Dong Jin Joo

Predictors of Kidney Volume Change and Delayed Kidney Function Recovery After Donor Nephrectomy

PURPOSE To our knowledge the effects of preoperative kidney volume in living donors on the post-donation change in size and function of the remaining kidney have not been investigated. We studied the association between preoperative kidney volume, and volume change and delayed kidney function recovery in donors. MATERIALS AND METHODS From 2007 to 2008 we investigated 222 living donors. Kidney volume before and 6 months after surgery was estimated using the voxel count method. We analyzed correlations of kidney volume with patient characteristics, kidney function and actual kidney weight. To identify predictors of the volume increase of the remaining kidney and predictors of delayed kidney function recovery we performed regression analysis. RESULTS Mean +/- SD total kidney volume was 311.9 +/- 50.6 cc and it correlated with weight, body surface area and kidney function (p <0.001). The mean volume increase in the remaining kidney was 27.6% +/- 9.7% (range 4.5% to 66.1%). Younger age (p <0.001) and lower preoperative volume of the remaining kidney (p = 0.019) were significant predictors of a greater increase in kidney volume on multiple linear regression analysis. Older age (OR 1.07, p <0.001), higher body mass index (OR 1.20, p = 0.008), lower preoperative kidney volume of the remaining kidney (OR 0.98, p = 0.003) and a lower preoperative diethylenetetramine pentaacetic acid glomerular filtration rate in the remaining kidney (OR 0.95, p = 0.017) were significant predictors of delayed kidney function recovery on multiple regression analysis. CONCLUSIONS Kidney volume measured by the voxel count method was accurate and correlated with kidney function. Preoperative kidney volume is an independent predictor of the volume increase and delayed kidney function recovery in donors that could be used clinically.

Role of surgical resection for multiple hepatocellular carcinomas

AIM To clarify the role of surgical resection for multiple hepatocellular carcinomas (HCCs) compared to transarterial chemoembolization (TACE) and liver transplantation (LT). METHODS Among the HCC patients who were managed at Yonsei University Health System between January 2003 and December 2008, 160 patients who met the following criteria were retrospectively enrolled: (1) two or three radiologically diagnosed HCCs; (2) no radiologic vascular invasion; (3) Child-Pugh class A; (4) main tumor smaller than 5 cm in diameter; and (5) platelet count greater than 50 000/mm(3). Long-term outcomes were compared among the following three treatment modalities: surgical resection or combined radiofrequency ablation (RFA) (n = 36), TACE (n = 107), and LT (n = 17). The survival curves were computed using the Kaplan-Meier method and compared with a log-rank test. To identify the patients who gained a survival benefit from surgical resection, we also investigated prognostic factors for survival following surgical resection. Multivariate analyses of the prognostic factors for survival were performed using the Cox proportional hazard model. RESULTS The overall survival (OS) rate was significantly higher in the surgical resection group than in the TACE group (48.1% vs 28.9% at 5 years, P < 0.005). LT had the best OS rate, which was better than that of the surgical resection group, although the difference was not statistically significant (80.2% vs 48.1% at 5 years, P = 0.447). The disease-free survival rates were also significantly higher in the LT group than in the surgical resection group (88.2% vs 11.2% at 5 years, P < 0.001). Liver cirrhosis was the only significant prognostic factor for poor OS after surgical resection. Clinical liver cirrhosis rates were 55.6% (20/36) in the resection group and 93.5% (100/107) in the TACE group. There were 19 major and 17 minor resections. En bloc resection was performed in 23 patients, multi-site resection was performed in 5 patients, and combined resection with RFA was performed in 8 patients. In the TACE group, only 34 patients (31.8%) were recorded as having complete remission after primary TACE. Seventy-two patients (67.3%) were retreated with repeated TACE combined with other therapies. In patients who underwent surgical resection, the 16 patients who did not have cirrhosis had higher 5-year OS and disease-free survival rates than the 20 patients who had cirrhosis (80.8% vs 25.5% 5-year OS rate, P = 0.006; 22.2% vs 0% 5-year disease-free survival rate, P = 0.048). Surgical resection in the 20 patients who had cirrhosis did not provide any survival benefit when compared with TACE (25.5% vs 24.7% 5-year OS rate, P = 0.225). Twenty-nine of the 36 patients who underwent surgical resection experienced recurrence. Of the patients with cirrhosis, 80% (16/20) were within the Milan criteria at the time of recurrence after resection. CONCLUSION Among patients with two or three HCCs, no radiologic vascular invasion, and tumor diameters ≤ 5 cm, surgical resection is recommended only in those without cirrhosis.

Invasive pulmonary aspergillosis after solid organ transplantation: diagnosis and treatment based on 28 years of transplantation experience.

Invasive pulmonary aspergillosis (IPA) is a serious and lethal complication among organ transplant recipients. This report described the clinical manifestations and treatment of IPA over a 28-year period. From January 1979 to December 2007, 3215 organ transplant patients (2954 kidney and 261 liver recipients) were enrolled in the study. Nine patients developed IPA (7 kidney and 2 liver recipients), yielding an incidence of 0.003% (9/3215). Five IPA patients (55.6%) were diagnosed by transbronchial lung biopsy or autopsy, and 3 (33.3%) by sputum culture study. One patient was diagnosed through clinical manifestations and observations of IPA characteristics on chest X ray. We used amphotericin B (n = 4; 44.4%), voriconazole (n = 2; 22.2%), or fluconazole (n = 1; 11.1%) as the primary antifungal agents, but 2 patients could not receive antifungal agents due to rapid disease progression and sequential mortality. This study showed a high mortality rate among IPA patients (55.6%; 5/9). Only patients who received early antifungal agent thereby after a prompt diagnosis recovered from IPA. This survival advantage warrants careful monitoring for invasive fungal infections after organ transplantation with immediate administration of antifungal agents or surgical intervention.

Sirolimus-Induced Pneumonitis After Renal Transplantation: A Single-Center Experience

PURPOSE Sirolimus is a potent immunosuppressive agent used with increasing frequency in kidney transplantation. However, sirolimus can increase the rate of unexplained interstitial pneumonitis. The aim of this study was to evaluate the clinical characteristics of sirolimus-induced pneumonitis and the therapeutic results in renal transplant recipients. PATIENTS AND METHODS Seventy-two patients received sirolimus, conversion or de novo regimen, at our center between January 2007 and April 2011. Twelve of the 72 patients (16.7%) developed interstitial pneumonitis. The patients were divided into three groups according to the following indications of sirolimus use: de novo, early conversion, and late conversion groups. RESULTS The mean duration of follow-up was 11.0 ± 11.5 months. The mean blood level of sirolimus measured by microparticulate enzyme immunoassay was 16.5 ± 7.4 ng/mL at the time of diagnosis. The mean time from the start of sirolimus to pneumonitis onset was 14.7 ± 8.0 months. The clinical presentation included fever, cough, dyspnea, general weakness, and periorbital edema. In most cases, radiological imaging tests revealed bilateral lower-lobe involvement. Bronchoalveolar lavage was performed in three patients and two patients showed lymphocytic alveolitis. Sirolimus was discontinued or reduced for the treatment of pneumonitis. All cases of pneumonitis were resolved within 2 to 4 weeks. CONCLUSION Sirolimus blood level should be monitored tightly and early intervention is important when sirolimus-induced pneumonitis is suspected.

Clinical Assessment of Renal Function Stabilization After Living Donor Nephrectomy

BACKGROUND Few studies have evaluated the long-term effects of kidney donation on the donors themselves. This study investigated postoperative renal function stabilization in kidney donors after living-donor transplantation to determine the optimal follow-up period. METHODS Between March 2006 and July 2010, 203 patients in our hospital underwent live donor nephrectomy. Renal function recovery patterns were analyzed by calculating the postoperative rate of change of their Modification of Diet in Renal Disease study equation estimating glomerular filtration rate (MDRD-GFR) versus their preoperative level (%MDRD). We divided normal (n = 121) versus chronic kidney disease subjects (CKD; MDRD-GFR < 60 mL/min/1.73 m(2) at 6 months postoperatively, n = 82) for 1 year follow-up to compare time to renal function stabilization using the repeated measured data method. RESULTS When all donors were considered together at 1 month after transplantation, MDRD-GFRs were significantly increased compared with earlier follow-up times (for postoperative days 1, 4, and 7), P values were < .001, .006, and .002, respectively). Among all donors, there was no significant difference between MDRD-GFRs at 1 versus 3, 6, and 12 months posttransplantation (P < .05 in all three comparisons), indicating renal function stabilization. Importantly the %MDRD was significantly higher among the normal than the CKD group at postoperative months 1, 3, and 6 (P < .05 for all comparisons), although after 12 months there was no significant difference between the groups (69.06 ± 9.28% versus 70.14 ± 8.38%, P = .442). CONCLUSION After live donor kidney transplantation, renal function began to stabilize at 1 month postoperatively. Poor renal functional recovery and CKD later were predicted by inferior stabilization at 1 month postnephrectomy. These data suggested that even patients with normal GFRs should be followed beyond 1 year postoperatively to determine their ultimate renal functional outcomes.

Chronologically different incidences of post‐transplant malignancies in renal transplant recipients: single center experience

The incidence of malignancy in transplant recipients is known to be higher than the same in the general population. However, the types of malignancies vary geographically, and the relative risks (RR) for malignancy in transplant recipients, compared with that of the general population, also differ country‐by‐country. In this study, we investigated the incidence and characteristics of malignancies after renal transplantation in a single center. A total of 2630 renal recipients who underwent surgery between April 1979 and June 2007 were enrolled in this study. The cumulative and interval incidences of malignancies were calculated for every 3 years post‐transplantation. One‐hundred ninety cases of postrenal transplant malignancies among 177 recipients (6.73%) were reported until 2007. The post‐transplant malignancies were detected from 6 to 290 months after transplantation, with a mean duration of 112.6 ± 66.0 months. Skin cancer [35 (18.4%)] was the most common post‐transplant malignancy, followed by thyroid [25 (13.2%)], stomach [22 (11.6%)], colorectal [22 (11.6%)], and urologic cancers [19 (10.0%)]. As the post‐transplant period increased, the interval incidence of malignancy correspondingly increased. Virus‐related malignancies, such as Kaposi’s sarcoma and cervical cancer, developed earlier within the post‐transplant period, while urologic cancer, colorectal cancer developed late in the post‐transplant period. The recipient’s age at the time of transplantation was the sole independent risk factor for post‐transplant malignancy based on the multivariate analysis (RR = 2.723, P < 0.0001 in the >50‐year‐old age group). We should establish strategies for post‐transplant malignancy‐screening based on the recipient’s age at the time of transplantation, the post‐transplant interval, and the national trend of post‐transplant malignancy.

AEB-071 Versus Tacrolimus Monotherapy to Prevent Acute Cardiac Allograft Rejection in the Rat: A Preliminary Report

Inhibition of T-cell activation is the most efficient way to prevent transplant rejection. Protein kinase C (PKC) is an important signaling enzyme in the activation and regulation of T lymphocytes. AEB-071 (AEB) is a low-molecular-weight compound that blocks early T-cell activation via selective inhibition of PKC, a mechanism that differs from that of the calcineurin inhibitors. The present study sought to compare the effects of AEB versus tacrolimus (Tac) to prevent acute rejection in rats that had undergone heterotopic heart transplantation. We investigated the Brown Norway-Lewis rat strain combination for cardiac graft survival over 30 days after transplantation using varying doses of oral AEB and Tac monotherapy. Grafts were monitored by daily palpation; cessation of palpable ventricular contraction was considered to be rejection. Apart from necropsy, we performed histologic examinations of cardiac graft at 7 days after transplantation. In untreated recipients, allograft mean survival times (MST) was 6.83+/-0.41 days. AEB at 15, 30, or 60 mg/kg versus Tac at 1.2 mg/kg significantly prolonged graft survival to a MST of 12.33+/-1.21, 16.67+/-1.21, and 19.33+/-3.83, versus 17.00+/-6.90 days, respectively. Histologic assessment at 7 days after transplantation showed that high-dose AEB significantly decreased the histologic rejection score, indicative of decreased inflammatory cell infiltration into the graft. These results suggested that the administration of AEB (medium or high-dose), a PKC inhibitor, mitigated acute rejection and displayed significantly longer MST, similar to high-dose Tac after heterotopic heart transplantation in the rat.

Acoustic Radiation Force Impulse Measurement in Renal Transplantation: A Prospective, Longitudinal Study With Protocol Biopsies.

AbstractInterstitial fibrosis and tubular atrophy (IF/TA) is a common cause of kidney allograft loss. Several noninvasive techniques developed to assess tissue fibrosis are widely used to examine the liver. However, relatively few studies have investigated the use of elastographic methods to assess transplanted kidneys. The aim of this study was to explore the clinical implications of the acoustic radiation force impulse (ARFI) technique in renal transplant patients.A total of 91 patients who underwent living donor renal transplantation between September 2010 and January 2013 were included in this prospective study. Shear wave velocity (SWV) was measured by ARFI at baseline and predetermined time points (1 week and 6 and 12 months after transplantation). Protocol biopsies were performed at 12 months.Instead of reflecting IF/TA, SWVs were found to be related to time elapsed after transplantation. Mean SWV increased continuously during the first postoperative year (P < 0.001). In addition, mixed model analysis showed no correlation existed between SWV and serum creatinine (r = −0.2426, P = 0.0771). There was also no evidence of a relationship between IF/TA and serum creatinine (odds ratio [OR] = 1.220, P = 0.7648). Furthermore, SWV temporal patterns were dependent on the kidney weight to body weight ratio (KW/BW). In patients with a KW/BW <3.5 g/kg, mean SWV continuously increased for 12 months, whereas it decreased after 6 months in those with a KW/BW ≥3.5 g/kg.No significant correlation was observed between SWV and IF/TA or renal dysfunction. However, SWV was found to be related to the time after transplantation. Renal hemodynamics influenced by KW/BW might impact SWV values.

Renal transplantation in sensitized recipients with positive luminex and negative CDC (complement-dependent cytotoxicity) crossmatches.

Recently, Luminex‐crossmatch (LumXm) was introduced. The aim of this study was to evaluate clinical outcomes in sensitized recipients with a positive Luminex‐crossmatch (LumXm (+)) and a negative complement‐dependent cytotoxicity crossmatch (CDCXm (−)) after renal transplantation. Fifty‐five renal transplant recipients with a CDCXm (−) and PRA class I or II ≥20% were enrolled in this study between February 2008 and December 2010 at Severance Hospital. Eighteen patients displayed LumXm (+) defined as LumXm positive class I or II and 37 patients displayed LumXm (−). Mean duration of follow‐up was 18.9 ± 8.3 months. During this period, no patient death or graft loss occurred. The incidence of biopsy‐proven or clinically presumed rejection was higher in the LumXm (+) group (n = 12, 66.7%) than in the LumXm (−) group (n = 6, 18.2%) (P = 0.001). All biopsy‐proven acute rejections (n = 12) were diagnosed as acute cellular rejection. No significant difference in mean serum creatinine level or eGFR was observed between the groups at 18 months post‐transplantation. The short‐term outcome of renal transplantation in sensitized patients with a LumXm (+) and a CDCXm (−) may be considered to be acceptable. However, patients with a LumXm (+) have a substantially higher immunological risk for the development of acute cellular rejection.

Statin therapy is associated with the development of new‐onset diabetes after transplantation in liver recipients with high fasting plasma glucose levels

New‐onset diabetes after transplantation (NODAT) and dyslipidemia are important metabolic complications after liver transplantation (LT) that can adversely affect both allograft and patient survival. Statins are used as first‐line therapies for dyslipidemia because of their effectiveness and safety profile. However, it has recently been reported that statin therapy is associated with new‐onset diabetes in the nontransplant population. The aim of this study was to investigate the association between statin therapy and the development of NODAT in LT recipients. Three hundred sixty‐four LT recipients who underwent transplantation between the ages of 20 and 75 years without a previous history of diabetes were enrolled in this study. We evaluated the incidence of NODAT with respect to statin use as well as other risk factors. The incidence of NODAT was significantly higher in the statin group (31.7%) versus the control group (17.6%, P = 0.03). The mean follow‐up period was 37.8 ± 19.0 months for the statin group and 42.7 ± 16.0 months for the control group (P = 0.07). Statin use was significantly associated with NODAT development after adjustments for other risk factors [hazard ratio (HR) = 2.32, 95% confidence interval (CI) = 1.23‐4.39, P = 0.01]. Impaired fasting glucose before transplantation was also a risk factor for NODAT development (HR = 2.21, 95% CI = 1.36‐3.62, P = 0.001). There were no significant differences in age, body mass index, cumulative corticosteroid dose, or fasting plasma glucose (FPG) levels between the groups. Patients with high FPG levels were more likely to develop NODAT when they were placed on statins after LT (P = 0.002). In conclusion, statin treatment could contribute to the development of NODAT in LT recipients, especially if they have high baseline FPG levels. Liver Transpl 20:557–563, 2014.