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Background: Pneumonia caused by opportunistic fungi is a serious complication in immunocompromised patients. Hypercalcemia has been described in renal transplantation associated with Pneumocystis jirovecii (PJP) or Histoplasma capsulatum (HCP) pneumonia., Methods: We describe 5 patients who underwent kidney transplant between 2014 and 2019 and developed hypercalcemia before the diagnosis of pulmonary fungal infection: 4 patients with PJP and 1 with HCP. We assessed calcium metabolism and kidney function by total and ionized calcium, phosphorus, intact parathormone (iPTH), 25-OH vitamin D, 1,25(OH)2 vitamin D, and serum creatinine levels., Results: Mean albumin-corrected calcium and ionized calcium were 12.56 mg/dL (range, 10.8-13.8 mg/dL) and 1.57 mmol/L (range, 1.43-1.69 mmol/L). Patients were normocalcemic, at 10.12 mg/dL (range, 9.6-10.5 mg/dL), before diagnosis and resolved hypercalcemia after antifungal treatment, at 8.86 mg/dL (range, 8.0-9.5 mg/dL). All patients had low or normal iPTH values, at 29.1 pg/mL (range, <3-44 pg/mL), with higher PTH levels 3 months before diagnosis and after treatment, at 147.3 pg/mL (range, 28.1-479 pg/mL) and 117.5 pg/mL (range, 18.2-245 pg/mL), respectively. The mean value for 25-OH vitamin D was 30.8 ng/mL (range, 14.6-62.8 ng/mL). This supports a PTH-independent mechanism, and we postulated an extrarenal production of 1,25(OH)2 vitamin D., Conclusion: In kidney transplant patients, hypercalcemia independent of PTH and refractory to treatment should alert for the possibility of opportunistic fungal pneumonia., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Living kidney donor (LKD) transplantation is increasing due to organ shortage. Clinical studies have shown that the risk of developing end-stage renal disease (ESRD) in donors is similar to that in the general population. Our goal was to evaluate postdonation renal outcomes assessed by glomerular filtration rate (GFR), proteinuria, and blood pressure., Methods: A total of 210 LKD transplants were performed at Hospital Italiano de Buenos Aires between 2000 and 2014. Postdonation outcomes were analyzed in 109 donors. GFR was assessed by 24-hour creatinine clearance (as 24-hour ClCr) and estimated using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Additionally, we correlated the predonation renal functional reserve (RFR) with postdonation GFR. Donor results were compared to the expected GFR (adjusted to age and single kidney). Other renal outcome indicators measured were albuminuria and blood pressure, and they were compared (predonation and postdonation) using univariate analysis., Results: A total of 109 patients were followed up for 47 ± 34 months (range, 12-168): 70% were female, age at donation was 48.58 years (range, 25-70), and predonation serum creatinine was 0.85 ± 0.17 mg/dL. Postnephrectomy GFR (24-hour ClCr) was significantly lower compared to predonation GFR (105.38 ± 21.78 mL/min/1.73 m 2 vs 90.14 ± 17.78 mL/min/1.73 m 2 ). However, postdonation GFR was not significantly different compared to the expected GFR. No differences were found for blood pressure or albuminuria. Age >50 and an RFR (<20%) was associated with a lower GFR., Conclusions: In this population of LKD, renal outcome (24-hour CrCl, albuminuria, and blood pressure) was within the expected outcome for healthy individuals after uninephrectomy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The use of expanded criteria donor (ECD) kidneys has increased the overall availability of renal transplants. This study assessed the use of sirolimus in patients receiving Argentina-ECD kidneys., Methods: This observational, open-label, 1-arm, prospective, longitudinal pilot study was conducted at 8 transplant centers in Argentina. Adults receiving kidney transplants (without pancreas) from ECDs were eligible if they were converted to sirolimus 1 to 36 months' posttransplantation, with sirolimus becoming base therapy within 1 month after conversion. Patients were followed up for 1 year. Outcomes included reasons for conversion, acute rejection, patient and graft survival, graft status, and safety., Results: The intention-to-treat population included 52 patients (mean age, 48.7 years). Calcineurin inhibitor nephropathy (40%) and chronic allograft nephropathy (25%) were the most frequent reasons for conversion. Two acute rejections occurred during follow-up, but no patients experienced graft loss. One patient died during follow-up, and 3 patients died within 1 month of the last sirolimus dose. Levels of serum creatinine and creatinine clearance remained stable from baseline to week 52/53. Mean proteinuria measured in a subset of patients was 0.2 ± 0.2 g/24 hours before conversion and increased to 0.6 ± 1.2 g/24 hours at week 24/25 and 0.5 ± 0.6 g/24 hours at week 52/53. Adverse events were consistent with those in previous conversion trials; the most common were infections and infestations (54%)., Conclusions: This pilot study illustrates the potential benefits of sirolimus in recipients of ECD kidneys in Argentina. Larger, randomized controlled trials are needed to confirm these findings and to clarify the long-term benefits of sirolimus in this patient population., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The Modification of Diet in Renal Disease (MDRD) equation is widely used to estimate glomerular filtration rate (eGFR) in kidney transplant (KT) patients. The novel Chronic Kidney Disease-Epidemiology Collaboration equation (CKD-EPI) could improve accuracy of GFR estimation. Our aim was to compare both equations for staging of CKD in KT patients., Methods: In a cohort of KT patients, correlation of eGFR according to MDRD and CKD-EPI with 24-hour creatinine clearance (24h-CrCl) was evaluated. Concordance between both equations for CKD staging was performed. MDRD was used for initial CKD staging. The mean difference of GFR between 24h-CrCl and each equation was calculated and Bland-Altman analysis applied., Results: A cohort of 463 KT patients were studied: 67% female, overall average age 46 ± 14 years, 41% living donor, mean time of transplantation 71 months (3-95), and mean serum creatinine 1.68 ± 1.03 mg/dL. For the whole cohort (all CKD stages), eGFR by CKD-EPI was 5.33 mL/min/1.73 m(2) higher than by MDRD (P < .01). For CKD stages 1, 2, and 3A, the mean eGFR differences (CKD-EPI - MDRD) were 13.98 ± 3.27, 8.2 ± 1.98, and 5.34 ± 1.32 mL/min/1,73 m(2), respectively. The percentage of patients with eGFR <60 mL/min/1.73 m(2) decreased from 63.8% according to MDRD to 53.9% with the use of CKD-EPI. In women and patients ≤65 years old, eGFR by CKD-EPI was 5.98 and 5.81 mL/min/1.73 m(2) higher, respectively, than by MDRD (P < .01)., Conclusions: The novel CKD-EPI reduces the number of patients with eGFR <60 mL/min/1.73 m(2) and consequently assigns lower CKD stages to our KT population., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Everolimus (EVL)-based immunosuppressive strategies may permit the reduction of calcineurin inhibitors (CNI) and their side effects, while offering a safe and efficient treatment. Our aim was to describe our experience with EVL in everyday practice and provide information for its optimal utilization., Methods: Prospective, multicenter study of 181 kidney transplant recipients treated with EVL as part of their immunosuppressive regimen, with a follow-up of 24 months. We studied demographic data, transplant characteristics, clinical information, drugs used, serum creatinine, estimated glomerular filtration rate (eGFR), rejection episodes, and adverse events., Results: In total, 181 renal transplant recipients were included. Of these, 30 (16.6%) received EVL de novo and 151 (83.4%) were converted; median time from transplantation to conversion was 10 (range, 1-312) months. Main reasons for conversion were prevention of interstitial fibrosis and tubular atrophy (23.9%), intolerance to immunosuppressants (11.1%), neoplasia (13.9%), nephrotoxicity (8.9%), and cytomegalovirus infections (8.3%). The eGFR values at baseline, months 12, and 24 were 46.4 ± 27.4 mL/min, 54.8 ± 22.9 mL/min, and 55.9 ± 26.5 ml/min, respectively. Two of 181 (1.1%) patients died, 5 of 181 (2.8%) lost their grafts, 12 of 181 (6.6%) had an episode of acute rejection, 13 of 181 (7.2%) had ≥1 serious event and infection, and 85 of 181 (49.9%) had ≥1 nonserious adverse event or infection. Multivariate analysis showed that increased eGFR at month 24 was associated with lower donor age, shorter time from transplant to EVL introduction, and a baseline eGFR ≥40 mL/min., Conclusion: Through different strategies among centers, the inclusion of EVL improved renal function during the first 12 months., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The worldwide seroprevalence of human BK polyomavirus (BKV) in adults is 80%. About 10%-60% of renal transplant recipients experience BKV infection, nephropathy of the graft may occur in 5% of the cases, and up to 45% lose the graft. The aim of this work was to describe the prevalence of BK viruria during the 1st year after transplantation., Methods: An epidemiologic multicenter cross-sectional study was carried out in consecutive patients at each site with kidney transplantation from August 2011 to July 2012. Clinically significant viruria was defined as >10(7) copies/mL. Viral DNA was extracted with the use of silica columns. Quantification was performed with the use of real-time polymerase chain reaction with primers that amplify a fragment of the large T-antigen gene and with a specific Taqman-MGB probe for BKV. For each assay, a standard curve with a quantified plasmid was included., Results: Of 402 renal transplant recipients at 18 renal transplant sites, we analyzed 382; median age was 46.33 years, and 46.40% were female. The median of the temporal distribution for urine samples was 153 days. BK virus was detected in 50/382 samples (13%), 18 with values >10(7) copies/mL (4.7%). The median of the distribution of positive values was 123 days and the highest frequency of positive values was in months 3-7. The conditions of recipient older than 34 years and donor older than 41 years were the only ones that showed statistically significant association with BK viruria. No association with any specific immunosuppressive drug was observed., Conclusions: This is the first multicenter study conducted in Argentina to determine the prevalence of BK viruria in renal transplant recipients. Because of the growing number of the population susceptible to this infection, it is important to register and describe data about its epidemiology and associated risk factors.

Proliferation signal inhibitors, such as everolimus, offer immunosuppression without the toxicity of calcineurin inhibitors. This descriptive and prospective study reports outcomes at 1 year and predictors of improved estimated glomerular filtration rate (eGFR) in 174 renal transplant recipients from a national registry of the use of everolimus. At 1 year after conversion, 48.85% of patients had improved eGFR compared with baseline. The mean time from transplantation to initiation of treatment with everolimus was 47.97 months, the median 22 (range, 0-312) months. The kidneys were from deceased donors in 120 patients (68.79%) and from living donors in 54 (31.21%); 35 (20.83%) were expanded-criteria donors. When comparing the baseline versus 12-month values of laboratory results, total cholesterol levels and platelet counts differed significantly-191.55 ± 43.92 mg/dL versus 204.52 ± 41.29 mg/dL (P < .05) and 213,411 ± 63,231/mm(3) vs 255,571 ± 59,153/mm(3), respectively (P < .05)-but remained within clinically controllable ranges. Glycemia, triglycerides, hematocrit, hemoglobin, and leukocytes remained stable. Logistic regression analysis of baseline variables showed that the only independent prognostic factor for improved eGFR at 1 year was the conversion of patients to everolimus within the first 12 months after transplantation (odds ratio, 2.17; 95% confidence interval, 1.15-4.10). In conclusion, regarding the effectiveness of everolimus in our subjects, the only predictor of improved eGFR identified at 1 year was conversion within 12 months after transplantation.

Background: The development of intestinal transplant (Tx) programs introduces thymoglobulin donor treatment as well as an almost complete warm dissection of the abdominal organs to allocate them to different recipients. Our aim is to assess the reproducibility and feasibility of the surgical technique of multi-organ procurement with the use of thymoglobulin donor pre-treatment and report the short- and long-term outcomes of every graft harvested as part of multi-organ procurement (MTOp), including the intestine., Methods: Data were collected of all organs harvested from MTOp, including the intestines allocated to our center from March 2006 to July 2011. Data from 92 recipients and 116 organs procured from 29 MTOp were analyzed. Twelve hearts, 2 lungs, and 1 cardio-pulmonary block were transplanted; primary graft dysfunction developed in 4 of the 12 hearts and in the cardio-pulmonary block., Results: The survival rate was 75% and 100% for hearts and lungs, respectively. Nineteen livers, 9 kidney-pancreas, 19 kidneys, and 29 intestines were transplanted. Delayed graft function (DGF) of the pancreas developed in 3 of 9 kidney-pancreas, and the other 3 exhibited DGF of the kidney; 4 of 19 Tx kidneys had DGF. The survival was 84%, 78%, 95%, and 65.5% for livers, kidney-pancreas, kidneys, and intestines, respectively., Conclusions: Organs procured during MTOp including the intestine can be safely used, increasing organ availability and transplant applicability without compromising allocation, quality, and long-term results of the non-intestinal-procured organs., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Proteinuria (P) is a early sign of inflammation and renal damage. It has an important role in the detection, diagnosis, and monitoring of renal disease in transplanted patients. The aim of this study was to examine the correlation between random urinary proteinuria/creatininuria index (P/CI) and 24-hour total protein excretion among stable renal transplant patients., Materials and Methods: We obtained 1511 samples of 24-hour protein excretion (24-hr P) with corresponding P/CI were obtained from 197 adult patients beyond 6 months post-transplantation between 2009 and 2011. The population was divided into 2 groups: One to obtain a population of justification (755) and another, of validation (755). A scatter graft yielded was obtained by Pearson's coefficient of correlation. A "receiver operater characteristic curve" analysis was carried out to evaluate the sensitivity and specifity of PCI and 24hr-P, showing a cutoff of 0.15 for PCI., Results: The PCI and 24 hr P Pearson's correlation was significant (r = 0.89; P = .0001). The sensitivities of the P/CI for the justification and the validation samples were 97% and 94%, respectively; the a cutoff was 0.15. Their negative predictive values for P/CI were 92% and 84% respectively (cutoff, 0.15). The specificity was below 50% in both groups., Conclusions: We observed a significant correlation between P/CI and 24 hr P. The sensitivity was slightly higher than the specificity (50%) but the negative predictive value was >92%. The use of P/CI seemed to be adequate for screening of protein excretion during renal transplant recipient follow-up., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The tacrolimus is metabolized primarily by CYP3A5, a member of the single nucleotide polymorphism family. It shows cytochrome P450 (SNP) in intron 3, which consists of a change of base, G for A, producing a stop codon. The result is a nonfunctional protein (allele *3). Allele *1 is the wild type. The patients that show the allelic variant *3 in homozygosis (G/G) are slow metabolizers of the immunosuppressant, increasing its concentration in blood. In contrast, heterozygote A/G alleles *1/*3 are intermediate metabolizers, whereas those of allele *1 in homozygosis (A/A) are normal metabolizers. The aim of this study was to determine CYP 3A5 polymorphism among adult renal transplant recipients and the general Argentinean population. We analyzed 21 recipients and 36 healthy controls. All subjects gave written informed consent approved by the local committee. To determine the polymorphism, we extracted DNA from peripheral blood and used polymerase chain reaction (PCR) to amplify intron 3 of the CYP 3A5. The presence of variant was confirmed by direct sequencing. Among the controls the CYP3A5 genotype *3/*3 (G/G) was detected in 32 individuals, 4 showed *1/*3 (A/G), and none had *1/*1 (A/A); among the recipients, the results were as follows: 18, 2, and 1, respectively. The frequencies of polymorphism in both groups were similar, although they differed from those published for other populations. These results are the basis for the development of a pharmacogenomic program applied to organ transplantation. The genetic polymorphisms can determine responses to drugs. The molecular diagnosis must be transferred to clinical practice so as to guide selection of medicine and drug doses to be optimal for each individual.