Adriamycin produces a reproducible teratogenic model of vertebral, anal, cardiovascular, tracheal, esophageal, renal, and limb anomalies in the mouse

Background/Purpose

The Adriamycin rat model is an established model for vertebral, anal, cardiac, tracheal, esophageal, renal, and limb (VACTERL) anomalies and gastrointestinal atresias. Mice are the foremost mammal studied by developmental biologists, providing greater availability of molecular probes, antibodies, and transferable knowledge with transgenic studies. Only tracheoesophageal malformations have been previously described in the Adriamycin mouse model. The aim of this study was to carry out a dose-response analysis of the teratogenicity of Adriamycin in the mouse to determine the effect of the dose and timing of exposure in producing tracheoesophageal malformations and show if it causes other VACTERL anomalies.

Methods

CBA/Ca mice were accurately time mated (n = 30). Four different doses (0 [saline], 4, 5, and 6 mg/kg) of Adriamycin (EBEWE Pharma Ges.m.b.H. Nfg.KG, A-4866 Unterach, Austria) at 3 different timings of injections were compared. Dams received 2 intraperitoneal injections, 24 hours apart, commencing on day 7, 7.5, or 8. Fetuses were harvested on day 18. Anomalies were examined using a dissecting microscope and serial transverse sections.

Results

Administering Adriamycin at 6 mg/kg on days 7 and 8 had the most teratogenic effect, with 80% of fetuses having 3 or more VACTERL anomalies: anorectal malformation, 100%; tracheoesophageal malformation, 50%; right-sided aortic arch, 58.3%; bladder agenesis/bilateral hydronephrosis, 100%.

Conclusion

This study establishes a mouse model that should provide insights into the cellular and molecular mechanisms underlying VACTERL anomalies.     

Effects of early vesicostomy in obstructive uropathy on bladder development

Purpose

Creation of a vesico-amniotic shunt for obstructive uropathy removes the normal fetal urination cycle. It is unclear how this affects bladder function at term. The authors measured the bladder volume and reviewed the bladder histology after fetal vesicostomy.

Methods

The authors created an obstructive uropathy in fetal lambs at 60 days’ gestation by ligating the urethra and urachus. Vesicostomy (female) or urethrostomy (male) were performed 21 days after obstruction to release the obstruction. The fetuses were killed at term (145 days).

Results

Thirteen fetuses were shunted. Seven fetuses miscarried after shunting. Six survived, and 3 had a successful shunt with a very small bladder (5 to 7 mL). Two had incomplete shunts that failed some time after shunting. These both had huge bladders (399 mL). In one, the obstruction was unsuccessful. Histologic examination showed that the obstruction caused bladder muscle hypertrophy. Shunted lambs had severe fibrosis of the bladder wall and very poor bladder compliance.

Conclusions

Shunt operations after obstructive uropathy may salvage the kidney but fail to preserve bladder function. The fetus needs a normal urination cycle for normal bladder development. This requirement exists even when the obstruction is successfully bypassed.     

Investigation of histopathologic changes in the ureter walls in experimental congenital obstructive uropathy

Background/Purpose

The aim of this study is to determine the histopathologic changes in the ureter wall in experimental urinary bladder hypoplasia and agenesis.

Methods

Timed pregnant rats were randomly divided and received intraperitoneal Adriamycin (ADR) at 2 mg/kg on gestational days (GD) 6 to 9 (ADR group) and saline at 2 mL/kg on GD 6 to 9 (SF group). The control (C) group did not receive any medication in their pregnancy. Fetuses were harvested near term on GD 21 and dissected under a dissecting microscope and examined for urinary system abnormalities.

Results

Diameter of ureter lumen was significantly increased, but wall thickness, tunica muscularis, and epithelial thickness of the ureter were decreased in the ADR group as compared with the C and SF groups.

Conclusions

Diameter of the ureter lumen was increased, but wall thickness, tunica muscularis, and uroepithelium of the ureter were decreased in the ADR group in the intrauterine period. The diameter of the ureter lumen and wall thickness of ureter (tunica muscularis of ureter and uroepithelium) were increased following obstructive uropathy after the birth.     

Serial amnioinfusions prevent fetal pulmonary hypoplasia in a large animal model of oligohydramnios

Background/Purpose

Severe neonatal pulmonary hypoplasia incurs mortality rates approaching 71% to 95%. We sought to determine the utility of serial amnioinfusions through a subcutaneously implanted intraamniotic catheter to prevent pulmonary hypoplasia in fetal obstructive uropathy.

Methods

Fetal lambs (n = 32) were divided into 3 groups. Group I (n = 12) underwent a sham operation, group II (n = 15) underwent a complete urinary tract obstruction via ligation of the urachus and urethra with a subcutaneous tunneled intraamniotic port-a-cath without amnioinfusions, and group III (n = 5) underwent a creation of a complete urinary tract obstruction with a port-a-cath as described in group II with serial amnioinfusions. Lung tissue was analyzed by lung volume to body weight ratios and stereology. Statistical analysis was performed by analysis of variance and Bonferroni comparisons (P < .05).

Results

Obstructed fetuses grossly had smaller lungs than treated and control animals. Lung volume to body weight ratios were statistically significant between groups. Airspace fractions were comparable between groups I and III (average = 0.53 and 0.55, respectively), although both were significantly greater than group II (average = 0.48) (P = .049).

Conclusions

Serial amnioinfusions through an intraamniotic port-a-cath prevented pulmonary hypoplasia in an ovine model of complete obstructive uropathy. The use of an easily accessible device for amnioinfusions may be a viable option to treat oligohydramnios.     

Prenatal urinary matrix metalloproteinase profiling as a potential diagnostic tool in fetal obstructive uropathy

Background/Purpose

The diagnostic evaluation, patient stratification, and prenatal counseling for congenital obstructive uropathy remain sub-optimal. Matrix metalloproteinase (MMP) expression profiles are emerging as a valuable diagnostic tool in assorted disease processes. We sought to determine whether congenital obstructive uropathy impacts MMP expression in fetal urine.

Methods

Fetal lambs (n = 25) were divided in two groups: group I (n = 12) underwent a sham operation and group II (n = 13) underwent creation of a complete urinary tract obstruction. Gelatin zymography panels for 4 MMP species were performed on fetal urine in both groups at comparable times post-operatively. Statistical analysis was by the Fisher's exact test (P < .05).

Results

Overall fetal survival was 80% (20/25). A variety of significant differences in MMP expression between the two groups were identified. The following profiles were present only in obstructed animals: any MMP other than MMP-2 (P = .029), including any MMP other than 63 kDa and 65 kDa (P = .009); 2 or more MMPs excluding MMP-2s (0.029); and 3 or more MMPs (P = .029).

Conclusions

Limited matrix metalloproteinase expression is present in the urine of normal ovine fetuses. Fetal obstructive uropathy impacts urinary MMP expression in various distinguishable patterns. Prenatal urinary MMP profiling may become a practical and valuable diagnostic tool in the evaluation of congenital obstructive uropathy.     

Pressure-limited vesico-amniotic shunt tube for fetal obstructive uropathy

Introduction

In utero shunting (vesico-amniotic shunt) of obstructive uropathy in fetal lambs produces a shrunken, noncompliant bladder. We hypothesized that using a ventriculo-peritoneal shunt for the vesico-amniotic shunt may preserve the filling/emptying cycle and thus normal bladder development.

Materials and Methods

We created obstructive uropathy in 60-day gestation fetal lambs, ligating the urethra and urachus. Vesico-amniotic shunting was performed 21 days later using the valve end of a ventriculo-peritoneal shunt (valve shunt) or silastic tubing (nonvalve shunt). They were delivered at term (145 days), and the bladder volume was measured and compared to normal term fetuses. The lambs were sacrificed, and the kidneys and bladder removed for histology.

Results

Twenty-seven lambs were shunted. Of 14 valve shunts, 8 were effective. Of 13 nonvalve shunts, 11 were effective. The mean bladder volume was 57 ± 41 mL with a valve shunt and 8.8 ± 4.7 mL with a nonvalve shunt (P < .05) (normal term lambs, 65 ± 18 mL, n = 5). Histology of the shunted bladders showed increased fibrosis in the submucosal and muscle layers. This was less obvious in lambs with a valve shunt.

Conclusion

A pressure controlled shunt for fetal obstructive uropathy improves bladder volume but does not prevent bladder wall fibrosis.     

Validating the MSKCC nomogram and a clinical decision rule in the prediction of non-sentinel node metastases in a Portuguese population of breast cancer patients

Background

In order to assess the risk of non-sentinel node involvement in breast cancer patients, some prediction tools have been developed and tested. However, a wide range of results are observed. We tested a simplified clinical decision rule, against the complex nomogram created from the MSKCC sentinel node database.

Methods

Two single institutional consecutive series of patients with a positive SN, submitted to SN biopsy plus axillary dissection from June 1999 to October 2007, were evaluated. A receiver operating curve was drawn and the area under the curve was calculated as well as the negative predictive value for both tests, assuming discriminative values of 10 and 15%.

Results

Considering the derivation series, our results showed an area under the curve of 0.69 for both our clinical decision rule and the MSKCC nomogram. The analysis of the validation series showed an area under the curve of 0.65 for our clinical decision rule and of 0.67 for the MSKCC nomogram. The nomogram results are inferior to those found in the original population and are similar to our clinical decision rule results.

Conclusions

Individual centres should develop and prospectively test their own clinical decision rules, based on their institutional Sentinel Node data.     

Cancer-specific and other-cause mortality after radical prostatectomy versus observation in patients with prostate cancer: competing-risks analysis of a large North American population-based cohort

Background

Initial treatment options for low-risk clinically localized prostate cancer (PCa) include radical prostatectomy (RP) or observation.

Objective

To examine cancer-specific mortality (CSM) after accounting for other-cause mortality (OCM) in PCa patients treated with either RP or observation.

Design, setting, and participants

Using the Surveillance Epidemiology and End Results Medicare-linked database, a total of 44 694 patients ≥65 yr with localized (T1/2) PCa were identified (1992-2005).

Intervention

RP and observation.

Measurements

Propensity-score matching was used to adjust for potential selection biases associated with treatment type. The matched cohort was randomly divided into the development and validation sets. Competing-risks regression models were fitted and a competing-risks nomogram was developed and externally validated.

Results and limitations

Overall, 22 244 (49.8%) patients were treated with RP versus 22450 (50.2%) with observation. Propensity score-matched analyses derived 11 669 matched pairs. In the development cohort, the 10-yr CSM rate was 2.8% (2.3-3.5%) for RP versus 5.8% (5.0-6.6%) for observation (absolute risk reduction: 3.0%; relative risk reduction: 0.5%; p < 0.001). In multivariable analyses, the CSM hazard ratio for RP was 0.48 (0.38-0.59) relative to observation (p < 0.001). The competing-risks nomogram discrimination was 73% and 69% for prediction of CSM and OCM, respectively, in external validation. The nature of observational data may have introduced a selection bias.

Conclusions

On average RP reduces the risk of CSM by half in patients aged ≥65 yr, relative to observation. The individualized protective effect of RP relative to observation may be quantified with our nomogram.     

EAU guidelines on testicular cancer: 2011 update

Context

On behalf of the European Association of Urology (EAU), guidelines for the diagnosis, therapy, and follow-up of testicular cancer were established.

Objective

This article is a short version of the EAU testicular cancer guidelines and summarises the main conclusions from the guidelines on the management of testicular cancer.

Evidence acquisition

Guidelines were compiled by a multidisciplinary guidelines working group. A systematic review was carried out using Medline and Embase, also taking Cochrane evidence and data from the European Germ Cell Cancer Consensus Group into consideration. A panel of experts weighted the references, and a level of evidence and grade of recommendation were assigned.

Results

There is a paucity of literature especially regarding longer term follow-up, and results from a number of ongoing trials are awaited. The choice of treatment centre is of the utmost importance, and treatment in reference centres within clinical trials, especially for poor-prognosis nonseminomatous germ cell tumours, provides better outcomes. For patients with clinical stage I seminoma, based on recently published data on long-term toxicity, adjuvant radiotherapy is no longer recommended as first-line adjuvant treatment. The TNM classification 2009 is recommended.

Conclusions

These guidelines contain information for the standardised management of patients with testicular cancer based on the latest scientific insights. Cure rates are generally excellent, but because testicular cancer mainly affects men in their third or fourth decade of life, treatment effects on fertility require careful counselling of patients, and treatment must be tailored taking individual circumstances and patient preferences into account.     

The early effects of urinary tract obstruction on glomerulogenesis

Purpose

Our obstructive uropathy model in fetal lambs showed that renal cystic changes appeared 3 weeks after obstruction. In this study, the authors investigated the changes resulting from complete urinary tract obstruction in the first 7 days after obstruction.

Methods

An obstructive uropathy was created in fetal lambs at 60 days’ gestation by ligating the urethra and urachus. They were delivered 48 hours, 3 days, 5 days, and 7 days later by cesarian section. The kidneys were removed and processed for histologic examination.

Results

Eighteen fetuses were operated on and 15 (4 at 48 hours, 4 at 3 days, 2 at 5 days, and 5 at 7 days; 83%) survived. Macroscopically, bladder dilatation and slightly dilated ureters were identified from 48 hours. Microscopically, dilatation of proximal tubules started from 48 hours after obstruction and increased by 7 days. Glomerular cysts in the nephrogenic zone also were identified from 48 hours. Dysplastic changes were not found.

Conclusions

The first areas in the developing kidney that suffer damage after obstructive uropathy are the proximal tubule and the nephrogenic zone. This change started 48 hours after obstruction. Shunting procedures need to be performed considerably earlier than previously thought.     

Impact of prenatal evaluation and protocol-based perinatal management on congenital diaphragmatic hernia outcomes

Background/Purpose

Although intuitive, the benefit of prenatal evaluation and multidisciplinary perinatal management for fetuses with congenital diaphragmatic hernia (CDH) is unproven. We compared the outcome of prenatally diagnosed patients with CDH whose perinatal management was by a predefined protocol with those who were diagnosed postnatally and managed by the same team. We hypothesized that patients with CDH undergoing prenatal evaluation with perinatal planning would demonstrate improved outcome.

Methods

Retrospective chart review of all patients with Bochdalek-type CDH at a single institution between 2004 and 2009 was performed. Patients were stratified by history of perinatal management, and data were analyzed by Fisher's Exact test and Student's t test.

Results

Of 116 patients, 71 fetuses presented in the prenatal period and delivered at our facility (PRE), whereas 45 infants were either outborn or postnatally diagnosed (POST). There were more high-risk patients in the PRE group compared with the POST group as indicated by higher rates of liver herniation (63% vs 36%, P = .03), need for patch repair (57% vs 27%, P = .004), and extracorporeal membrane oxygenation use (35% vs 18%, P = .05). Despite differences in risk, there was no difference in 6-month survival between groups (73% vs 73%).

Conclusions

Patients with CDH diagnosed prenatally are a higher risk group. Prenatal evaluation and multidisciplinary perinatal management allows for improved outcome in these patients.     

Promotion to professor: a career development resource

Background

Patients with penetrating injuries are known to have worse outcomes than those with blunt trauma. We hypothesize that within each injury mechanism there should be no outcome difference between insured and uninsured patients.

Methods

The National Trauma Data Bank version 7 was analyzed. Patients aged 65 years and older and burn patients were excluded. The insurance status was categorized as insured (private, government/military, or Medicaid) and uninsured. Multivariate analysis adjusted for insurance status, mechanism of injury, age, race, sex, injury severity score, shock, head injury, extremity injury, teaching hospital status, and year.

Results

A total of 1,203,243 patients were analyzed, with a mortality rate of 3.7%. The death rate was significantly higher in penetrating trauma patients versus blunt trauma patients (7.9% vs 3.0%; P < .001), and higher in the uninsured (5.3% vs 3.2%; P < .001). On multivariate analysis, uninsured patients had an increased odds of death than insured patients, in both penetrating and blunt trauma patients. Penetrating trauma patients with insurance still had a greater risk of death than blunt trauma patients without insurance.

Conclusions

Insurance status is a potent predictor of outcome in both penetrating and blunt trauma.     

Surgical experimental jejunoileal atresia in rat embryo

Purpose

Jejunoileal atresia represents about 40% of intestinal atresia. After surgical repair, intestinal motility disorders are burdened with the postoperative outcome, and the origin of these troubles remains unclear. To specify the physiopathologic feature of jejunoileal atresia, we developed an experimental surgical model in fetal rat.

Methods

Time-dated pregnant rats were operated on at 18 days of gestational age. Hysterotomy was performed, followed by fetal wall incision. The exteriorization of the bowel loop was obtained by saline injection; the intestine was ligated and returned to the abdominal cavity before incisions were closed. Fetal intestine was excised at day 21, after cesarean delivery.

Results

Twenty-one pregnant rats underwent operation with 90% maternal survival rate. Among the 56 fetuses successfully operated on, 49 survived (87%). In fetuses with atresia, the mean birth weight (4.5 ± 0.6 g) and the mean intestinal length (12.8 ± 1.3 cm) were significantly lower compared to sham fetuses and controls.

Conclusion

The rat model offers the advantage of a low-expense mammal model with a wide panel of probes and reagents available for the study of the gut. This model of jejunoileal atresia could be used to study the consequences of prenatal intestinal obstruction on fetal gut.     

Prosthetic patches for congenital diaphragmatic hernia repair: Surgisis vs Gore-Tex

Purpose

The sequelae of congenital diaphragmatic hernia (CDH) continue well beyond the perinatal period. Up to 50% of these patients have subsequent recurrent herniation or small bowel obstruction (SBO). A recent trend has been toward the use of bioactive prosthetic materials. We reviewed different patch closure techniques used for CDH repair at our institution and their association with these sequelae.

Methods

A retrospective review was performed of 152 records for patients with CDH. Newborns that underwent patch repair for CDH and survived for at least 30 days were included in the analysis. Primary outcomes evaluated were recurrent herniation and SBO. Two types of prostheses were examined, Gore-Tex, an artificial material, and Surgisis, a bioactive material.

Results

Twelve (44%) of 27 patients who had Surgisis repair had recurrent herniation. Seventeen (38%) of 45 patients who had a Gore-Tex repair had recurrent herniation. Two additional patients in each group presented with SBO. No significant difference in recurrent herniation rates was observed (P > .5). The time to recurrence was similar in both groups (log-rank, P = .75), with most recurrences (92% Surgisis, 76% Gore-Tex) occurring in the first year.

Conclusion

The rates of recurrent herniation and SBO after neonatal prosthetic patch repair of CDH were similar regardless of the prosthetic material used (Surgisis or Gore-Tex).     

Notable sequential alterations in notochord volume during development in the Adriamycin rat model

Background/Purpose

The Adriamycin rat model (ARM) is a well-established model of the vertebral, anorectal, cardiac, tracheoesophageal, renal, and limb association. An important finding in the ARM is that Adriamycin induces abnormal notochord morphology in the region of the foregut. Having recently demonstrated notochord hypertrophy in ARM embryos, the authors designed this study to assess notochord volume sequentially from gestational days 10 to 14 (E10-E14) to test the hypothesis that notochord hypertrophy occurs maximally soon after Adriamycin administration.

Methods

Adriamycin (1.75 mg/kg) was administered intraperitoneally to pregnant rats on E7, E8, and E9. Control animals were given saline. Embryos were recovered at E10, E11, E12, E13, and E14 and embedded in paraffin. Quantitative morphology using the Cavalieri technique was performed on hematoxylin and eosin-stained transverse serial sections to determine total embryo and total notochord volume.

Results

The percentage volume of notochord per embryo was significantly increased (P < .05) in Adriamycin-treated embryos at all gestational time frames from E10 to E14 when compared with equivalent controls. This increased volume of notochord was found to be maximal at E11.

Conclusions

These data support the authors' previous finding that Adriamycin induces notochord hypertrophy and suggest that notochord volume is increased relative to embryo volume soon after Adriamycin administration and is maximal on E11. The abnormal increase in notochord volume during the critical phase of development may interfere with organogenesis, resulting in the vertebral, anorectal, cardiac, tracheoesophageal, renal, and limb association.     

Adriamycin induces notochord hypertrophy with conservation of sonic hedgehog expression in abnormal ectopic notochord in the adriamycin rat model

Background/purpose

The Adriamycin rat model (ARM) is a well-established model of the Vertebral, Anorectal, Cardiac, Tracheoesophageal, Renal, Limb (VACTERL) association. The notochord, which expresses Sonic Hedgehog (Shh), has been found to be grossly malformed with ventral ectopic branches in the foregut region of embryos in the ARM. The authors designed this study to test the hypothesis that Shh-expressing ectopic notochord could contribute to an increased volume of notochord relative to total embryo volume, resulting in an increased concentration of Shh in the notochord of affected embryos.

Methods

Adriamycin was administered intraperitoneally to rats on days 7 (E7), E8, and E9 of gestation and saline to control animals. Embryos recovered at E12 and E14 were examined immunohistochemically for Shh expression. Quantitative morphology using the Cavalieri technique was performed to determine embryo and notochord volume.

Results

Embryos in both Adriamycin and control groups at E12 and E14 showed comparable levels of Shh expression in notochord at all locations. The percentage of notochord per embryo was significantly increased in Adriamycin embryos at E12 and E14 compared with equivalent controls.

Conclusions

These data suggest that Adriamycin induces notochord hypertrophy. With all regions of the notochord secreting Shh, this could result in a higher concentration gradient of Shh in close abnormal proximity to the foregut, possibly contributing to the malformations found in the VACTERL association.     

Vesicoamniotic shunt for complete urinary tract obstruction is partially effective

Purpose

The long-term outcome for children after antenatal intervention for obstructive uropathies is disappointing. We reported that renal dysplastic changes are well established 3 weeks after obstruction in a fetal lamb model. We used this model to explore renal development and bladder function after fetal intervention.

Methods

We created an obstructive uropathy in fetal lambs at 60 days gestation by ligating the urethra and urachus. A vesicostomy (female) or urethrostomy (male) were performed 21 days later. The fetuses were killed at term (145 days) and bladder volume and compliance were measured. The urinary tract was processed for histologic examination.

Results

Twenty two fetuses were shunted. Nine were miscarried or were still-born. Thirteen survived, and 11 had a successful shunt with a small bladder (8 ± 5 mL) compared with controls (71 ± 19 mL) (P < .05). Shunted bladders had poor compliance. Histologically, they had thickened submucosal connective tissue with hypertrophied muscle. Histology of the renal tissue demonstrated relatively well-preserved renal architecture with reduced nephron mass (oligonephronia) in 2 lambs and multicystic dysplastic change in 3. Six (55%) had normal nephrogenesis.

Conclusions

In our model, shunt operations after obstructive uropathy fail to preserve bladder function. Shunting ameliorated the development of cystic dysplasia, but half of the lambs had oligonephronia or multicystic dysplastic kidney. These might develop renal failure later in life.     

Current outcome of antenatally diagnosed exomphalos: an 11 year review

Purpose

The aim of this study was to determine the outcome of antenatally diagnosed exomphalos.

Methods

The database of a tertiary referral Fetal Medicine Centre was searched for all cases of antenatally diagnosed exomphalos between January 1991 and December 2002. Patients, general practitioners, and hospitals were contacted for outcome details.

Results

In total, 445 cases of exomphalos were identified. In 250 (56%) cases, the fetal karyotype was abnormal (group A), in 135 (30%) cases, the karyotype was normal (group B), and in 60 (14%) cases, karyotyping was declined (group C). In group A, there were 248 (99%) terminations of pregnancy (TOP) or fetal deaths and 2 live births. In group B, 74 (54%) fetuses had other structural anomalies; 82 (61%) pregnancies resulted in TOP or fetal death, 42 (31%) in live births, and 11 (8%) were lost to follow-up. In group C, 38 (63%) fetuses had other structural anomalies; 41 (69%) pregnancies resulted in TOP or fetal death, 11 (18%) in live births, and 8 (13%) were lost to follow-up. Of the 55 live births, 11 died preoperatively and 44 had surgery. There were no postoperative deaths.

Conclusions

Less than 10% of the antenatal diagnostic workload reached operative repair. In our unit, these babies are a highly selected group, which is a factor in the high postoperative survival.     

Significant Decrease in Glomerular Filtration Rate at 5 Years Posttransplantation in the Recipients of Live Donor Kidneys 50 Years of Age or Older

Introduction

Age is an established predictor of renal failure among recipients of cadaveric transplants; however, the impact of donor age on recipient glomerular filtration rate (GFR) among living donor kidney (LDK) transplantations is not well established.

Methods

We retrospectively analyzed recipient posttransplantation GFR at 12, 36, and 60 months among 315 LDK allograft recipients. The impact of donor age was assessed on the recipient estimated GFR (eGFR) using multivariate linear regression stratified according to donor age <50 years (n = 246) and ≥50 years (n = 69).

Results

Whites comprised the majority of both donors and recipients (77%). The majority (58.4%) of donors were female. Mean age (± SD) of the donors was 41.0 ± 10.2 years (range, 20-65 years). The mean age and body mass index (BMI) of the recipients were 43.3 ± 12.4 years and 26.0 ± 4.9, respectively. There was no statistically significant difference in the rejection rate between the 2 groups (P = .571). Mean eGFR at 12 months in the younger group was 63.3 ± 23.7 compared with 54.8 ± 19.7 in the older group (P = .015). Similarly, a significant difference was observed at the end of 36 months and 60 months of follow-up (61.5 ± 23.1 vs 49.4 ± 18.9, and 59.4 ± 23.0 vs 45.3 ± 20.8, respectively; both P = .001). Donor age was a statistically significant predictor of eGFR throughout the study period (P < .05).

Conclusion

Donor age predicts recipient renal function after living kidney transplantation and needs to be evaluated through a larger prospective investigation.     

Efficacy of double filtration plasmapheresis in removing xenoantibodies and prolonging xenograft survival in an ex vivo swine perfusion model

Introduction

In xenotransplantation, antibodies mediate humoral rejection, resulting in organ dysfunction. Removal of xenoantibodies is likely a first step for successful transplantation. Double filtration plasmapheresis (DFPP) selectively removes large molecular weight pathogenic substances, such as immunoglobulins (Ig), without other plasma proteins. The antibodies fractions removed and the changes in blood biochemistry are unanswered questions after DFPP in addressed this ex vivo swine heart perfusion model.

Materials and Methods

Twelve swine hearts were perfused with human blood in a modified Langendorff's apparatus. The perfusate containing human blood was divided into 2 groups: controls (N = 6) and DFPP-treated group (N = 4). Blood counts, biochemistry data, and immunological profiles were compared at 3 time points: before and after DFPP and after heart perfusion.

Result

Perfusion times of control and DFPP groups were 5.43 ± 1.81 vs 9.25 ± 3.00 hours, respectively. Only the values of albumin and total protein showed difference. The immunologic profile revealved complete removal of IgM and most IgG, IgA, C3, and C4, namely, 79.95%, 88.58%, 83.15%, and 87.97%, respectively.

Conclusion

DFPP showed excellent efficacy to remove xenoantiboidies and prolong xenograft survival in an ex vivo perfusion model.