Do Patient Assessments of Hospital Quality Correlate With Kidney Transplantation Surgical Outcomes?

BACKGROUND: Currently, transplant patients have limited metrics available to understand transplant center quality. Graft and patient survival do not capture the patient experience, and patients may use more general consumer assessments of hospital care to help select transplant centers. We evaluated whether consumer assessments of hospital quality correlate with short- and long-term kidney transplant center performance. MATERIALS AND METHODS: CMS uses the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) to publicly report patients' perspectives on hospital care. We merged 2012 SRTR kidney transplant (n = 200 centers), HCAHPS and American Hospital Association survey data. Center performance was determined by variation in observed-to-expected (O/E) ratios for 1-month and 1-year graft failure. We used multivariate regression to determine whether HCAHPS measures correlate with center performance, after risk-adjusting for structural characteristics and volume. RESULTS: Center-specific graft failure varied significantly (30 day O/E range: 0-4.1). At 30 days, compared to average centers, cleanliness (OR = 1.26, P = .001), patient recommendation (OR = 1.18, P = .005), and high overall ratings (OR = 1.11, P = .036) predicted high performance. Poor nursing-patient communication (OR = 0.70, P = .030), lower cleanliness (OR = 0.67, P < .001), poor overall ratings (OR = 0.79, P = .038), and no recommendation (OR = 0.68, P = .019) correlated with average/low performance. There was no significant correlation between HCAHPS measures and 1-year outcomes. CONCLUSIONS: The association between hospital consumer assessments of hospital care and center performance after kidney transplantation is limited. More specific metrics oriented to capturing transplant patient perspectives may be valuable in further defining transplant quality.

Increasing the Use of Kidneys From Unconventional and High-Risk Deceased Donors.

In this paper, we have reviewed the literature and report on kidney donors that are currently used at relatively low rates. Kidneys from donors with acute kidney injury (AKI) seem to have outcomes equivalent to those from donors without AKI, provided one can rule out significant cortical necrosis. Kidneys from donors with preexisting diabetes or hypertension may have marginally lower aggregate survival but still provide patients with a significant benefit over remaining on the wait list. The Kidney Donor Profile Index derives only an aggregate association with survival with a very modest C statistic; therefore, the data indicated that this index should not be the sole reason to discard a kidney, except perhaps in patients with extremely low estimated posttransplant survival scores. It is important to note that the Scientific Registry of Transplant Recipients models of risk adjustment should allay concerns regarding regulatory issues for observed outcomes falling below expectations. The successful utilization of kidneys from donation after cardiac death over the past decade shows how expanding our thinking can translate into more patients benefiting from transplantation. Given the growing number of patients on the wait list, broadening our approach to kidney acceptance could have an important impact on the population with end-stage renal disease. Many lives could be prolonged by carefully considering use of kidneys that are often discarded.

Gene Expression in Biopsies of Acute Rejection and Interstitial Fibrosis/Tubular Atrophy Reveals Highly Shared Mechanisms That Correlate With Worse Long-Term Outcomes.

Interstitial fibrosis and tubular atrophy (IFTA) is found in approximately 25% of 1-year biopsies posttransplant. It is known that IFTA correlates with decreased graft survival when histological evidence of inflammation is present. Identifying the mechanistic etiology of IFTA is important to understanding why long-term graft survival has not changed as expected despite improved immunosuppression and dramatically reduced rates of clinical acute rejection (AR) (Services UDoHaH. http://www.ustransplant.org/annual_reports/current/509a_ki.htm). Gene expression profiles of 234 graft biopsy samples were obtained with matching clinical and outcome data. Eighty-one IFTA biopsies were divided into subphenotypes by degree of histological inflammation: IFTA with AR, IFTA with inflammation, and IFTA without inflammation. Samples with AR (n = 54) and normally functioning transplants (TX; n = 99) were used in comparisons. A novel analysis using gene coexpression networks revealed that all IFTA phenotypes were strongly enriched for dysregulated gene pathways and these were shared with the biopsy profiles of AR, including IFTA samples without histological evidence of inflammation. Thus, by molecular profiling we demonstrate that most IFTA samples have ongoing immune-mediated injury or chronic rejection that is more sensitively detected by gene expression profiling. These molecular biopsy profiles correlated with future graft loss in IFTA samples without inflammation.

Rapid Resolution of Donor-Derived Glomerular Fibrin Thrombi After Deceased Donor Kidney Transplantation.

The aim of this study was to determine the clinical and histologic outcomes related to transplanting kidneys from deceased donors with glomerular fibrin thrombi (GFT). We included all cases transplanted between October 2003 and October 2014 that had either a preimplantation biopsy or an immediate postreperfusion biopsy showing GFT. The study cohort included 61 recipients (9.9%) with GFT and 557 in the control group without GFT. Delayed graft function occurred in 49% of the GFT group and 39% in the control group (p = 0.14). Serum creatinine at 1, 4, and 12 months and estimated GFR at 12 months were similar in the two groups. Estimated 1-year graft survival was 93.2% in the GFT group and 95.1% in the control group (p = 0.22 by log-rank). Fifty-two of the 61 patients in the GFT group (85%) had a 1-month protocol biopsy, and only two biopsies (4%) showed residual focal glomerular thrombi. At the 1-year protocol biopsy, the prevalence of moderate to severe interstitial fibrosis and tubular atrophy was 24% in the GFT group and 30% in the control group (p = 0.42). We concluded that GFT resolves rapidly after transplantation and that transplanting selected kidneys from deceased donors with GFT is a safe practice.

Transplanting Kidneys from Deceased Donors With Severe Acute Kidney Injury.

Our aim was to determine outcomes with transplanting kidneys from deceased donors with acute kidney injury, defined as a donor with terminal serum creatinine ≥2.0 mg/dL, or a donor requiring acute renal replacement therapy. We included all patients who received deceased donor kidney transplant from June 2004 to October 2013. There were 162 AKI donor transplant recipients (21% of deceased donor transplants): 139 in the standard criteria donor (SCD) and 23 in the expanded criteria donor (ECD) cohort. 71% of the AKI donors had stage 3 (severe AKI), based on acute kidney injury network (AKIN) staging. Protocol biopsies were done at 1, 4, and 12 months posttransplant. One and four month formalin-fixed paraffin embedded (FFPE) biopsies from 48 patients (24 AKI donors, 24 non-AKI) underwent global gene expression profiling using DNA microarrays (96 arrays). DGF was more common in the AKI group but eGFR, graft survival at 1 year and proportion with IF/TA>2 at 1 year were similar for the two groups. At 1 month, there were 898 differentially expressed genes in the AKI group (p-value <0.005; FDR <10%), but by 4 months there were no differences. Transplanting selected kidneys from deceased donors with AKI is safe and has excellent outcomes.

Molecular classifiers for acute kidney transplant rejection in peripheral blood by whole genome gene expression profiling.

There are no minimally invasive diagnostic metrics for acute kidney transplant rejection (AR), especially in the setting of the common confounding diagnosis, acute dysfunction with no rejection (ADNR). Thus, though kidney transplant biopsies remain the gold standard, they are invasive, have substantial risks, sampling error issues and significant costs and are not suitable for serial monitoring. Global gene expression profiles of 148 peripheral blood samples from transplant patients with excellent function and normal histology (TX; n = 46), AR (n = 63) and ADNR (n = 39), from two independent cohorts were analyzed with DNA microarrays. We applied a new normalization tool, frozen robust multi-array analysis, particularly suitable for clinical diagnostics, multiple prediction tools to discover, refine and validate robust molecular classifiers and we tested a novel one-by-one analysis strategy to model the real clinical application of this test. Multiple three-way classifier tools identified 200 highest value probesets with sensitivity, specificity, positive predictive value, negative predictive value and area under the curve for the validation cohort ranging from 82% to 100%, 76% to 95%, 76% to 95%, 79% to 100%, 84% to 100% and 0.817 to 0.968, respectively. We conclude that peripheral blood gene expression profiling can be used as a minimally invasive tool to accurately reveal TX, AR and ADNR in the setting of acute kidney transplant dysfunction.

Oral paricalcitol reduces the prevalence of posttransplant hyperparathyroidism: results of an open label randomized trial.

Postkidney transplant hyperparathyroidism is a significant problem. Vitamin D receptor agonists are known to suppress parathyroid hormone (PTH) secretion. We examined the effect of oral paricalcitol on posttransplant secondary hyperparathyroidism by conducting an open label randomized trial in which 100 incident kidney transplant recipients were randomized 1:1 to receive oral paricalcitol, 2 µg per day, for the first year posttransplant or no additional therapy. Serial measurements of serum PTH, calcium and bone alkaline phosphatase, 24-h urine calcium and bone density were performed. The primary endpoint was the frequency of hyperparathyroidism 1-year posttransplant. Eighty-seven patients completed the trial. One-year posttransplant, 29% of paricalcitol-treated subjects had hyperparathyroidism compared with 63% of untreated patients (p = 0.0005). Calcium supplementation was discontinued in two control and 15 treatment patients due to mild hypercalcemia or hypercalcuria. Paricalcitol was discontinued in four patients due to hypercalcuria/hypercalcemia and in one for preference. Two subjects required decreasing the dose of paricalcitol to 1 µg daily. Hypercalcemia was asymptomatic and reversible. Incidence of acute rejection, BK nephropathy and renal function at 1 year were similar between groups. Moderate renal allograft fibrosis was reduced in treated patients. Oral paricalcitol is effective in decreasing posttransplant hyperparathyroidism and may have beneficial effects on renal allograft histology.

Genetic differences in Native Americans and tacrolimus dosing after kidney transplantation.

Tacrolimus pharmacokinetics vary due to single nucleotide polymorphisms (SNPs) in metabolizing enzymes and membrane transporters that alter drug elimination. Clinically we observed that Native Americans require lower dosages of tacrolimus to attain trough levels similar to Caucasians. We previously demonstrated that Native Americans have decreased oral clearance of tacrolimus, suggesting that Native Americans may have more variant SNPs and, therefore, altered tacrolimus pharmacokinetic parameters. We conducted 12-hour pharmacokinetic studies on 24 adult Native American kidney transplant recipients on stable doses of tacrolimus for at least 1 month posttransplantation. Twenty-four Caucasian kidney transplant recipients were compared as controls. SNPs encoding the genes for the enzymes (CYP3A4, CYP3A5) and transporters (ABCB1, BCRP, and MRP1) were typed using TaqMan. The mean daily tacrolimus dose in the Native Americans was 0.03 ± 0.02 compared with the Caucasians 0.5 ± 0.3 (mg/kg/d; P = .002), with no significant differences in trough levels, (6.7 ± 3.1 vs 7.4 ± 2.1 ng/dL; P = .4). Many Native Americans, but not Caucasians, demonstrated the 3/*3 - C3435T CC and the *3/*3 -G2677T GG genotype combination previously associated with low tacrolimus dosing. Native Americans required significantly lower tacrolimus doses than Caucasians to achieve similar tacrolimus trough levels, in part due to lower tacrolimus clearance from decreased drug metabolism and excretion.

Resolution of long-standing necrobiosis lipoidica diabeticorum (NLD) lesion after restoration of euglycemia following successful pancreas after kidney (PAK) transplantation: a case report.

Necrobiosis lipoidica diabeticorum (NLD) is an inflammatory skin disorder of unknown cause which can be seen in patients with diabetes mellitus. Various treatments, including immunosuppressive agents have been tried, without consistent efficacy. NLD is generally thought not to correlate well with tight diabetic control. Pancreas transplantation is the only widely and clinically used treatment that restores euglycemia in type I diabetic recipients. We report a case of resolution of NLD that had been unchanged for decades before pancreas after kidney transplantation. Another unique aspect of our case was that immunosuppression was discounted as a confounding factor, because the patient had been exposed to the same antirejection regimen for 3 years preceding the pancreas transplantation.

Impact of acute rejection on kidney allograft outcomes in recipients on rapid steroid withdrawal.

Background. Our aim was to study the impact of clinical acute rejection (CR) and subclinical rejection (SR) on outcomes in kidney transplant recipients treated with rapid steroid withdrawal (RSW). Methods. All patients who received a living or deceased donor kidney transplant and were treated with RSW were included. The primary outcome was death-censored graft survival. Biopsies with Banff borderline changes were included with the rejection groups. Results. 457 kidney transplant recipients treated with RSW were included; 46 (10%) experienced SR, and 36 (7.8%) had CR. Mean HLA mismatch was significantly higher in the CR group. The Banff grade of rejection was higher in the CR group. There was a larger proportion of patients in both rejection groups with the combination of IFTA and persistent inflammation on the follow-up protocol biopsy done at 1 year. The estimated 5-year death-censored graft survival was 81% in SR, 78% in CR, and 97% in the control group (P < .0001). Significant differences were observed in allograft survival between the CR and control group (HR 9.06, 95% CI 3.39-24.2) and between the SR and control group (HR 4.22, 95% CI 1.30-13.7). Conclusion. Both SR and CR are associated with an inferior graft survival in recipients on RSW.

Outcomes after simultaneous pancreas and kidney transplantation and the discriminative ability of the C-peptide measurement pretransplant among type 1 and type 2 diabetes mellitus.

BACKGROUND: Earlier studies reporting outcomes after pancreas transplantation have included a combination of C-peptide cutoffs and clinical criteria to classify type 2 diabetes mellitus (T2DM). However, because the kidney is the major site for C-peptide catabolism, C-peptide is unreliable to discriminate the type of diabetes in patients with kidney disease. METHODS: To improve the discriminative power and better classify the type of diabetes, we used a composite definition to identify T2DM: presence of C-peptide, negative glutamic acid decarboxylase antibody, absence of diabetic ketoacidosis, and use of oral hypoglycemics. Additionally among T2DM patients with end-stage renal disease (ESRD), body mass index of <30 kg/m(2) and use of <1 u/kg of insulin per day were selection criteria for suitablity for simultaneous pancreas and kidney transplantation (SPKT). We compared graft and patient survival between T1DM and T2DM after SPKT. RESULTS: Our study cohort consisted of 80 patients, 10 of whom were assigned as T2DM based on our study criteria. Approximately 15% of patients with T1DM had detectable C-peptide. Cox regression survival analyses found no significant differences in allograft (pancreas and kidney) or patient survival between the 2 groups. The mean creatinine clearance at 1 year estimated by the modification of Diet in Renal Disease (MDRD) equation was not significantly different between the 2 groups. Among those with 1 year of follow-up, all patients with T2DM had glycosylate hemoglobin of <6.0 at 1 year versus 92% of those with T1DM. CONCLUSION: SPKT should be considered in the therapeutic armamentarium for renal replacement in selected patients with T2DM and ESRD. Use of C-peptide measurements for ESRD patients can be misleading as the sole criterion to determine the type of diabetes.

Alemtuzumab with rapid steroid taper in simultaneous kidney and pancreas transplantation: comparison to induction with antithymocyte globulin.

We compared our experience with alemtuzumab induction and rapid steroid taper (RST) in simultaneous kidney and pancreas transplantation (SKPT) with a historic control group who received rabbit antithymocyte globulin (r-ATG) induction with RST. 74 SKPTs performed at our center between January 2005 to November 2008 who underwent immunosuppression with RST in combination with r-ATG induction (n = 33; 1.5 mg/kg x 4 for a total dose of 6 mg/kg) or alemtuzumab induction (n = 41; 30 mg single dose). Maintenance immunosuppression consisted of tacrolimus and mycophenolate mofetil. Steroids were discontinued after postoperative day 4. Recipient and transplant characteristics were similar between the 2 groups, with 82% of the r-ATG and 80% of the alemtuzumab group steroid free at 1 year. The rate of clinical acute rejection episodes was 12% in the r-ATG group and 15% in the alemtuzumab group. The rates of cytomegalovirus (CMV) infection, BK nephropathy, and graft survival were similar between the 2 groups. There was no difference in mean serum creatinine, calculated GFR, or fasting blood sugar at 1 year between the 2 groups, whereas glycosylated hemoglobin (HbA1c) was lower at 1 year in the alemtuzumab (5.3 +/- 0.4) versus the r-ATG group (5.6 +/- 0.4; P = .0021). Induction with r-ATG or alemtuzumab with RST was safe and effective in SKPT. The incidences of acute rejection episodes, CMV infection, and BK nephropathy were similar. Mean HbA1C at 1 year was lower among the alemtuzumab group. Further long-term follow-up is needed to confirm these results.

Successful transplantation of a split crossed fused ectopic kidney into a patient with end-stage renal disease.

Potential donors with congenital renal anomalies but normal renal function are often overlooked because of a possible increase in technical difficulty and complications associated with the surgery. However, as the waiting list for a deceased donor kidney transplant continues to grow, it is important to consider these kidneys for potential transplant. This paper describes the procurement of a crossed fused ectopic kidney, and subsequent parenchymal transection prior to transplantation as part of a combined simultaneous kidney pancreas transplant. The transplant was uncomplicated, and the graft had immediate function. The patient is now two years from transplant with excellent function.

Impact of subclinical inflammation on the development of interstitial fibrosis and tubular atrophy in kidney transplant recipients.

Our aim was to study the impact of subclinical inflammation on the development of interstitial fibrosis and tubular atrophy (IF/TA) on a 1-year protocol biopsy in patients on rapid steroid withdrawal (RSW). A total of 256 patients were classified based on protocol biopsy findings at months 1 or 4. Group 1 is 172 patients with no inflammation, group 2 is 50 patients with subclinical inflammation (SCI), group 3 is 19 patients with subclinical acute rejection (SAR) and group 4 is 15 patients with clinical acute rejection (CAR). On the 1-year biopsy, more patients in group 2 (SCI) (34%, p = 0.004) and group 3 (SAR) (53%, p = 0.0002), had an IF/TA score > 2 compared to group 1 (control) (15%). IF/TA was not increased in group 4 (CAR) (20%). The percent with IF/TA score > 2 and interstitial inflammation (Banff i score > 0) was higher in group 2 (16%, p = 0.004) and group 3 (37%, p < 0.0001) compared to group 1 (3%). In a multivariate analysis, patients in groups 2 or 3 had a higher risk of IF/TA score > 2 on the 1-year biopsy (OR 6.62, 95% CI 2.68-16.3). We conclude that SCI and SAR increase the risk of developing IF/TA in patient on RSW.

Pilot study: association of traditional and genetic risk factors and new-onset diabetes mellitus following kidney transplantation.

INTRODUCTION: New-onset diabetes mellitus, which occurs after kidney transplant and type 2 diabetes mellitus (T2DM), shares common risk factors and antecedents in impaired insulin secretion and action. Several genetic polymorphisms have been shown to be associated with T2DM. We hypothesized that transplant recipients who carry risk alleles for T2DM are "tipped over" to develop diabetes mellitus in the posttransplant milieu. METHODS: We investigated the association of genetic and traditional risk factors present before transplantation and the development of new-onset diabetes mellitus after kidney transplantation (NODAT). Markers in 8 known T2DM-linked genes were genotyped using either the iPLEX assay or allelic discrimination (AD)-PCR in the study cohort testing for association with NODAT. We used univariate and multivariate logistic regression models for the association of pretransplant nongenetic and genetic variables with the development of NODAT. RESULTS: The study cohort included 91 kidney transplant recipients with at least 1 year posttransplant follow-up, including 22 who developed NODAT. We observed that increased age, family history of T2DM, pretransplant obesity, and triglyceridemia were associated with NODAT development. In addition, we observed positive trends, although statistically not significant, for association between T2DM-associated genes and NODAT. CONCLUSIONS: These findings demonstrated an increased NODAT risk among patient with a positive family history for T2DM, which, in conjunction with the observed positive predictive trends of known T2DM-associated genetic polymorphisms with NODAT, was suggestive of a genetic predisposition to NODAT.

Deceased donor kidney transplantation from donors with acute renal failure due to rhabdomyolysis.

With the current shortage of solid organs for transplant, the transplant community continues to look for ways to increase the number of organ donors, including extending the criteria for donation. In rhabdomyolysis, the byproducts of skeletal muscle breakdown leak into the circulation resulting in acute renal failure in up to 30% of patients. In nonbrain dead patients, this condition is reversible and most patients recover full renal function. Seven potential donors had rhabdomyolysis with acute renal failure as evidenced by the presence of urine hemoglobin, plasma creatinine kinase levels of greater than five times the normal and elevated creatinine. One donor required dialysis. At our institution, 10 kidneys were transplanted from the seven donors. Two grafts had immediate function, five grafts experienced slow graft function and three grafts had delayed graft function requiring hemodialysis. At a mean of 8.7 months posttransplant (2.4-25.2 months), all patients have good graft function, are off dialysis and have a mean creatinine of 1.3 (0.7-1.8). In conclusion, our experience suggests that rhabdomyolysis with acute renal failure should not be a contraindication for donation, although recipients may experience slow or delayed graft function.

Outcomes of simultaneous kidney-pancreas transplantation with positive cross-match.

We studied 72 consecutive simultaneous pancreas kidney transplant (SPKT) recipients. There were 14 patients with positive pretransplant cross-matches (positive CDC- B cell and/or positive flow T or B cross-match). The control group included all 58 SPKT recipients with a negative crossmatch. The study group received induction with low dose intravenous immunoglobulin (IVIg), rabbit antithymocyte globulin (rATG; total dose 6 mg/kg), or alemtuzumab (30 mg single dose) and maintenance with tacrolimus, mycophenolate mofetil (MMF), and corticosteroids. The control group was treated similarly, but with steroid avoidance and no IVIg. Biopsy-proven acute rejection (BPAR) of the kidney allograft occurred in 7 study patients (50%) compared with 10% in the control group (P = .022). One patient experienced acute cellular rejection (ACR); the other 6 (43%), antibody-mediated rejection (AMR). None of the cross-match negative patients had AMR (P = .001). The mean follow-up period was 18.7 months in the study group, and 18.3 months in the control group. The 1-year actuarial patient survival was 91.7% in the study group and 97% in the control group. Kidney allograft survival was 91.7% in the study group and 95.2% in the control group. Pancreas allograft survival was 76.9% in study group and 89.6% in the control group (P = .088). We concluded that patients with a positive pretransplant CDC-B cross-match and/or positive flow cross-match have an increased risk of AMR; more intensive desensitization is needed with low-dose IVIg and induction with either rATG or alemtuzumab.

Diffuse parenchymal urine leak after kidney transplantation following degloving injury during donor nephrectomy.

Laparoscopic donor nephrectomy can result in trauma to the kidney which may affect recipient graft function. In this case, the kidney sustained a complete degloving of the capsule during extraction. The kidney was transplanted and had immediate, good renal function, but postoperative course was complicated by a large urinoma that drained through the wound. Exploration was negative for a defined urine leak, but the surface of the denuded kidney was leaking a significant amount of unconcentrated urine. The patient was successfully treated with tissue glue treatment to the kidney surface and peritoneal window.