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Biomedical subjects

Abdolreza Haririan

Publications and source records attributed to Abdolreza Haririan.

13 recordsLinked to original sources

BK virus infection after non-renal transplantation.

Infection with BK virus (BKV), a member of the Polyomavirus (PV) family, is ubiquitous, with the virus remaining in a latent form in the kidney and urinary tract. This infection is usually asymptomatic, but with impairment of the cellular immune system the virus can reactivate and lead to tissue damage. In recipients of bone marrow and solid organ transplants, PV reactivation can be associated with disease in urinary tract and kidneys. BKV was first discovered in 1971 from the urine of a kidney transplant recipient who had developed ureteral stenosis 4 months after transplantation. While much of the subsequent research focuses on patients after renal transplantation, we will review PV impact in patients after bone marrow transplant (BMT) and those with non-renal solid organ transplants.

BK Virus↗

The effects of blood pressure and lipid control on kidney allograft outcome.

Despite the improvement in short- and long-term kidney allograft survival in recent years, a significant number of grafts are lost because of chronic allograft nephropathy (CAN) or death secondary to cardiovascular disease (CVD). There is growing evidence that both hypertension and hyperlipidemia play important roles in the progression of CAN and CVD in kidney transplant recipients. Large, randomized, controlled studies to determine the optimal target levels for BP and serum lipids, as well as the choice of drug therapy, are lacking. However, based on the available data, we suggest that currently recommended target levels in non-transplant patients should also be used after transplantation. We believe that achieving these target levels for BP and serum lipids are of primary importance, and that the non-lipid-lowering effects of HMG-CoA reductase inhibitors might exert additional benefits in prolonging graft survival.

Blood Pressure↗

Induction therapy with basiliximab versus Thymoglobulin in African-American kidney transplant recipients.

BACKGROUND: It has been suggested that the use of antilymphocyte induction therapy in African-American (AA) renal transplant recipients reduces the risk of acute rejection (AR) and improves graft survival. It is not clear whether the efficacy of basiliximab (BSX) is different from that of Thymoglobulin (ATG) in this regard. METHODS: We retrospectively assessed the effect of induction therapy with BSX versus ATG in 88 AA renal allograft recipients receiving transplants at our center between July 2001 and June 2003 and followed for 19+/-7 months. All patients were maintained on mycophenolate mofetil, prednisone, and either tacrolimus or sirolimus. Study endpoints included patient and graft survival, graft function, and incidence of AR and cytomegalovirus infection. Regression models were used to evaluate the independent effect of each induction agent on these endpoints. RESULTS: Thirty-six patients received ATG, and 52 received BSX. The groups were comparable with regard to donor race and age, and recipient sex, body mass index, human leukocyte antigen (HLA) matching, and hepatitis C virus serostatus. The ATG group was younger, more likely to receive retransplant, had longer duration of end-stage renal disease and higher panel reactive antibody, and was less likely to receive live-donor organs. However, after adjusting for all these variables, graft outcomes, as well as renal function, were comparable between the two induction groups. We found that the degree of HLA mismatch, delayed graft function, and AR were the only significant predictors of graft loss. CONCLUSION: The results of our study suggest that the choice of induction agent may not have a major impact on graft outcomes in AA renal-allograft recipients.

Adult↗

A SAGE-based comparison between glomerular and aortic endothelial cells.

Endothelial cells have many characteristics in common, but significant morphological and functional differences exist between endothelial cells from different anatomic sites. The specific glomerular endothelial (GEn) cell transcript repertoire is unknown. We sought to determine whether endothelial cells derived from bovine glomeruli display a distinct transcriptional profile compared with bovine aortic endothelium (BAE) under identical conditions. Serial analysis of gene expression (SAGE), which includes known and unknown transcripts, was used to make the comparison. The GEn and BAE SAGE libraries contain 36,844 and 26,452 total tag sequences, respectively. Among 6,524 unique tag sequences represented at least 2 times in the 2 libraries, 2,094 (32%) were matched to well-characterized bovine cDNA sequences (358 tags) or expressed sequence tags (EST). Identification of the human homolog was achieved for 1,035 of these tags. Forty-two tags were differentially expressed in GEn. For 25 of these, the bovine cDNA or EST, and for 17 the human homolog was identified. Among all transcripts with a known bovine and human tag, seven were expressed at levels more than 10-fold higher in cultured GEn cells compared with all other SAGE libraries. The transcript "DKFZp564B076" was localized by in situ hybridization to glomerular endothelium in vivo and was shown by real-time RT-PCR to be highly abundant in glomeruli compared with aortic intima. This work supports the concept that differences in the transcriptional profile of endothelial cells from distinct origins are observed under otherwise equivalent conditions. Furthermore, we have identified the first known transcript predominant in glomerular endothelium in vivo.

Animals↗

Preliminary results with early corticosteroid withdrawal in African American renal allograft recipients.

BACKGROUND: There is a paucity of data regarding the use of steroid-avoidance immunosuppression (SAI) in African American (AA) renal allograft recipients, traditionally considered a high-risk subgroup of patients with higher reported rates of acute rejection and graft loss. METHODS: We compared the outcomes of 27 AA renal allograft recipients receiving SAI (SA group; mean follow-up period, 12 +/- 3 mo) with those of 20 patients receiving a steroid taper (ST group; 24 +/- 11 mo). In both groups, thymoglobulin was used for induction, and mycophenolate mofetil and tacrolimus were used for maintenance. Four doses of methylprednisolone were given on days 0 to 3. In the SA group no further steroids were given, whereas in the ST group a prednisone taper was continued thereafter. RESULTS: ST patients were more likely to have current panel reactive antibody titers greater than 10%, undergo retransplantation, and receive more doses of thymoglobulin. There were no significant differences between the SA and ST groups with regard to patient survival (96% vs 95%), graft survival (96% vs 90%), acute rejection (11% vs 14%), cytomegalovirus infection (7% vs 10%), posttransplant diabetes mellitus (11% vs 24%), or mean serum creatinine concentration at 6 months (1.6 vs 1.5 mg/dL), respectively, with a trend toward less percent weight gain in SA patients at 6 months (5% vs 11%, P = .06). CONCLUSIONS: SAI can produce excellent short-term results in AA kidney transplant patients when compared with a conventional ST protocol. Our results will need to be verified in larger numbers of patients with longer follow-up evaluation.

Acute Disease↗

Cytomegalovirus prophylaxis with valganciclovir in African-American renal allograft recipients based on donor/recipient serostatus.

There is a paucity of data examining the efficacy of valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis in kidney transplant patients, particularly with regard to utilization of a risk-stratified dosing regimen. Eighty adult African-American (AA) renal allograft recipients transplanted from November 3, 2001 to May 28, 2003 and followed for 22 +/- 8 months received VGC once daily for 90 d post-transplant dosed according to donor/recipient (D/R) serostatus: high risk (D+/R-) received 900 mg (n = 12); moderate risk (D+/R+, D-/R+) received 450 mg (n = 60); and low risk (D-/R-) received no prophylaxis (n = 8). Thymoglobulin or basiliximab was used for induction, and mycophenolate mofetil, prednisone, and either tacrolimus or sirolimus for maintenance immunosuppression. Only six patients (7.5%) developed symptomatic CMV infection diagnosed by pp65 antigenemia, three in the high-risk (25%) and three in the moderate-risk (5%) group (p = 0.02). All patients were on tacrolimus for at least 3 months prior to diagnosis. There were no cases of tissue-invasive disease, resistance to treatment, or recurrence. D+/R- serostatus was the only significant independent predictor for CMV infection using multivariate analysis (odds ratio 10.5; p = 0.04). Thymoglobulin induction was not associated with CMV infection. None of 43 patients who were exposed to sirolimus for >30 d developed CMV infection, vs. six of 37 who were not (p = 0.006). We conclude that VGC dosed according to D/R serostatus provides safe and effective CMV prophylaxis in AA renal allograft recipients.

Adult↗

West Nile virus encephalitis: an emerging disease in renal transplant recipients.

West Nile virus (WNV) has emerged as an important cause of several outbreaks of febrile illness and encephalitis in North America over the past few years. The most common manifestation in symptomatic patients is a transient febrile illness. Neuroinvasive disease, that can be fatal, occurs most often in elderly and immunocompromised hosts. The role of this virus as a cause of meninoencephalitis in organ transplant recipients is becoming better recognized. We describe herein the clinical course of two renal allograft recipients who developed WNV encephalitis. One patient developed status epilepticus and eventually died, while the other had a full recovery. In both cases, the diagnosis was confirmed by detection of WNV-specific IgM in CSF or serum, with a delayed antibody response in one patient. This viral infection should be considered in all renal transplant recipients who present with a febrile illness associated with neurological symptoms.

Aged↗

Sirolimus-induced angioedema.

Sirolimus (SRL) is a macrolide immunosuppressant that has gained widespread use in organ transplantation. Its full spectrum of side-effects is yet to be defined. We describe herein three cases of SRL-induced angioedema (AE) in African-American (AA) primary renal allograft recipients who received SRL in combination with mycophenolate mofetil and steroids. In two cases, AE manifested after SRL was restarted after a period of discontinuation. The third case presented upon initial exposure to the drug. None of the patients was receiving any drug that has been previously associated with AE. Complete resolution occurred only after SRL was withdrawn. AE has not recurred in any of the patients during a follow-up period of up to 21 months. We conclude that AE is a previously unrecognized adverse event associated with SRL use. Close monitoring for this side-effect, especially in AA patients, is warranted.

Black or African American↗

Polyomavirus reactivation in native kidneys of pancreas alone allograft recipients.

BACKGROUND: Polyomavirus infection is common in childhood, with a seroprevalence of 60% to 100%. These viruses remain latent mostly in the kidney. Impairment in cellular immunity can allow reactivation of the virus. Reactivation can occur in 10% to 45% of renal allografts. A higher intensity of immunosuppression and the allogeneic microenvironment of the graft have been suggested to predispose to reactivation. There are limited data on the status of viral activity in the native kidneys of non-renal solid organ recipients. METHODS: Thirty-eight recipients of pancreas transplant alone were evaluated for evidence of polyomavirus reactivation by urine cytology. All had received induction therapy and were maintained on tacrolimus, mycophenolate mofetil, and prednisone. The renal function and degree of exposure to immunosuppressive agents of patients shedding polyomavirus-infected renal tubular cells were compared with those of patients with negative urine cytology. RESULTS: Screening cytology was performed 16 months (mean) after transplantation. Four subjects (11%) had polyomaviruria. The renal function at baseline and time of screening was comparable between the two groups. The 12-hour trough levels of tacrolimus were significantly higher in patients with positive cytology compared with those without viruria. The doses of mycophenolate mofetil and prednisone were not different between the two groups. CONCLUSION: This study shows that polyomavirus reactivation in native kidneys and urinary tract of pancreas transplant alone patients is not uncommon. In these recipients, viral reactivation was not associated with significant renal functional impairment. The results also suggest that patients who are exposed to higher blood levels of tacrolimus are at higher risk of viral reactivation.

Adult↗

Polyomavirus nephropathy in native kidneys of a solitary pancreas transplant recipient.

BACKGROUND: Latent polyomavirus (PV) infection of the urinary tract can be reactivated by immunosuppression. When this occurs in the renal allograft, permanent loss of allograft function can occur. Polyomavirus reactivation could potentially affect the native kidneys of nonrenal transplant recipients and cause renal dysfunction. METHODS: This article describes a case of PV nephropathy in the native kidneys of a solitary-pancreas transplant recipient. This patient had a progressive increase in serum creatinine. Screening urine cytology showed numerous cells with cytopathic changes suggestive of polyomavirus infection. RESULTS: Biopsy of the native kidneys of this patient showed renal tubular cells with intranuclear inclusions characteristic of PV infection, which was confirmed by immunohistochemistry. Electron microscopy showed intranuclear viral particles. Patchy inflammation and fibrosis also were noted. CONCLUSION: Polyomavirus reactivation can occur in the native kidneys of nonrenal solid organ transplant recipients. This should be considered in the differential diagnosis of renal impairment in these patients. The effects of PV reactivation on long-term native kidney function are not known.

Diabetes Mellitus, Type 1↗

Cytomegalovirus-induced glomerular vasculopathy in renal allografts: a report of two cases.

Cytomegalovirus (CMV) remains a major viral pathogen complicating renal transplantation. Tubulointerstitial nephritis is the commonly acknowledged and well-characterized pathologic feature of renal allograft CMV disease. There is controversy about whether there is a distinct entity as a CMV glomerulopathy in the absence of tubulointerstitial disease. We describe two patients with renal allograft dysfunction who displayed distinct features of CMV glomerular vasculopathy, in the absence of overt viral cytopathic changes involving the tubules.

Adolescent↗

Predictive value of human leucocyte antigen epitope matching using HLAMatchmaker for graft outcomes in a predominantly African-American renal transplant cohort.

The HLAMatchmaker program is based on the donor/recipient comparison of the polymorphic triplet amino-acid sequences of the antibody-accessible regions on the human leucocyte antigen (HLA) molecule. The previous reports on its predictive value for renal allograft outcomes are conflicting. We conducted a retrospective study in a predominantly African-American (AA) cohort (N = 101, 94% AA). HLA typing was performed by molecular methods and triplet matching using HLAMatchmaker. Study end points included graft survival and incidence of acute rejection. The relationship between the number of triplet mismatches (TMM) and the degree of HLA antigen MM was evaluated using Pearson's correlation coefficient. Logistic regression models were used to examine the association between triplet matching and the study end points. Kaplan-Meier and Cox proportional hazard models were used for graft survival analysis. The strongest relationship between the number of TMM and HLA antigen MM was observed for HLA-DQ (r = 0.88). The association between triplet matching at HLA-A, -B, -DR and -DRw HLA loci and the study end points was not statistically significant. However, after grouping, the unadjusted estimates of graft survival for those with more than 10 Class I TMM were significantly worse than the others (p = 0.03). Adjusting for the effect of donor source, recipient characteristics and the immunosuppressive regimen did not change this association (hazard ratio = 0.2, confidence interval = 0.04-1.1). We conclude that triplet matching using HLAMatchmaker can provide useful prognostic information in kidney transplantation and that more than 10 donor/recipient Class I HLA TMM is predictive of worse graft outcome.

Adult↗

Infectious complications after kidney transplantation: current epidemiology and associated risk factors.

BACKGROUND: The impact of newer immunosuppressive and antimicrobial prophylactic agents on the pattern of infectious complications following kidney transplantation has not been well studied. METHODS: This is an observational study in 127 adult recipients transplanted from 2001 to 2004. Patients received thymoglobulin (ATG) (50%) or basiliximab (50%) for induction and were maintained on mycophenolate mofetil, either tacrolimus (73%) or sirolimus (SRL) (27%), and prednisone (79%). Antimicrobial prophylaxis included perioperative cefazolin, trimethoprim/sulfamethaxazole for six months, valganciclovir for three months and nystatin for two months. Regression models were used to examine the association of various factors with infections. RESULTS: We observed 127 infections in 65 patients, consisting of urinary tract infection (UTI) (47%), viral infections (17%), pneumonia (8%) and surgical wound infections (7%). UTI was the most common infection in all post-transplant periods. Enterococcus spp. (33%) and Escherichia coli (21%) were the most prevalent uropathogens. Of six patients with cytomegalovirus infection, none had tissue-invasive disease. There were no cases of pneumocystis pneumonia or BK nephropathy. Six patients developed fungal infections. Two deaths due to disseminated Rhizopus and Candida albicans accounted for a 1.5% infection-related mortality. Retransplantation and ureteral stents were independently associated with UTI (OR=4.5 and 2.9, p=0.06 and 0.03, respectively), as were ATG and SRL with bacterial infections (OR=3.3 and 2.5, p=0.009 and 0.047, respectively). CONCLUSION: This study suggests that the use of newer immunosuppressive agents in recent years is associated with some changes in the epidemiology of post-transplant infections. Enterococci have become the predominant uropathogen. Invasive fungal infections, although rare, are often fatal.

Adult↗