Okechukwu N. Ojogho

Nephrogenic fibrosing dermopathy after liver transplantation successfully treated with plasmapheresis

Nephrogenic fibrosing dermopathy (NFD) is a recently described cutaneous fibrosing disorder associated with renal dysfunction. It appears similar to scleromyxedema but with some notable exceptions, including the lack of involvement of the face and absence of plasma cells on histology, systemic involvement, and paraproteinemia. Patients can present with thickened or edematous skin with indurated papules and plaques involving the extremities and the trunk. We report the first three cases of NFD after liver transplantation successfully treated with plasmapheresis. Two patients underwent liver transplantation for hepatitis C virus–induced cirrhosis and one for hepatitis B virus–induced cirrhosis. All the patients had encephalopathy, refractory ascites, and malnutrition prior to transplantation. Like those patients with NFD, all three of our patients had renal dysfunction and required hemodialysis before and after transplantation. Two were not dependent on dialysis at the time of diagnosis, however. These patients had excellent liver allograft function, but the other patient had allograft failure secondary to recurrent hepatitis C. Immunosuppression therapy consisted of basiliximab, mycophenolate mofetil, calcineurin inhibitor, and prednisone. The patients developed “woody” skin induration of the distal extremities, erythematous papules, and contractures at 1, 2, and 120 months after transplantation. Skin biopsies resembled NFD. No paraproteinemia was evident. One to three 5-day courses of plasmapheresis resulted in moderate to marked clinical improvement. The improvement of the kidney function in two of our patients did not appear to correlate with that of the skin disorder, because the kidney function was improving at the time the diagnosis of NFD was made. In conclusion, we report the first three cases of NFD after liver transplantation. Plasmapheresis was moderately successful in resolving the skin-indurated papules, severe skin induration, and associated joint contractures. Preliminary studies (unpublished data) show that decreasing plasma levels of transforming growth factor-&bgr;1 after plasmapheresis appear to correlate with the amelioration of this clinical condition.

Posttransplant lymphoproliferative disorders and gastrointestinal manifestations of Epstein-Barr virus infection in children following liver transplantation

BACKGROUND Epstein-Barr virus (EBV) infection is common after liver transplantation in children and is associated with the risk of posttransplant lymphoproliferative disorders (PTLD). METHODS This retrospective study examined the frequency of gastrointestinal (GI) symptoms and the risk of PTLD in pediatric liver recipients who developed symptomatic EBV infection. We reviewed 172 children who received orthotopic liver transplants between March 1988 to December 1994. Twenty-two cases were retransplants. The mean age at transplantation was 3.7 years (range, 0.1-17 years). The immunosuppressive regimens consisted of induction therapy with Minnesota antilymphocyte globulin/antithymocyte globulin/OKT3 in most cases and maintenance therapy with prednisone and either cyclosporine or tacrolimus (FK506). RESULTS After 1 year of minimum follow-up, 54 of 172 patients had symptomatic EBV infections (confirmed by serology, histology, or whole blood polymerase chain reaction. At the time of infection, 38.5% (21/54) had either diarrhea or GI bleeding or both. PTLD developed in 11 patients (6.4%). The incidence of PTLD was 42.9% (9/21) when GI bleeding or diarrhea was associated with EBV infections, compared with 6.1% (2/33) when EBV infection was not associated with GI symptoms. Seven of 10 (70%) patients with GI bleeding and 2 of 11 (18.2%) with diarrhea developed PTLD. Of seven patients examined by endoscopy for GI bleeding, two had biopsy-proven PTLD of the GI tract, whereas one of two patients examined by endoscopy for diarrhea had biopsy-proven PTLD. DISCUSSION In summary, a high incidence of PTLD was found in patients who developed GI bleeding or diarrhea associated with EBV infection after pediatric liver transplantation. In these patients, endoscopy and biopsy may lead to early diagnosis of PTLD.

Monitoring peripheral blood CD4+ adenosine triphosphate activity in a liver transplant cohort: Insight into the interplay between hepatitis C virus infection and cellular immunity

Peripheral blood CD4+ adenosine triphosphate [ATP (ng/mL)] release [ImmuKnow Immune Cell Function Assay (ATP)] correlates to immunoreactivity. We hypothesized that ATP levels could provide insight into hepatitis C virus (HCV) infection and recurrent liver disease in liver transplantation (LT). We studied our centers LT cohort, in which ATP levels had been measured off protocol from February 2005 through July 2006. Of the 280 LTs performed since 1993, 114 (58.2%) fit the selection criteria, with a mean age of 49 ± 10 years. LT (alone/combination) indications included HCV (58%), alcoholic liver disease (41%), hepatocellular carcinoma (16%), and other (33%). Four hundred seventy‐seven ATP levels were obtained: 3 (1‐17) per patient 25 months (4 days to 19 years) from the time from transplantation. Final diagnoses were normal allograft function (n = 166, 35%), recurrent disease (n = 199, 42%), septic event (n = 34, 7%), other (n = 51, 11%), and undetermined (n = 27, 6%). Two hundred eighty‐one ATP levels were obtained [3 (1‐18) per patient] in 66 HCV(+) patients. Forty‐five (68%) developed biopsy‐proven recurrent liver disease [188/281 (67%) ATP levels]. The median ATP level (ng/mL) was 162 (1‐761); it was lower in HCV(+) patients (151 ± 109) versus HCV(−) patients (211 ± 139; P < 0.0001). ATP ranges in HCV(+) patients were stable from the time from transplantation. In HCV(−) patients, ATP ranges were initially high and eventually decreased to HCV(+) levels (P = 0.01). Immunosuppressant levels were low in 62% of HCV(−) patients versus 38% of HCV(+) patients (P = 0.04). In HCV(+) patients, ATP was lower in disease recurrence (139 ± 97) versus none (181 ± 141; P = 0.01) with similar immunosuppression, and ATP decreased with grade (P = 0.05) but not stage. Time from transplantation, aspartate aminotransferase/alanine aminotransferase >1, and low ATP were independently associated with recurrent HCV. In conclusion, after LT, global cellular immune function appears depressed at baseline in HCV(+) patients versus HCV(−) patients and more so in HCV(+) recurrent disease. Liver Transpl 14:1313–1322, 2008.

Control of the renal artery and vein with the nonabsorbable polymer ligating clip in hand-assisted laparoscopic donor nephrectomy.

Background. The large and variable size of the renal vein has prompted most surgeons to select linear stapling devices to secure the vein during laparoscopic donor nephrectomy. Although effective, these stapling devices have a potential for misfire. Use of the nonabsorbable polymer ligating (NPL) clip during laparoscopic donor nephrectomy provides increased graft vessel length compared with the stapling device, and the NPL clip has a locking mechanism which may increase security compared with standard titanium clips. The objective of this study was to evaluate the safety and efficacy of the NPL clip for control of the renal artery and vein during hand-assisted laparoscopic donor nephrectomy (HALDN). Methods. A retrospective chart review of 50 consecutive HALDN patients was conducted where two parallel NPL clips were used to control both the renal artery and vein. Information collected included demographic data, operative and postoperative data, and complications. Results. Mean donor age was 33.4 years and body mass index was 25.8 kg/m2. Mean operative time was 266.0 min, mean hospital stay was 3.2 days, and mean warm ischemia time was 123.3 seconds. There were no transfusions, open conversions, or complications related to use of the NPL clip. A

Mycophenolate mofetil in pediatric renal transplantation: non-induction vs. induction with basiliximab.

16,300 disposable cost savings was seen during this 1-year period alone. Conclusions. The NPL clip was 100% safe and effective in controlling the renal artery and vein during HALDN, allowed for additional vessel length, and resulted in a disposable cost savings of

Increased plasma nitric oxide, L-arginine, and arginase-1 in cirrhotic patients with progressive renal dysfunction

362 per patient.

Comparison of outcomes with low-dose anti-thymocyte globulin, basiliximab or no induction therapy in pediatric kidney transplant recipients: a retrospective study.

Abstract:  North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) reports have shown anti‐T cell antibody, OKT3, to be deleterious in pediatric renal transplant recipients treated with mycophenolate mofetil (MMF). Unlike OKT3, basiliximab is a chimeric monoclonal antibody to the alpha subunit of the interleukin‐2 receptor on activated T‐lymphocytes. We sought to examine the outcome of MMF with or without basiliximab induction therapy in pediatric renal transplantation. Between January 1998, and June 2001, 49 pediatric renal transplants were performed at our center and 41 met the criteria for this study. We retrospectively analyzed the records of 25 patients who received MMF, Prednisone, CSA or TAC, alone (group I) and 16 patients who received MMF, CSA or TAC, and Prednisone in combination with basiliximab (group II). The two groups were similar with respect to recipient or donor age, gender, ethnicity, donor source (LD vs. CAD), cold ischemia time, and primary diagnosis. The basiliximab group had a shorter follow up period because of its more recent addition to our pediatric immunosuppression protocol, 12.9 ± 5.9 months vs. 35.5 ± 7.2 months for group I (p < 0.0001). At 6 months, the acute rejection rate was 16% (group I) compared with 25% (group II) (p = 0.689). The patient and graft survival at 6 and 12 months were 100% respectively for both groups. Basiliximab was well tolerated without significant adverse events. At 6 months, there was no significant difference between the groups in the incidence of urinary tract infection or cytomegalovirus infection. These data suggest that in the short‐term, MMF with or without basiliximab induction therapy appears to yield excellent and statistically similar outcomes. However, further controlled studies are necessary to verify these findings as well as to define the role of basiliximab in MMF‐treated pediatric renal transplant recipients.

The impact of intercurrent EBV infection on ATP levels in CD4+ T cells of pediatric kidney transplant recipients

Background and Aims:  Increased levels of nitric oxide (NO) are hypothesized to contribute to renal dysfunction in patients with decompensated cirrhosis. In this study, we examined whether splanchnic and/or peripheral NO levels and L‐arginine (L‐Arg) correlate with progressive renal dysfunction in cirrhotics.

Billing for outpatient transplant pharmacy services.

Abstract: It is unclear which induction therapy yields the best outcomes in pediatric kidney transplantation. Retrospective data of 88 children receiving a renal allograft between November 1996 and October 2003 were analyzed. Patients received ATGI (n = 12), BI (n = 29), or NAI (n = 47). The mean ATG dose was 5.1 ± 2.1 mg/kg. At 12 months, graft survival rates were 91.7%, 100%, and 97.9% for ATGI, BI, and NAI groups, respectively. Acute rejection rates at 12 months were 0 (ATGI), 20.6% (BI), and 10.7% (NAI). The mean GFR for ATGI (42.4 ± 25.9 mL/min) was lower than for BI (78.3 ± 27.2 mL/min), and NAI (66 ± 28.3 mL/min) at 12 months (p < 0.05). One ATGI patient developed CMV pneumonia but none developed post‐transplant lymphoproliferative disorder. Although there was no renal allograft survival benefit with either ATGI or BI, relative to NAI, the absence of acute rejection and equivalent rates of viral infections in the higher‐risk ATGI recipient group suggests that the treatment strategy is promising. A large prospective study is needed to better define the role of ATGI in pediatric kidney transplantation.

Mycophenolate mofetil without antibody induction in cadaver vs. living donor pediatric renal transplantation.

Abstract:  ImmuKnow® measures ATP (ng/mL) in PHA‐activated CD4+ T cells from patient’s whole blood. According to published reports, median ImmuKnow® is 258 ng/mL in stable pediatric kidney transplant (PKT) recipients ≥12 yr, and 165 ng/mL in those <12 yr. However, data on the effect of infection or AR on ImmuKnow® are scarce. We studied the effect of Epstein‐Barr virus (EBV) viremia on ImmuKnow® in PKT with GD. Twenty‐eight PKT with GD were reviewed. Group 1 has 19 PKT ≥12 yr, and group 2 has nine PKT <12 yr. Mean follow‐up was 19.4 ± 12 months. All ImmuKnow® values discussed in this study were measured during GD ± fever. None had ImmuKnow® pretransplant. EBV DNA was isolated from patient blood by real‐time PCR. Group 1 has eight boys and 11 girls (mean age = 16.6 ± 2.4 yr). Group 2 has two boys and seven girls (mean age = 6 ± 3.1 yr). Median ImmuKnow® was 292 ng/mL in group 1, and 370 ng/mL in group 2. Nine children developed EBV viremia: two in group1 (median ImmuKnow® = 273 ng/mL), and seven in group 2 (median ImmuKnow® = 475 ng/mL). Overall mean ImmuKnow® in the nine EBV viremic patients was higher than that in the 19 non‐viremic ones (422 ± 176 ng/mL, and 302 ± 113 ng/mL, respectively, unequal variance t‐test, p = 0.08). Eight children developed AR (all in G1, median ImmuKnow® = 272 ng/mL). In group 1, one patient developed concurrent EBV viremia and rejection, while another patient developed EBV viremia six months following a rejection episode. In group 2, none developed simultaneous AR, CMV, or BK virus infection with EBV viremia. None developed post‐transplant lymphoproliferative disease. In summary, EBV viremia was paradoxically associated with high ImmuKnow® in PKT <12 yr. This suggests strong co‐stimulation of PHA‐activated CD4+ T cells by EBV‐transformed B cells.