Pedro W. Baron

Gadodiamide-Associated Nephrogenic Systemic Fibrosis: Why Radiologists Should Be Concerned

OBJECTIVE Nephrogenic systemic fibrosis (NSF) is a rare multisystemic fibrosing disorder that principally affects the skin but may affect other organs of patients with renal insufficiency. The purpose of our study was to identify any common risk factors and determine whether i.v. gadodiamide is associated with the development of NSF. MATERIALS AND METHODS A retrospective chart review was performed for all 12 patients diagnosed with NSF at our institution between 2000 and 2006 to identify the clinical manifestations, timing, and dose of gadodiamide administration; dialysis records; concurrent medications; comorbid conditions and surgeries; laboratory findings; imaging findings; and clinical outcome. A review of the dialysis and MR records between 2000 and 2006 showed 559 MRI examinations on 168 dialysis patients (including 301 contrast-enhanced examinations). RESULTS NSF was diagnosed by clinical findings and tissue diagnosis. All 12 patients had renal insufficiency--eight with dialysis-dependent chronic renal insufficiency and four with acute hepatorenal syndrome. All 12 patients developed skin fibrosis within 2-11 weeks after gadodiamide administration. The odds ratio for development of NSF after gadodiamide exposure was 22.3. No other common event or exposure could be found. Four patients had abnormal scintigraphic bone scans with skin and muscle uptake and lower-extremity MRI finding of edema in the muscles, intermuscular fascia, and skin. Despite the fact that 10 patients were dialyzed within 2 days of gadodiamide administration, this did not prevent the development of NSF. CONCLUSION Development of NSF was strongly associated with gadodiamide administration in the setting of either acute hepatorenal syndrome or dialysis-dependent chronic renal insufficiency.

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.

Guillain-Barre syndrome in organ and bone marrow transplant patients.

Background. Guillain-Barre Syndrome (GBS) is believed to be caused by autoimmune mechanisms that are predominantly T-cell mediated. We report GBS in organ transplant patients and bone marrow transplant patients, both of whom have iatrogenically suppressed T-cell function. Methods. We reviewed the Duke University Medical Center database from 1989–1999 for all patients who met the criteria for GBS. There were a total of 212 patients. Of these patients, two had undergone organ transplantation and two had undergone autologous bone marrow transplantation. Results. Our report supports the notion that the humoral immune system is involved in the pathogenesis of GBS. Contrary to previous reports, however, functional recovery can occur without return of T-cell function. Conclusions. This suggests that in organ transplant patients, GBS may be humorally mediated and, even more importantly, responds well to treatment.

Laparoscopic Donor Nephrectomy: Effect of Perirenal Fat upon Donor Operative Time

PURPOSE Previous attempts to correlate preoperative patient characteristics with operative complexity and operative time prior to laparoscopic donor nephrectomy have found few consistent relationships. The purpose of this study is to determine the effect of abdominal and perirenal fat measured with preoperative computerized tomography (CT) upon subsequent operative time and complexity during hand-assisted laparoscopic donor nephrectomy. MATERIALS AND METHODS A retrospective chart, database, and CT angiogram review was conducted on 103 consecutive patients who underwent a hand-assisted laparoscopic donor nephrectomy. Perirenal fat and abdominal wall fat were correlated with a variety of parameters including operative time. Univariate and multivariate regression analysis was performed and p values<0.05 were considered significant. RESULTS There was no correlation between operative time and body mass index (BMI), abdominal fat measurements, or spleno-renal distance. There was a significant positive correlation between operative time and anterior perirenal fat (r=0.28, p=0.005), posterior perirenal fat (r=0.20, p=0.05), and donor CPK levels (r=0.53, p<0.001). Men had greater perirenal fat, while women had greater abdominal fat. A multivariate model including anterior perirenal fat measurement accounted for 20% of the variance in operative time. CONCLUSION This is the first study to demonstrate that increased perirenal fat increases operative complexity as measured by operative time. This information may potentially be used to help predict operative complexity based upon measurable preoperative variables and help improve operating room efficiency and donor and recipient outcomes.

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.

Donor Smoking Negatively Affects Donor and Recipient Renal Function following Living Donor Nephrectomy.

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.