Pediatric Renal Transplantation: Evaluation of Long-Term Outcomes and Comparison to Adult Population.

BACKGROUND: In Europe, pediatric transplantation accounts for only about 4% of all kidney transplantations performed. The aim of our work is to evaluate the evolution of pediatric renal transplantation in our department over time, but also to compare this special population with the adult one. METHODS: We evaluated all pediatric renal transplantations performed in our department between January 1981 and December 2016. We performed the analysis of clinical, analytical, and surgical factors to look for predictive factors of graft loss or decrease of survival. In addition, we performed a comparative study of pediatric and adult populations and an evaluation of the evolution of pediatric renal transplantation in our department over time. RESULTS: We evaluated 101 renal transplantations performed in patients younger than 18 years. Pediatric transplantations corresponded to 3.4% of all renal transplantations performed in our department. The rate of living donors was 12%. Donors of grafts for the pediatric population were significantly younger than in the adult population. The increase in donor age was associated with lower renal graft survival rates. Acute rejections were more frequent in the pediatric population. Eleven pediatric recipients (10.9%) died in the follow-up period. Renal graft survival in the pediatric population was 94.8%, 77.4%, and 66.5% at 1, 5, and 10 years, respectively. There was no significant difference in graft survival in the pediatric and adult population. The pediatric overall survival rate at 1, 5 and 10 years was 97.9%, 96.8%, and 91.9%, respectively. CONCLUSION: Pediatric renal transplantation presents results identical to those identified in adults.

Targeted alpha therapy using Radium-223: From physics to biological effects.

With the advance of the use of ionizing radiation in therapy, targeted alpha therapy (TAT) has assumed an important role around the world. This kind of therapy can potentially reduce side effects caused by radiation in normal tissues and increased destructive radiobiological effects in tumor cells. However, in many countries, the use of this therapy is still in a pioneering phase. Radium-223 (223Ra), an alpha-emitting radionuclide, has been the first of its kind to be approved for the treatment of bone metastasis in metastatic castration-resistant prostate cancer. Nevertheless, the interaction mechanism and the direct effects of this radiopharmaceutical in tumor cells are not fully understood neither characterized at a molecular level. In fact, the ways how TAT is linked to radiobiological effects in cancer is not yet revised. Therefore, this review introduces some physical properties of TAT that leads to biological effects and links this information to the hallmarks of cancer. The authors also collected the studies developed with 223Ra to correlate with the three categories reviewed - properties of TAT, 5 R's of radiobiology and hallmarks of cancer- and with the promising future to this radiopharmaceutical.

De Novo Urologic Malignancies in Renal Transplant Recipients.

BACKGROUND: Immunosuppressed organ transplant patients have an elevated risk of malignancies. The aim of this study was to determine the incidence of urologic malignancies in renal transplant recipients, as well as to evaluate their monitoring, treatment, and outcomes. METHODS: We conducted a retrospective single-center study of 2897 renal transplants between January 1987 and December 2016. Recipients presenting with de novo urologic malignancies were evaluated. We retrospectively assessed the stage of the disease, treatment performed, and subsequent oncologic outcome. Patients with a history of preexisting cancers were excluded. RESULTS: Sixty-one de novo urologic malignancies were recorded in 58 patients. The overall incidence of urologic malignancies was 2.2%. We identified 29 cases of prostate cancer, 23 of renal cell carcinoma, 6 of transitional cell carcinoma of the bladder, and 1 case of penile carcinoma. No cases of testicular tumors were found. The mean age at tumor diagnosis was 58.7 ± 10.1 years. The median time between renal transplantation and tumor development was 84 months (range, 2-310 months). Fifty-six (96.6%) patients received deceased donor kidneys. The overall survival rate at 5 years after diagnosis of urologic tumor was 82.8%. Tumor-related death was reported in 13.8% of patients. Nineteen (32.8%) patients had graft loss. Of these, 8 patients had no functional graft when the diagnosis of urologic tumor was made. The therapeutic options did not differ from those used in nontransplanted patients. CONCLUSIONS: Due to the increased incidence of tumors and possibly worse prognosis, renal transplant recipients should be screened more regularly.

Pretransplant biopsy in expanded criteria donors: do we really need it?

INTRODUCTION: Renal transplantation is the best treatment for end-stage renal disease, including when using expanded criteria donors (ECD) kidneys. However, these suboptimal kidneys should be evaluated rigorously to meet their usefulness. Opinions differ about the best way to evaluate them. MATERIALS AND METHODS: We retrospectively reviewed kidneys from ECD harvested by a single academic institution between January 2008 and September 2013. Needle biopsies were performed at the time of the harvest when considered relevant by the transplant team. Two pathologists where responsible for their analysis; the Remuzzi classification has been used in all cases. RESULTS: We evaluated 560 ECD kidneys. Biopsies were made in 197 (35.2%) organs, 20 of which were considered not usable and 36 good only for double transplantation. Sixty-three kidneys (11.3%) were discarded by the transplant team based on the biopsy result and clinical criteria. Donors who underwent a biopsy were older (P < .001) and had a worse glomerular filtration rate (GFR; P = .001). Comparing donors approved and rejected by the biopsy, the rejected donors were heavier (P = .003) and had a lower GFR (P = .002). Cold ischemia time was longer for the biopsy group (P < .001). Regarding graft function, the biopsy overall score correlated with the transplant outcome in the short and long term. Separately, glomeruli and interstitium scores were correlated with recipient's GFR in the earlier periods (3 months; P = .025 and .037), and the arteries and tubules correlated with GFR in the longer term (at 3 years P = .004 and .010). CONCLUSION: The decision on the usability of ECD grafts is complex. At our center, we chose a mixed approach based on donor risk. Low-risk ECD do not require biopsy. In more complex situations, especially older donors or those with a lower GFR, prompted a pretransplant biopsy. The biopsy results proved to be useful as they relate to subsequent transplant outcomes, thereby allowing us to exclude grafts whose function would most probably be less than optimal.

N-Hexyl-3-(4-hy-droxy-3,5-dimeth-oxy-phen-yl)propanamide.

In the title compound, C(17)H(27)NO(4), which is an hydro-sinapic acid derivative with increased lipophilicity conferred by an additional alkyl chain, the central and the hexyl linear chains contain slightly shorter bond lengths [C-N = 1.316 (2) Å; average linear chain C-C = 1.487 (6) Å] than reported average values [Csp(2)-N = 1.334, C-C for CH(2)-CH(2) = 1.524 and 1.513 Šfor CH(2)-CH(3)]. The 4-hy-droxy-3,5-dimeth-oxy-phenyl plane [r.m.s. deviation 0.055 (12) Å] makes an angle of 59.89 (5)° with the central plane of the mol-ecule (composed of the N atom, the carbonyl group and the two methyl-ene C atoms linking the carbonyl group and the ring, [r.m.s. deviation 0.0026 (10) Å], which, in turn, makes an angle of 64.24 (13)° with the essentially planar hexyl chain [r.m.s. deviation 0.035 (18) Å]. The N-H group of the amide group is involved in a bifurcated hydrogen bond towards the hy-droxy and one of the meth-oxy O atoms of the 4-hy-droxy-3,5-dimeth-oxy-phenyl substituent of a neighbouring mol-ecule, forming a two-dimensional network in the (100) plane. In addition, the same hy-droxy group acts as a donor towards the carbonyl O atom of another neighbouring mol-ecule, forming chains running along the b axis.

6-Methyl-ideneandrost-4-ene-3,17-dione.

In the title compound, C(20)H(26)O(2), which is the 6-methyl-ene derivative of androstenedione and a synthetic percursor of exemestane, the steroid A ring approximates to a sofa (or envelope) conformation, with the methyl-ene group adjacent to the link to the B ring lying out of the plane of the other atoms. The B and C rings have slightly flattened chair conformations and the D ring is an envelope, with the CH group forming the flap. In the crystal, mol-ecules are linked by two distinct C-H⋯O hydrogen bonds, involving acidic H atoms close to C=C and C=O double bonds.

5α-Androst-3-en-17ß-yl acetate.

In the crystal structure of the title compound, C(21)H(32)O(2), ring A is highly distorted, with a conformation inter-mediate between 10ß-sofa and 1α,10ß-half chair; rings B and C have slightly flattened chair conformations. Ring D assumes an unusual 13ß-envelope conformation, probably induced by the acet-oxy substituent. Cohesion of the crystal structure is due only to weak van der Waals inter-actions.

3α,4α-Ep-oxy-5α-androstan-17ß-yl acetate.

The title compound, C(21)H(32)O(3), results from modifications of the A and D rings of the aromatase substrate androstenedione. Ring A adopts a conformation between 10ß-sofa and 1α,10ß half-chair. Rings B and C are in slightly flattened chair conformations. Ring D approaches a 13ß-envelope conformation, probably due to the acet-oxy substituent, and shows a very short Csp(3)-Csp(3) bond next to the epoxide ring, which is characteristic of 3-4 epoxides. .

5alpha-Androst-3-en-17-one oxime.

The title compound, C(19)H(29)NO, is a C17-oxime derivative of a potent aromatase inhibitor, which surprisingly has been found to have no inhibitory power. It crystallizes with two independent molecules in the asymmetric unit. C=N-O-H...N hydrogen bonds link pairs of molecules to form dimers almost parallel to the bc plane. Cohesion of the structure is also due to another three C-H...O hydrogen bonds directed along the a axis. This hydrogen-bonding scheme can be correlated to the almost complete loss of inhibitory power of the title compound.

3,17-Dioxoandrost-4-en-4-yl acetate.

The title compound, C(21)H(28)O(4), has a 4-acetoxy substituent positioned on the steroid alpha face. The six-membered ring A assumes a conformation intermediate between 1alpha,2beta-half chair and 1alpha-sofa. A long Csp(3)-Csp(3) bond is observed in ring B and reproduced in quantum-mechanical ab initio calculations of the isolated molecule using a molecular-orbital Hartree-Fock method. Cohesion of the crystal can be attributed to van der Waals interactions and weak C-H...O hydrogen bonds.

17-Oxo-5alpha-androstane-3alpha,4beta-diyl diacetate and 17-oxo-5beta-androstane-3alpha,4beta-diyl diacetate.

The title compounds, both C23H34O5, are the 5alpha and 5beta configurations of two diacetate epimers. The 5beta-diacetate crystallizes in an hexagonal structure, unusual for steroid molecules. The unit cell has an accessible solvent volume of 358 A(3), responsible for clathrate behaviour. The 5beta-epimer also features some shorter than average bond lengths in the 3alpha,4beta-acetoxy groups. The conformations of the molecules of both epimers are compared with those obtained through ab initio quantum chemistry calculations. Cohesion of the crystals can be attributed to van der Waals and weak molecular C-H...O interactions.