Polymerase Chain Reaction Viral Load Research Articles

Prevalence, Risk Factors, Treatment, and Overall Impact of BK Viremia on Kidney Transplantation

BK viremia (BKV) is a recognized and potentially serious problem in renal transplantation. The risk factors and the impact of BKV on renal allograft and patient survival are controversial. This study reports an 8-year, single-center experience on the prevalence, risk factors, and outcomes of BKV in kidney transplant recipients. This is a retrospective analysis of all patients who received a kidney transplant at the University of Kentucky and had BK viral titers available from 2009 to 2017. BKV was defined by a polymerase chain reaction viral load of ≥ 10,000 copies per mL. Demographic, clinical, and laboratory data generated during routine outpatient follow up and inpatients records were collected. Independent risk factors for BKV were determined using uni- and multivariate analysis. Graft and patient survival was compared using Kaplan-Meier analysis, and the severity of polyomavirus nephropathy on biopsy was scored using the Banff 2017 classification. We identified 122 BK positive (19%) and 527 BK negative (81%) patients. BKV developed after a median of 115 days (range, 80–249 days) following kidney transplantation. The 1-, 5-, and 10-year graft survival was 97%, 75%, and 33% in the BKV group and 96%, 85%, and 71% in the BK negative group, respectively. Likewise, the 1-, 5-, and 10-year patient survival was 98%, 84%, and 52% in the BKV group and 98%, 92%, and 84% in the BK negative group. Male sex, age at transplantation, maintenance steroids, and alemtuzumab induction were associated with developing BKV in the multivariate analysis. We concluded that BKV is not uncommon after renal transplantation. The determinants for BKV are male sex, older transplant recipients, and maintenance steroids. BKV adversely affected graft and patient survival. A unified approach for BKV and polyomavirus nephropathy treatment is needed.

Cytomegalovirus Viral Load in Bronchoalveolar Lavage to Diagnose Lung Transplant Associated CMV Pneumonia.

The diagnostic yield for cytomegalovirus (CMV) polymerase chain reaction (PCR) viral load in bronchoalveolar lavage (BAL) or in plasma to diagnose CMV pneumonia in lung transplant recipients remains uncertain and was investigated in a large cohort of consecutive lung transplant recipients. Bronchoscopies within the first year of lung transplantation with CMV detectable in BAL by PCR (ie, viral load, ≥273 IU/mL) were included (66 recipients; 145 bronchoscopies); at each bronchoscopy episode, 2 independent experts reviewed clinical and laboratory information to determine whether the patient at that time fulfilled the criteria for CMV pneumonia per current international recommendations. Corresponding plasma CMV PCR viral load determined at time of the bronchoscopy (n = 126) was also studied. Optimal CMV PCR viral load cutoff for CMV pneumonia diagnosis was determined using receiver operating characteristics. CMV was detected in BAL with CMV PCR in 145 episodes, and 34 (23%) of these episodes fulfilled the criteria for CMV pneumonia. The area under the curve-receiver operating characteristics for CMV in BAL was 90% at the optimum cutoff (4545 IU/mL) with a corresponding sensitivity of 91% and specificity of 77% (in plasma the corresponding values were 274 IU/mL, 63% and 76%, respectively). CMV PCR viral load in BAL had a high performance to diagnose CMV pneumonia in lung transplant recipients; plasma CMV viral load did not reliably aid as a diagnostic tool.

Prevalence of Polyomavirus Among United Arab Emirates Kidney Transplant Recipients: Results From a Single Center

BackgroundBK viremia and nephropathy are increasing problems in renal transplant recipients. The absence of a safe and effective antiviral therapy made screening-based prevention a recommended strategy. The prevalence of its reactivation among recipients of kidney transplants in the Middle East has not been well established. Our objective was to determine the prevalence of BK virus (BKV) infection for renal transplant recipients at our medical center. MethodsAll renal transplant recipients followed up in our transplantation clinic between 2012 and 2013 (n = 116) were screened. Urine and blood quantitative real-time polymerase chain reaction (PCR) for the BKV were performed in all of the study patients. Renal biopsy was performed only in patients with deteriorating renal function associated with positive PCR. Patients who showed positive BKV PCR were followed up for 6 to 12 months. This included clinical and kidney function assessment along with BKV PCR viral load. ResultsAmong the 116 kidney transplant recipients studied, 65 (56%) were male, age 51 ± 15 years, with a transplantation vintage of 131 ± 61 months; 17 (14.7%) were positive for BKV PCR. Three (2.7%) showed viremia; 2 of them had deterioration of kidney function, renal biopsy confirmed the diagnosis of BK nephropathy (NP) in both cases. The 3 cases were managed by reducing the immunosuppressive treatment with stabilization of their kidney function. Cases with stable renal function and positive urine for BKV cleared the virus spontaneously during follow-up after minor reduction of the immunosuppressive treatment or without any intervention. None of our patients lost the graft due to BK NP. ConclusionOur study suggests that BKV is not uncommon in our kidney transplant recipients. Routine screening suggested by the KDIGO Guidelines could help minimize its detrimental impact on the transplant outcome.

Occurrence of the polyomavirus among kidney transplant recipients: A single-center study

Polyoma virus-associated nephropathy is an increasingly recognized cause of graft dysfunction among kidney transplant recipients and could be the result of use of potent immunosuppression following transplantation. Because there is no safe and effective anti-viral therapy available presently, screening-based prevention and pre-emptive strategy are recommended. This study, which was conducted at the Nephrology Unit, Internal Medicine Department, Alexandria University, consisted of two phases: Phase 1 was a cross-sectional study and phase 2 was a 6-month follow-up study only for polyoma virus-positive cases. Phase 1 included 75 renal allograft recipients from living donors. Urine cytology for decoy cells and quantitative real-time blood polymerase chain reaction (PCR) for the BK virus (BKV) were performed on all the study patients. Renal biopsy was performed only in patients with deteriorating renal function associated with positive urine cytology. Patients who showed positive urine cytology for decoy cells and/or positive quantitative BKV PCR assay were followed-up for six months. During follow-up, the serum creatinine level, with or without urine cytology for decoy cells, and BKV PCR viral load assay were performed. Among the 75 kidney transplant recipients studied, eight were positive for decoy cells (11%), three showed viremia by quantitative PCR for BKV (4.1%), while two others showed nephropathy (2.7%) in the form of tubulointerstitial nephritis with intra-nuclear inclusions in the tubular cells. Cases with stable renal function and positive decoy cells or viremia cleared the virus spontaneously during follow-up without any intervention. Only one case with biopsyproven nephropathy and deteriorating graft function, with undetectable BKV in blood, lost the graft while another case with viremia died during follow-up due to septicemia. Our study suggests that polyoma virus should be considered as a cause of nephropathy in renal transplant recipients. Further research is required to understand this entity better.

The impact of surveillance and rapid reduction in immunosuppression to control BK virus-related graft injury in kidney transplantation

We prospectively screened 609 consecutive kidney (538) and kidney-pancreas (71) transplant recipients for BK viremia over a 4-year interval using polymerase chain reaction viral load detection and protocol kidney biopsies. We found that BK viremia is common at our center: total cases 26.7%, cases during first year 21.3% (mean 4 months), and recipients with ≥ 10 000 copies/ml 12.3%. We found few predictive clinical or demographic risk factors for any BK viremia or viral loads ≥ 10,000 copies/ml, other than prior treatment of biopsy confirmed acute rejection and/or higher immunosuppressive blood levels of tacrolimus (P = 0.001) or mycophenolate mofetil (P = 0.007). Viral loads at diagnosis (<10 000 copies/ml) demonstrated little impact on graft function or survival. However, rising copy numbers demand early reductions in immunosuppressive drug doses of at least 30-50%. Viral loads >185 000 copies/ml at diagnosis were predictive of BK virus-associated nephropathy (BKVAN; OR: 113.25, 95% CI: 17.22-744.6, P < 0.001). Surveillance for BK viremia and rapid reduction of immunosuppression limited the incidence of BKVAN to 1.3%. The addition of leflunomide or ciprofloxacin to immunosuppressive dose reduction did not result in greater rates of viral clearance. These data support the role of early surveillance for BK viremia to limit the impact on transplant outcome, although the most effective schedule for screening awaits further investigation.

Evaluation and Treatment of Hepatitis C in Patients with Human Immunodeficiency Virus

The rate of treatment of hepatitis C virus (HCV) infection in human immunodeficiency virus-hepatitis C virus (HIV-HCV) co-infected patients remains historically low. We undertook a retrospective study to review our treatment rate and factors that have negatively influenced this rate. In those treated, we reviewed outcomes and compared results with prior studies. A total of 233 patients infected with HIV and HCV were followed for 7 years in the infectious diseases (ID) clinic of East Carolina University. Proper follow-up evaluation was determined based on the presence of HCV polymerase chain reaction viral load and genotype testing. The number of patients treated, response to treatment, and reason for no treatment were determined by chart review. Of 233 patients with positive HCV serology, 48 were excluded due to undetectable HCV viral load. Of the remaining 185 patients, 142 (77%) were evaluated by testing for HCV viral load and genotype, but only 112 of those who were followed up in the clinic regularly were considered eligible for therapy. Fourteen of 112 (12.5%) of patients underwent treatment and only 1 in 14 (7%) attained sustained virological response (SVR). Of the patients tested, 96% had HCV genotype 1, and 81% were African American. The majority of our HIV-HCV co-infected patients received a proper HCV evaluation, but only 12.5% were offered therapy. Of those treated, only one patient achieved SVR. The higher proportion of genotype 1 and African American patient population are considered the main reasons for the low SVR. Low SVR rate, high rate of adverse effects, and the unique demography of our patient population have been the main reasons for the lower treatment rate.

Can Oral Fluid Testing Be Used to Replace Blood-Based HIV Rapid Testing to Improve Access to Diagnosis in South Africa?

Can Oral Fluid Testing Be Used to Replace Blood-Based HIV Rapid Testing to Improve Access to Diagnosis in South Africa?