Late Cytomegalovirus Infection in Kidney Transplant Recipients after a Six-Month Prevention Protocol.

BACKGROUND: Despite a reduction in the incidence of cytomegalovirus (CMV) infections after kidney transplantation, less is known about late CMV infection in kidney transplant recipients. OBJECTIVE: To assess incidence of CMV infection in a cohort of patients under a high surveillance CMV prevention protocol and identify factors associated with late CMV infection. METHODS: Analysis of a consecutive cohort of 181 kidney allograft recipients between January 2012 and Aug 2015. CMV prevention-protocol consisted of 6-month universal prophylaxis and pre-emptive therapy for high-risk group (D+/R- or patients submitted to lymphocyte-depleting agent for induction or rejection treatment) and pre-emptive therapy for standard-risk group (D±/R+). Stopping valganciclovir was followed by CMV screening in the next two appointments. RESULTS: CMV infection was identified in 73 of 181 patients; the rate in high-risk group and standard-risk group was similar (p=0.443). However, in the latter group, the infection occurred mostly in the first 6 months. Late CMV infection occurred in 25 of 181 patients (5 of standard-risk group and 20 of high-risk group), after a median (IQR) of 253 (230.3-312.3) days after transplantation and 55 (41-89.5) days after the protocol period. Screening for CMV after valganciclovir discontinuation revealed 56% of late CMV infections. In high-risk group, D+/R- was associated with late CMV infection (HR 2.7, p=0.039) and in standard-risk group; lower age was associated with late CMV infection (HR 0.89, p=0.02). CONCLUSION: The incidence of CMV infection was similar to that reported in the literature. In high-risk patients, antigenemia surveillance during prophylaxis did not appear to reduce late CMV infections. Antigenemia screening after valganciclovir had limited results in the diagnosis of late CMV infection. D+/R- was associated to late CMV infection in high-risk group. Lower age appeared to influence late CMV infection in standard-risk group.

Intravenous Immunoglobulin and Rituximab in HLA Highly Sensitized Kidney Transplant Recipients.

INTRODUCTION: HLA-sensitized patients are penalized both in the access to kidney transplantation (KT) and, once transplanted, in the incidence of rejections and long-term allograft survival despite aggressive induction and maintenance therapy. METHODS: This study retrospectively evaluates the impact of combining T- and B-cell-depleting agents and intravenous immunoglobulin for induction therapy in 45 highly sensitized KT patients (anti-panel reactive antibodies >60%, positive flow cytometry crossmatch or donor specific antibodies at the time of transplantation). The outcome data included the occurrence of biopsy-proven acute rejection, new-onset proteinuria, development of leukopenia, incidence of poliomavirus infection (BK or JC virus), fungal or bacterial infection after KT, de novo neoplasia, graft function, graft loss, or death with functioning KT. RESULTS: The average panel reactive antibody was 62.5%; 41 patients (91.1%) had ≥3 HLA mismatches with the donor and 91.1% of patients had class I or II anti-HLA antibodies. Fourteen patients (31.1%) presented pre-KT donor-specific antibodies and 6 patients (13.3%) had a positive flow cytometry cross-match at the time of transplantation. The incidence of acute rejection in the first 6 months was 24.4% and the cumulative incidence was 37.8%. Two patients were diagnosed with leukopenia in the first 6 months after KT. Two patients (4.5%) had cytomegalovirus disease, 17 patients (37.8%) were diagnosed with bacterial infections. Cutaneous neoplasms were identified in 5 patients (11.1%) and solid tumors in 4 (8.9%). The death-censored graft survival was 100% in the first 6 months and 93.5% at the last evaluation. Patient survival in the same periods was 97.8% and 93.3%, respectively. CONCLUSIONS: Induction immunosuppressive therapy with intravenous immunoglobulin and rituximab is effective; outcomes demonstrate an excellent patient and allograft survival and allograft function over the follow-up period.

Hepatitis C Virus Eradication in Kidney Transplant Recipients: A Single-Center Experience in Portugal.

INTRODUCTION: Hepatitis C (HCV) is a major cause of liver impairment post-kidney transplantation (KT). Anti-HCV direct-acting antivirals (DAA) made viral eradication possible. METHODS: We performed a retrospective review of KT patients (n = 23) who received DAA at our hospital. Sustained viral response (SVR) was defined as absence of viral detection 12 weeks after cessation of therapy. RESULTS: From 1985 to September 2017, 1440 patients underwent transplantation at Hospital Santa Cruz. From a total of 32 HCV RNA+ KT recipients on follow-up, we describe the first 23 patients treated with DAA. They were 56.7 ± 9.1 years old; 22 were white, 52.2% were males, they underwent transplantation 18.8 ± 9.0 years ago, and 13 had genotype 1B, 21 were naïve, and 9 had stages F3/F4. All but 2 patients, treated with grazoprevir/elbasvir, received sofosbuvir (18 with ledispasvir, 2 with daclastavir, and 4 with simultaneous ribavirin). Pretreatment, intra-treatment, and post-treatment creatinine clearances were 61.4, 60.6, and 60.7 mL/min/1.73 m2, respectively (not significant [NS]). Cyclosporine A was the basis of immunosuppression in the majority [(n = 14); pretreatment and intra-treatment levels were 79.5 ± 23.0 and 91.8 ± 26.0 ng/mL, respectively (P = .08)]; tacrolimus (n = 8) and mammalian target of rapamycin (mTOR) levels (n = 5) were also similar. One patient interrupted ribavirin after 7 weeks due to anemia; all other patients completed the treatment course without major side effects. Only 3 patients presented positive viral RNA at the fourth week of treatment and SVR was achieved in 100% of the patients 12 weeks after treatment. CONCLUSIONS: DAA therapy was well tolerated and effective in 100% of our treated patients, without significant impact on the renal function or on the immunosuppression.

HCV-infected Renal Transplant Recipients: Our Experience before the Availability of New Antiviral Drugs.

BACKGROUND: Natural history of HCV-infected renal transplant recipients is about to change with the invention of new drugs available for the treatment of HCV. OBJECTIVE: To analyze the evolution of renal transplant recipients infected with HCV in 30 years of activity of a Renal Transplantation Unit. METHODS: We studied 1334 patients who underwent renal transplantation between 1985 and 2015. RESULTS: 189 (14.2%) of these 1334 were found HCV seropositive. 60 were HCV RNA-positive for >6 months. 5 died with a functioning graft; 19 lost their graft and resumed dialysis. Most of the rejections occurred within the first year of the transplantation and none resulted in immediate loss of the graft. In post-transplantation period, 14 patients developed clinical hepatic disease, 10 manifested new-onset diabetes after transplantation, and 4 had de novo neoplasia, none of them had hepatocellular carcinoma. The outcomes of the different variables analyzed were similar between patients with HCV-infection and those with HCV and HBV co-infection. The median survival time was 13.4 (95% CI: 10.7-16.1) years; the median survival time of patients without HCV infection was 14.6 (95% CI: 13.8-15.4) years (p=0.23). CONCLUSION: In the era before the availability of new anti-HCV drugs, our experience with HCV-infected renal transplant recipients revealed similar post-transplantation complications, graft and patient survival as those not infected with HCV.

Kidney Graft Leiomyosarcoma: A Case Report.

BACKGROUND: Kidney transplant (KT) recipients have a higher incidence of malignancy than the general population. Smooth muscle tumors (SMT), including leiomyosarcoma, are rare in kidney transplant recipients, and most cases are associated with Epstein-Barr virus (EBV) infection. CASE REPORT: A 57-year-old man received a deceased donor kidney transplant at the age of 53 years, with 5 human leukocyte antigen (HLA) mismatches. Before the transplantation, the patient was IgG positive for EBV viral capsid antigen (VCA), negative for IgM EBV VCA, and also negative for IgG EBV nuclear antigen (EBNA), suggesting a prior EBV infection. He received immunosuppressive induction with basiliximab, and maintenance with tacrolimus, mycophenolate mofetil, and prednisolone. Two years after transplantation, he had an acute cellular rejection episode treated with methylprednisolone. An increased graft size was found 4 years after transplantation. A computed tomographic scan showed 3 solid tumors involving the renal graft with extension to the perinephric fat; no secondary localizations were found. A nephrectomy of the graft was performed. The histologic diagnosis was a high-grade leiomyosarcoma. In situ hybridization for EBV was negative. Nine months after nephrectomy, local recurrence was diagnosed. The surgical approach was unsuccessful, and the patient died after a brief period. CONCLUSION: Kidney leiomyosarcoma is a very rare clinical condition. Most of these neoplasms that arise in transplanted recipients are associated with EBV in tumor tissue. Only one case of renal graft leiomyosarcoma without EBV RNA in the tumor has been previously reported.

JC polyomavirus nephropathy confirmed by using an in-house polymerase chain reaction method.

We report the case of an isolated JC virus (JCV) infection, without co-infection by polyoma BK virus (BKV), associated with nephropathy 4 years after kidney transplantation. Clinical suspicion followed the observation of a decrease in estimated glomerular filtration rate (eGFR) and a renal allograft biopsy revealing polyomavirus-associated tubulointerstitial nephritis and positivity for SV40. An in-house real-time polymerase chain reaction assay, targeting the presence of JCV and the absence of BKV in biopsy tissue, confirmed diagnosis. Thirteen months after diagnosis, and following therapeutic measures, eGFR remains stable.

New law of renal transplantation in Portugal associated with more acute rejection episodes and higher costs.

The new law implemented in August 2007 changed the criteria to select renal transplantation (RT) candidates in Portugal, favoring hyperimmunized subjects and those on the waiting list for a longer time, making human leukocyte antigen (HLA) compatibilities less important. The authors compared patients who received a deceased donor kidney between 2005 and 2010. Patients were divided in group A who underwent transplantation before August 2007 (n = 132) and group B (n = 125) after that date. We considered a value of P < .05. Overall mean age at RT was 46.6 ± 13.9 years with 58.8% men, 88% on hemodialysis (HD), with a mean dialysis time of 82.8 ± 119 months. Also, 10.5% of patients underwent a previous transplantation. The mean follow-up was 35 ± 17.1 months. Group B showed significant adverse differences, including dialysis time (50.9 vs. 117 months), length of hospitalization (14.4 vs. 23.2 days), need for HD (1 vs. 3.4 days), HLA match (3.3 vs. 1.4 compatibilities), previous sensitization (4.4% vs. 21.7%), acute rejection episodes in the 1st year (23% vs. 37%), greater use of immunosuppressive drugs, higher costs of induction therapy (2790 vs 4360ϵ), and greater costs of drugs during first hospitalization (3456 vs. 7144ϵ). Among the 16 subjects who lost their grafts, 7 were in group A (3 in the first year) and 9 in group B all in the first year. There was a 5.1% decrease in graft survival at 12 months (P = .07). Univariate analysis showed an association of acute rejection episodes with HLA mismatches, hyperimmunized patients, absence of immediate graft function, hospitalization time, longer HD need, and higher creatinine level at months 1, 2, 3, and 6. Multivariate analysis revealed acute rejection episodes to be associated with a lower number of HLA compatibilities (odds ratio = 0.65; 95% confidence interval, [0.46-0.9]). Application of the law has led to a greater number of acute rejection episodes in the first year and increased costs.

Prevention of cytomegalovirus disease in renal transplantation: single-center experience.

Cytomegalovirus (CMV) infection and CMV disease remain important issues in renal transplantation. Incidence depends on individual patient risk. There are different possible strategies for CMV prophylaxis. In our center CMV prevention includes prophylaxis with low-dose valganciclovir for all high-risk recipients; for the remaining patients, valganciclovir is only prescribed when there is evidence of CMV replication. All recipients are monitored for viral replication. We evaluated the results of this preventive strategy in all 135 patients who underwent transplantation between 2006 and 2007 in our center. Average follow-up time was 16 months (6-30 months). Fifty-one recipients (38%) received CMV prophylaxis. The median duration of prophylaxis was 84 days. In 37% of the recipients (50 patients) CMV antigenemia became positive, and were given therapeutic doses of valganciclovir. Of these patients, 32% were high-risk recipients undergoing prophylaxis. CMV infection rate was 40% in the group not receiving prophylaxis. No association was observed between CMV infection and prophylaxis duration. However, 50% of patients who suspended prophylaxis before completion of the first 3 months became infected. There were 3 cases of CMV disease (2.2%). Leukopenia was seen in 34% of patients receiving prophylaxis. Valganciclovir prophylaxis for high-risk patients seems to be effective and safe among subjects who complete the full duration of treatment. Despite CMV-positive antigenemia in 40% of patients not undergoing prophylaxis, pre-emptive therapy with valganciclovir was effective to prevent CMV disease, but close monitoring is essential for disease prevention.

[Consequences of the correction of post-transplantation hypophosphatemia on mineral metabolism]. / Consequências no metabolismo mineral da correcção da hipofosfatemia pós-transplante.

AIM: To study the effect of the correction of post-transplantation Hypophosphatemia on mineral metabolism. PATIENTS: 15 patients with renal transplants for 3 to 12 months, Serum Creatinine "177 micmol/1, were treated with oral phosphorus (P) for persistent hypophosphatemia. METHODS: 3 periods of blood and urine collection at intervals of 3 weeks. T1 under basal treatment with oral P, T2 after 3 weeks off medication with P, Ca, or P binders. T3 3 weeks after going back on oral P supplements. RESULTS: Serum P dropped from T1 to T2 (1.03 +/- 0.03 mmol/L to 0.83 +/- 0.03 mmol/L, p "0.0001), rising again in T3 to 1.06 +/- 0.03 mmol/L. From T1 to T2, PTHi decreased from 95.4 +/- 8.7 to 66.8 8.9pg/ml), osteocalcin rose from 3.8 +/- 1.2 to 16.6 +/- 2.3ng/ml (p<0.001) and 25-Vit D rose from 16.7 +/- 1.9 to 21.4 +/- 2.1 ng/l (p<0.001), with the reversal of these changes from T2 to T3 when serum P increased once again. There was a significant correlation between serum P and PTHi and serum P and 25-Vit D. There were no significant variations of the serum Ca, Alk. Phosph., ICTP and CaFE values in the three periods. CONCLUSIONS: 1-Serum P never dropped below 0.55 mmol/L, which had no clinical consequences, 2- When the P dropped, PTHi also dropped and osteocalcin and 25-Vit D rose, without any major variation in bone catabolism, 3- Correction of hypophosphatemia may delay recovery from secondary hyperparathyroidism.

[Hemodialysis with bicarbonate 30 mEq/l versus 34 mEq/l and acetate: better hemodynamic tolerance and electrolyte and acid-base homeostasis]. / Hemodiálise com bicarbonato 30 mEq/l versus 34 mEq/l e acetato: a melhor tolerância hemodinâmica e homeostasia electrolítica e ácido-base.

The use of bicarbonate buffer in dialysis is more physiological than acetate. The aim of this prospective study was to compare the hemodynamic stability, acid-base and electrolyte balance changes in a group of 5 hospital hemodialysis (HD) patients, with 3 different dialysis fluids: one with 30 mEq/l of bicarbonate (B30), another with 34 mEq/l of bicarbonate (B34) and the last with acetate (ACE). All the patients had more than 12 months in HD. Each patient had HD treatment with one of the 3 different dialysis fluids: ACE, B30, B34. Each HD had a duration of 4 hours, with less than 5% dry weight ultrafiltration (UF) and continuous cardiac monitoring. The following clinical and laboratory data were evaluated: arterial blood pressure (BP), cardiac rate (CR), respiratory rate (RR), cardiac arrhythmias, blood urea, creatinine, sodium, potassium, magnesium, total calcium (Ca), ionised calcium (Ca++), pH, bicarbonate (HCO3-) and pCO2. Statistic analysis was performed using Student's paired t test and ANOVA with Bonferroni correction. Clinical evaluation showed a CR increase only in the ACE group (pre X = 78.4 to 4 degrees h X = 102.6 p < 0.001). Analytical results demonstrated, at the 1st h, Ca++ stability in the B30 group; in the first 30' the pH decreased in the ACE group (pre X = 7.35 to 30' X = 7.34); during HD, HCO3- was not corrected in the ACE group (pre X = 19.4 to 4th h X = 20.0); at 4th, pCO2 also decreased in this group (pre X = 34.5 to 4th h X = 28.4 p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Subcutaneous recombinant human erythropoietin in hemodialysis and continuous ambulatory peritoneal dialysis.

We compared the effect of twice weekly subcutaneous recombinant human erythropoietin (SC rHuEPO) in two groups of patients treated with a starting dose of 80 U/kg body weight/week: group I, 7 hemodialysis (HD) patients; group II, 8 continuous ambulatory peritoneal dialysis (CAPD) patients. In a third group (group III) of 4 patients transferred from HD to CAPD with anemia previously corrected with intravenous (IV) rHuEPO, we studied the changes in the maintenance SC dose to maintain the same hemoglobin. In groups I and II the mean SC doses required to correct anemia and to maintain hemoglobin/hematocrit levels were similar; the mean time for the correction of anemia was significantly longer in HD patients (p = 0.032). In group III the maintenance SC rHuEPO does was reduced to more than 50% at 12 weeks of CAPD. Subcutaneous rHuEPO is effective in reversing anemia in HD and CAPD patients, but it takes longer to correct anemia in HD with the same initial SC rHuEPO low dose. CAPD patients need lower doses of SC rHuEPO than HD patients in IV therapy to maintain the same hemoglobin levels.

[Identification of a period of renal ischemic vulnerability studying the changes in the indicators of acute renal insufficiency after heart surgery with extracorporeal circulation]. / Identificação de um período de vulnerabilidade isquémica renal pelo estudo da evolução dos indicadores de insuficiência renal aguda após cirurgia cardíaca sob circulação extra corporal.

We studied the pre operative status and the 1st, 4th, 12th and 24th hours of the post operative period after open heart surgery with cardiopulmonary bypass with a crystalloid solution containing 10 gr of mannitol. We considered acute renal failure (ARF) as being any increase in plasma creatinine values of 0.25 mg/dl for the first 24 hours and 0.5 mg/dl for periods longer than 24 hours. Six patients had transitory ARF (28.5%). The maximum value of plasma creatinine was 2.3 mg/dl and no patients required renal function substitution. There were no deaths. We used as ischemia ARF indicators the urinary flow rate, urine/plasma creatinine ratio, urine/plasma osmolality ratio, sodium fractional excretion and free water reabsorption. We also measured the urinary N-A-Glucosaminidase (NAG). We found that creatinine clearance reached its lowest in the first and fourth hours. Beyond the fourth hour we observed, the urinary flow rate reduce significantly, the urine/plasma creatinine and osmolality ratios reach values traditionally associated prerenal ARF, an increase main free water reabsorption and a decrease in sodium fractional excretion with a close relationship between the less than 1 value and the increase in plasma creatinine. There was a significant NAG increase in the 24 th hour. The evidence of a vulnerability period for renal ischemic lesions between the 4 th and 12 th hour suggests a second mannitol administration during the first four hours of the post operative period.

[Prevention of thrombogenesis in the extracorporeal circuit of hemodialysis with a low molecular heparin: standardization of the dosage with a better hemorrhagic risk/effectiveness ratio]. / Prevenção da trombogénese no circuito extracorporal de hemodiálise com uma heparina de baixo peso molecular: padronização da dose com melhor relação risco hemorrágico/eficácia operacional.

PURPOSE: To test the efficacy and safety of a low molecular. Weight heparin (LMWH)--Fraxiparine, for hemodialysis (HD) anticoagulation, compared with conventional heparin (H) or serum lavage without other anticoagulation (L). DESIGN: Prospective controlled study. PATIENTS AND METHODS: Twenty-nine consecutive patients referred for dialysis in a tertiary care hospital were divided in 3 groups A, B and C, each group A and B patient submitted to 2 dialysis, AI and AII, BI and BII. Group A--n = 10, no bleeding risk, single needle technique, blood flow (Qb) less than 200 ml/min. HD-AI used LMWH 10,000 U pre-HD, HD-AII used H for an ACT 1.5 to 2 times baseline; group B--n = 10, high bleeding risk, double needle dialysis, Qb--200 to 300 ml/min. HD-BI used LMWH 5000 U pre-HD, and HD-BII used only L; Group C--n = 9, no bleeding risk, Qb less than 200 ml/min, all received LMWH 5000 U pre-HD. A semiquantitative screening was done in each dialysis for the presence of dialyser or venous chamber clots, APTT and Anti Xa activity were measured every 30 min., as well as pre and post-dialysis Hb, Htc, and platelets. RESULTS: APTT didn't rise significantly during HD with LMWH in contrast with the AII group with H (32.2 +/- 7.1 vs 63 +/- 25.8, p less than 0.05). The APTT levels in all dialysis with LMWH were identical to BII dialysis With L. Anti xa activity had an early peak at 30 to 60 min. With LMWH (0.62 +/- 0.45 em AI) and a late one at 180 min with H (0.39 +/- 0.2). There was no significant differences between pre and post-dialysis corrected platelet counts, but the lavage group showed the greater decrements (-20% +/- 24). In all the 49 dialysis we had 5 cases of complete clotting of the blood circuit, all of them in the lavage group C. No patients with high risk of hemorrhage had any bleeding increment. CONCLUSION: LMWH prevents clotting as effectively as H, in low doses of 5000 anti Xa units it doesn't interfere with PTT and is far more effective than HD with serum lavage in patients with bleeding risk and/or low blood flow in the dialysis circuit.