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.

Early small bowel obstruction complicating hand-assisted laparoscopic donor nephrectomy: an uncommon etiology.

Laparoscopic donor nephrectomy is gaining widespread acceptance as a minimally invasive technique for kidney donation. Although it has been associated with decreased patient morbidity and more rapid recovery, it exposes patients to possible complications inherent in its transperitoneal route. We report a case of a small bowel obstruction secondary to midjejunal intussusception occurring on the third postoperative day after a hand-assisted laparoscopic donor nephrectomy. The intussusception proved to be idiopathic since no lead point was identified. The patient recovered without significant sequela after reduction of the intussusceptum. Postoperative ideopathic intussusception is an uncommon cause of bowel obstruction in adults. Surgeons that perform laparoscopic donor nephrectomy will need to remain vigilant for complications that can be associated with the intraperitoneal route of this technique.

Adenine phosphoribosyltransferase deficiency and renal allograft dysfunction.

Adenine phosphoribosyltransferase (APRT) deficiency is a rarely diagnosed cause of renal allograft dysfunction. We report the case of a 42-year-old man who presented in 1996 with idiopathic renal failure. Native kidney biopsy showed extensive microcrystalline interstitial nephritis. The patient subsequently underwent a living-related kidney transplant with excellent early graft function. During the next year, however, he had worsening allograft function, and allograft biopsy showed recurrent interstitial nephritis. Further chemical and spectroscopic analysis showed this lesion to be an annular microcrystalline nephritis consistent with APRT deficiency. This diagnosis was confirmed on erythrocyte assay. Treatment with allopurinol and a low-purine diet led to improvement and stabilization of renal function. APRT is a rare cause of renal allograft dysfunction requiring a high index of suspicion for early diagnosis and treatment. Increased physician awareness in the United States may hasten diagnosis and limit the morbidity associated with this disease.

Completely reversed acute rejection is not a significant risk factor for the development of chronic rejection in renal allograft recipients.

Although acute rejection (AR) has been shown to correlate with decreased long-term renal allograft survival, we have noted AR in recipients who subsequently had stable function for more than 5 years. We reviewed 109 renal graft recipients with a minimum of 1 year graft survival and follow-up of 5-8 years. Post-transplant sodium iothalamate clearances (IoCI) measured at 3 months and yearly thereafter were used to separate recipients into 2 groups. In 61 patients (stable group), there was no significant decrease ( > 20 % reduction in IoCl over 2 consecutive years) in IoCl. Forty-eight patients had significant declines in IoCl (decline group). Groups were compared for incidence, severity, timing, and completeness of reversal of AR. Rejection was considered completely reversed if the post-AR serum creatinine (Scr) returned to or below the pre-AR nadir Scr after anti-rejection therapy. The incidence of AR was not significantly different between groups (47% vs 52%). A trend toward a lower mean number of AR episodes per patient was noted in the stable group (0.69 vs 1.04, P = 0.096), but the timing of AR was not different. Steroid-resistant AR occurred in approximately 25 % of both groups. A striking difference was seen in complete reversal of AR, with the stable group having 100% (42/42 episodes of AR in 29 patients) complete reversal whereas only 32 % (8/25) of the patients in the decline group had complete reversal (P < < 0.001). Of 8 declining patients with complete reversal, graft loss was due to chronic rejection (CR) in only 3. Seventeen declining patients had incomplete reversal of AR, and 82 % (14/17) lost their grafts to CR. Overall, only 8% (3/37) of the recipients with complete reversal of AR developed CR. No patients with incompletely reversed AR had stable long-term function as measured by IoCl. AR is not invariably deleterious to long-term renal graft function if each episode of AR can be completely reversed.

Transplantation and 2-year follow-up of kidneys procured from a cadaver donor with a history of lupus nephritis.

BACKGROUND: Two patients underwent cadaver transplantation with kidneys from a donor with a history of World Health Organization Class IV/V lupus nephritis, and we report their clinical and pathological outcome. METHODS: The donor had a diagnosis of lupus nephritis made by renal biopsy 5 years before donation. At the time of donation, a biopsy was performed on the donor and on one of the recipients at 2 months and 1 year after the transplant. RESULTS: Both recipients underwent uneventful renal transplantation. On the first postoperative day, the donor's final pathological results became available. Although the frozen section seemed to be quite benign, the permanent sections revealed World Health Organization Class II/V lupus nephritis, with full house immunofluorescence and multiple electron dense deposits. Biopsies were performed on recipient #2 at 8 weeks and 1 year after the transplant. These revealed marked diminution followed by complete resolution of all tubular reticular structures and deposits as well as immunofluorescent activity. Both recipients remain with normal renal function and urinalysis at 3 years after the transplant. CONCLUSION: Although a history of clinically significant renal disease has been considered an absolute contraindication to kidney donation, with appropriate workup and caution, select patients may still be considered, which would increase the potential donor pool.

Long-term maintenance of therapeutic cyclosporine levels leads to optimal graft survival without evidence of chronic nephrotoxicity.

Since the introduction of cyclosporine into clinical use, a major area of concern within the transplant community has been the fear of chronic nephrotoxicity. Although progressive renal damage does appear to occur in native kidneys of heart and liver transplant patients receiving cyclosporine, it has been our contention that its use is not a major cause of deterioration in renal allografts. We therefore undertook a study of 91 consecutive renal transplants performed over a three-year period with a minimum graft survival of 1 year and a follow-up of 7-9 years. Serial serum creatinine values, iothalamate clearances and cyclosporine levels were obtained at 3 months after transplantation and yearly thereafter. Biopsies were performed on all grafts that had failed as well as on the majority of patients with deteriorating renal function, and were interpreted by two nephropathologists. As measured by iothalamate clearances, 65% of the patients in this series exhibited absolutely stable renal function despite the maintenance of cyclosporine levels of more than 200 ng/ml for 7-9 years. Since these stable patients did not reveal any decline in renal function, it therefore follows that they did not experience chronic cyclosporine nephrotoxicity. Furthermore, none of the patients with declining renal function or with failed grafts showed any evidence of nephrotoxicity on biopsy. Chronic cyclosporine nephrotoxicity may be a cause of declining function or graft loss with renal transplant recipients, but if so, it is exceedingly rare.

Capsulectomy: a cure for the page kidney.

Hypertension is a known complication after renal trauma. The cause of posttraumatic hypertension can be renal scarring, infarction, hydonephrosis, infection, vascular injury, and parenchymal compression. The authors report on the case of a 16-year-old boy who experienced hypertension after blunt renal trauma. He had a dense fibrous pseudocapsule causing renal parenchymal compression, which lead to hypertension, a Page kidney. Evaluation with computed tomographic (CT) scan, radioisotope renal scan, renal Doppler, and angiogram confirmed the diagnosis. Removal of the renal capsule and the constricting fibrous pseudocapsule was curative.

Failure to cure Mycobacterium gordonae peritonitis associated with continuous ambulatory peritoneal dialysis.

Nontuberculous mycobacteria are increasingly recognized as important pathogens in peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD). Mycobacterium gordonae rarely causes human infection and is the least likely mycobacterium to produce clinical infection in CAPD patients. We describe a patient with persistent M. gordonae peritonitis acquired while undergoing CAPD. During 18 months of treatment, clinical improvement occurred but a microbiological cure could not be achieved. Principles of therapy for mycobacterial peritonitis developing during CAPD are reviewed, and potential explanations for our patient's failure to respond to therapy are discussed.

Trough serum vancomycin levels predict the relapse of gram-positive peritonitis in peritoneal dialysis patients.

We reviewed 31 episodes of gram-positive peritonitis that occurred in our peritoneal dialysis population between 1990 and 1993 in an attempt to identify the risk factor(s) for peritonitis relapse. All patients were treated with 4 weekly doses of intravenous vancomycin. Vancomycin doses no. 1 and 2 were based on body weight (15 mg/kg with a 1-g minimum); vancomycin doses no. 3 and 4 were adjusted in an attempt to maintain the trough serum vancomycin level at greater than 12 mg/L. Nine peritonitis episodes complicated by a relapse were identified. Peritonitis episodes preceding a relapse were similar to relapse-free episodes with respect to patient age, diabetes, peritoneal dialysis modality, duration of peritoneal dialysis treatment, residual urea clearance, peritoneal fluid cell count, causative organism, and weekly vancomycin dose. However, cumulative 4-week mean trough vancomycin levels were consistently lower during peritonitis episodes preceding a relapse (7.8 +/- 0.6 mg/L during relapse-prone episodes v 13.7 +/- 0.9 mg/L during relapse-free episodes; P = 0.0004). Furthermore, relapses developed during nine of 14 peritonitis episodes demonstrating a 4-week mean trough vancomycin level less than 12 mg/L compared with zero of 17 episodes with a 4-week trough level greater than 12 mg/L (P < 0.05). The detection of a low initial 7-day trough vancomycin level also was a useful marker for subsequent peritonitis relapse. In 13 peritonitis episodes associated with an initial trough level less than 9 mg/L, nine were complicated by a relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Association of post-renal transplant erythrocytosis and microalbuminuria: response to angiotensin-converting enzyme inhibition.

Angiotensin-converting enzyme (ACE) inhibitor therapy has recently been shown to be effective in the treatment of post-renal transplant erythrocytosis (PTE). In an attempt to assess the effect of drug treatment on serum erythropoietin level, glomerular filtration rate, and urinary protein excretion, we prospectively evaluated 8 consecutive cadaveric renal transplant recipients with PTE treated with ACE inhibitor therapy for 3 months. In response to ACE inhibition, the mean hematocrit (HCT) value decreased from 53.7 +/- 0.6% before treatment to 42.7 +/- 2.2% at the conclusion of the study (p = 0.03). However, 1 patient failed to respond to ACE inhibition (HCT > 50%), and 2 patients with PTE developed anemia (HCT < 35%) while maintained on drug treatment. Although the mean serum erythropoietin level decreased during ACE inhibition (from 22.8 +/- 8.4 to 9.4 +/- 5.3 mU/ml; p = 0.06), a consistent change in individual erythropoietin levels was not identified. At the conclusion of the study, the serum erythropoietin levels were undetectable in 4 patients, decreased in 1, unchanged in 2, and increased in the only patient with PTE who failed to respond to drug treatment. All patients tolerated the ACE inhibitor therapy without developing cough or hyperkalemia. In addition, serum creatinine levels, 125I-iothalamate clearances, and mean arterial blood pressures were unchanged throughout the study. Microalbuminuria (spot urinary albumin/creatinine ratio between 30 and 200 mg/g) developed in 5 patients with PTE and coincided with the onset of erythrocytosis (25.2 +/- 7 mg/g before PTE and 76.3 +/- 36.7 mg/g at the time of PTE detection).(ABSTRACT TRUNCATED AT 250 WORDS)

Predictive value of Doppler ultrasonography in renal transplantation.

During a 17-month period, 268 Doppler sonography studies were performed on 46 consecutive renal transplant patients. There were 35 episodes of acute rejection in 10 patients, 8 episodes of delayed function and 47 episodes of high cyclosporine levels (greater than 800 ng/dl by TDX method) in 21 patients. Defining an abnormal resistive index (RI) as greater than 0.8 or a 20% increase above baseline, the test has a specificity of 99% and a sensitivity of 94% in the 1st month post-transplant and had an overall predictive value of 99%. Episodes of high cyclosporine levels ranging from 800 to 1650 ng/dl did not correlate with a high RI except in one circumstance with concurrent acute rejection. Within the 1st month post-transplant, only 1 false-negative study occurred. An additional 8 false-negative studies occurred beyond 1 month post-transplant. Patients with delayed function are separated into three groups based on the Doppler ultrasounds: Group I, patients with an accelerated acute rejection with high RI (N = 2); Group II, patients with true ischemic acute tubular necrosis with normal RI (N = 2); and Group III, patients with possible immunologically-mediated delayed function with intermediate RI between 0.6 and 0.8 (N = 4). Doppler ultrasound is a useful ancillary test to confirm the clinical suspicion of acute rejection. Since high cyclosporine levels do not cause an increase in RI, Doppler ultrasound may help to avoid confusion between acute rejection and cyclosporine toxicity. Additionally, this test may offer insight into the cause of early post-transplant renal dysfunction.