ABO-incompatible kidney transplantation with and without splenectomy.
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ABO Blood-Group System↗
Biomedical subjects
Mark Stegall
Publications and source records attributed to Mark Stegall.
Blood pressure and renal function after kidney donation from hypertensive living donors.
BACKGROUND: Rising numbers of patients reaching end-stage kidney disease intensify the demand for expansion of the living-kidney-donor pool. On the basis of low risk in white donors with essential hypertension, our transplant center undertook a structured program of accepting hypertensive donors if kidney function and urine protein were normal. This study reports outcomes of hypertensive donors 1 year after kidney donation. METHODS: We studied detailed measurements of blood pressure (oscillometric, hypertensive therapy nurse [RN], and ambulatory blood pressure monitoring [ABPM]), clinical, and renal characteristics (iothalamate glomerular filtration rate [GFR], urine protein, and microalbumin) in 148 living kidney donors before and 6 to 12 months after nephrectomy. Twenty-four were hypertensive (awake ABPM>135/85 mm Hg and clinic/RN BP>140/90 mm Hg) before donation. RESULTS: After 282 days, normotensive donors had no change in awake ABPM pressure (pre 121 +/- 1/75 +/- 2 vs. post 120 +/- 1/ 5 +/- 1 mm Hg), whereas BP in hypertensive donors fell with both nonpharmacologic and drug therapy (pre 142 +/- 3/85 +/- 2 to post 132 +/- 2/80 +/- 1 mm Hg, P<.01). Hypertensive donors were older (53.4 vs. 41.4 years, P<.001) and had lower GFR after kidney donation (61 +/- 2 vs. 68 +/- 1 mL/min/1.73m, P<.01). After correction for age, no independent BP effect was evident for predicting GFR either before or after nephrectomy. Urine protein and microalbumin did not change in either group after donor nephrectomy. CONCLUSIONS: Our results indicate that white subjects with moderate, essential hypertension and normal kidney function have no adverse effects regarding blood pressure, GFR, or urinary protein excretion during the first year after living kidney donation. Although further studies are essential to confirm long-term safety, these data suggest that selected hypertensive patients may be accepted for living kidney donation.
Adult↗
Randomized trial of tacrolimus + mycophenolate mofetil or azathioprine versus cyclosporine + mycophenolate mofetil after cadaveric kidney transplantation: results at three years.
METHODS: Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive tacrolimus (TAC) + mycophenolate mofetil (MMF), TAC + azathioprine (AZA), or cyclosporine (Neoral; CsA) + MMF. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function (DGF). Patients were followed-up for 3 years. RESULTS: The results at 3 years corroborate and extend the findings of the 2-year results. Patients with DGF treated with TAC+MMF experienced an increase in 3-year allograft survival compared with patients receiving CsA+MMF (84.1% vs. 49.9%, P=0.02). Patients randomized to either treatment arm containing TAC exhibited numerically superior kidney function when compared with CsA. During the 3 years, new-onset insulin dependence occurred in 6, 3, and 11 patients in the TAC+MMF, CsA+MMF, and TAC+AZA treatment arms, respectively. Furthermore, patients randomized to TAC+MMF received significantly lower doses of MMF as compared with those who received CsA+MMF. CONCLUSION: All three immunosuppressive regimens provided excellent safety and efficacy. However, the best results overall were achieved with TAC+MMF. The combination may provide particular benefit to kidney allograft recipients with DGF. In patients who experienced DGF, graft survival was better at 3 years in those patients receiving TAC in combination with either MMF or AZA as compared with the patients receiving CsA with MMF.
Acute Disease↗
ABO-incompatible liver transplant: is it justifiable?
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ABO Blood-Group System↗
Blood pressure evaluation among older living kidney donors.
With more patients reaching end-stage renal disease, the demand for living kidney donation is increasing rapidly. Many potential donors are now in older age groups. The effects of increasing BP with age and the measurement criteria for hypertension in this group are not well defined. A total of 238 potential donors between 18 and 72 yr of age were prospectively studied, with a comparison of "clinic" BP values measured in the outpatient clinic with an oscillometric recorder (Dinamap; Critikon), ambulatory BP monitoring (ABPM) findings, and standardized BP values determined by nurses using American Heart Association criteria. Renal function was evaluated on the basis of iothalamate clearance (GFR) and urinary protein and microalbumin excretion. Ninety-six percent of subjects were Caucasian. All subjects exhibited normal GFR and urinary protein excretion. Three age groups were defined (group I, </=35 yr, n = 64; group II, 36 to 49 yr, n = 109; group III, >/= 50 yr, n = 65). BP increased with age, as determined with all methods. Subjects >/= 50 yr of age exhibited the highest clinic readings (145 +/- 2/83 +/- 1 mmHg, compared with 129 +/- 2/76 +/- 1 mmHg for group I, P < 0.01). Awake ABPM and nurse-determined BP measurements were lower than clinic readings, including those for group III (131 +/- 2/80 +/- 1 mmHg, compared with 145 +/- 2/83 +/- 1 mmHg in the clinic, P < 0.001). With the use of systolic BP values of >140 mmHg and/or diastolic BP values of >90 mmHg, 36.7% of subjects were initially considered hypertensive; this proportion decreased to 11% overall with awake ABPM findings (>135/85 mmHg). Measurement variability (SD in ABPM) and the effects of misclassification were greatest for donors >/= 50 yr of age. Multivariate regression indicated that GFR of both donors and recipients decreased with age, but regression identified no independent effect of BP. Recipient outcomes for up to 2 yr were equally good for donor kidneys considered normotensive or hypertensive on the basis of clinic BP measurements. These data indicate that higher arterial BP with age can lead to misclassification of many older living kidney donors. Sixty-two subjects with excellent kidney function were misclassified as hypertensive with clinic oscillometric measurements alone. Detailed evaluations of ABPM findings, GFR, and urinary protein levels are warranted for Caucasian subjects with high clinic BP readings who are otherwise suitable potential donors.
Adolescent↗
Gene expression during acute allograft rejection: novel statistical analysis of microarray data.
High-throughput microarrays promise a comprehensive analysis of complex biological processes, yet their applicability is hampered by problems of reproducibility and data management. The current study examines some of the major questions of microarray use in a well-described model of allograft rejection. Using the Brown Norway to Lewis heterotopic heart transplant model, highly purified RNA was isolated from cardiac tissue at postoperative days (POD) 3, 5 and 7 and hybridized onto Affymetrix U34A microarrays. Using the log average ratio (LAR), changes in gene expression were monitored at each timepoint and p-values generated through statistical analysis. Microarray data were verified for 13 significant transcripts using RT-PCR. Of the 8800 transcripts studied, 2864 were increased on POD 3, 1418 on POD 5 and 2745 on POD 7. Verifying previous studies, many up-regulated genes appeared to be associated with the inflammatory process and graft infiltrating cells. Down-regulated transcripts included many novel molecules such as SC1 and decorin. LAR analysis provides a useful approach to analyze microarray data. Results were reproducible and correlated well with both RT-PCR and prior studies. Most importantly, these results provide new insights into the pathogenesis of acute rejection and suggest new molecules for future studies.
Animals↗