D. Casadei

A randomized and prospective study comparing treatment with high-dose intravenous immunoglobulin with monoclonal antibodies for rescue of kidney grafts with steroid-resistant rejection.

Background. The aim of this study was to compare the effectiveness of intravenous immunoglobulin (IVIg) versus monoclonal anti-CD3 as a treatment for steroid-resistant rejections. From January 1995 to June 1997, 30 patients were analyzed. They were randomized into two groups. Resistant rejections were diagnosed by core biopsy. Group A received 500 mg/kg/day IVIg (Sandoglobulin) for 7 consecutive days, whereas group B received 5 mg/day of OKT3 for 14 consecutive days. Daily T cell CD3+ peripheral count was performed for 14 days for group B. The immunosuppression was similar for both groups. Cyclosporine was stopped during both treatments. Methods. Demographic factors, HLA mismatch, creatinine levels before and after treatment, and the incidence of rejections after treatment (up to 1 month) were taken into account for this study. Results. Data from different samples were compared using Fisher’s exact test. Graft and patient survival were analyzed using the Kaplan-Meier method. The were no significant differences found in age, graft origin, HLA mismatch, or time of follow-up until the episode of rejection. Success was achieved for 11 (73.3%) of 15 of group A and 13 (86.6%) of 15 of group B (P =0.79). Creatinine levels before and after treatment were as follows: A, 2.99±1.30 mg/dl and 2.1±0.70 mg/dl versus B, 3.1±1.1 mg/dl and 2.5±0.8 mg/dl. Besides, we did not observe differences in the creatinine 1 month after treatment (A: 2.35±0.78 mg/dl; B: 2.51±1.10 mg/dl;P =0.66) nor in the third month (A: 1.83±0.58 mg/dl; B: 2.30±0.89 mg/dl;P =0.24). The incidence of rejections after treatment was 5 (46%) of 11 for group A and 9 (75%) of 12 for group B (P =0.4). The patient survival rates 2 years after treatment were 87 and 92% for A and B groups, respectively. Graft survival was identical (80% in both groups). Conclusion. Should the favorable result presented in this report be confirmed in larger number of patients, IVIg could become the preferable choice of rejection treatment for steroid-resistant rejection because of a complete absence of the unwanted side effects commonly associated with OKT3.

Risk factors for Pneumocystis carinii pneumonia in kidney transplant recipients: a case–control study

Objective. To analyze risk factors for Pneumocystis carinii pneumonia (PCP) in kidney transplant recipients.

Tuberculosis in renal transplant recipients

Tuberculosis (TB) has been described in kidney transplant recipients as an infection with predominantly pulmonary involvement. We report the impact of TB in kidney transplantation. Clinical records of adult kidney recipients, transplanted between 1 January 1986 and 31 December 1995 were analyzed for sex, age, graft origin, immunosuppressive therapy, TB sites, diagnostic methods and concomitant infections. Annual incidence, mean time of onset, relation to rejection treatment, tuberculin skin test (PPD) and outcome were analyzed. Patients with a history of TB or graft loss in the first month were excluded. TB was diagnosed in 14 of 384 (3.64%). Mean age at transplantation was 35 years. Twelve of these received the graft from a living donor. All had triple immunosuppression with cyclosporine. Ten had pulmonary TB, three extrapulmonary infection and one disseminated disease. In 13 cases an invasive diagnostic procedure was performed. Mycobacterium tuberculosis cultures were positive in all cases; microscopy revealed acid-fast bacilli (AFB) in 6, and adenosine deaminase was elevated in CSF and pleural effusion in 2. Annual incidence varied from 0% to 3.1%. At the time of TB presentation 8 patients had other concomitant infections (cytomegalovirus, nocardia, Pneumocystis carinii, disseminated herpes simplex virus). Median time of onset was 13 months. Diagnostic results became available post-mortem in 2 cases, and one had TB in a failing allograft. TB was treated with 4 drugs including rifampin in 10 patients. Cyclosporine was discontinued in one, lowered in one and increased in 8. During treatment 5 patients had rejection episodes. At 1 year, graft survival was 72.7% and patient survival 90.9%. TB was more prevalent when recipient and donor were both PPD positive. In summary: although TB is a growing threat in the transplant setting, early and aggressive diagnosis with meticulous monitoring of immunosuppression allows a successful outcome for both patient and graft. Optimal prophylaxis guidelines have yet to be completely defined.Abstract: Tuberculosis (TB) is a frequent infectious complication in patients on renal replacement therapy, as a result of immunosuppression from uremia and drugs in the post‐transplantation period. A retrospective study of all renal transplantation patients from 1989 to date was conducted. This study tried to examine the prevalence, course, and outcome of TB in renal transplant recipients. A comparison with the occurrence of TB in other modalities of renal replacement therapy was also made. We also discussed the treatment protocols for TB in this group of patients. No difference in the prevalence, age, or male/female ratio of TB was seen among the 3 modes of renal replacement therapy. TB of the lung was the more favored site of infection in patients on hemodialysis (77.3%), when compared with those on CAPD (30%) and renal transplant recipients (33.3%). In renal transplant recipients, no deaths occurred due to TB. In 7 patients there was co‐infection with cytomegalovirus and in 3 patients there was Aspergillus lung infection.

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.

Gene expression profile in delay graft function: inflammatory markers are associated with recipient and donor risk factors.

Background. Delayed graft function (DGF) remains an important problem after kidney transplantation and reduced long-term graft survival of the transplanted organ. The aim of the present study was to determine if the development of DGF was associated with a specific pattern of inflammatory gene expression in expanded criteria of deceased donor kidney transplantation. Also, we explored the presence of correlations between DGF risk factors and the profile that was found. Methods. Seven days after kidney transplant, a cDNA microarray was performed on biopsies of graft from patients with and without DGF. Data was confirmed by real-time PCR. Correlations were performed between inflammatory gene expression and clinical risk factors. Results. From a total of 84 genes analyzed, 58 genes were upregulated while only 1 gene was downregulated in patients with DGF compared with no DGF (P = 0.01). The most relevant genes fold changes observed was IFNA1, IL-10, IL-1F7, IL-1R1, HMOX-1, and TGF-β. The results were confirmed for IFNA1, IL-1R1, HMOX-1 and TGF-β. A correlation was observed between TGF-β, donor age, and preablation creatinine, but not body mass index (BMI). Also, TGF-β showed an association with recipient age, while IFNA1 correlated with recipient BMI. Furthermore, TGF-β, IFNA1 and HMOX-1 correlated with several posttransplant kidney function markers, such as diuresis, ultrasound Doppler, and glycemia. Conclusions. Overall, the present study shows that DGF is associated with inflammatory markers, which are correlated with donor and recipient DGF risk factors.

Laparoscopic biopsies in pancreas transplantation

As there is no precise laboratory test or imaging study for detection of pancreas allograft rejection, there is increasing interest in obtaining pancreas tissue for diagnosis. Pancreas allograft biopsies are most commonly performed percutaneously, transcystoscopically, or endoscopically, yet pancreas transplant surgeons often lack the skills to perform these types of biopsies. We have performed 160 laparoscopic pancreas biopsies in 95 patients. There were 146 simultaneous kidney–pancreas biopsies and 14 pancreas‐only biopsies due to pancreas alone, kidney loss, or extraperitoneal kidney. Biopsies were performed for graft dysfunction (89) or per protocol (71). In 13 cases, an additional laparoscopic procedure was performed at the same operation. The pancreas diagnostic tissue yield was 91.2%; however, the pancreas could not be visualized in eight cases (5%) and in 6 cases the tissue sample was nondiagnostic (3.8%). The kidney tissue yield was 98.6%. There were four patients with intraoperative complications requiring laparotomy (2.5%) with two additional postoperative complications. Half of all these complications were kidney related. There were no episodes of pancreatic enzyme leak and there were no graft losses related to the procedure. We conclude that laparoscopic kidney and pancreas allograft biopsies can be safely performed with very high tissue yields.

Acute pulmonary involvement by paracoccidiodomycosis disease immediately after kidney transplantation: Case report and literature review

Paracoccidioides brasiliensis is the cause of paracoccidioidomycosis, one of the most important systemic mycoses in Latin America. Human disease has been observed in a limited geographic and ecological niche, and it is attributed to exposure to the fungus in soil. Most primary infections are subclinical, as the infection is contained by the host mainly through cell‐mediated immune response. However, as the fungus has the ability to survive in a dormant state for long periods, an impairment of the immune response may lead to reactivation and clinical disease. Surprisingly, paracoccidioidomycosis has rarely been reported in transplanted patients. The aim of this communication is to report a case occurring in a kidney recipient in an acute clinical form immediately after transplantation, and to review the available information on previously reported cases.

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

IMPACT OF THE STRICT GLYCEMIC CONTROL IN THE POST-OPERATIVE PERIOD OF TRANSPLANTATION WITH ECD KIDNEYS. PRELIMINARY RESULTS OF A PROSPECTIVE AND RANDOMIZED TRIAL: 221

Introduction: Delayed graft function (DGF) and acute rejection (AR) are events that strongly correlate with a lower graft survival rate. Glucose metabolism aberrancies can negatively impact on post-transplant outcomes including DGF and AR. Post-transplant hyperglycemia is associated with surgical stress, use of drugs with diabetogenic effects (i.e steroids) and previous diabetes or glucose intolerance in the recipient. At our center DGF is very common with an incidence of ~80% when ECD kidneys are used. We hypothesized that both glycemic control and insulin infusion would be beneficial in this situation. Objective and methods: To evaluate the safety and the efficacy of the strict glycemic control in the immediate post-operative period of ECD kidney transplantation until 5 days post-transplant surgery. To address this issue we designed a prospective, open and single center study where patients were randomized to receive a continuous insulin IV infusion to maintain glycemia b/w 70 and 110 mg/dl (group I, intensive group) vs. SC insulin q6hrs per sliding scale (group II, control group). All the patients received the same IS consisting of Thymoglobulin induction for 7-14 days and sirolimus (812 ng/ml), MMF and prednisone as immunosuppressive medications. A protocol biopsy was performed by 7 days post-transplant to assess the presence and severity of ATN, as well as comparison with the post-reperfusion biopsy (T0). Results: 47 of the 60 (78.3%) planned patients have been enrolled by 02/15/10 (26 in Group I, 21 in Group II). The glucose level was consistently lower in the intensive group. Otherwise both groups were equal in regards to demographic data. Table

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.