Prevalence and Risk Factors of BK Viremia in Patients With Kidney Transplantation: A Single-Center Experience From Turkey.

BACKGROUND: BK virus is the cause of nephropathy, which can progress to graft loss after kidney transplantation. In this study, we aimed to investigate the prevalence and risk factors of BK viremia in patients with kidney transplantation at our center. METHODS: This was a retrospective single-center study. We included recipients transplanted between 2010 and 2015. Patients were stratified according to BK virus DNA follow-up values into three groups (0-999 copies/mL, 1000-9999 copies/mL and ≥10,000 copies/mL). The parametric t test and the non-parametric χ2 test were used to detect differences between groups. Multivariate analysis was used to identify risk factors for BK viremia. RESULTS: One hundred eighty-three patients were included in the study, with mean follow-up time of 33.6 ± 14.9 months. BK viremia prevalence was found 15.8% (n = 29), and time to detection of viremia was 7.6 months. Cadaveric transplantation and matching human leukocyte antigen (HLA) A24 and HLA B55 subgroups were found to be independent risk factors for BK viremia [odds ratio (OR), 3.65; 95% confidence interval (CI), 1.42-9.39; P < .001; OR, 4.94; 95% CI, 1.84-13.2; P < .001 and OR, 14.03; 95% CI, 1.07-183.5; P = .04, respectively]. Risk factors for BKV level ≥10,000 copies/mL cadaveric transplantation, male sex, and HLA A24 matching (OR, 4.53; 95% CI, 1.49-13.7; P < .001; OR, 3.47; 95% CI, 1.11-10.86; P = .03 and OR, 3.63; 95% CI, 1.08-12.1; P = .03, respectively). CONCLUSIONS: Patients should be followed more carefully for BK viremia who have cadaveric transplantation, are male, and have matching in certain HLA groups, which were independent risk factors in the present study. Our results are important to individualize screening methods and provide early diagnosis in our country.

Urgency Priority in Kidney Transplantation: Experience in Turkey.

BACKGROUND: In Turkey, according to the directions of National Organ and Tissue Transplant Coordination System, a system has been established since 2008 of urgency priority for kidney transplantation in cases with imminent lack of access for either hemodialysis or peritoneal dialysis. In this study, we compared patient and graft outcomes between patients on the national waiting list having urgency priority for kidney transplantation (UKT) and those having the other kidney from the same deceased donor (control group). METHODS: We examined retrospective data of patients, who underwent transplantation under urgency priority allocation in Turkey from 2010 to 2014 and compared that group with other patients receiving kidney transplants from the same deceased donors (control group). Then we compared these patients for early and long-term patient and graft outcomes. RESULTS: Forty-seven patients had UKT, and 40 patients received transplants from the same deceased donors. Mean follow-up of patients after transplantation was 18 ± 12 months. Eight patients with UKT and 4 patients in the control group lost their grafts. At follow-up, 7 patients died in the UKT group, and 4 patients died in the control group. Patient survival in the UKT group was 90% at 1 year and 83% at 2 years, and in the control group was 93% at 1 year and 84% at 2 years (P = .384). Graft survival was 87% at 1 year and 81% at 2 years in UKT, and 91% at both 1 and 2 years in the control group (P = .260). CONCLUSIONS: Although patients with UKT showed lower graft and patient survivals than the control group, the difference was statistically nonsignificant. UKT can be an obligatory treatment model for patients with lack of vascular or peritoneal access for dialysis.

Pregnancy After Kidney Transplantation: Outcomes, Tacrolimus Doses, and Trough Levels.

Although pregnancy after kidney transplantation has been considered as high risk for maternal and fetal complications, it can be successful in properly selected patients. It is well known that pregnancy can induce changes in the plasma concentrations of some drugs; however, there has been very limited information about tacrolimus pharmacokinetics during pregnancy. In this study, we evaluated the tacrolimus doses, blood levels, and the outcomes of pregnancies in kidney allograft recipients. From 2004 to 2014, we found 16 pregnancies in 12 kidney allograft recipients at our center. We reviewed the files and data reports including fetal outcomes, graft function, complications, tacrolimus trough levels, and doses. We analyzed the tacrolimus trough levels and doses before pregnancy, during pregnancy (monthly), and in the postpartum period. Throughout the pregnancy, we aimed to achieve tacrolimus trough levels between 4 and 7 ng/mL. All patients were on triple immunosuppression, including tacrolimus, azathioprine, and prednisolone. In total, 11 of 16 (68.7%) pregnancies were successful, with a mean weight gain of 12.5 ± 1.66 kg. One patient developed gestational diabetes mellitus and 2 had preeclampsia. Although 5 of 11 babies were found to have low birth weight, 4 of these were premature. Two patients lost their grafts, 1 due to acute rejection and the second due to progression of chronic allograft dysfunction. We have shown that tacrolimus doses need to be significantly increased to keep appropriate trough levels during pregnancy (the doses: before, 3.20 ± 0.9 mg/day; first trimester, 5.03 ± 1.5; second trimester, 6.50 ± 1.8; third trimester, 7.30 ± 2.3; post-partum, 3.5 ± 0.9). In conclusion, the dose of tacrolimus needs to be increased to provide safe and stable tacrolimus trough levels during pregnancy. Although pregnancy can be successful in most cases, it should be kept in mind that there is an increased risk of maternal and fetal complications, including allograft loss, low birth weight, spontaneous abortus, and preeclampsia.

Evaluation of Infectious Complications in the First Year After Kidney Transplantation.

Kidney transplantation (KT) is the best available therapy for patients with end-stage renal disease. Infectious complications are a common cause of morbidity and mortality. In this study, we evaluated the risk factors and outcomes of infectious complications in the first year after transplantation. This is a retrospective and observational study of kidney transplant recipients at Ankara University's Ibni Sina Hospital between January 2009 and August 2013. A total of 206 kidney transplant recipients were evaluated. In 129 patients, 298 infectious episodes occurred: 55 (26.7%) had 1; 33 (16%) 2; 19 (9.2%) 3; 7 (3.4%) 4; and 15 (7.3%) had 5 or more infectious episodes. The most common bacterial infection was urinary tract infection (128, 42.9%). Only 4 urinary tract infection episodes (3.1%) were associated with bacteriemia. Seventeen patients (5.7%) had bacteremia. Viral infections after transplantation were CMV infection (10.1%), BK virus infection (5.7%), and zona zoster (1.1%). Deceased donor kidney transplantation was the independent risk factor. Mean follow-up period was 66 months and was the same for the patients with and without infections. There was no significant difference in 5-year survival and creatinine levels at the last follow-up (logrank P = .409). Infections are the second most common cause of mortality in KT patients. The successful treatment of these complications and effective prophylaxis may decrease these complications.

Predictive Role of Neutrophil Gelatinase-Associated Lipocaline in Donor-Specific Antibody-Positive and Donor-Specific Antibody-Negative Renal Transplant Patients.

BACKGROUND: Renal transplantation is the best choice for the treatment of dialysis patients with end-stage renal failure because it provides better quality of life and more life time. However, despite successful surgical techniques, immunological issues in kidney transplantation are not completely resolved. Thus, after transplantation, patients must be followed up closely. Although patient follow-up with the use of creatinine and renal biopsy are common, it is thought that biopsy is too invasive and that creatinine is unreliable. Hence, new parameters that correlate with the patient's immunological condition are needed in clinical monitoring. METHODS: One of the biomarkers that has been studied recently is neutrophil gelatinase-associated lipocalin (NGAL). Its diagnostic value in cases of acute renal failure, delayed graft function, and IgA nephropathy is widely investigated. However, data are insufficient as to whether NGAL can be used for follow-up in the chronic process after renal transplantation. We aimed to investigate the predictive value of NGAL in terms of rejection in donor-specific antibody (DSA)-positive and DSA-negative renal transplant patients. Ninety patients were included. RESULTS: We found that rejection rates were higher in patients whose NGAL values were ≥ 50 and DSA-positive. Delayed graft function was seen more frequently in patients whose NGAL values were ≥ 50. CONCLUSIONS: An increase in NGAL level does not always indicate renal injury because NGAL is also an acute-phase reactant. NGAL cannot be used alone to diagnose rejection, but, if NGAL level is high, it is necessary to study DSA, and sub-clinical rejection must be researched.

Kidney transplantation from hepatitis B (HB)-positive donors to HB negative recipients: anti-HB Core immunoglobulin G became positive in all recipients after the transplantation.

OBJECTIVE: Hepatitis B surface antigen (HBsAg)-positive donors are not accepted by many transplant centers as a kidney source owing to risk of transmission of hepatitis B; however, some reports show that these donors can be used under a special protocol. Herein, we report our cases of kidney transplantation from HBsAg(+) donors to HbsAg(-) recipients. METHODS: In the years 2010-2012, we transplanted 4 kidneys from 4 HBsAg(+) donors to HBsAg(-) recipients. They were all living related. All antiHBs(-) recipients were vaccinated before transplantation and became HBsAg(-), anti-HB core immunoglobulin G antibody negative [antiHBcIg(-)], and antiHBs(+). Pretransplantation antiHBs titers were targeted to be >100 IU. If lower, hepatitis B Ig was used at the time of transplantation. One patient received hepatitis B Ig at the time of transplantation (owing to titer of 62 IU/L antiHBs). Lamivudine was prescribed for all kidney allograft recipients after transplantation. RESULTS: Two patients had special induction treatment including rituximab, intravenous immunoglobulin, and plasmapheresis owing to the presence of donor-specific antibody. CONCLUSIONS: All patients became antiHBcIgG(+) at 1-6 months after the transplantation, despite the presence of antiHBs positivity, which might be explained by transmission of hepatitis B virus through the graft.

Kidney transplantation in immunologically high-risk patients.

An increased number of sensitized patients await kidney transplantation (KTx). Sensitization has a major impact on patient mortality and morbidity due to prolonged waiting time and may preclude live donor transplantation. However, recent reports have shown that KTx can be performed successfully using novel immunosuppressive protocols. This study presents our experience with patients displaying donor-specific antibody (DSA) (+). We enrolled 5 lymphocyte cross-match (LCM) negative (complement-dependent cytotoxicity) and panel-reactive antibody (PRA) plus DSA-positive patients mean fluorescein intensity [MFI] > 1000) who underwent living kidney donor procedures. All subjects were females and their mean age was 36.7 years. In our protocol, we started mycophenolate mofetil (2 g/d), tacrolimus (0.01 mg/kg) and prednisolone (0.5 mg/kg) on day -6. We performed 2 sessions of total plasma exchange (TPE) with albumin replacement and administered 2 doses of IVIG (5 g/d). On day -1, we added rituximab (200 mg). On the operation day and on day +4, the patients received doses of basiliximab. Serum samples were taken on days -6, 0, and 30 as well as at 1 year after transplantation. All patients displayed immediate graft function. Mean basal DSA titer was 5624 MFI. After desensitization, the MFI titers decreased at the time of transplantation to 2753 MFI, and were 2564 MFI at the 1st month and 802 MFI at 1st year. Three patients experienced acute rejection episodes (60%). After treatment for rejection, the average follow-up was 17 months and last creatinine levels were 0.6-0.8 mg/dL (minimum-maximum). In conclusion, KTx can be succesfully performed in sensitized patients displaying DSA. However, there seems to be a greater acute rejection risk. There is no consensus regarding adequate doses of IVIG or plasmapheresis treatments; furthermore, more studies are needed to clarify the safe MFI titer of the DSA.

Urinary angiotensinogen level is correlated with proteinuria in renal transplant recipients.

OBJECTIVE: Along with immunologic mechanisms, intrarenal renin-angiotensin system (RAS) activation has been suggested to play a role in the development and progression of chronic allograft injury. In various glomerular diseases, urinary angiotensinogen (AGT) level is a good indicator for the activation of intrarenal RAS. In this study, we aimed to investigate the parameters associated with urinary AGT level in patients with kidney transplantation. METHODS: Seventy renal transplant patients with stable graft function (≥ 6 months after transplantation, serum creatinine level <2 mg/dL) and 21 healthy volunteers were included in the study. Patients were taking standard triple immunosuppressive treatment. Demographic characteristics of patients and healthy volunteers, drug use, and 24-hour ambulatory blood pressure measurements were recorded. Morning second urine and fasting blood samples were taken from all participants. Serum biochemical markers and urine Na, K, uric acid, creatinine, and protein levels were measured. Urinary AGT levels were determined by enzyme-linked immunosorbent assay. RESULTS: Mean systolic and diastolic blood pressures in patients with renal transplantation were higher than in healthy volunteers. Both urinary AGT-urinary creatinine ratio (UAGT/UCr) and urinary protein-urinary creatinine ratio (UPro/UCr) were higher in kidney transplant patients than in healthy volunteers (P < .01; P < .0001; respectively). In patients with renal transplantation, UAGT/UCr was positively correlated with UPro/UCr and negatively correlated with estimated glomerular filtration rate (eGFR) (r = 0.738; P = .01; and r = -0.397; P = .01; respectively). There was no correlation between UAGT/UCr and other study parameters, including bood pressure levels. CONCLUSIONS: Our findings indicate that high urinary excretion of AGT is associated with proteinuria and lower eGFR in kidney transplant recipients without overt chronic allograft injury. These preliminary results encourage us to design a long-term longitudinal analysis using urinary AGT along with multiple markers to obtain early diagnosis and to predict the prognosis of chronic allograft dysfunction.

Constrictive pericarditis after renal transplantation: three case reports.

INTRODUCTION: Pericardial exposure can be see in chronic kidney disease, but constrictive pericarditis (CP) development, which is usually present with signs of right-sided heart failure is rare. In renal transplant recipients CP can lead to graft dysfunction and serious liver disease. We present herein 3 such CP patients. PATIENT 1: A 37-year-old male patient with end-stage renal disease (ESRD) due to membranoproliferative glomerulonephritis was on chronic hemodialysis (HD). He underwent living donor kidney transplantation in 1995. In 2006 he was admitted with complaints of shortness of breath, weakness, and abdominal distention. PATIENT 2: A 17-year-old male patient with ESRD due to vesicoureteral reflux had 6 months of HD and underwent living donor kidney transplantation in 2008. Six months after transplantation, he showed leg edema, massive ascites, hepatosplenomegaly, and pretibial edema. PATIENT 3: A 52-year-old male patient was 21 years after HD initiation when cadaveric donor kidney transplantation was performed in August 2011. Four months after transplantation, he presented with a shortness of breath and fatigue. Echocardiography revealed 2-3 degree aortic regurgitation and increased pericardial brightness. CONCLUSION: All patients underwent right-sided heart catheterization, leading to a diagnosis of constrictive pericarditis, requiring total pericardiectom. Pathological examination of the pericardium showed typical diffuse fibrosis.

Nephron-sparing surgery for renal cell carcinoma of the allograft after renal transplantation: report of two cases.

The risk of renal transplanation patients developing de novo malignancy is increased 100-fold compared with the healthy nontransplantation population. Renal cell carcinoma (RCC) arising from native kidneys is diagnosed among up to 4.6% of the renal transplant recipients as a consequence of immunosuppression. These tumors tend to behave more aggressively.(1) Although tumors occurring in allografted kidneys can be treated by partial (to save functional graft) or total nephrectomy, there is a paucity of data the outcomes. From 1978 to 2012, we performed 804 kidney transplantations including two cases in which RCC arose from the allografted kidney, both of which were treated with nephron-sparing surgery. The first patient has been followed for 30 months with a well functioning graft without an RCC recurrence. The second patient has returned to dialysis after 6 months due to an insufficient remnant nephron mass. In conclusion, nephron-sparing surgery is a novel alternative to total nephrectomy for allograft RCC. The remaining kidney can preserve function and the patient may not need chronic dialysis.