Hepatic Transplant Recipients Research Articles

Validation of Roche LightCycler Epstein-Barr Virus Quantification Reagents in a Clinical Laboratory Setting

Epstein-Barr virus (EBV) is associated with a wide range of benign and malignant diseases, including infectious mononucleosis, lymphoma, posttransplant lymphoproliferative disorder, and nasopharyngeal carcinoma. Measurement of EBV viral load in plasma is increasingly used for rapid assessment of disease status. We evaluated the performance characteristics of an EBV polymerase chain reaction assay that uses commercial reagents and instruments from Roche Diagnostics (Indianapolis, IN). DNA was extracted from plasma using a MagNaPure instrument, and viral load was measured by real-time polymerase chain reaction on a LightCycler. Analyte-specific reagents included primers and hybridization probes targeting the EBV LMP2 gene and a spiked control sequence. Accuracy and reproducibility were established using DNA from three cell lines. The assay was sensitive to approximately 750 copies of EBV DNA per milliliter of plasma and was linear across at least four orders of magnitude. The assay detected EBV DNA in three of five samples from nasopharyngeal carcinoma patients, seven of nine infectious mononucleosis samples, and 34/34 samples from immunosuppressed patients with clinically significant EBV-related disease, whereas EBV DNA was undetectable in plasma from 21 individuals without EBV-related disease. In conclusion, this LightCycler EBV assay is rapid, sensitive, and linear for quantifying EBV viral load. The assay appears to be useful for measuring clinically significant EBV levels in immunodeficient patients.

1547: Conversion to and from Sirolimus in Renal and Hepatic Transplant Recipients Treated with Calcineurin Inhibitors: Effect on Renal Function

1547: Conversion to and from Sirolimus in Renal and Hepatic Transplant Recipients Treated with Calcineurin Inhibitors: Effect on Renal Function

Dynamic EBV gene loads in renal, hepatic, and cardiothoracic transplant recipients as determined by real‐time PCR light cycler

Epstein-Barr virus (EBV) is recognised as one of the causative agents for most cases of post-transplant lymphoproliferative disease (PTLD). Elevated levels of EBV DNA are known to be associated with the onset of PTLD, but little information is available regarding how EBV loads change with time in asymptomatic transplant recipients following transplantation. Our aims were to study the trend of EBV loads in renal (RTx), hepatic, and cardiothoracic transplant recipients and to compare their EBV loads with other healthy and patient controls. A prospective study was performed using a real-time TaqMan polymerase chain reaction technique to measure EBV DNA loads from three types of organ transplant recipients and haemodialysis patients (HD). Their results were then compared with those from the healthy controls (HC); monospot test negative (MN-) and infectious mononucleosis positive (IM+) patients; patients who were previously treated for PTLD (pPTLD); those who were currently diagnosed to have PTLD (PTLD+); and patients who had a stable renal, hepatic, or cardiothoracic graft for more than a year. Post-transplant EBV loads were significantly higher than the pre-transplant levels. Asymptomatic transplant recipients were differentiated from the PTLD+group at 600 genome copies of EBV/mug DNA, and from IM+group at 100 genome copies. Both HC and MN- groups had significantly lower EBV loads than the three transplant groups. The dynamic change of EBV loads in RTx was greater in the first post-transplant month when compared with the HD group. All transplant recipients had transient rises of EBV loads whereas EBV load continued to rise in one suspected PTLD patient. Asymptomatic transplant recipients had higher baseline post-transplant EBV levels than the non-transplant and MN- groups. The rising post-transplant EBV load in these transplant recipients did not seem to be sustained for longer than 2 weeks. However, in a PTLD+patient the rising EBV load continued over a period of 4 weeks. Hence, the dynamic pattern of EBV loads is more important than absolute EBV DNA measurements alone in identifying those who might go on to develop PTLD.

LONG-TERM FOLLOW-UP OF ACITVE IMMUNIZATION AGAINST DE NOVO HEPATITIS B VIRUS INFECTION IN PEDIATRIC PATIENTS AFTER LIVER TRANSPLANTATION

O98* Aims: The shortage of donor organs occasionally mandates the use of hepatic allografts from anti-HBc (+) donors. Active immunization presents a better alternative than the use of HBIG or lamivudine for the prevention of de novo HBV infection in naive patients, because there are attendant problems such asd mutant strain emergence and high cost. Accordingly, we recently reported the outcome of HBV vaccination in pediatric hepatic transplant recipients. The aim of this study was to investigate the long-term outcome of active immunization in these pediatric patients Methods: Between July 1999 and October 2001, 19 pediatric recipients were administered HBV vaccinations after liver transplantation at Seoul National University Hospital. Nine patients received a graft from anti-HBc (+) donors, and 10 from anti-HBc (−) donors. When steroid was withdrawn, recombinant HBV vaccine was administered. During the follow up period, booster was administered at 12–36 months postoperatively, one or two times. The median follow up period after vaccination was 37.2 ± 5.0 (range 29–46) months. Results: Eighteen of the 19 patients showed a positive response to vaccination. In 9 patients who received grafts from anti-HBc (+) donors, one patient showed no response, 5 patients low response (peak HBsAb titer < 1000 IU/L), and 3 patients high response (peak HBsAb titer ≥ 1000 IU/L). De novo HBV infection developed in one patient who showed no response to vaccination. In 10 patients who received grafts from anti-HBc (−) donors, 6 showed a low response and 6 a high response. Conclusions: HBV vaccination in pediatric patients after liver transplantation appeared to be effective at protecting patients that received a graft from anti-HBc (+) donors from de novo HBV infection.

Therapeutic drug monitoring of cyclosporine

Therapeutic drug monitoring of cyclosporine has been established as part of the routine clinical treatment for patients after organ transplantation. The inability to define optimal dose (maximize efficacy/minimize toxicity) has been a problem related to drug monitoring of cyclosporine. The original cyclosporine formula showed high intra-patient and inter-patient variability and low bioavailability. The microemulsion formulation of cyclosporine (Neoral) was introduced to address the absorption problems related to the original cyclosporine formulation. With the introduction of Neoral, renewed interest in methods of therapeutic drug monitoring brought us from trough monitoring (C0) to levels measured 2 hours after dosing (C2). The pharmacokinetic rationale for using C2 to monitor patients receiving Neoral has demonstrated a reduced incidence of rejection in de novo patients and improvements in safety profile in both renal and hepatic transplant recipients. Monitoring C2 levels is a more precise method for optimizing cyclosporine dosing and a better way to individualize therapy. Further data are required from prospective trials to evaluate the clinical benefits of adopting C2 monitoring in cardiac and lung transplant recipients as well as in long-term maintenance patients.

Active immunization against de novo hepatitis B virus infection in pediatric patients after liver transplantation

The shortage of donor organs occasionally mandates the use of hepatic allografts from anti-HBc (+) donors. HBIG and/or lamivudine are recommended for the prevention of de novo HBV infection in naive patients, but there are attendant problems, such as mutant strain emergence and high cost. Active immunization presents a better alternative than the use of HBIG or lamivudine, if it can be proven to be effective. Accordingly, we investigated the outcome of HBV vaccination in pediatric hepatic transplant recipients. Between July 1999 and October 2001, 19 pediatric recipients were administered HBV vaccinations after liver transplantation at Seoul National University Hospital. Nine patients received a graft from anti-HBc (+) donors and 10 from anti-HBc (−) donors. When steroid was withdrawn, recombinant HBV vaccine was administered. The median follow-up period after vaccination was 10.0 ± 5.2 months. Seventeen of the 19 patients showed a positive response to vaccination. In 9 patients who received grafts from anti-HBc (+) donors, 2 patients showed no response, 4 patients low response (peak HBsAb titer <1,000 IU/L), and 3 patients high response (peak HBsAb titer ≥1,000 IU/L). De novo HBV infection developed in 1 of 2 patients who showed no response to vaccination. In 10 patients who received grafts from anti-HBc (−) donors, 5 showed a low response and 5 a high response. In conclusion, HBV vaccination in pediatric patients after liver transplantation appeared to exhibit some effectiveness at protecting young children that received a graft from anti-HBc (+) donors from de novo HBV infection. (H epatology 2003;37:1329-1334.)

Different time course of circulating adhesion molecules and hyaluran during hepatic allograft rejection.

Inducible adhesion molecules are involved in cell-mediated allograft rejection. In addition, the endothelium is the main target of this process. This study investigated, whether soluble (s) forms of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) are elevated during cellular rejection and whether hyaluran is a useful marker of endothelial function in liver transplantation. Serum levels of sICAM-1, sVCAM-1, and hyaluran were determined in 24 controls and 27 hepatic transplant recipients. These patients were divided in two groups: group I, 14 patients without rejection; and group II, 13 patients with rejection. Samples were collected on day 1 and 7 after transplantation, on the day of liver biopsy, and after treatment of the rejection. We found a significant increase in sICAM-1 levels in the postoperative period in the rejection group compared with the non rejection group. It persisted significantly elevated until the diagnosis of rejection was made. In contrast, sVCAM-1 was only significantly elevated in the rejection group when diagnosis of rejection was evident. Hyaluran levels were also significantly elevated in the rejection group at diagnosis of rejection. We noticed a significant decline in sICAM-1, sVCAM-1, and hyaluran levels after successful treatment of rejection. In addition, we observed in the non-rejection group a stable lower levels of hyaluran during the entire postoperative period. The release of circulating adhesion molecules is a prominent feature coinciding with the first episode of hepatic rejection. Differential patterns of sICAM-1 and sVCAM-1 exist during rejection. In addition, hyaluran levels may be a sensitive marker of liver endothelial cell function in the postoperative period of liver transplantation.

Review of cyclosporine pharmacokinetic trials in healthy volunteers and kidney and liver transplant recipients: SangCyA versus neoral and sandimmune

SangCyA is a novel cyclosporine formulation that was compared with Neoral and Sandimmune (Novartis Pharmaceutical, E. Hanover, NJ) in various pilot and pivotal trials in healthy volunteers and in transplant patients to assess pharmacokinetic parameters, bioequivalence, and safety end points. Eleven studies compared SangCyA solution and Neoral (Novartis Pharmaceuticals, E. Hanover, NJ) or Sandimmune solutions using various designs. Study conditions in healthy volunteers included fasted and fed conditions, male and female gender, white and black race, TDx, Emit and HPLC assays, different Neoral manufacturing lots, and renal and hepatic transplant recipients. Multiple blood samples were obtained over 36 hours in healthy volunteers and 12 hours in transplant recipients and analyzed using different cyclosporine assays. Pharmacokinetic parameters were estimated using noncompartmental methods. SangCyA and Neoral were bioequivalent in healthy volunteer trials under fasted or fed conditions, in males and females, in whites and blacks, and using any of three assays (TDx, Emit, and HPLC). Bioequivalence and similar safety profiles of Sang-CyA and Neoral were also observed in renal and hepatic transplant recipients. Although Sandimmune and SangCyA were not bioequivalent in renal transplant, patients could be converted safely with a small dose decrease needed to maintain similar drug exposure. SangCyA and Neoral solutions are bioequivalent and interchangeable.

Cyclosporine conversion from conventional to microemulsion formulation: Effect on renal concentration ability in stable hepatic transplant recipients

Cyclosporine conversion from conventional to microemulsion formulation: Effect on renal concentration ability in stable hepatic transplant recipients

Muromonab CD3: a reappraisal of its pharmacology and use as prophylaxis of solid organ transplant rejection.

The murine monoclonal antibody muromonab CD3 (OKT3) is directed against the CD3 antigen on peripheral human T cells and effectively blocks all T cell function. Prophylaxis with muromonab CD3 (5mg intravenously once daily for 10 to 14 days) as induction therapy together with corticosteroids, azathioprine and delayed cyclosporin (sequential therapy) optimises early graft function by delaying the potentially nephrotoxic and hepatotoxic effects of cyclosporin until graft function is established. Although clinical data are limited (by inconsistencies in trial design and trial size), prophylactic muromonab CD3-based sequential therapy is significantly more effective than standard triple therapy in the prophylaxis of allograft rejection in renal and hepatic, but not cardiac, transplant recipients. Benefits are particularly notable in patients with delayed graft function. No significant between-treatment differences in patient survival have been observed. The overall efficacy of muromonab CD3- and polyclonal-based prophylactic regimens appears to be similar, although results vary between investigators and confirmation is needed. An anti-interleukin-2 monoclonal antibody-based prophylactic regimen improved graft and patient survival compared with muromonab CD3-based prophylaxis in hepatic transplant recipients. Antimuromonab CD3 antibodies may develop; however, muromonab CD3 may be successfully reused in patients with low titres. Preliminary pharmacoeconomic data suggest that mean drug costs are greater with quadruple immunosuppressive regimens containing muromonab CD3, antithymocyte globulin (ATG) or antilymphocyte globulin (ALG) than with triple therapy. Drug costs with prophylactic muromonab CD3-based regimens were similar or greater than those with polyclonal-based protocols. The first doses of muromonab CD3 are associated with the 'cytokine-release syndrome'. More severe first-dose events include aseptic meningitis, intragraft thromboses, seizures and potentially fatal pulmonary oedema. The incidence and/or severity of cytomegalovirus infection with prophylactic muromonab CD3 based immunosuppression is similar to or greater than that with triple therapy and ATG- or ALG-based regimens. However, the risk of infection and also the observed increase in lymphoproliferative disorders appears to be related to the degree of immunosuppression rather than to the drug itself Thus, sequential muromonab CD3-based therapy is more effective than standard triple therapy (in renal and hepatic transplant recipients) and appears to be similar to that of polyclonal-based regimens in the prophylaxis of transplant rejection. Although the routine use of prophylactic muromonab CD3 in low-risk patients with primary graft function does not appear to be justified, prophylactic muromonab CD3-based therapy has a role in patients at high risk of rejection.

Aerosolized Pentamidine as Alternative Primary Prophylaxis Against Pneumocystis carinii Pneumonia in Adult Hepatic and Renal Transplant Recipients

To examine the safety and efficacy of aerosolized pentamidine (AP) as alternative primary prophylaxis against Pneumocystis carinii pneumonia (PCP) in adult liver and kidney transplant recipients. Retrospective review of medical records. Tertiary care urban teaching hospital with active liver and kidney transplant programs. Adult liver and kidney transplant recipients intolerant of trimethoprim-sulfamethoxazole (TMP-SMX) therapy and referred to the AP clinic between June 1991 and December 1994. Each patient received monthly AP, 300 mg, delivered by a nebulizer (Respirgard-II), preceded by inhaled albuterol, 180 micrograms. During the period of follow-up, information related to side effects of AP and incidence of PCP was recorded. A total of 35 patients were identified, 18 liver and 17 kidney transplant recipients. Fourteen patients received AP as initial prophylaxis because of prior sensitivity to TMP-SMX. In another 19 patients, initial TMP-SMX therapy was discontinued for leukopenia (5), elevated liver function test values (4), rash (3), nausea (2), renal failure (2), seizure (2), and thrombocytopenia (1). In addition, two patients received AP in the setting of organ rejection. Liver transplant recipients received AP for an average of 4.28 +/- 1.6 months, and renal transplant recipients received AP for an average of 5.71 +/- 4.3 months. Adverse effects of AP included bronchospasm (two), dyspnea (one), cough (one), and nausea (one). AP therapy was discontinued in only one patient due to severe bronchospasm. There were no cases of PCP in the 35 patients receiving AP. These observations suggest that AP is well tolerated and may be an effective alternative for PCP prophylaxis in adult liver and kidney transplant recipients intolerant to TMP-SMX therapy.

Oxygen radical formation due to the effect of varying hydrogen ion concentrations on cytochrome P450-catalyzed cyclosporine metabolism in rat and human liver microsomes.

Cyclosporin A (CyA) is a hydrophobic cyclic undecapeptide whose potent immunosuppressive effects have resulted in its widespread usage for suppressive allograft rejection. However, its metabolism by the cytochrome P450 mixed-function oxidase (MFO) system frequently results in hepatotoxicity as seen by jaundice and altered serum enzyme in hepatic transplant recipients, hyperbilirubinemia, hypoproteinemia, and albuminemia in rats (Whiting et al., 1983). In previous experiments, the sources of the hepatotoxicity associated with CyA metabolism was implicated as being oxygen radicals (Ahmed et al., 1993). Xenobiotics, like CyA or FK-506, lead to the production of free radicals by a redox cycle involving one-electron reductions by oxidoreductase that reduce molecular oxygen to superoxide. Not only can superoxide result in the observed toxicity, but it may, in the presence of transition metals such as iron, generate reactive hydroxy radicals by the Haber-Weiss or the Fenton reaction. Oxidoreductase is a vital element of the cytochrome P450 system which catalyzes the biotransformation of xenobiotics by either oxidation or reduction. Oxidoreductase usually transfers two reducing equivalents from NADPH to the cytochrome P450-substrate complex resulting in substrate oxidation and subsequent product release. This reductase-mediated transfer of electrons is characterized as an electron flux. Certain investigators have measured metabolite ratios of different substrates at varying pH (Grogan et al., 1993 and Hille et al., 1981) and have reported differences in the electron transfer from oxidoreductase to cytochrome P450. These results have prompted us to investigate the possible role of pH in either uncoupling the electron-flux at the level of oxidoreductase and P450 or that of P450 and CyA with the generation of hydroxy radicals as seen by lipid peroxidation.

Stellenwert der Angiographie und radiologischen Intervention vor und nach Lebertransplantation

The study demonstrates the value of angiography and radiological interventions before and after liver transplantation. From September 1988 till February 1991 84% out of 124 hepatic transplant recipients underwent pretransplant angiography evaluation for the exact demonstration of arterial and portal venous blood supply of the liver. Posttransplant angiography was performed in cases with suspected vascular complications, chronic rejection, and spleno-hepatic steal syndrome. Radiological interventions were performed for bacteriological examination and percutaneous drainage of encapsulated fluid collections.

General Principles of Perioperative Transplant Care

Along with the development of more specific and potent immunosuppressive agents, improvements in perioperative care of the allograft recipient have made transplantation of nonrenal organs a reality and contributed greatly to overall improvements in graft and patient survival. Thorough pretransplant evaluation, intensive care therapy and monitoring (when indicated), and meticulous postoperative care are essential to a successful outcome and to minimize the occurrence of complications.

An Evaluation of the Cyclosporine and Metabolites Whole Blood TDx Assay

The new Abbott TDx cyclosporine and metabolites fluorescent polarization immunoassay procedure provides a 20-min sample turn-around time, using 50 microliters of sample for the analysis of cyclosporine in whole blood. A precipitation agent and a lysing agent are utilized as a pretreatment step. The range of the whole blood assay is from 0 to 2,000 ng/ml, with a sensitivity of 50 ng/ml. Precision studies at 3 control levels provided coefficients of variation of 2.1-4.8% for both assays. In order to compare this assay with the currently used Sandoz polyclonal radioimmunoassay (RIA) method. 200 whole blood samples were obtained from 20 renal, cardiac, and hepatic transplant recipients. The mean whole blood cyclosporine concentrations for samples above the sensitivity level were as follows: TDx 754 ng/ml (+/- 31) and RIA 619 ng/ml (+/- 22). Blood TDx levels correlated strongly with RIA levels, with a regression coefficient of r = 0.915. This new assay provides reliable blood cyclosporine concentrations that correlate well with RIA measurements. This assay offers rapid sample turn-around times, making same-day results for outpatient drug monitoring possible.

An Evaluation of the Cyclosporine and Metabolites Whole Blood TDx Assay

Summary: The new Abbott TDx cyclosporine and metabolites fluorescent polarization immunoassay procedure provides a 20-min sample turn-around time, using 50 μl of sample for the analysis of cyclosporine in whole blood. A precipitation agent and a lysing agent are utilized as a pretreatment step. The range of the whole blood assay is from 0 to 2,000 ng/ml, with a sensitivity of 50 ng/ml. Precision studies at 3 control levels provided coefficients of variation of 2.1-4.8% for both assays. In order to compare this assay with the currently used Sandoz polyclonal radioimmunoassay (RIA) method, 200 whole blood samples were obtained from 20 renal, cardiac, and hepatic transplant recipients. The mean whole blood cyclosporine concentrations for samples above the sensitivity level were as follows: TDx 754 ng/ml (±31) and RIA 619 ng/ml (±22). Blood TDx levels correlated strongly with RIA levels, with a regression coefficient of r = 0.915. This new assay provides reliable blood cyclosporine concentrations that correlate well with RIA measurements. This assay offers rapid sample turn-around times, making same-day results for outpatient drug monitoring possible.

Considerations for Anesthetic Management During Veno-venous Bypass in Adult Hepatic Transplantation

Intraoperative data from 42 adult orthotopic hepatic transplant recipients were analyzed retrospectively to assess the hemodynamic, coagulation, and thermal effects of heparinless veno-venous bypass using a constrained vortex pump. Transient hemodynamic changes occurring at the onset of bypass included decreases in temperature (-10.7%), heart rate (-18.7%) and arterial pressure (-15.1%); and increases in central venous pressure (27.6%) and ECG T wave amplitude (231.6%). Abrupt decreases in cardiac output and pump flow occurred with termination of the portal limb of bypass, which is required to allow completion of the portal vein anastomosis. However, significant continuous decreases were observed in bypass flow and cardiac output during the entire bypass period. The blood volume became concentrated as indicated by increases in hematocrit, colloid osmotic pressure, serum osmolality and serum sodium. Changes in colloid osmotic pressure were inversely related to bypass flow. These data, along with an accumulating base deficit, suggest that veno-venous bypass is associated with less than optimal perfusion of the abdomen and lower extremities. Flow dependent third space fluid accumulation is most likely responsible for decreasing cardiac output and pump flow during the bypass period. No clinically significant coagulopathy could be attributed to the use of veno-venous bypass. There were no significant changes in platelet counts, fibrinogen levels or prothrombin times. The activated partial thromboplastin time decreased from 60.5 to 50.2 seconds. Patient core temperature decreased three times more rapidly (0.9 degrees C/hr) during bypass than at any other time during the procedure.

Biliary complications after liver transplantation in children.

To evaluate the role of interventional radiologic procedures in the diagnosis and treatment of biliary complications in children after liver transplantation, the authors reviewed the cases of 58 pediatric patients who underwent transplantation over a 4-year period. In 21 patients suspected of having biliary complications, 31 diagnostic percutaneous transhepatic cholangiographic studies, 19 transhepatic biliary drainages, eight pressure-flow studies, five percutaneous drainages of abdominal fluid collections, 11 balloon dilations, and one basketing procedure were performed. Biliary complications were seen in 38% of allografts, with obstruction being more common than leakage. Complications were most frequent in patients with cholecystojejunostomy reconstructions. Only two children had biliary complications that were thought to be related to arterial compromise. No significant intervention was required in 17% of complications. Percutaneous techniques were associated with a low frequency of significant complications (6%). The authors conclude that interventional radiologic techniques can be used effectively in the evaluation and management of biliary complications in pediatric hepatic transplant recipients.

SUCCESSFUL RETREATMENT OF ALLOGRAFT REJECTION WITH OKT3

OKT3 is a murine monoclonal antibody to the CD3 antigen of human T lymphocytes. The production of human antimurine antibodies after treatment with OKT3 has been perceived as a major limitation to its extended use and reuse. Treatment of 142 patients with 168 courses of OKT3 resulted in the development of antimouse antibody in 28% of the patients. Twenty-six patients (16 kidney, 6 liver, 3 heart, 1 pancreas) have been retreated with 27 courses of OKT3. Eighteen patients had no antimurine antibodies present, and the rejection reversal rate was 83% (15/18). Six patients had a low-titer antimurine antibody present, and rejection reversal occurred in 5 (83%). Rejection was not reversed in 2 patients with a high-titer antibody. Development of antimurine antibody was more frequent in renal transplant recipients (33%) than in hepatic (12%) or cardiac transplant recipients (18%). We believe that this reflects the fact that concomitant immunosuppressive therapy is more likely to be reduced during OKT3 therapy in renal transplant recipients than in hepatic or cardiac transplant recipients. Retreatment of patients with no anti-OKT3 antibody resulted in depletion of CD3+ cells from the peripheral blood, but it took longer than in patients being treated with OKT3 for the first time. Similarly, serum OKT3 levels rose more slowly in retreated patients compared to first treatment. In retreating patients with a low-titer antimurine antibody, it often was necessary to increase the dose of OKT3 in order to achieve adequate serum OKT3 levels and to deplete CD3+ cells. De novo antimurine antibody developed in 4 of the 18 (22%) antibody-negative patients who were retreated. In conclusion, retreatment with OKT3 should not be considered unless the antibody status of the patient is known. Development of low-titer antibodies does not preclude successful retreatment with OKT3; however, alternate antirejection therapy should be used in patients with high-titer antimurine responses.

Porokeratosis of mibelli in transplant recipients.

Four of 602 renal and hepatic transplant recipients had porokeratosis of Mibelli develop in the posttransplant period. Porokeratosis is an uncommon, autosomally dominant inherited disorder that presents in adolescence as a proliferation of an abnormal clone of epidermal cells. Clinically, it is characterized by nonhealing plaques that develop most commonly on the limbs. Porokeratosis, a premalignant condition, must be added to the list of potential cutaneous complications seen in immunosuppressed organ transplant recipients.