Hsin-Lin Tsai

Therapeutic Effects of Umbilical Cord Blood-Derived Mesenchymal Stem Cell Transplantation in Experimental Lupus Nephritis:

Mesenchymal stem cells (MSCs) have been shown to possess immunomodulatory properties. Systemic lupus erythematosus is an autoimmune disease that results in nephritis and subsequent destruction of renal microstructure. We investigated whether transplantation of human umbilical cord blood-derived MSCs (uMSCs) is useful in alleviating lupus nephritis in a murine model. It was found that uMSCs transplantation significantly delayed the development of proteinuria, decreased anti-dsDNA, alleviated renal injury, and prolonged the life span. There was a trend of decreasing T-helper (Th) 1 cytokines (IFN-γ, IL-2) and proinflammatory cytokines (TNF-α, IL-6, IL-12) and increasing Th2 cytokines (IL-4, IL-10). The in vitro coculture experiments showed that uMSCs only inhibited lymphocytes and splenocytes proliferation but not mesangial cells. Long-term engraftment of uMSCs in the kidney was not observed either. Together, these findings indicated that uMSCs were effective in decreasing renal inflammation and alleviating experimental lupus nephritis by inhibiting lymphocytes, inducing polarization of Th2 cytokines, and inhibition of proinflammatory cytokines production rather than direct engraftment and differentiating into renal tissue. Therapeutic effects demonstrated in this preclinical study support further exploration of the possibility to use uMSCs from mismatched donors in lupus nephritis treatment.

The epidemiology and prognostic factors of mortality in critically ill children with acute kidney injury in Taiwan

The incidence of acute kidney injury (AKI) in critically ill children varies among countries. Here we used claims data from the Taiwanese National Health Insurance program from 2006 to 2010 to investigate the epidemiological features and identify factors that predispose individuals to developing AKI and mortality in critically ill children with AKI. Of 60,338 children in this nationwide cohort, AKI was identified in 850, yielding an average incidence rate of 1.4%. Significant independent risk factors for AKI were the use of extracorporeal membrane oxygenation, mechanical ventilation or vasopressors, intrinsic renal diseases, sepsis, and age more than 1 year. Overall, of the AKI cases, 46.5% were due to sepsis, 36.1% underwent renal replacement therapy, and the mortality rate was 44.2%. Multivariate analysis showed that the use of vasopressors, mechanical ventilation, and hemato-oncological disorders were independent predictors of mortality in AKI patients. Thirty-two of the 474 patients who survived had progression to chronic kidney disease or end-stage renal disease. Thus, although not common, AKI in critically ill children still has a high mortality rate associated with a variety of factors. Long-term close follow-up to prevent progressive chronic kidney disease in survivors of critical illnesses with AKI is mandatory.

A longitudinal cohort study of incidence rates of inguinal hernia repair in 0- to 6-year-old children.

BACKGROUND/PURPOSE This study provides epidemiologic data on the incidence of inguinal hernia repair in preschool children using the Taiwan National Health Insurance Research Database. We believe that the data on hernia repair in said database provide a close approximation of the true incidence of inguinal hernia in young children. METHOD A cohort of 1,073,891 deidentified individuals was randomly selected from an insured population of 23 million. Subjects born during the period 1997-2004 were followed from birth to 6 years. The chi-square test and logistic regression modeling were used for statistical analyses. RESULT A total of 92,308 individuals were born during the study period. Of these individuals, 3881 underwent hernia repairs. The cumulative incidence of hernia repair in children aged 0 to 6 years was 4.20%/7 years. The boy/girl ratio was 4.27:1 and the unilateral/bilateral ratio was 3.77:1. The incidence of hernia repair among boys was highest during the first year of life, but then decreased with age. In contrast, the incidence among girls remained stable during the first 6 years of life. Boys younger than 1 year had more bilateral repairs than boys in other age groups (p<0.0001) and girls had significantly more bilateral repairs than boys (p<0.0001). Subjects with a history of preterm birth also had a higher incidence of hernia repair than subjects who were born at full term (odds ratio=2.34, p<0.0001). CONCLUSION Yearly incidence of hernia repair was obtained from a nationwide database. Some of the observations have not been reported elsewhere.

Conditioned mesenchymal stem cells attenuate progression of chronic kidney disease through inhibition of epithelial-to-mesenchymal transition and immune modulation

Mesenchymal stem cells (MSCs) have been shown to improve the outcome of acute renal injury models; but whether MSCs can delay renal failure in chronic kidney disease (CKD) remains unclear. In the present study, the were cultured in media containing various concentrations of basic fibroblast growth factor, epidermal growth factor and ascorbic acid 2‐phosphate to investigate whether hepatocyte growth factor (HGF) secretion could be increased by the stimulation of these growth factors. Then, TGF‐β1‐treated renal interstitial fibroblast (NRK‐49F), renal proximal tubular cells (NRK‐52E) and podocytes were co‐cultured with conditioned MSCs in the absence or presence of ascorbic acid 2‐phosphate to quantify the protective effects of conditioned MSCs on renal cells. Moreover, male Sprague‐Dawley rats were treated with 1 × 106 conditioned MSCs immediately after 5/6 nephrectomy and every other week through the tail vein for 14 weeks. It was found that basic fibroblast growth factor, epidermal growth factor and ascorbic acid 2‐phosphate promoted HGF secretion in MSCs. Besides, conditioned MSCs were found to be protective against TGF‐β1 induced epithelial‐to‐mesenchymal transition of NRK‐52E and activation of NRK‐49F cells. Furthermore, conditioned MSCs protected podocytes from TGF‐β1‐induced loss of synaptopodin, fibronectin induction, cell death and apoptosis. Rats transplanted with conditioned human MSCs had a significantly increase in creatinine clearance rate, decrease in glomerulosclerosis, interstitial fibrosis and increase in CD4+CD25+Foxp3+ regulatory T cells counts in splenocytes. Together, our studies indicated that conditioned MSCs preserve renal function by their anti‐fibrotic and anti‐inflammatory effects. Transplantation of conditioned MSCs may be useful in treating CKD.

Domino liver graft from a patient with homozygous familial hypercholesterolemia.

Liu C, Niu D‐M, Loong C‐C, Hsia C‐Y, Tsou M‐Y, Tsai H‐L, Wei C. Domino liver graft from a patient with homozygous familial hypercholesterolemia.
Pediatr Transplantation 2010: 14:E30–E33.

Venoplasty of hepatic venous outflow with a venous patch in domino liver transplantation.

The domino donor (DD) was a 16-year-old boy with homozygous familial hypercholesterolemia. He received a whole liver graft from a 9-year-old deceased donor. We designed the hepatic outflow to be reconstructed by side-to-side cavocaval anastomosis for the first liver transplantation, so the DD hepatectomy was performed with preservation of the inferior vena cava (IVC) and the stumps of 3 hepatic veins were preserved as long as possible.

Surgical treatment of chylothorax caused by cardiothoracic surgery in children

Four pediatric cases of chylothorax after cardiothoracic surgery, which were managed surgically, are reviewed retrospectively. All patients underwent right thoracotomy and mass ligation of the right thoracic duct without detecting the true site of leakage. Although 1 patient died from heart failure the day after operation, the other 3 recovered quickly without sequelae. Based on our limited experience, we suggest that right thoracotomy with mass ligation of the right thoracic duct can successfully cure chylothorax on either side, particularly if identification of the site of leakage is considered too risky because of severe adhesion from previous cardiothoracic surgery.

OUTCOME AND RISK FACTORS FOR MORTALITY IN PEDIATRIC PERITONEAL DIALYSIS

♦ Background: The mortality rate among children requiring renal replacement therapy is higher than in children without end-stage renal disease (ESRD). Some factors, such as hypoalbuminemia, high peritoneal transport rate, age, malnutrition, cardiovascular disease, and recurrent peritonitis, appear to be associated with lower survival in adult peritoneal dialysis patients. Data regarding risk factors of mortality in children with continuous ambulatory peritoneal dialysis (CAPD) are limited. The aims of this study were to analyze the clinical characteristics of patients and investigate if routinely used laboratory and clinical variables are independent risk factors for mortality in children on CAPD. ♦ Methods: We performed a retrospective chart analysis of pediatric ESRD patients on CAPD between January 1997 and September 2008. 29 patients undergoing CAPD for more than 3 months were enrolled. An analysis was performed on clinical and biochemical variables for survivors and nonsurvivors to identify potential risk factors for mortality. ♦ Results: Mean age was 12.18 ± 4.57 years. During the follow-up period, 8 patients transferred to hemodialysis and 13 patients received deceased donor renal transplantation. By the end of the study, 5 patients had died. Actuarial survival rate at 2 and 5 years was 96.55% and 91.19% respectively. The major complication during therapy was peritonitis (1 episode/57.79 patient-months). In the univariate analysis, younger age at initiation of dialysis, presence of comorbid disease, higher peritoneal transport rate, increased protein losses through peritoneal dialysis, high total daily protein loss, hypoalbuminemia, and hypophosphatemia were variables associated with mortality in pediatric CAPD patients. However, in the multivariate analysis, only low serum albumin (b = –2.089, p = 0.006; hazard ratio 8.06, 95% confidence interval 0.028 – 0.546) was independently associated with mortality. ♦ Conclusion: Mortality was low in our pediatric patients receiving CAPD. Hypoalbuminemia showed a significant association with death in CAPD patients.

Epidemiology and Predictors of End-stage Renal Disease in Taiwanese Children With Idiopathic Nephrotic Syndrome

Background The incidence of idiopathic nephrotic syndrome (INS) varies among countries, with Asia reporting a higher incidence in comparison with Western countries. We investigated the epidemiologic features of INS and attempted to identify factors that predispose individuals to develop end-stage renal disease (ESRD). Methods Claims data from the Taiwanese National Health Insurance program from 1996 to 2008 were used to investigate the epidemiologic features and clinical variables of INS (International Classification of Diseases, Ninth Revision, Clinical Modification code, 581) in children younger than 18 years. Results We enrolled 4083 children (male-female ratio, 1.91:1). During the 13 years of observation, annual incidence decreased from 9.91 to 3.36 per 100 000 children. Annual number of hospital admissions progressively decreased during the first 3 years after diagnosis. At 3.14 ± 2.77 years after INS onset, ESRD had developed in 145 (3.6%) children. Independent predictors of ESRD included older age at onset, acute renal failure (ARF), hypertensive encephalopathy, and a histologic subtype with focal segmental glomerulosclerosis (FSGS). Conclusions Pediatric INS in Taiwan was more frequent in boys. Unlike India, the current incidence of pediatric INS in Taiwan is very similar to that reported in Western studies. Older age at disease onset, ARF, hypertensive encephalopathy, and FSGS on biopsy are important predictors of poor renal outcome.

Renal Cell Carcinoma in Children and Young Adults

Renal cell carcinoma (RCC) is a relatively uncommon tumor in childhood. Its biologic behavior and prognostic factors have rarely been documented. We report treatment and survival of 4 children (aged 8, 9, 11, and 14 years) who had RCC, along with a review of the literature to analyze the frequency of major symptoms, clinical stage, and prognostic factors based on 130 published cases of RCC in individuals younger than 20 years of age. Two of our cases had renal tumors detected by ultrasound screening, and all 4 cases were followed for a considerable length of time and were alive and free of disease after treatment. An analysis of these 130 published cases of pediatric RCC showed tumor staging and cell type to be the factors that affected patient survival. Tumors composed of granular cells or mixed cells, or at advanced stages, had a poor prognosis. Age, sex, tumor size, symptom duration, and cellular pattern were not related to patient prognosis. Children older than 10 years of age, who have an abdominal mass, flank pain, and/or hematuria should alert clinicians to consider the possibility of RCC. The importance of early diagnosis of renal tumors, using ultrasound as a tool of screening, is emphasized, since surgical treatment leads to a favorable prognosis only in the early stage of RCC.