Biomedical subjects
L E Ratner
Publications and source records attributed to L E Ratner.
Osmotic nephrosis in a renal transplant recipient.
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Microscopic intrarenal particles after pulsatile machine preservation do not adversely affect outcomes after renal transplantation.
INTRODUCTION: Our center has recently observed foreign carbohydrate-appearing particles (FP) on transplant postreperfusion biopsy specimens: (PRBx). METHODS: To further characterize FPs, we reviewed all renal transplant RBx (30-45 minutes) performed between September 1, 2004 and December 3, 2005. Donor, preservation, and outcome variables were collected among patients with FP. RESULTS: A total of 135 PRBx were performed (45 deceased donors [DD] and 90 live donors [LD]). Fifteen PRBx demonstrated FP. All 15 cases were DD kidneys that underwent machine perfusion (MP) on the Waters RM3 (Waters Medical Systems, Rochester, Minn, United States) with Belzer MP solution (Trans Med, Elk River, Minn, United States). Donor age was 39.8 +/- 15.7 years. Terminal creatinine level was 1.45 +/- 0.8 mg/dL. Two of 15 were flushed in situ with HTK solution (no starch). Cold ischemia time was 28.8 +/- 9.1 hours with 14.3 +/- 5.1 hours of MP. In 13 of 15 patients, perfusion parameters were excellent (flow > 100 mL; resistance < .35). CHARACTERISTICS OF FP: Particles were 10-30 mu and globular in shape. FP were not visible on hematoxylin and eosin stain, but stained strongly periodic acid-Schiff-(PAS) positive and were refractile under polarized light. FP were seen segmentally within glomerular capillaries in all cases and in peritubular capillaries in 3. In 11 of the 15 cases with FP, focal glomerular fibrin thrombi or intracapillary neutrophil margination was seen. Ten of 15 patients with FP had a biopsy within the first week with no identifiable FP. OUTCOMES: Recipient age was 45.3 +/- 11.6 years. Eight patients (53.3%) had delayed graft function. Biopsy-proven rejection occurred in 3 patients (20%). Three-month creatinine level was 1.59 +/- 0.35 mg/dL. One graft was lost to early thrombosis in a patient with a hypercoagulable state and 1 patient died of sepsis at 2 months. All remaining 13 patients are alive with excellent graft function at a median follow-up of 6.7 months (range, 3-17 months). CONCLUSIONS: Microscopic intrarenal particles may be seen on DD kidney PRBx after MP. These FPs likely originate from surgical gloves. FPs are too small to be captured by standard filters but clear spontaneously and do not have deleterious effects on renal function or outcomes.
Renal transplantation with iliac vein transposition.
UNLABELLED: We evaluated a technique for implantation of right kidneys with short renal veins without the need for venous reconstruction. METHOD: The technique of iliac vein transposition was performed in six recipients who received right kidneys with short renal veins. Two cases were living related donors, two were living unrelated, one was an autotransplant, and one was a cadaver kidney recipient. The common and external iliac veins and arteries of the recipient were thoroughly mobilized, allowing for the lateral transposition of the external iliac vein with respect to the external iliac artery. The renal vessels were subsequently implanted in an end to side fashion onto the corresponding transposed external iliac vessels. After implantation, the iliac vein remained lateral with respect to the iliac artery. CONCLUSIONS: The technique described allows for the implantation of right kidneys without the need for venous reconstruction. Such an approach is especially useful in cases of grafts with short veins.
Preemptive therapy with plasmapheresis/intravenous immunoglobulin allows successful live donor renal transplantation in patients with a positive cross-match.
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The contribution of sociodemographic, medical, and attitudinal factors to blood donation among the general public.
BACKGROUND: Few studies have simultaneously assessed the relative importance of sociodemographic, medical, and attitudinal factors in explaining which individuals are more likely to donate blood. STUDY DESIGN AND METHODS: A cross-sectional telephone survey of households in Maryland was conducted to identify the relation of sociodemographic, medical, and attitudinal factors to blood donation history among the general public. Random digit dialing was used to identify households; individuals aged 18 to 75 years were randomly selected within households. In multivariate analyses, the independent relationship of these factors with prior history of blood donation was assessed, and the amount of variation in prior history of blood donation among the study population that could be explained by these factors was determined. RESULTS: Of 385 participants (84% of randomized homes), 228 (59%) had donated blood at least once in the past. After adjusting for potential confounders, women, black participants, and those agreeing with the statement "I am afraid of hospitals" had 60 to 80 percent lower odds of prior donation when compared with men, white participants, and those who did not agree with the statement (OR [95% CI]: 0.2 [0.1-0.4], 0.4 [0.2-0.8], and 0.3 [0.2-0.6], respectively). The effect of fear of hospitals was consistent across sex and race. Trust, fear, and suspicion of hospitals were among factors contributing most to variation in prior donation history. CONCLUSION: Female sex, black race, and fear of hospitals are three major factors negatively associated with prior history of blood donation. Fear of hospitals affects blood donation patterns across race and sex groups. Future study is needed to determine whether recruitment of blood donors may be more efficient if focused toward women, minorities, and donors' fears of healthcare facilities or hospitals.
Interaortocaval renal artery dissection for right laparoscopic donor nephrectomy.
Laparoscopic donor nephrectomy is gaining increasing popularity because the procedure helps reduce disincentives to live kidney donation and has increased the live kidney donor pool. The left kidney of the donor is the preferred allograft because the right renal vein is shorter. Similarly, the right renal artery might be foreshortened because it hides behind the inferior vena cava during laparoscopic transperitoneal dissection. There are instances, however, in which it is not practical to take the left kidney due to vascular anomalies or asymmetric function. We describe a novel technique for obtaining greater renal arterial length utilizing laparoscopic interaortocaval dissection.
Donor horseshoe kidneys for transplantation.
BACKGROUND: Experience with donor horseshoe kidneys for transplantation is very limited. Currently, horseshoe kidneys may be underutilized for transplantation because of the greater incidence of vascular anomalies, associated renal anomalies, and predisposition to renal disease. METHODS: In this report, we review five transplantations using horseshoe kidneys: the largest reported institutional experience. In addition, a review of all published cases in the English literature is performed. RESULTS: All five patients underwent successful renal transplantations with a median follow-up of 35 months. One patient lost his kidney from recurrent disease soon after transplantation. CONCLUSION: With appropriate reconstruction of the vessels, careful division of the isthmus, and avoidance of ureteral obstruction, long-term data revealed good graft survival of donor horseshoe kidneys in renal transplantation.
Effect of Bw4 and Bw6 epitope mismatches on antibody production, acute and chronic rejection, and graft survival in renal allografts.
BACKGROUND: Highly sensitized patients often have antibodies directed against the HLA Bw4 and Bw6 epitopes. Because of the high frequency of these epitopes, when present, these antibodies result in a high incidence of positive cross-matches. We sought to determine whether antibodies specific for Bw4 or Bw6 affected renal allograft outcome. METHODS: The effect of mismatches for the HLA class I public epitopes, Bw4 and Bw6, was examined in 72 recipients of one haplotype matched recipients of living, related donor renal allografts selected to control for degree of HLA mismatch. Analysis of the production of HLA-specific antibody was performed for 180 recipients of failed cadaveric allografts by complement-dependent cytotoxicity tests and by an enzyme-linked immunoadsorbent assay (ELISA). RESULTS: No significant difference was observed in the incidence of acute rejection, number of rejection episodes or 1-year allograft survival among Bw4/6 matched versus mismatched recipients of one haplotype matched allografts. Additionally, no significant difference in the development of chronic allograft nephropathy was noted among 56 recipients followed long-term (> or =3 years). In the recipients of failed cadaveric transplants, Bw4/6 mismatching was associated with the frequency and magnitude of production of HLA-specific antibody. However, the panel reactive antibodies correlated with the number of HLA-A and -B mismatches, and there was no additional impact of Bw4/6 mismatching. IgG, HLA-specific antibodies were found to be significantly increased among patients homozygous for Bw4 or Bw6, whether or not there was a Bw4/6 mismatch. CONCLUSIONS: Mismatching for Bw4 or Bw6 does not confer any independent, increased risk for humoral sensitization or renal allograft failure.
Successful renal transplantation after endovascular bifurcated stent graft repair of an abdominal aortic aneurysm.
Renal transplantation after repair of aortoiliac aneurysms with traditional prosthetic vascular grafts has been shown to be effective. Vascular surgery continues to rapidly evolve, most notably with the advancement of endovascular repair of abdominal aortic aneurysms. Controlled trials continue to support the trend toward the use of endovascular bifurcated aortic stent grafts. For this we describe the first renal transplant in a patient with an endovascular bifurcated aortoiliac stent graft. No intraoperative difficulties were encountered. At 1-year follow-up, the transplanted kidney is functioning well with a normal serum creatinine level of 1.3 mg/dl, and the patient has no worsening of peripheral vascular disease. We recommend that the presence of an endovascular aortic graft not be a contraindication to renal transplantation.
Should the indications for laparascopic live donor nephrectomy of the right kidney be the same as for the open procedure? Anomalous left renal vasculature is not a contraindiction to laparoscopic left donor nephrectomy.
BACKGROUND: The left kidney is preferred for live donation. In open live donor nephrectomy, the right kidney is selected if the left kidney has multiple renal arteries or anomalous venous drainage. With laparoscopic live donor nephrectomy (LLDN), there is reluctance to procure the right kidney because of the more difficult exposure and further shortening of the right renal vein (RRV) after a stapled transection. An experience with LLDN is reviewed to determine whether the right kidney should be procured laparoscopically. METHODS: From February 1995 to November 1999, 227 patients underwent live donor renal transplants with allografts procured by LLDN. The results of these transplants were analyzed. RESULTS: Of the 227 kidneys transplanted, 17 (7.5%) were right kidneys. In the early experience, three (37.5%) of the eight right renal allografts developed venous thrombosis, two of which had duplicated RRV. Based on these initially unacceptable results, donor evaluation and LLDN techniques were modified. Spiral computerized tomography (CT) replaced conventional angiography to define better the venous anatomy. LLDN was modified in one of three ways: (1) changing the stapler port placement such that the RRV was transected in a plane parallel to the inferior vena cava, (2) relocation of the incision for open division of RRV, or (3) lengthening of the donor RRV with a panel graft constructed of recipient greater saphenous vein. Finally, the recipient operation enjoined complete mobilization of the left iliac vein with transposition lateral to the iliac artery. With these modifications, there were no vascular complications with the subsequent nine right renal allografts (P<0.05). Of the left kidneys transplanted, 31 had multiple renal arteries, 14 had retroaortic or circumaortic veins, 4 had both multiple arteries and venous anomalies, and 1 had a duplicated IVC draining the left renal vein. There were no vascular complications with left renal allografts that had multiple arteries or venous anomalies. CONCLUSIONS: LLDN of the left kidney is technically easier. Left kidneys with multiple arteries or anomalous venous drainage are not problematic. The right kidney can be procured with LLDN; however, a rational approach to preoperative angiographic imaging, donor operation, and recipient operation is crucial.
Elimination of alloantibodies by immunoablative high-dose cyclophosphamide.
BACKGROUND: Alloimmunization is a major problem for patients being considered for solid organ transplantation and in patients who require blood transfusion support. We previously demonstrated that high-dose cyclophosphamide (200 mg/kg) without hematopoietic stem cell transplantation leads to durable complete remissions in aplastic anemia and other autoimmune disorders. We now examine the ability of high-dose cyclophosphamide to eliminate alloreactivity. METHODS: IgG-specific antibodies to HLA class I were assayed using enzyme-linked immunosorbent assays in 18 consecutive patients with severe aplastic anemia before and after treatment with high-dose cyclophosphamide. RESULTS: Anti-HLA antibodies were detected before or shortly after therapy in 5 of the 18 patients studied. Complete remission of aplastic anemia was achieved in four of these five patients. High-dose cyclophosphamide markedly reduced anti-HLA antibody titers in these four patients; they were completely eradicated in three patients. Only one patient did not achieve significant reduction in the alloantibody titer after high-dose cyclophosphamide. CONCLUSIONS: High-dose cyclophosphamide without stem cell transplantation can eradicate HLA-specific alloantibody.
Prolonged preservation time obviates the benefits of 0 HLA mismatches in renal transplantation.
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Laparoscopic live donor nephrectomy. A review of the first 5 years.
Laparoscopic live donor nephrectomy is technically feasible. The operation has evolved over the last 5 years and is greatly improved compared with the procedure originally described. Advantages to the donor when compared with the standard open operation are decreased postoperative pain, shorter hospitalization, a quicker recuperation, an earlier return to driving, and an earlier return to employment. These improvements have resulted in fewer lost wages and a lower financial burden for donors. Live donor nephrectomy also provides improved cosmetic results. It successfully removes many of the disincentives to live kidney donation and has resulted in an increased willingness of individuals to donate their kidneys. The operative risk seems to be equivalent to that of the open donor operation performed through a flank approach. Although there is no financial advantage of the laparoscopic operation in terms of hospital costs, the increase seen in live donor transplantation may result in long-term cost savings overall. Kidneys procured laparoscopically function well in recipents in the short and long term. There is no increased risk for rejection or technical complications, and the recipent's length of hospitalization is unaffected. The laparoscopic donor operation does not have any apparent deleterious effect on the recipient. The procedure is being adopted rapidly by transplant centers around the world and has been performed at more than 100 centers on five continents. The authors believe that laparoscopic live donor nephrectomy will become the standard of care in the not too distant future.
Characterization of HLA class I specific antibodies by ELISA using solubilized antigen targets: II. Clinical relevance.
Until recently, the nature of humoral sensitization to HLA has been characterized by data from lymphocyte-based assays, predominantly cytotoxicity tests. We have examined the characteristics, determined by enzyme-linked immunosorbent assay (ELISA), of sera from 191 subjects known to have produced HLA-specific antibody. We found that ELISA detected higher frequencies compared with cytotoxicity of many (74.5%), but not all, HLA-specific antibodies; in many cases (42.6%) the frequencies of these antibodies were higher than predicted from population frequencies whereas some antibodies (23.4%) occurred with lower than expected frequencies. Some of the increase in frequencies can be accounted for by crossreactivity, i.e., sensitization to epitopes shared among two or more allelic products. The presence of epitopes shared between a recipient's antigen and a mismatched antigen in a donor also tended to narrow the specificity of antibody produced. However the data also indicate differences in immunogenicity among different antigens suggesting that crossreactive group matching would be beneficial in some but not all cases. Finally, we present case studies to illustrate the value of ELISA in predicting humoral rejection episodes and in monitoring the efficacy of rejection therapies.
Unilateral renal agenesis with pelvic renal ectopy.
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Impact of donor/recipient traits independent of rejection on long-term renal function.
This study describes renal function at multiple points in time after transplantation and the influence of donor and recipient factors independent of rejection on this function. Donor and recipient records for 83 consecutive cadaveric renal transplants performed between 1992 and 1994 at Johns Hopkins Bayview Medical Center were reviewed retrospectively. Donor age, gender, weight, terminal serum creatinine (Cr), intensive care unit days, blood pressure, presence of cardiac arrest, kidney only versus multiple organ donation, and cold ischemia time and recipient age, gender, weight, pretransplant pregnancy status, and rejection episodes were recorded. The influences of each of these parameters on changes in recipient Cr clearance over time (derived using the Cockcroft-Gault formula from recipient serum Cr at 3 months and annually up to 5 years) were analyzed first individually, then together in an analysis with multiple explanatory variables. Parameters indicative of donor ischemia (ie, donor blood pressure, pressor administration, and occurrence of cardiac arrest) were not predictive of the course of recipient Cr clearance. With the inclusion of rejection, this analysis shows the magnitude of the independent effects that donor age, donor Cr clearance, and recipient gender have on the subsequent time course of recipient Cr clearance (P < 0.05). Recipient gender and the presence of rejection appear to have a fixed effect on the level of Cr clearance, whereas donor age and donor Cr clearance appear to influence the level and the time course of recipient Cr clearance. Of all these factors, donor age appears to have the greatest impact on recipient Cr clearance at all times. Analyzing renal function in this way may prove to be a more sensitive indicator than actuarial survival analysis for evaluating the early effects of changes in transplantation protocols and pharmacologic interventions.
Parathyroidectomy promotes wound healing and prolongs survival in patients with calciphylaxis from secondary hyperparathyroidism.
BACKGROUND: Calciphylaxis is a rare but life-threatening condition occasionally affecting patients with secondary hyperparathyroidism. Parathyroidectomy has been advocated as the only potentially curative intervention. METHODS: Between January 1989 and May 2000, 13 patients with pathologic/clinical criteria of calciphylaxis were treated at our institution. Of these 13 patients, 7 were managed with medical therapy alone, and 6 were referred for parathyroidectomy. The medical records were reviewed, and patients/relatives were interviewed. RESULTS: All patients had cutaneous wounds requiring local debridement predominantly located on the lower extremities or abdominal wall. Six patients underwent subtotal (3.5 gland) parathyroidectomy without morbidity. All 6 had significant reductions in parathyroid hormone levels after surgery (mean decrease, 94% +/- 0%), and all reported resolution of pain and healing of cutaneous wounds. Of the remaining 7 patients who had medical management alone, 5 eventually died of complications related to calciphylaxis. In comparing the 2 groups, patients who underwent parathyroidectomy had a significantly longer median survival than those who did not have surgery (36 vs 3 months, P =.021). CONCLUSIONS: Calciphylaxis frequently causes gangrene, sepsis, and eventual death. Parathyroidectomy can be performed with minimal morbidity and is associated with resolution of pain, wound healing, and a significantly longer median survival. Therefore, patients with secondary hyperparathyroidism and signs/symptoms of calciphylaxis should be referred promptly for consideration of parathyroidectomy.