The impact of induction therapy on the risk of posttransplant lymphoproliferative disorder in adult kidney transplant recipients with donor-recipient serological Epstein-Barr virus mismatch.

Posttransplant lymphoproliferative disorder (PTLD) poses a significant concern in Epstein-Barr virus (EBV)-negative patients transplanted from EBV-positive donors (EBV R-/D+). Previous studies investigating the association between different induction agents and PTLD in these patients have yielded conflicting results. Using the Organ Procurement and Transplant Network database, we identified EBV R-/D+ patients >18 years of age who underwent kidney-alone transplants between 2016 and 2022 and compared the risk of PTLD with rabbit antithymocyte globulin (ATG), basiliximab, and alemtuzumab inductions. Among the 6620 patients included, 64.0% received ATG, 23.4% received basiliximab, and 12.6% received alemtuzumab. The overall incidence of PTLD was 2.5% over a median follow-up period of 2.9 years. Multivariable analysis demonstrated that the risk of PTLD was significantly higher with ATG and alemtuzumab compared with basiliximab (adjusted subdistribution hazard ratio [aSHR] = 1.98, 95% confidence interval [CI] 1.29-3.04, P = .002 for ATG and aSHR = 1.80, 95% CI 1.04-3.11, P = .04 for alemtuzumab). However, PTLD risk was comparable between ATG and alemtuzumab inductions (aSHR = 1.13, 95% CI 0.72-1.77, P = .61). Therefore, the risk of PTLD must be taken into consideration when selecting the most appropriate induction therapy for this patient population.

Kidney after liver transplantation does not have an increased risk of rejection compared to liver alone.

BACKGROUND: Simultaneous liver kidney (SLK) transplant protects against acute cellular rejection. In 2017, UNOS implemented a "safety net" policy to allow patients with renal recovery to avoid renal transplantation. Whether kidney after liver transplantation (KALT) increases the risk of rejection is unknown. METHODS: We performed a retrospective analysis of the Organ Procurement and Transplantation Network (OPTN) database of adult patients who received liver transplant, SLK or KALT between 2010 and 2020. We examined rejection of the liver within 6 months and 1 year of the liver transplant, as well as rejection of the kidney within 6 months and 1 year of receiving the kidney, as well as patient and graft loss. RESULTS: Sixty-six thousand seventy-nine patients were transplanted; 60 168 with liver transplant alone, 5627 with SLK, and 284 with KALT. Acute or chronic liver rejection rates within 6 or 12 months were statistically higher in the KALT group (10.0% and 10.9%) compared to the SLK group (6.1% and 7.5%), but comparable to the LTA group (9.3% and 11.1%). Kidney rejection and graft survival rates were not different. Liver graft survival was worse in KALT than SLK or LTA (Kaplan-Meier estimates .61 vs. .89 and .90), but these patients were more ill at the time of transplantation. KDPI and LDRI scores were notably lower in the SLK than KALT group. Patient survival was not clinically different between the groups. CONCLUSION: KALT does not increase the risk of acute or chronic kidney rejection. SLK has a lower risk of early liver rejection, but this effect diminishes by one year to being not clinically different compared to KALT. Given that KALT is immunologically safe, and potentially avoids unnecessary renal graft use, it should be preferred over SLK. BRIEF SUMMARY: Patients undergoing sequential kidney after liver transplant do not have an increased risk of liver or kidney rejection when compared to liver transplant alone or simultaneous liver and kidney transplant.

The use of semaglutide in patients with renal failure- a retrospective cohort study.

OBJECTIVE: Semaglutide, a glucagon-like peptide-1 receptor agonist is approved for weight loss and diabetes treatment, but limited literature exists regarding semaglutide use in patients with advanced chronic kidney disease (CKD). Therefore, this project assessed the safety and efficacy of semaglutide among patients with eGFR (estimated glomerular filtration rate) 15-29 mL/min/1.73m2 (CKD stage 4), eGFR<15 mL/min/1.73m2 (CKD stage 5) or on dialysis. METHODS: This is a retrospective Electronic Medical Record based analysis of consecutive patients with advanced CKD (defined as CKD 4 or greater) who were started on semaglutide (injectable or oral). Data was collected between Jan 2018 and Jan 2023. Investigators verified CKD diagnosis and manually extracted data. Data were analyzed using Fisher's exact test, paired T-test, linear mixed effects models and Wilcoxon signed rank test. RESULTS: Seventy-six patients with CKD 4 or greater who initiated semaglutide were included. Most patients had a history of T2DM (96.0%), and most were male (53.9%). The mean age was 66.8 y (SD 11.5) with the mean BMI was 36.2 (SD 7.5). The initial doses were 3 mg orally and 0.25 mg by injection. Maximum prescribed dose was 1mg (injectable) in 28 (45.2%) patients and 14 mg (orally) in 2 (14.2%) patients. Patients received semaglutide for a median duration of 17.4 (IQR 0.43, 48.8) months. Forty-eight (63.1%) patients reported no adverse effects associated with the therapy. Mean weight decreased from 106.2(SD 24.2) to 101.3 (SD 27.3) kg (p<0.001). Eight patients (16%) with type 2 diabetes (T2DM) discontinued insulin after starting semaglutide. Mean HbA1c decreased from 8.0 % (SD 1.7) to 7.1 % (SD 1.3) (p<0.001). Adverse effects were the primary reason for semaglutide discontinuation (37.0%), with nausea, vomiting, and abdominal pain being the most common complaints. CONCLUSIONS: Based on this retrospective study semaglutide appears to be tolerated by most individuals with CKD 4 or greater despite associated gastrointestinal side effects similar to those observed in patients with better kidney function and leads to an improvement of glycemic control and insulin discontinuation in patients with T2DM. Modest weight loss (approximately 4.6 % of the total body weight) was observed on the prescribed doses. Larger prospective randomized studies are needed to comprehensively assess the risks and benefits of semaglutide in patients with CKD 4 or greater and obesity.

Improved outcomes of kidney after liver transplantation after the implementation of the safety net policy.

The number of kidney after liver transplants (KALT) increased after the implementation of the United Network of Organ Sharing (UNOS) safety net policy, but the effects of the policy on KALT outcomes remain unknown. Using the UNOS database, we identified KALT between 60 and 365 days from liver transplant from January 1, 2010, to December 31, 2020. The main outcome was 1- and 3-year patient, liver, and kidney graft survival. Secondary outcomes included 6-month and 1-year acute rejection (AR) of liver and kidney, and 1-year kidney allograft function. Of the 256 KALT, 90 were pre-policy and 166 post-policy. Compared to pre-policy, post-policy 1- and 3-year liver graft survival was higher (54% and 54% vs. 86% and 81%, respectively, p <0.001), while 1- and 3-year kidney graft survival (99% and 75% vs. 92% and 79%, respectively, p =0.19), and 1- and 3-year patient survival (99% and 99% vs. 95% and 89%, respectively, p =0.11) were not significantly different. Subgroup analysis revealed similar trends in patients with and without renal failure at liver transplant. Liver AR at 6 months was lower post-policy (6.3% vs. 18.3%, p =0.006) but was similar (10.5% vs. 13%, p =0.63) at 1 year. Kidney AR was unchanged post-policy at 6 months and 1 year. Creatinine at 1 year did not differ post-policy versus pre-policy (1.4 vs. 1.3 mg/dL, p =0.07) despite a higher proportion of deceased donors, higher Kidney Donor Profile Index, and longer kidney cold ischemia time post-policy ( p <0.05 for all). This 3-year follow-up after the 2017 UNOS policy revision demonstrated that the safety net implementation has resulted in improved liver outcomes for patients who underwent KALT with no increased AR of the liver or the kidney allografts.

Coronavirus Disease 2019 Vaccine-Breakthrough Infections Requiring Hospitalization in Mayo Clinic Florida Through August 2021.

We characterized coronavirus disease 2019 (COVID-19) breakthrough cases admitted to a single center in Florida. With the emergence of delta variant, an increased number of hospitalizations was seen due to breakthrough infections. These patients were older and more likely to have comorbidities. Preventive measures should be maintained even after vaccination.

Low antispike antibody levels correlate with poor outcomes in COVID-19 breakthrough hospitalizations.

BACKGROUND: While COVID-19 immunization programs attempted to reach targeted rates, cases rose significantly since the emergence of the delta variant. This retrospective cohort study describes the correlation between antispike antibodies and outcomes of hospitalized, breakthrough cases during the delta variant surge. METHODS: All patients with positive SARS-CoV-2 polymerase chain reaction hospitalized at Mayo Clinic Florida from 19 June 2021 to 11 November 2021 were considered for analysis. Cases were analyzed by vaccination status. Breakthrough cases were then analyzed by low and high antibody titers against SARS-CoV-2 spike protein, with a cut-off value of ≥132 U/ml. Outcomes included hospital length of stay (LOS), need for intensive care unit (ICU), mechanical ventilation, and mortality. We used 1:1 nearest neighbor propensity score matching without replacement to assess for confounders. RESULTS: Among 627 hospitalized patients with COVID-19, vaccine breakthrough cases were older with more comorbidities compared to unvaccinated. After propensity score matching, the unvaccinated patients had higher mortality (27 [28.4%] vs. 12 [12.6%], p = 0.002) and LOS (7 [1.0-57.0] vs. 5 [1.0-31.0] days, p = 0.011). In breakthrough cases, low-titer patients were more likely to be solid organ transplant recipients (16 [34.0%] vs. 9 [12.3%], p = 0.006), with higher need for ICU care (24 [51.1%] vs. 22 [11.0%], p = 0.034), longer hospital LOS (median 6 vs. 5 days, p = 0.013), and higher mortality (10 [21.3%] vs. 5 [6.8%], p = 0.025) than high-titer patients. CONCLUSIONS: Hospitalized breakthrough cases were more likely to have underlying risk factors than unvaccinated patients. Low-spike antibody titers may serve as an indicator for poor prognosis in breakthrough cases admitted to the hospital.

Terlipressin and the Treatment of Hepatorenal Syndrome: How the CONFIRM Trial Moves the Story Forward.

Hepatorenal syndrome (HRS) is a form of acute kidney injury (AKI) occurring in patients with advanced cirrhosis and is associated with significant morbidity and mortality. The pathophysiology underlying HRS begins with increasing portal pressures leading to the release of vasodilatory substances that result in pooling blood in the splanchnic system and a corresponding reduction in effective circulating volume. Compensatory activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system and release of arginine vasopressin serve to defend mean arterial pressure but at the cost of severe constriction of the renal vasculature, leading to a progressive, often fulminant form of AKI. There are no approved treatments for HRS in the United States, but multiple countries, including much of Europe, use terlipressin, a synthetic vasopressin analogue, as a first-line therapy. CONFIRM (A Multi-Center, Randomized, Placebo Controlled, Double-Blind Study to Confirm Efficacy and Safety of Terlipressin in Subjects With Hepatorenal Syndrome Type 1), the third randomized trial based in North America evaluating terlipressin, met its primary end point of showing greater rates of HRS reversal in the terlipressin arm. However, due to concerns about the apparent increased rates of respiratory adverse events and a lack of evidence for mortality benefit, terlipressin was not approved by the Food and Drug Administration (FDA). We explore the history of regulatory approval for terlipressin in the United States, examine the results from CONFIRM and the concerns they raised, and consider the future role of terlipressin in this critical clinical area of continued unmet need.

Sodium-glucose cotransporter 2 inhibitors for treatment of diabetes mellitus after kidney transplantation.

INTRODUCTION: Diabetes mellitus in kidney transplant recipients is a risk factor for cardiovascular events and premature death. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are increasingly used in nontransplant populations to improve diabetes control and cardiovascular and renal benefits. Limited literature exists regarding the safety and efficacy of these agents in renal transplant recipients. METHODS: We retrospectively reviewed all kidney transplant recipients within our health system who were prescribed a SGLT2i after transplantation for diabetes. The safety, tolerability, and effectiveness of SGLT2i were analyzed. RESULTS: Thirty-nine kidney transplant recipients were initiated on SGLT2i therapy, twenty-seven of which remained on therapy for at least 1 year. Ten (25%) patients experienced an adverse event while on a SGLT2i, with urinary tract infections (UTI) being the most common. Seventeen patients (43%) discontinued the SGLT2i at the time of chart review, most commonly due to cost and kidney function decline. The median [IQR] hemoglobin A1c (HbA1c) at SGLT2i initiation of 8.4% [7.8-9.2] decreased to 7.5% [6.8-8.0%] after 3 months and 7.5% [6.5-7.9] after 12 months. No meaningful change in kidney function or tacrolimus exposure was observed. CONCLUSION: SGLT2i may be a safe and effective treatment for diabetes in kidney transplant recipients. Cost is a barrier to SGLT2i therapy, and UTIs were the most frequently encountered adverse events in this cohort. More studies are needed to understand the safety profile and determine the effect of SGLT2i on diabetes-related comorbidities among kidney transplant recipients.

Histologic acute graft pyelonephritis after kidney transplantation: Incidence, clinical characteristics, risk factors, and association with graft loss.

BACKGROUND: Histologic acute graft pyelonephritis (HAGPN) after kidney transplantation (KT) has been assessed less frequently than urinary tract infections (UTIs) or clinical acute graft pyelonephritis. Risk factors for HAGPN, its association with graft loss, and measures that might prevent it are not known. METHODS: We performed a retrospective review of HAGPN cases identified from KT occurring between January 2008 and December 2017 at our institution. We compared the HAGPN cases to a randomly selected control group of KTs to identify risk factors using univariate and multivariate Cox regression models. The association between HAGPN and graft loss was also assessed, similarly. RESULTS: HAGPN was identified in 46 of 1391 patients (cumulative incidence, 5% [95% CI, 3%-7%]) undergoing KT at a single center from January 2008 through December 2017 (median time to diagnosis, 241 days after KT; interquartile range, 122-755 days). Indications for biopsy were follow-up of treated rejection (n = 20 [43%]), KT protocol biopsy (n = 19 [41%]), and acute kidney injury (n = 7 [15%]). Histologic rejection, UTI, and asymptomatic bacteriuria (ASB) were present in 23 (50%), 9 (20%), and 16 (35%). Multivariate Cox proportional hazards models comparing KT recipients with or without HAGPN (n = 46 and n = 138, respectively) showed that HAGPN was associated with urologic complication by day 30, delayed graft function, previous UTI or ASB, and a history of rejection. In the univariate and multivariate analyses, HAGPN was associated with an increased risk of graft loss. CONCLUSION: HAGPN is an infrequent, unanticipated, and clinically significant complication of KT.

Association of Abdominal Arterial Calcification Score with Patients' Survival and Kidney Allograft Function after Kidney Transplant.

BACKGROUND: Abdominal arterial calcification (AAC) is common among candidates for kidney transplant. The aim of this study is to correlate AAC score value with post-kidney transplant outcomes. METHODS: We modified the coronary calcium score by changing the intake data points and used it to quantitate the AAC. We conducted a retrospective clinical study of all adult patients who were transplanted at our center, between 2010 and 2013, and had abdominal computed tomography scan done before transplantation. Outcomes included mortality, pulse pressure (PP) measured by 24 h ambulatory blood pressure monitoring system, and kidney allograft function measured by iothalamate clearance. RESULTS: For each 1000 increase of AAC score value, there is an associated 1.05 increase in the risk of death (95% CI 1.02, 1.08) (p < 0.001). Overall median AAC value for all patients was 1784; Kaplan-Meier curve showed reduced survival of all-cause mortality for patients with AAC score value above median and reduced survival among patients with cardiac related mortality. The iothalamate clearance was lower among patients with total AAC score value above the median. Patients with abnormal PP (< 40 or > 60 mmHg) had an elevated median AAC score value at 4319.3 (IQR 1210.4, 11097.1) compared to patients with normal PP with AAC score value at 595.9 (IQR 9.9, 2959.9) (p < 0.001). CONCLUSION: We showed an association of AAC with patients' survival and kidney allograft function after kidney transplant. The AAC score value could be used as a risk stratification when patients are considered for kidney transplant.

The Current Management of Hepatorenal Syndrome-Acute Kidney Injury in the United States and the Potential of Terlipressin.

Acute kidney injury (AKI) in the setting of cirrhosis (hepatorenal syndrome [HRS]-AKI) is a severe and often fatal complication of end-stage liver disease. The goals of treatment are to reverse renal failure and prolong survival in patients who are critically ill. However, interventions have limited efficacy, and mortality rates remain high. In the United States, the mainstay of pharmacologic therapy consists of the off-label use of vasoconstrictive agents in combination with plasma expanders, a strategy that produces modest effects. Liver transplantation is the ultimate solution but is only an option in a minority of patients because contraindications to transplantation are common and organ availability is limited. Renal replacement therapy is a temporary option but is known to confer an extremely poor short-term prognosis in patients with HRS-AKI and at best serves as a bridge to liver transplantation for the minority of patients who are transplantation candidates. The high mortality rate associated with HRS-AKI in the United States is a reflection of the suboptimal standard of care. Improved therapeutic options to treat HRS-AKI are sought. Terlipressin is a drug approved in Europe for treatment of HRS-AKI and supported by recommendations for first-line therapy by some liver societies and experts around the world. This review article will discuss the substantial unmet medical need associated with HRS-AKI and the potential benefits if terlipressin was approved in the United States.

Post-Liver Transplant Early Allograft Dysfunction Modifies the Effect of Pre-Liver Transplant Renal Dysfunction on Post-Liver Transplant Survival.

Pre-liver transplantation (LT) renal dysfunction is associated with poor post-LT survival. We studied whether early allograft dysfunction (EAD) modifies this association. Data on 2,856 primary LT recipients who received a transplant between 1998 and 2018 were retrospectively reviewed. Patients who died within the first post-LT week or received multiorgan transplants and previous LT recipients were excluded. EAD was defined as (1) total bilirubin ≥ 10 mg/dL on postoperative day (POD) 7, (2) international normalized ratio ≥1.6 on POD 7, and/or (3) alanine aminotransferase or aspartate aminotransferase ≥2000 IU/mL in the first postoperative week. Pre-LT renal dysfunction was defined as serum creatinine >1.5 mg/dL or on renal replacement therapy at LT. Patients were divided into 4 groups according to pre-LT renal dysfunction and post-LT EAD development. Recipients who had both pre-LT renal dysfunction and post-LT EAD had the worst unadjusted 1-year, 3-year, and 5-year post-LT patient and graft survival, whereas patients who had neither renal dysfunction nor EAD had the best survival (P < 0.001). After adjusting for multiple factors, the risk of death was significantly higher only in those with both pre-LT renal dysfunction and post-LT EAD (adjusted hazard ratio [aHR], 2.19; 95% confidence interval [CI], 1.58-3.03; P < 0.001), whereas those with renal dysfunction and no EAD had a comparable risk of death to those with normal kidney function at LT (aHR, 1.12; 95% CI, 0.86-1.45; P = 0.41). Results remained unchanged when pre-LT renal dysfunction was redefined using different glomerular filtration rate cutoffs. Pre-LT renal dysfunction negatively impacts post-LT survival only in patients who develop EAD. Livers at higher risk of post-LT EAD should be used with caution in recipients with pre-LT renal dysfunction.

Establishing best practices in measles, mumps, and rubella serologic screening for kidney transplant candidates.

Optimizing immunity against vaccine-preventable diseases improves outcomes in kidney transplant (KT) patients (Arora et al, World J Transplant, 2019, 9:1; Sester et al, Transplant Rev, 2008, 22:274; Fishman, N Engl J Med, 2007, 357:2601). The American Society for Transplantation (AST) Clinical Practice Guidelines advises that serologic screening for measles, mumps, and rubella (MMR) be conducted for all KT candidates, since live-attenuated vaccines are contraindicated post-transplantation (Malinis et al, Clin Transplant, 2019, 33:e13548). Our team at Mayo Clinic Florida (MCF) conducted a quality improvement (QI) initiative to establish a best MMR screening and immunizations clinical practice in KT candidates using a Plan-Do-Study-Act (PDSA) model. By retrospective chart review of all KT candidates evaluated at our institution from January 1, 2016 to December 31, 2017, baseline data determining the rate of MMR serologic screening was established. PDSA cycles were implemented to adopt protocol-driven testing for MMR serologies, immunization documentation, and vaccination in cases of seronegativity to any of the three MMR viruses in all pre-KT candidates. Two PDSA cycles were completed in 4 months. The study population totaled 447 patients (baseline n = 283, PDSA 1 n = 61, PDSA 2 n = 103). Baseline data showed that 83% (n = 235) of pre-KT candidates received infectious disease consultation (IDC). Complete MMR (all three viruses) serological screening in KT candidates improved from baseline 3.9%-87.4% post-PDSA cycle 2 (P < .001). Necessary immunizations per AST guidelines were ordered in only 41.1% (n = 23) of the control cohort vs 100% (n = 12) and 96.9% (n = 31) of PDSA cycles 1 and 2, respectively (P < .001). The data reflect significant practice improvements in MMR screening and immunization rates among KT candidates by using protocol-driven orders combined with our pre-existing IDCs.

The changing impact of pre-liver transplant renal dysfunction on post-transplant survival: results of 2 decades from a single center.

INTRODUCTION AND OBJECTIVES: Renal dysfunction before liver transplantation (LT) is associated with higher post-LT mortality. We aimed to study if this association still persisted in the contemporary transplant era. MATERIALS AND METHODS: We retrospectively reviewed data on 2871 primary LT performed at our center from 1998 to 2018. All patients were listed for LT alone and were not considered to be simultaneous liver-kidney (SLK) transplant candidates. SLK recipients and those with previous LT were excluded. Patients were grouped into 4 eras: era-1 (1998-2002, n = 488), era-2 (2003-2007, n = 889), era-3 (2008-2012, n = 703) and era-4 (2013-2018, n = 791). Pre-LT renal dysfunction was defined as creatinine (Cr) >1.5 mg/dl or on dialysis at LT. The effect of pre-LT renal dysfunction on post-LT patient survival in each era was examined using Kaplan Meier estimates and univariate and multivariate Cox proportional hazard analyses. RESULTS: Pre-LT renal dysfunction was present in 594 (20%) recipients. Compared to patients in era-1, patients in era-4 had higher Cr, lower eGFR and were more likely to be on dialysis at LT (P < 0.001). Pre-LT renal dysfunction was associated with worse 1, 3 and 5-year survival in era-1 and era-2 (P < 0.005) but not in era-3 or era-4 (P = 0.13 and P = 0.08, respectively). Multivariate analysis demonstrated the lack of independent effect of pre-LT renal dysfunction on post-LT mortality in era-3 and era-4. A separate analysis using eGFR <60 mL/min/1.73 m2 at LT to define renal dysfunction showed similar results. CONCLUSIONS: Pre-LT renal dysfunction had less impact on post-LT survival in the contemporary transplant era.

Improved National Results With Simultaneous Liver-Kidney Transplantation Using Donation After Circulatory Death Donors.

Previous large registry studies have demonstrated inferior outcomes for simultaneous liver-kidney transplantation (SLKT) recipients of grafts from donation after circulatory death (DCD) donors compared with those from donation after brain death (DBD) donors in the era from 2000 to 2010. Given the improving national results in liver transplantation alone using grafts from DCD donors, the present study aimed to investigate if results with DCD-SLKT have improved in the modern era. Patients undergoing SLKT between 2000 and 2018 were obtained from the United Network for Organ Sharing Standard Analysis and Research file and divided into 2 eras based on the date of SLKT: era 1 (2000-2010) and era 2 (2011-2018). Improvement in DCD-SLKT patient, liver graft, and kidney graft survival rates was seen between era 1 and era 2 (P < 0.001). Concurrently, there was a decrease in the proportion of critically ill (P = 0.02) and retransplant (P = 0.006) candidates undergoing DCD-SLKT. When DCD-SLKT in era 2 was compared with a propensity-matched cohort of DBD-SLKT in era 2, no differences in patient (P = 0.99), liver graft (P = 0.19), or kidney graft (P = 0.90) survival were observed. In addition, both bilirubin (0.5 versus 0.5 mg/dL; P = 0.86) and creatinine (1.2 versus 1.2 mg/dL; P = 0.68) at last follow-up were not different between the DCD-SLKT and DBD-SLKT patients in era 2. In conclusion, in the most recent era, patients undergoing DCD-SLKT were able to achieve similar outcomes compared with matched patients undergoing DBD-SLKT. DCD-SLKT represents a viable option for appropriately selected recipients.

Can ferric citrate lead to iron overload in peritoneal dialysis patients?
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Ferric citrate (FC), a novel oral phosphate binder, is approved by the U.S. Food and Drug Administration (FDA) for the treatment of hyperphosphatemia in end-stage renal disease (ESRD) patients receiving dialysis. FC binds to dietary phosphate in the gastrointestinal (GI) tract producing ferric phosphate that is excreted in feces. However, a small quantity of iron is systemically absorbed. There are limited data regarding the safety of the maximum approved dose of FC among peritoneal dialysis (PD) patients. We present a series of 3 PD patients who developed iron overload while receiving FC for management of hyperphosphatemia. These cases highlight the importance of close monitoring of iron studies and question whether a lower maximum dose of FC should be recommended in PD patients. Further studies are needed to assess the safety of the maximum approved dose of FC among PD patients.

Karyomegalic interstitial nephritis in a renal allograft.

Karyomegalic interstitial nephritis (KIN) is a rare renal interstitial disease entity characterized by large tubular nuclei, accompanied by interstitial inflammation, tubular atrophy, and interstitial fibrosis. Approximately 50 cases of KIN have been described in the native kidney. In this case study, we describe the first case of KIN in a kidney allograft. A 41-year-old man presented with declining kidney function and a serum creatinine of 2.7 mg/dL. The native kidney biopsy showed large pleomorphic nuclei in the proximal and distal tubular epithelial cells, which was associated with interstitial inflammation, and extensive interstitial fibrosis and tubular atrophy. Immunohistochemistry for cytomegalovirus, adenovirus, and simian virus 40 were negative. A diagnosis of KIN was rendered. The patient received a living-related kidney transplant from his sister. At 4-, 12-, and 24-months posttransplant, protocol allograft biopsies showed KIN with large pleomorphic nuclei in the proximal and distal tubules with mild interstitial inflammation, minimal tubular atrophy, and interstitial fibrosis. At 24.7 months of follow-up, the patient has stable renal function with a serum creatinine of 1.6 mg/dL. The KIN may represent recurrent KIN or donor-associated KIN. Recognition of this rare disease entity is important as it can be mistaken for a viral infection.

Arterial Blood Pressure at Liver Transplant Evaluation Predicts Renal Histology in Candidates With Renal Dysfunction.

Renal dysfunction is common in liver transplantation (LT) candidates, but differentiating between reversible and irreversible renal injury can be difficult. Kidney biopsy might be helpful in differentiating reversible from irreversible renal injury, but it is associated with significant complications. We aimed to identify pre-LT predictors of potentially reversible renal injury using histological information obtained on pre-LT renal biopsy. Data on 128 LT candidates who underwent pre-LT kidney biopsy were retrospectively collected and correlated with renal histological findings. Indications for kidney biopsy were iothalamate glomerular filtration rate (iGFR) ≤40 mL/minute, proteinuria >500 mg/day, and/or hematuria. According to the biopsy diagnosis, patients were grouped into the following categories: normal (n = 13); acute tubular necrosis (ATN; n = 25); membranoproliferative glomerulonephritis (n = 19); minimal histological changes (n = 24); and advanced interstitial fibrosis (IF) and glomerulosclerosis (GS) (n = 47). Compared with patients having advanced IF/GS, patients with normal biopsies and those with ATN had lower systolic blood pressure (SBP) and diastolic blood pressure (DBP) and higher international normalized ratio and total bilirubin levels (<0.05 for all). Both SBP and DBP directly correlated with the degree of IF and GS (R = 0.3, P ≤ 0.02 for all). SBP ≤90 mm Hg was 100% sensitive and 98% specific in correlating with normal biopsies or ATN, whereas SBP ≥140 mm Hg was 22% sensitive and 90% specific in correlating with advanced IF/GS. Model for End-Stage Liver Disease score, serum creatinine, iGFR, urinary sodium excretion, and renal size did not correlate with biopsy diagnosis or degree of IF or GS. In conclusion, SBP at the time of LT evaluation correlates with renal histology, and it should be included along with other clinical and laboratory markers in the decision-making process to list patients with renal dysfunction for LT alone versus simultaneous liver-kidney transplantation.

Behçet's syndrome and focal segmental glomerulosclerosis with nephrotic syndrome - successful treatment with etanercept
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Behçet's syndrome (BS) often presents with aphthous and genital ulcers, uveitis, and erythema nodosum. Renal involvement has been reported with most cases presenting with renal amyloidosis, IgA nephropathy, or crescentic glomerulonephritis. We describe a case of a 49-year-old woman with relapsing BS symptoms coinciding with new-onset development of nephrotic syndrome. Renal biopsy showed focal segmental glomerulosclerosis (FSGS) that was treated with prednisone and etanercept for BS therapy. Both proteinuria and BS symptoms responded to treatment with complete remission. To our knowledge, our report is the first to show evidence of a possible connection between BS and FSGS and discusses the pathophysiologic mechanism that explains this link.
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Peripheral arterial disease preoperatively may predict graft failure and mortality in kidney transplant recipients.

Patients with end-stage renal disease undergoing kidney transplant often have diffuse atherosclerosis and high cardiovascular morbidity and mortality rates. We analyzed the correlation of peripheral arterial disease (PAD), here quantified by an abnormal ankle-brachial index (ABI) measured within the 5 years prior to kidney transplant, with graft failure and mortality rates (primary end points) after adjusting for known cardiovascular risk factors (age, sex, smoking history, hypertension, diabetes, stroke, known coronary artery disease or heart failure, years of dialysis). Of 1055 patients in our transplant population, 819 had arterial studies within the 5 years prior to transplant. Secondary end points included myocardial infarction; cerebrovascular accident; and limb ischemia, gangrene, or amputation. Low ABI was an independent and significant predictor of organ failure (OR, 2.77 (95% CI, 1.68-4.58), p<0.001), secondary end points (HR, 1.39 (95% CI, 0.97-1.99), p<0.076), and death (HR, 1.84 (95% CI, 1.26-2.68), p=0.002). PAD was common in this population: of 819 kidney transplant recipients, 46% had PAD. Low ABI was associated with a threefold greater risk of graft failure, a twofold greater risk of death after transplant, and a threefold greater risk of secondary end points. Screening for PAD is important in this patient population because of the potential impact on long-term outcomes.