The Incremental Cost of Incompatible Living Donor Kidney Transplantation: A National Cohort Analysis.

Incompatible living donor kidney transplantation (ILDKT) has been established as an effective option for end-stage renal disease patients with willing but HLA-incompatible living donors, reducing mortality and improving quality of life. Depending on antibody titer, ILDKT can require highly resource-intensive procedures, including intravenous immunoglobulin, plasma exchange, and/or cell-depleting antibody treatment, as well as protocol biopsies and donor-specific antibody testing. This study sought to compare the cost and Medicare reimbursement, exclusive of organ acquisition payment, for ILDKT (n = 926) with varying antibody titers to matched compatible transplants (n = 2762) performed between 2002 and 2011. Data were assembled from a national cohort study of ILDKT and a unique data set linking hospital cost accounting data and Medicare claims. ILDKT was more expensive than matched compatible transplantation, ranging from 20% higher adjusted costs for positive on Luminex assay but negative flow cytometric crossmatch, 26% higher for positive flow cytometric crossmatch but negative cytotoxic crossmatch, and 39% higher for positive cytotoxic crossmatch (p < 0.0001 for all). ILDKT was associated with longer median length of stay (12.9 vs. 7.8 days), higher Medicare payments ($91 330 vs. $63 782 p < 0.0001), and greater outlier payments. In conclusion, ILDKT increases the cost of and payments for kidney transplantation.

Quantifying the risk of incompatible kidney transplantation: a multicenter study.

Incompatible live donor kidney transplantation (ILDKT) offers a survival advantage over dialysis to patients with anti-HLA donor-specific antibody (DSA). Program-specific reports (PSRs) fail to account for ILDKT, placing this practice at regulatory risk. We collected DSA data, categorized as positive Luminex, negative flow crossmatch (PLNF) (n = 185), positive flow, negative cytotoxic crossmatch (PFNC) (n = 536) or positive cytotoxic crossmatch (PCC) (n = 304), from 22 centers. We tested associations between DSA, graft loss and mortality after adjusting for PSR model factors, using 9669 compatible patients as a comparison. PLNF patients had similar graft loss; however, PFNC (adjusted hazard ratio [aHR] = 1.64, 95% confidence interval [CI]: 1.15-2.23, p = 0.007) and PCC (aHR = 5.01, 95% CI: 3.71-6.77, p < 0.001) were associated with increased graft loss in the first year. PLNF patients had similar mortality; however, PFNC (aHR = 2.04; 95% CI: 1.28-3.26; p = 0.003) and PCC (aHR = 4.59; 95% CI: 2.98-7.07; p < 0.001) were associated with increased mortality. We simulated Centers for Medicare & Medicaid Services flagging to examine ILDKT's effect on the risk of being flagged. Compared to equal-quality centers performing no ILDKT, centers performing 5%, 10% or 20% PFNC had a 1.19-, 1.33- and 1.73-fold higher odds of being flagged. Centers performing 5%, 10% or 20% PCC had a 2.22-, 4.09- and 10.72-fold higher odds. Failure to account for ILDKT's increased risk places centers providing this life-saving treatment in jeopardy of regulatory intervention.

Temsirolimus as base immunosuppressant for a recipient with metastatic renal cancer: adequate immunosuppression and oncological control--case report.

Treating organ recipients who have metastatic renal cell carcinoma (mRCC) is challenging because of the dilemma between transplant-required immunosuppression and cancer control via boosting immunity with immunotherapy. We report such a patient whose case was successfully maintained only with temsirolimus and low-dose steroids, while achieving good allograft function and oncological outcomes. After removal of his primary renal cancer, a kidney recipient was found to have multiple metastases. Since recovery from surgery he has been administered 25 mg/wk temsirolimus for 2 more years. His mRCC is in partial remission, the serum creatinine level has been stable (∼ 1.6 mg/dL), and the performance score has been good. Adverse effects encountered include transient transaminitis, dyslipidemia, and poorly controlled hyperglycemia. The pharmacokinetics of sirolimus (the major first metabolite of temsirolimus) is depicted to speculate the underlying mechanism. To our knowledge, this is the first sustainable success using temsirolimus-based immunotherapy (both immunosuppression and cancer therapy) in a transplant recipient who has mRCC.

Post-transplant renal artery stenosis: impact of therapy on long-term kidney function and blood pressure control.

PURPOSE: We assessed the long-term outcome of different treatment methods for transplant renal artery stenosis. MATERIALS AND METHODS: Outcome data for 23 patients with transplant renal artery stenosis treated during a 16-year period were reviewed and analyzed. RESULTS: There was a higher incidence of renal artery stenosis in cadaveric donor kidneys compared to living donor kidneys (2% versus 0.3%, p < 0.02), and in cadaveric kidneys from pediatric donors less than 5 years old compared to those from adults (13.2% versus 1.3%, p < 0.01). Six patients underwent primary medical treatment for renal artery stenosis, with a successful outcome in 4 (mean followup plus or minus standard error 57 +/- 22 months) and failure in 2. Of the patients 16 were treated with percutaneous transluminal angioplasty, including 12 who were cured or improved with respect to hypertension (followup 44.7 +/- 7.6 months). Five patients underwent surgical revascularization for renal artery stenosis with postoperative improvement of hypertension (followup 18.8 +/- 11.6 months). Overall, 21 of 23 patients (91%) were treated successfully for transplant renal artery stenosis with cure or improvement of associated hypertension. Posttreatment renal function was stable or improved in 18 patients, while renal function deteriorated due to parenchymal disease in 3. CONCLUSIONS: Most patients with transplant renal artery stenosis can be treated successfully. Percutaneous transluminal angioplasty is the initial interventive treatment of choice for high grade renal artery stenosis. Surgical revascularization is indicated if percutaneous transluminal angioplasty cannot be done or is unsuccessful.

Long-term follow-up of kidneys transplanted from elderly cadaveric donors.

This report examines the long-term results obtained in 50 patients transplanted between 1977 and 1990 with kidneys from cadaveric donors aged 55-70 (median 59) years. The recipients comprised 27 men and 23 women aged 8-68 (median 42) years. In all, 20 patients (40%) had end-stage renal disease on the basis of glomerulonephritis, whereas 8 (16%) were diabetic. Immunosuppression was induced with antilymphocyte globulin and maintained with azathioprine and prednisone in all patients in addition to cyclosporine in the 35 patients transplanted since 1985. Immediate graft function occurred in 18 patients (36%), and 36 patients (72%) were off dialysis at 1 year posttransplant. Altogether, 25 patients (50%) had functioning grafts at 5 years posttransplant, and at up to 13 years of follow-up (mean 5.8 years), 22 patients (44%) are off dialysis and their serum creatinine levels range from 0.8 to 3.8 mg/dl (mean 2.0 mg/dl). In all, 12 patients (24%) expired from 2 months to 15.5 years posttransplant (mean 4.3 years), and 5 of these patients died with functioning grafts. These 5 deceased recipients and the 22 who remain alive with functioning grafts had a mean antigen match of 2.27 with their donors. The other 23 patients whose grafts failed had a mean antigen match of 2.13 (P = 0.77). The 15 recipients who were transplanted prior to the cyclosporine era had lower 1- and 5-year allograft survival rates of 67% and 47%, respectively, as compared with their counterparts, who took cyclosporine-based immunosuppression (74% and 51%, P = 0.58 and 0.76, respectively). Likewise, the 32 recipients with delayed graft function had lower 1- and 5-year allograft survival rates of 66% and 47%, respectively, as compared with the group with immediate graft function (83% and 56%, P = 0.18 and 0.56, respectively). We conclude that acceptable long-term patient and graft survival may be achieved by transplanting these organs and that the degree of HLA matching does not affect their outcome significantly. Patients with immediate allograft function also tended to do better over the long term. Although cyclosporine-based immunosuppression was advantageous within 1 year of transplant, its beneficial effect was less marked 5 years out.

Seminal vesicle volume as a sonographic predictor of prostate cancer stage.

OBJECTIVES: Accurate clinical staging of prostate cancer continues to challenge the urologist, with understaging a common problem. Preoperative identification of men with capsular penetration or seminal vesicle invasion would allow deferment of radical surgery unlikely to cure the patient. We investigated the ability of seminal vesicle volume as determined by transrectal ultrasound (TRUS) to predict the stage of prostate carcinoma. METHODS: Forty-seven consecutive men undergoing radical prostatectomy had preoperative determination of the seminal vesicle volume by TRUS. The volume was determined for each individual seminal vesicle as well as the total seminal vesicle volume. Asymmetry was defined as one seminal vesicle having twice the volume of the other. RESULTS: Average total seminal vesicle volume was statistically greater for patients with Stage C disease as opposed to those with organ-confined tumors. Seminal vesicle asymmetry was also present statistically more often in Stage C patients than Stage B men. The combination of total seminal vesicle volume less than 15 cc and symmetrical seminal vesicles yielded a possibility of only 18% of extraprostatic extension of tumor. CONCLUSIONS: We believe that seminal vesicle volume as determined by TRUS can aid in the staging of adenocarcinoma of the prostate and should be considered along with other parameters, such as prostate-specific antigen, acid phosphatase, and Gleason score, when planning therapy for this disease.

Living unrelated donor renal transplantation.

The organ shortage remains a major barrier to renal transplantation in the United States. Living unrelated kidney donors help to alleviate this problem. The current literature supports the use of living unrelated donors for kidney transplantation. This approach helps to reduce the cadaveric graft shortage and may improve results. A uremic patient should not be obligated to wait for a cadaveric kidney when a willing motivated living unrelated donor exists.

Renal vascular response to vasodilators following warm ischemia and cold storage preservation in dog kidneys.

The purpose of this study was to determine whether warm ischemia (WIT) and cold storage preservation (CSP) impair endothelium-dependent vascular relaxation in the kidney. Twenty-four canine kidneys were harvested, preserved with CSP for 24 or 48 hours, and then perfused with canine blood at 37 C for the determination of glomerular filtration rate (GFR), perfusion flow rate, and renal vascular resistance (RVR). There were four experimental groups: Group I--no WIT followed by 24 hours CSP, Group II--30 minutes WIT followed by 24 hours CSP, Group III--no WIT followed by 48 hours CSP, Group IV--30 minutes WIT followed by 48 hours CSP. Endothelial function in each group was evaluated using acetylcholine (ACh, 1 mg. bolus) as an endothelial dependent vasodilator, and sodium nitroprusside (NP, 10 mg. bolus) as an endothelial independent vasodilator. Glomerular filtration rate was significantly less (P < .05) and RVR was significantly greater (P < .05) for kidneys from Groups II, III and IV compared to group I. The highest RVR was observed in kidneys from Groups II and IV. Nitroprusside administration caused an equivalent reduction in RVR among all four study groups. ACh administration caused a similar reduction in RVR in Groups I and III; however, the change in RVR was significantly less in Groups II and IV (P < .05). We hypothesize that the more severe ischemic insult in the latter groups led to vascular endothelial damage with a consequent loss of ability to secrete endothelium-derived relaxing factor in response to ACh administration.

Sclerotherapy with tetracycline for hydroceles in renal transplant patients.

A total of 17 patients with hydroceles following renal transplantation underwent sclerotherapy with tetracycline hydrochloride (10 ml. of a 5% solution of tetracycline in 1% lidocaine). A successful outcome was obtained in 15 patients (88%). Post-sclerotherapy hydrocelectomy was necessary in 2 patients (12%). No major complications (testicular loss, scrotal abscess or necrosis) occurred in any patient. Pain at injection was the only adverse effect. Tetracycline sclerotherapy for hydroceles appears to be an effective and safe procedure in the renal transplant population. We recommend this procedure as the initial treatment modality for hydroceles in patients with a renal allograft.

Transplant renal artery stenosis in a canine model: evaluation of hemodynamic changes, renal function, and captopril renography.

The utility of captopril renography in the diagnosis of renal artery stenosis was examined in a canine model of renal autotransplantation with and without renal artery clipping. Autotransplantation of the left kidney to the right iliac fossa with contralateral nephrectomy was done in female mongrel dogs. One group served as controls (n = 6). A second group underwent constriction of the external diameter of the renal artery at the time of the operation to produce renal artery stenosis (n = 7). At two weeks postoperatively, glomerular filtration rate was significantly lower in the renal artery stenosis group (26.2 +/- 3.4 ml./min. vs. 38.2 +/- 3.2 ml./min., p less than 0.05), and deteriorated further after captopril administration (17.9 +/- 2.7 ml./min. vs. 26.2 +/- 3.4 ml./min., p less than 0.05). Despite the presence of hemodynamically significant renal artery stenosis, mean arterial pressure was not different between the two groups (134 +/- 4 mm. Hg vs. 132 +/- 6 mm. Hg, control vs. renal artery stenosis, p = NS). Captopril renography did not enable detection of renal artery stenosis in this autotransplant model.

Urinary PGE2 in rats with chronic partial unilateral ureteral obstruction.

Urinary prostaglandin E2 (PGE2) was measured in Munich-Wistar rats with surgically created chronic partial unilateral ureteral obstruction (UUO). Mean values of bladder urine PGE2 were higher in sham than in UUO (24.5 +/- 14.4 vs 12.9 +/- 8.2 ng/mg creatinine, respectively, P less than 0.05). Following diuresis, both ureters were cannulated and urine was collected. PGE2 excretion was increased in sham (66.5 +/- 34.4 and 70.1 +/- 44.5 ng/mg creatinine, left and right, respectively). But in UUO, the obstructed kidney excreted less PGE2 than the contralateral kidney (32.1 +/- 6.0 vs 62.3 +/- 40.4 ng/mg creatinine, obstructed vs contralateral, respectively, P = 0.08). PGE2 synthesis was then determined in separated renal medullary and cortical slices. Renal medullary slices from kidneys with severe obstruction synthesized less PGE2 than the contralateral unobstructed side (3.30 +/- 1.22 vs 10.52 +/- 3.23 ng/mg wet wt-30 min, respectively, P less than 0.05) and failed to respond to arachidonic acid stimulation with any significant increase in PGE2 synthesis (3.30 +/- 1.22 vs 4.47 +/- 1.04 ng/mg wet wt-30 min, baseline vs stimulated). In contrast, contralateral unobstructed kidney slices responded with a significant increase in PGE2 synthesis (10.52 +/- 3.23 vs 21.10 +/- 2.50 ng/mg wet wt-30 min, baseline vs stimulated, P less than 0.05). We conclude that chronic partial UUO in the Munich-Wistar rats resulted in significantly less PGE2 elaboration.