the preparatory stage before transplant using validated genetic markers that can predict posttransplant diabetes mellitus. The use of well-matched donors with tailored immunosuppression (using less diabetogenic agents and possibly steroid-free regimens) and lifestyle modifications are the best preventative strategies. Tight glycemic control, early introduction of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, and possibly conversion to less diabetogenic regimens can help to delay progression of diabetic nephropathy.

Comparative analysis for optimizing the modified release tacrolimus (Advagraf) after kidney transplantation: A prospective randomized trial.

Immunosuppression management in clinical transplantation aims to balance delivery of efficacy against adverse reactions using therapeutic drug monitoring. Adherence to posttransplant immunosuppressive medications and minimizing variability in drug exposure are important considerations in preventing rejection and maximizing overall transplant outcomes. The availability of once-daily tacrolimus may add a potential benefit by simplifying immunosuppressive regimens, though improving compliance among transplant recipients. The aim of our study is to investigate the safety and efficacy of the once-daily formulation of tacrolimus (Advagraf) against the usually used twice daily tablets (Prograf). A prospective randomized trial 1:2 was designed for 99 consecutive live-related renal transplant recipients who received their grafts at a single center (study group, Advagraf, 33 recipients and control group, Prograf, 66 recipients). The demographic data were homogeneous among both groups regarding donors and patients' characteristics. Posttransplant hypertension, infection, malignancy, and diabetes mellitus were comparable among both groups. Renal function and rejection episodes showed no statistical significance among recipients of both groups. Despite slight higher Advagraf unit doses, there was no statistical difference regarding the tacrolimus trough levels, between the two groups. Our singlecenter experience revealed that the availability of once-daily tacrolimus formulation could give potential benefit of improved medication compliance and better allograft outcomes by decreasing pill burden and thereby simplifying dosing schedule, Advagraf was non-inferior to twice-daily tacrolimus regarding safety and efficacy. Although being nonsignificant, a trend for better kidney function was noted in this short-term study in the Advagraf group, so long-term follow-up is needed to verify this.

Impact of Sex Disparities on Outcomes of Living-Donor Kidney Transplant in Egypt: Data of 979 Patients.

OBJECTIVES: Renal transplant is the criterion standard for treatment of end-stage renal disease. The effects of disparities between men and women on renal transplant outcomes have been evaluated in many studies but with debatable results. It has been suggested that female kidney donors have poor outcomes after transplant compared with male kidney donors, especially when implanted in a male recipient. The aim of the study was to evaluate the effects of sex on living-donor kidney transplant outcome. MATERIALS AND METHODS: The data of 979 patients who underwent living-donor kidney transplant from January 2000 to December 2010 at a single center were reviewed retrospectively. The patients were divided into 4 groups according to recipient and donor sex: male donor-to-male recipient (n = 307), male donor-to-female recipient (n = 132), female donor-to-male recipient (n = 411), and female donor-to-female recipient (n = 129). We compared the demographic characteristics, posttransplant rejection and complications, and graft and patient survival rates among the groups. RESULTS: Male recipients were older than female recipients, whereas male donors were younger than female donors (P < .001). No statistically significant differences were shown regarding recipient body mass index, ischemia time and time to diuresis, and acute and chronic rejection rates between the groups. Graft (P = .947) and patient (P = .421) survival rates were comparable between groups. CONCLUSIONS: Donor and recipient sex had no significant effect on outcomes of living-donor renal allograft recipients.

Optimizing Immunosuppressive Regimens Among Living-Donor Renal Transplant Recipients.

OBJECTIVES: We review different immunosuppressant protocols used for living-donor kidney transplant recipients at our center. MATERIALS AND METHODS: Many prospective randomized studies from our center have been reported between March 1976 and 2016, with more than 2700 renal transplant procedures conducted. The first study was a prospective randomized trial of azathioprine versus cyclosporine. The second study compared triple therapy (prednisolone + azathioprine + cyclosporine) versus conventional therapy (prednisolone + azathioprine). The third study was a cost-saving study, in which 100 patients received ketoconazole along with the triple regimen. Another trial demonstrated the advantages of a microemulsion form of cyclosporine. A subsequent trial compared calcineurin inhibitor minimization versus avoidance protocols. Rescue therapies were carried out to intensify immunosuppressive regimens after repeated rejection. In addition, steroid-free regimens were evaluated during both short- and long-term treatment. A recent trial reported a step-forward avoidance protocol with a calcineurin inhibitor and a steroid-free regimen, whereas another current study is the TRANSFORM one. The rationale behind antibody therapy was tho roughly evaluated among living-donor renal trans plant recipients with different agents, including basiliximab, daclizumab, antithymocyte globulin, and alemtuzumab. RESULTS: Earlier studies have demonstrated the efficacy of conventional regimens without induction therapy, especially in longer follow-up. The standard triple therapy has emerged with intensified immunosuppressive and lowered dose of each drug, especially cyclosporine. In minimization studies, no significant differences were encountered regarding patient and graft survival, even in the long-term. Steroid avoidance was safe and effective. Calcineurin inhibitors and steroid-free regimens have shown comparable patient and graft survival. Induction therapy has lowered the incidence and severity of acute rejection. CONCLUSIONS: A better 5-year graft survival and less posttransplant complications have been achieved with steroid avoidance after induction with basiliximab. Induction therapy did not affect graft and patient survival rates despite lowered incidence and severity of acute rejections.

The Long-Term Effect of Hepatitis C Virus on the Outcome of Live-Donor Kidney Transplant Recipients. A Retrospective Study.

OBJECTIVES: Hepatitis C virus infection occurs frequently among end-stage renal disease patients. Moreover, its effect on long-term patient and renal graft survival is controversial. This study was performed to assess the long-term effect of hepatitis C virus on the outcome of kidney allografts. MATERIALS AND METHODS: We retrospectively analyzed 273 hepatitis B negative renal transplant recipients who were transplanted at Mansoura Urology and Nephrology Center, for whom hepatitis C virus RNA polymerase chain reaction results were available before transplant, and followed them for at least 17 years after transplant. We compared graft and patient survival rates between viremic group (study group) and nonviremic group (control group). We also studied posttransplant hepatic function, graft performance, and incidence of posttransplant diabetes mellitus. RESULTS: Hepatitis C virus was detected in sera of 195 patients (71%). No statistically significant increased risk for graft failure (P = .29) or patient death (P = .47) was found among the groups. Hepatitis C virus viremic transplant recipients had significantly greater frequencies of biochemical chronic liver disease (P = .01). However, we did not report significant differences regarding incidence, quantity of proteinuria, biopsy-proven acute rejection, chronic allograft nephropathy, and incidence of posttransplant diabetes mellitus between the studied groups. CONCLUSIONS: Hepatitis C virus infection was shown to increase the incidence of chronic hepatitis posttransplant. However, no statistically significant adverse effect on long-term renal graft and patient survival was noted.

Apelin and New-Onset Diabetes After Transplant in Living Kidney Allograft Recipients.

OBJECTIVES: Apelin, a cytokine mainly secreted by adipocytes and several tissues, includes the gastrointestinal tract, adipose, brain, kidney, liver, lung, and various sites within the cardiovascular system. Apelin is closely related to glucose metabolism, and has been proposed to be a promising therapeutic agent in treating insulin resistance. Apelin and orphaned G-protein-coupled apelin exhibit roles in regulating fluid homeostasis. Circulating serum apelin suppresses insulin secretion by binding to the G-protein-coupled apelin receptor on B cells of islets of Langerhans. Several studies also have documented the altered level of serum apelin in type 2 diabetic patients, but the results remain controversial. This study sought to analyze apelin levels in new-onset diabetes after transplant. MATERIALS AND METHODS: Forty-seven diabetic renal transplant recipients were compared with 40 nondiabetic renal transplant recipients. Data were collected for positive family history of diabetes, body weight, body mass index, blood pressure, and blood chemistry including apelin level. Logistic multiple analysis were made for statistically significant data on univariate analysis. RESULTS: Apelin levels were significantly higher among obese, hypercholesterolemia new-onset diabetes after transplant patients, 428.7 ± 193.29, 256.8 ± 128 (P > .001). There was appositive correlation between serum apelin and proteinuria. CONCLUSIONS: Serum apelin has a high level in new-onset diabetes after transplant, than nondiabetic patients, and they positively correlate with proteuria in new-onset diabetes after transplant patients.

Long term prospective assessment of living kidney donors: single center experience.

Virtually, all studies reporting the outcomes of living kidney donation beyond the first year from donation were retrospective. In this prospective study, the outcome of 81 consecutive living kidney donors was thoroughly evaluated. Clinical, laboratory, and radiological assessments were carried out at predonation (basal), 3, 6, 12, and 24 months after donation. The mean age at time of donation was 37.8 ± 9.8 years and the majority was females (75.3%). The mean BMI increased significantly after donation (P < 0.04). The mean serum creatinine levels (mg/dl) were 0.75 ± 0.14, 1.01 ± 0.22, 0.99 ± 0.21, 0.98 ± 0.20, and 0.94 ± 0.20 (P < 0.0001). Likewise, the mean levels of measured creatinine clearance (mL/min) were 148.8 ± 35.7, 94.7 ± 26.6, 95.5 ± 24.6, 96.7 ± 20.2, and 101.6 ± 26.2 (P < 0.0001). The mean 24 hours urinary protein excretion (gm/dL) were 0.09 ± 0.03, 0.19 ± 0.18, 0.16 ± 0.09, 0.18 ± 0.25, and 0.17 ± 0.12 (P < 0.0001). There were significant increases in the means of the longitudinal and transverse diameters of the remaining kidney over time (P < 0.001). Out of 42 female donors, eleven female donors have got successful postdonation pregnancies. There were no reported surgical complications, either intra- or postoperative. Long-term follow-up is necessary for all living kidney donors through local institutional and world registries. This trial is registered with ClinicalTrials.gov NCT00813579.

Induction immunosuppressive therapy in kidney transplantation.

Induction therapy after kidney transplantation is intensive immunosuppression in the initial days after transplant when the immune system of the recipient has the first contact with donor antigens. Initial intensive immunosuppression may be required to prevent acute rejection and graft loss, and subsequent immunosuppression may be decreased to minimize adverse events associated with immunosuppressive drugs. Induction agents include lymphocyte-depleting antibodies such as rabbit antithymocyte globulin, alemtuzumab, muromonab-CD3, rituximab, and bortezomib; lymphocyte-nondepleting antibodies such as interleukin 2 receptor antibodies; and other discontinued or investigational agents such as efalizumab and alefacept. Induction therapy may be adjusted for special situations such as living-donor kidney transplant, pediatric transplant, hepatitis C virus-seropositive recipients, recipients who require desensitization, patients who are at risk for developing delayed graft function, and old donors. The optimal immunosuppressive regimen may vary, and clinical practice guidelines are available.