L. Leon

α-Lipoic Acid Protects Against Ischemia-Reperfusion Injury in Simultaneous Kidney-Pancreas Transplantation.

Background Multiple factors have been implicated in the process of ischemia-reperfusion injury (IRI) in organ transplantation. Among these factors, oxidative damage seems to initiate the injury. &agr;-lipoic acid (ALA) is a potent antioxidant that is used in patients with diabetic polyneuropathy. The aim of the present study was to determine the effect of ALA in patients undergoing simultaneous kidney-pancreas transplant by evaluating the functional recovery of the graft and biochemical markers of IRI. Methods Twenty-six patients were included in the following groups: (i) untreated control; (ii) donor and recipient (DR) ALA-treated, in which ALA was administered both to the deceased donor and to the recipients; and (iii) recipient ALA-treated group. The expression of inflammatory genes, as observed in biopsies taken at the end of surgery, as well as the serum cytokines, secretory leukocyte protease inhibitor, regenerating islet-derived protein 3&bgr;/pancreatitis-associated protein, amylase, lipase, glucose, and creatinine levels were quantified as markers of organ function. Results The DR group showed high levels of TGF&bgr; and low levels of C3 and TNF&agr; in the kidneys, whereas high levels of C3 and heme oxygenase were identified in pancreas biopsies. Decreases in serum IL-8, IL-6, secretory leukocyte protease inhibitor, and regenerating islet-derived protein 3 &bgr;/pancreatitis-associated protein were observed after surgery in the DR group. Serum lipase and amylase were lower in the DR group than in the control and recipient groups. Early kidney dysfunction and clinical pancreatitis were higher in the control group than in either treatment group. Conclusions These results show that ALA preconditioning is capable of reducing inflammatory markers while decreasing early kidney dysfunction and clinical posttransplant pancreatitis.

Oral Paricalcitol Versus Oral Calcitriol for the Treatment of Secondary Hyperparathyroidism in Renal Transplantation: 1707

Oliden C.1, Leon L.1, Tavera M.1, Minue E.1, Anzieta N.1, Colom P.1, Curcio D.1, Petroni J.1, Guardia O.1, Galdo T.1, Rial M.1, Casadei D.1 1Instituto de Nefrologia de Buenos Aires, Buenos Aires, Argentina Background: Secondary hyperparathyroidism (SHPT)is a common complication of chronic kidney disease. Selective activation of vitamin D receptors with oral paricalcitol reduced parathyroid hormone (PTH) levels without development hypercalcemia or hyperphosphatemia in hemodialysis patients. The efficacy of oral paricalcitol versus calcitriol for the treatment of SHPT in transplant patients is unclear. Study Design and methods: Prospective randomized uncontrolled clinical trial. We enrolled 12 patients with renal transplant, glomerular filtrate rate (eGFR) < 60 ml/min and SHPT. The exclusion criteria were GFR>60 ml/min, PTHi< 110pg/ml, corrected Ca2+ >10.5 mg, Phosphorus > 5.5 mg/dl. Patients were randomized to receive oral paricalcitol mg/ day or oral calcitriol 0.25 mg/day over a 24 weeks period. The primary endpoint was to evaluate the efficacy of paricalcitol therapy to decrease ≥ 30% PTHi concentration and to determine the percentage change in PTHi compared with oral calcitriol in patients with renal transplant at 24 weeks of treatment. Results: At the baseline clinical and demographic characteristics were similar in paricalcitol and calcitriol groups: gender (P=1.00), age (57,5±8 vs 52,3±6 years; p: NS ), type of transplant (cadaveric /live donor: p= NS), time of transplant (120,8 ± 132 mo vs 52,2±128 mo p:NS), type of immunosuppression (Srl/ICNs: 2/4 vs 4/2: p 0.1), calcium (9.15±0.7 vs 9.2±0.97: p =0.8), phosphorus (2.7±0.6 vs 3.2±1.2: p 0.4), 25OHD3 concentration (:18.1±7 vs 15±7: p 0.47), iPTH concentration (median 399 IQR 188-731 vs 352 IQR 167-447: p 0.37), proteinuria (481,6±126 vs 760±515; p 0.22), Mean arterial pressure (MAP) (101±9.3 vs 101±11.8; p 0.93). At 24 weeks of treatment 6/6 (100%) of patients in the paricalcitol group and 4/6 (66%) in the calcitriol group reduced the PTHi concentration (p 0.1). The paricalcitol-treated group presented a -53.8±16% (median -49.5%: IQR -69 to -39%) decrease in the iPTH concentration, in the calcitriol-treated group the iPTH reduced in -15.6±27%(median 20.5% IQR -38 to +7.5%) (p 0.01). All the patients (6/6) in the paricalcitol-treated group achieve the primary endpoint at the end of the evaluation, while, only 3/6 (50%) in the calcitriol-treated group reduced the iPTH >30% at 24weeks of treatment (p 0.046), the odds of a reduction iPTH for paricalcitol-treated patients were consistently greater (OR 2; 95% CI 1.1 to 4.4; p 0.046). At the end of the study, the 25OHD3 concentration increased significantly in both groups(paricalcitol 29.3±8.8ng/ml, p 0.03 and calcitriol 28.1±1 ng/ml, p 0.02 with respect to the baseline level). In the same way only in the paricalcitol-treated group we seen a significative reduction in proteinuria (481,6±126,5 to 203±284;p 0.02) as well as a tendence in reduction in MAP (101.2±9.3 to 90.1±9.4; p 0.06). Episodes of hyperphosphatemia and hypercalcemia were not significantly different between the 2 groups. Conclusion: Paricalcitolis effective in reduce the SHPT in transplant patients compared with calcitriol with minimal effect on serum calcium and phosphorus 1710

Polyomavirus BK-Associated Nephropathy After Kidney Transplantation: A Single-Center Retrospective Analysis

Polyomavirus BK-associated nephropathy is cause of kidney transplant morbidity and graft failure. Reported prevalence can vary significantly between centers, probably depending on the immunosuppressive regime used, averaging 5% and the reported incidence of allograft failure ranges from 15 to 50% of affected individuals. Aim To evaluate the evolution of BK virus nephropathy in our transplant center Materials: A descriptive, retrospective study of the clinical evolution of BK virus nephropathy in adult kidney transplant patients from 10 / 2011-10 / 2016. The diagnostic suspicion was through the technique of screening and / or renal dysfunction and confirm by kidney biopsy. Screening was performed by Polymerasa Chain Reaction for BKV(+ greater than 10 4 copies / ml) at 2-6-9-12-month and then annually and after the treatment episode due to graft rejection. Patients with a diagnosis of BK nephropathy we decided 1- Reduction of immunosuppression (suspension of mycophenolate by leflunomide and tacrolimus reduction (maintaining dosages average 5ng / ml )or sirolimus, corticoids and leflunomide), and following with 2-Evaluation of renal function,3- Viral load, 4-antiHLA antibodies and 5-Renal biopsy. Half of the patients also received IVIG 400mg / kg / day for 5 days as a treatment. Results 18/774 renal tx patients had BK nephropathy, at 553 ± 355 days of transplant. 6 for screening and the rest for renal dysfunction. Age 42 ± 12y, 50% women, 14 LD, 4 DD. 6/18 presented previous rejections 2 Mixed 4 cellular Kidney. Biopsies showed Stage I Nephropathy 8 patients (44.4%), S II 9 patients (50%) and S III 1 patient (5.6%). Average basal creatinine (n = 18) 2.5 ± 0.18, 6 months (n = 16) 3.1 ± 1.6, 12 m (n = 15) 2.7 ± 0.8, 24 m (n = 10) 2.62 ± 0.8, 36m (n = 6) 2.9 ± 0.2. 2 patients presented by biopsy, cellular rejection at 3 months of the diagnosis, treated with steroid pulses. No development of de novo antiHLA DSA was observed in this group of patients. The negativization of the viral load BKV was at 3 months in 5 patients and the rest at 6 months. Only 12 renal biopsies were performed(X 12m), presenting an increase in interstitial infiltration and tubulitis in 2 patients). Loss of grafts in 3 patients (16.6%), 2/18 at 4 months and 1/18 at 10 months. There were no deaths. Conclusions A low incidence (2,34%) of BK virus nephropathy is observed in this population. There were no differences in the evolution of patients treated with / without IVIG (pNS) especially in the negativization of viral load. Higher percentage of living donors (77%) with BK nephropathy due probably immunosuppression charge and / or unidentified serology of BK virus in donors.

Cryptococcal Infections in Kidney Transplant Recipients. A Single Center Experience

Introduction Cryptococcal infections are reported to be an infrequent but important cause of morbidity and mortality in solid organ transplant recipients. Best treatment and the need for secondary prophylaxis are still debated. The aim of this research was to describe incidence, clinical presentation, treatment and outcomes of kidney transplant recipients with cryptococcal infections observed at our institution. Materials and Methods Retrospective analysis of cryptococcal infections observed in patients (Pts) transplanted from January 1st 2008 to October 1st 2017. Data on demography, immunosuppression, clinical presentation, treatment and outcome was recollected. Results and Discussion 1413 transplants were performed in the period 2008-2017. A total of 12 cases of cryptococcal infection was observed (incidence:0.85%). Pts were 3 males/9 females. Age: Median 53.87 (range 20-72) years. Donors were: Deceased: 7 (58.3%); Living related 3 (25 %) Living non-related 2(16.7%.%). Immunosuppression: 10 received induction with timoglobulin. Maintenance immunosuppression: Tacrolimus (FK)- mycophenolic acid (MPA)- prednisone (P): 8 (67%), MPA-P/FK-MPA-P- belatacept/Belatacept MPA-P/and;, sirolimus-FK-MPA-P: 1 each.Four Pts suffered rejections previous to cryptococcal infection (Median time before cryptococcosis: 344.5 (Range: 83-1022) days). Time to infection after transplantation: Median 27.37 (range 3.2-84.3) months. Clinical forms: Meningeal: 6 (50%); Disseminated: 4 (33.3%); Pulmonary: 1 (8.3%); Pleural: 1 (8.3%). Median CD4 count at diagnosis: 88/mm3 (range 47-172). One Pt had a post-mortem diagnosis. Treatment: (Induction): Liposomal Amphotericin B (L-AmB) 9 Pts; L-AmB+Fluconazole: 2 pt. Immunosuppression was temporarily minimized on all Pts until infection was controlled. Consolidation: Fluconazole 11 Pts. (2 pt. still on treatment), 9 pt. completed treatment (median: 12 (range 8,5-20) months,). Outcomes All treated Pts (11/11) cured. 9 Pts maintained a functioning graft. Of these, 7 completed treatment (with no secondary prophylaxis) with no relapse of follow-up (FU). Median FU: 13,17 (range 3,44-72,33) months. 2 Pts lost the graft on FU (unrelated to cryptococcosis), and 1 Pt died of unrelated cause. Conclusion Treatment with induction with L-AmB (with or without fluconazole), combined with appropriate immunosuppression management was successful in all clinical forms of cryptococcal infection. No relapses were observed in Pts with treatment completed and no secondary prophylaxis.