Biomedical subjects

Martha Pavlakis

Publications and source records attributed to Martha Pavlakis.

10 recordsLinked to original sources

PubMed2006

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↗

PubMed2005

Intensive care unit extubation does not preclude extrarenal organ recovery from donors after cardiac death.

BACKGROUND: We have sought to increase the utilization of both renal and extrarenal organs from donors after cardiac death (DCD), including DCD donors with ICU extubation. METHODS: Extubation occurred in the intensive care unit (ICU; n=15) and operating room (OR; n=5). The charts of donors were reviewed for demographics, cause of death, time of asystole and cold perfusion. Recipient's charts were reviewed for graft function, length of hospitalization, serum creatinine (Cr) at discharge and last follow-up. Peak transaminases, amylase, and lipase for liver and pancreas recipients were also reviewed. Data are presented as means+/-SEM. RESULTS: From December 2002 until December 2004, 20 DCD donors were utilized yielding 34 kidney transplants (33 recipients), five liver (1 liver-kidney), and two pancreas (SPK) transplants. Mean follow-up overall is 260 days. ICU extubation occurred in 26/33 (78.8%) kidneys, 3/5(60%) livers and 1/2 (50%) pancreata performed. Time from extubation to asystole was 15.9+/-1.9 min and overall warm ischemia time was 12.5+/-1.0 min. Serum Cr at discharge and at last follow-up for renal grafts are 4.3+/-0.5 and 1.9+/-0.3 mg/dl, respectively. Peak AST and ALT levels after OLTx were 3620+/-951 and 1955+/-266 i.u., respectively. Peak and discharge total bilirubin were 8.1+/-0.9 and 2.5+/-0.5 mg/dl. Length of hospitalization was 9.6+/-1.0 and 15.8+/-2.3 days for kidney and liver recipients, respectively. Both pancreas recipients were insulin free after transplant. CONCLUSIONS: ICU extubation should not eliminate extrarenal organs from consideration and may be preferable to OR extubation by improving family support and eliminating OR staff concerns about their role in end-of-life care.

Adolescent↗

PubMed2005

On the intraoperative molecular status of renal allografts after vascular reperfusion and clinical outcomes.

Many hypothesize that subtle inflammation and immune activity detected in the intraoperative period are linked to adverse postkidney transplant clinical outcomes. To this end, renal allografts were analyzed for expression of pro-inflammatory, inflammation-induced adhesion molecules, immune activation as well as anti-apoptotic genes expressed 15 min after vascular reperfusion (zero-hour) to determine whether this analysis can aid in predicting the occurrence of delayed graft function (DGF), acute rejection (AR), and the quality of graft function at 6 mo. Intraoperative biopsies were obtained from 75 consecutively performed renal allografts in which consent was obtained 15 min after vascular reperfusion. These biopsies were analyzed by quantitative real-time PCR for transcription of 15 select genes and by standard histopathology. Posttransplant clinical outcomes were also analyzed in respect to intraoperative transcriptional profiles and clinical parameters available at the time of transplantation. This study demonstrates that a limited and hypothesis-driven PCR-based transcriptional profile of the zero-hour kidney biopsy predicts posttransplant clinical outcomes including DGF, early AR, and the quality of renal function 6 mo posttransplantation. For some clinical endpoints, the combined use of molecular analysis and established clinical indicators available at the time of transplantation further enhances the quality of prognosis. The transcriptional profiling data provide absolutely essential data to the predictive models, particularly with respect to AR and renal function 6 mo posttransplantation.

Biomarkers↗

PubMed2005

New-onset diabetes after transplantation.

New-onset diabetes after transplantation (NODAT) is associated with significant morbidity and mortality. Given the availability of simple diagnostic methods and the known benefits of strict glycemic control, patients should be screened frequently after organ transplantation. The management of NODAT is multifaceted and aimed at both treatment and prevention of complications. Evaluation of patient risk for post-transplant diabetes mellitus and its complications is an important consideration in initial selection and subsequent modification of the immunosuppressive regimen.

Diabetes Mellitus↗

PubMed2005

Older living donors provide excellent quality kidneys: a single center experience (older living donors).

BACKGROUND: The role of advanced age live donors remains controversial because of decline in glomerular filtration rate and perceived increased risks of perioperative complications. METHODS: A retrospective review of all live donor transplants performed from January 2000 to December 2003. RESULTS: Seventy-eight live donor transplants were performed during the period of review, 47 (60.3%) female and 31 (39.7%) male. Twenty-two (28.2%) of the donors were >50 yr old, 15 (68%) female and seven (32%) male. Living related donation was performed in 56 (74.4%) and unrelated in 20 (35.6%). Laparoscopic nephrectomy was performed in 29 (37.2%) and open nephrectomy in 49 (62.8%). More donors >50 underwent laparoscopic nephrectomy, 13 of 22 (59.1%) vs. 16 of 56 (28.6%). Overall patient and graft survival at 1 yr are 97 and 97%. One-year patient and graft survival is 100% vs. 96% and 100% vs. 96% in the older vs. young donors. Rejection occurred in nine of 78 (11.5%), but was not different between groups. Older donors had a reduced creatinine clearance 107.5 +/- 3.4 vs. 124.2 +/- 3.1 mL/min (p = 0.002) and a reduced clearance normalized for body surface area 60.6 +/- 3.6 mL/(min m2) vs. 70.2 +/- 2.6 mL/(min m2) (p = 0.045). Recipient serum creatinine was higher on postoperative day 1 in the older donor group 5.4 mg/dL vs. 4.4 mg/dL (p = 0.009). There was no difference in recipient serum creatinine at postoperative day 7, 30, 90, 180, 365 and 730. Donor serum creatinine was not different between groups on postoperative days 1, 7 and 30 but was higher in group 1 vs. group 2 on postoperative day 365, 1.26 +/- 0.26 mg/dL vs. 1.01 +/- 0.18 mg/dL (p = 0.020). CONCLUSIONS: Despite a reduced initial creatinine clearance, renal function is comparable in recipients of both young and old donor kidneys. Older donors had a slightly reduced serum creatinine 1 yr post-donation that warrants additional follow-up to determine if the observations continue. The introduction of laparoscopic nephrectomy may provide additional incentive for older donors to present for live donor nephrectomy.

Adult↗

PubMed2005

Reproduction and transplantation: report on the AST Consensus Conference on Reproductive Issues and Transplantation.

It has been almost 50 years since the first child was born to a female transplant recipient. Since that time pregnancy has become common after transplantation, but physicians have been left to rely on case reports, small series and data from voluntary registries to guide the care of their patients. Many uncertainties exist including the risks that pregnancy presents to the graft, the patient herself, and the long-term risks to the fetus. It is also unclear how to best modify immunosuppressive agents or treat rejection during pregnancy, especially in light of newer agents available where pregnancy safety has not been established. To begin to address uncertainties and define clinical practice guidelines for the transplant physician and obstetrical caregivers, a consensus conference was held in Bethesda, Md. The conferees summarized both what is known and important gaps in our knowledge. They also identified key areas of agreement, and posed a number of critical questions, the resolution of which is necessary in order to establish evidence-based guidelines. The manuscript summarizes the deliberations and conclusions of the conference as well as specific recommendations based on current knowledge in the field.

Female↗

PubMed2004

Donor kidney exchanges.

Kidney transplantation from live donors achieves an excellent outcome regardless of human leukocyte antigen (HLA) mismatch. This development has expanded the opportunity of kidney transplantation from unrelated live donors. Nevertheless, the hazard of hyperacute rejection has usually precluded the transplantation of a kidney from a live donor to a potential recipient who is incompatible by ABO blood type or HLA antibody crossmatch reactivity. Region 1 of the United Network for Organ Sharing (UNOS) has devised an alternative system of kidney transplantation that would enable either a simultaneous exchange between live donors (a paired exchange), or a live donor/deceased donor exchange to incompatible recipients who are waiting on the list (a live donor/list exchange). This Regional system of exchange has derived the benefit of live donation, avoided the risk of ABO or crossmatch incompatibility, and yielded an additional donor source for patients awaiting a deceased donor kidney. Despite the initial disadvantage to the list of patients awaiting an O blood type kidney, as every paired exchange transplant removes a patient from the waiting list, it also avoids the incompatible recipient from eventually having to go on the list. Thus, this approach also increases access to deceased donor kidneys for the remaining candidates on the list.

Cadaver↗

PubMed2002

Expression of protective genes in human renal allografts: a regulatory response to injury associated with graft rejection.

BACKGROUND: Long-term survival of a graft requires inhibition of host immune effectors, but protective responses emanating from the graft might be equally important. Expression of the "protective" genes A20, heme-oxygenase-1 (HO-1), and Bcl-xL in rodent allo and xenografts correlates with long-term survival. Little is known of the pattern of expression of such protective genes and the implication thereof in clinical transplantation. METHODS: We analyzed, by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry, expression of A20, HO-1, and Bcl-xL in 31 renal allograft biopsies from patients with suspected rejection. RESULTS: A20 is not expressed in nonrejecting (NR) grafts. Its expression is increased in grafts undergoing acute and chronic rejection (AR and CR) but is weaker in CR. HO-1 is not expressed in NR grafts; it is up-regulated in AR but not CR. Bcl-xL is detected in all biopsies with decreased levels in CR. Expression of A20, HO-1, and Bcl-xL localizes mainly to endothelial, smooth muscle, and infiltrating mononuclear cells. CONCLUSIONS: This data demonstrate that A20 and HO-1 are up-regulated in response to immune injury inferred by AR. Given the antiapoptotic and antiinflammatory functions of these genes, we hypothesize that their expression survives to limit graft injury by maintaining cell viability and controlling inflammation. Their reduced expression in CR as compared with AR represents either inadequate response to injury or a sequelae of prior injury that jeopardizes further tissue response to immune attack.

Adolescent↗

PubMed2002

Activated intrarenal transcription of CTL-effectors and TGF-beta1 in children with focal segmental glomerulosclerosis.

BACKGROUND: The pathogenesis of childhood nephrotic syndrome (NS), whether the lesion is minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS), remains elusive. Based on the presence of elevated cytokine levels in peripheral blood, a T cell-induced injury could be postulated. METHODS: To test the hypothesis that infiltrating T cells actively contribute to the glomerular injury in children with NS, we studied the intrarenal transcription of various T cell-related chemokines, cytokines and cytotoxic T-lymphocyte (CTL) effector molecules in the renal biopsy tissue of 52 nephrotic children with a variety of histologic lesions. Intrarenal gene expression was studied using reverse transcription (RT)-assisted-polymerase chain reaction (PCR). RESULTS: Interleukin-2 (IL-2) and IL-4 transcripts were not observed in any of the specimens. IL-2 receptor alpha mRNA was detected in 24 of 40 proteinuric patients, but also in 6 of 10 patients in remission and showed no significant differences with regard to steroid response. Intrarenal gene expression of CTL mediators and transforming growth factor-beta1 (TGF-beta1) was noted particularly in patients with progressive disease leading to chronic renal failure. TGF-beta1 gene expression was noted in 23 of 29 steroid resistant (SR) children with NS not caused by lupus nephritis and in 18 of 20 FSGS patients. In contrast TGF-beta1 gene expression was detected in only 3 of 14 steroid-sensitive patients (P < 0.001). Two of these patients later developed FSGS. In patients with steroid-resistant NS, intrarenal TGF-beta1 gene expression showed a positive predictive value of 90% and a negative predictive value of 88% to identify FSGS (P < 0.0001). CONCLUSION: These results support the notion that immunologically mediated events contribute to the progressive renal damage seen in children with FSGS.

Biopsy↗

PubMed2002

Determinants of hypofiltration during acute renal allograft rejection.

This study sought to determine the extent to which GFR is decreased during acute renal allograft rejection in human subjects and to determine the mechanism of the decrease in GFR. Eight patients with biopsy-proven acute rejection were compared with 18 recipients of optimally functioning renal allografts. GFR and renal plasma flow (RPF) were measured as the clearance of inulin and para-aminohippuric acid, respectively. Arterial BP was determined, blood was sampled, and plasma oncotic pressure (pi(A)) was measured. Glomeruli obtained by biopsy during rejection were subjected to morphometric analysis, for determination of K(f). Control morphometric values for healthy glomeruli were provided by 10 living donors from whom biopsies were obtained at the time of organ donation. The subjects in the acute rejection group exhibited a significantly reduced GFR of 17 +/- 4 ml/min per 1.73 m(2), compared with 72 +/- 4 ml/min per 1.73 m(2) for control subjects (P < 0.001). With the use of a sensitivity analysis to take into account the unknown para-aminohippuric acid extraction ratio, the RPF rate was calculated to have likely been significantly decreased, by 45 to 70%, in the acute rejection group. Neither the plasma oncotic pressure nor the mean arterial pressure differed between the two groups. Morphometric analysis revealed no difference in the single-nephron K(f) values for the acute rejection group, compared with the control group. These results indicate that acute renal allograft rejection causes a profound decrease in GFR, which is attributable to a decrease in RPF alone or in combination with a decrease in the glomerular transcapillary hydraulic pressure gradient (DeltaP).

Acute Disease↗