Improvement in Echocardiographic Indexes of Systolic Heart Failure Post Kidney Transplantation - a retrospective analysis.

INTRODUCTION: End-stage renal disease (ESRD) is a major risk factor for cardiovascular morbidity and mortality, which can be partially eliminated by kidney transplantation. Systolic heart failure might be considered as contraindication for kidney transplant although some patients demonstrate myocardial recovery post-transplant. We aim to identify and characterize the phenomenon of reverse myocardial remodelling in kidney transplanted patients. METHODS: The study is a retrospective cohort of patients undergoing kidney transplant between 2016-2019 (n=604) at Rabin Medical Center. Patients were assessed according to availability of two echocardiographic examinations: pre- and post-kidney transplant. The change in estimated ejection fraction (EF) and possible predictors of myocardial recovery were examined. RESULTS: Data of 293 patients was available for the final analysis. Eighty-one (28%) patients had a LVEF improvement equal or above 5%, whereas 36 (12%) patients had a LVEF improvement 10% or more post transplantation. Twenty-five patients (8.5%) had moderate or severe systolic heart failure with LVEF reduced to 40% or less at baseline. 13 of them (52%) had a LVEF improvement of ≥5% and 10 patients (40%) had an improvement of ≥10% in their EF. Cox regression analyses identified female gender as the only independent variable associated with LVEF improvement of at least 10%. Conclusion Renal transplantation might lead to improved LV systolic function in some patients.

The Importance of Early Diagnosis and Intervention in Chronic Kidney Disease: Calls-to-Action from Nephrologists Based Mainly in Central/Eastern Europe.

BACKGROUND: Chronic kidney disease (CKD) has a global prevalence of 9.1-13.4%. Comorbidities are abundant and may cause and affect CKD. Cardiovascular disease strongly correlates with CKD, increasing the burden of both diseases. SUMMARY: As a group of 15 clinical nephrologists primarily practicing in 12 Central/Eastern European countries, as well as Israel and Kazakhstan, herein we review the significant unmet needs for patients with CKD and recommend several key calls-to-action. Early diagnosis and treatment are imperative to ensure optimal outcomes for patients with CKD, with the potential to greatly reduce both morbidity and mortality. Lack of awareness of CKD, substandard indicators of kidney function, suboptimal screening rates, and geographical disparities in reimbursement often hamper access to effective care. KEY MESSAGES: Our key calls-to-action to address these unmet needs, thus improving the standard of care for patients with CKD, are the following: increase disease awareness, such as through education; encourage provision of financial support for patients; develop screening algorithms; revisit primary care physician referral practices; and create epidemiological databases that rectify the paucity of data on early-stage disease. By focusing attention on early detection, diagnosis, and treatment of high-risk and early-stage CKD populations, we aim to reduce the burdens, progression, and mortality of CKD.

Lower Incidence of Hypoglycemia With Angiotensin Receptor Blocker Versus ACE Inhibitor Therapy in People With or Without Diabetes.

This article describes a study examining the association between treatment with ACE inhibitors or angiotensin receptor blockers (ARBs) and incident hypoglycemia in patients with or without diabetes who were admitted to the internal medicine departments of a tertiary hospital in the Tel Aviv district of Israel. The authors found that treatment with ARBs, but not ACE inhibitors, compared with treatment with neither, was associated with a reduced risk of hypoglycemia regardless of diabetes status.

Novel insights in classic versus relative glomerular hyperfiltration and implications on pharmacotherapy.

PURPOSE OF REVIEW: Glomerular filtration rate (GFR) assessment and its estimation (eGFR) is a long-lasting challenge in medicine and public health. Current eGFR formulae are indexed for standardized body surface area (BSA) of 1.73 m2, ignoring persons and populations wherein the ratio of BSA or metabolic rate to nephron number might be different, due to increased BSA, increased metabolic rate or reduced nephron number. These equations are based on creatinine, cystatin C or a combination of the two, which adds another confounder to eGFR assessment. Unusually high GFR values, also known as renal hyperfiltration, have not been well defined under these equations. RECENT FINDINGS: Special conditions such as solitary kidney in kidney donors, high dietary protein intake, obesity and diabetes are often associated with renal hyperfiltration and amenable to errors in GFR estimation. In all hyperfiltration types, there is an increased intraglomerular pressure that can be physiologic, but its persistence over time is detrimental to glomerulus leading to progressive glomerular damage and renal fibrosis. Hyperfiltration might be underdiagnosed due to BSA standardization embedded in the formula. Hence, timely intervention is delayed. Reducing intraglomerular pressure in diabetes can be achieved by SGLT2 inhibitors or low protein diet to reverse the glomerulopathy process. SUMMARY: Accurate identification of glomerular hyperfiltration as a pre-CKD condition needs accurate estimation of GFR in the above normal range should establish a threshold for timely intervention.

Acute Kidney Injury and Hair-Straightening Products: A Case Series.

RATIONALE & OBJECTIVE: Keratin-based hair-straightening treatment is a popular hair-styling method. The majority of keratin-based hair-straightening products in Israel contain glycolic acid derivatives, which are considered safe when used topically. Systemic absorption of these products is possible, and anecdotal reports have described kidney toxicity associated with their use. We report a series of cases of severe acute kidney injury (AKI) following use of hair-straightening treatment in Israel during the past several years. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We retrospectively identified 26 patients from 14 medical centers in Israel who experienced severe AKI and reported prior treatment with hair-straightening products in 2019-2022. FINDINGS: The 26 patients described had a median age of 28.5 (range, 14-58) years and experienced severe AKI following a hair-straightening procedure. The most common symptoms at presentation were nausea, vomiting, and abdominal pain. Scalp rash was noted in 10 (38%) patients. Two patients experienced a recurrent episode of AKI following a repeat hair-straightening treatment. Seven patients underwent kidney biopsies, which demonstrated intratubular calcium oxalate deposition in 6 and microcalcification in tubular cells in 1. In all biopsies, signs of acute tubular injury were present, and an interstitial infiltrate was noted in 4 cases. Three patients required temporary dialysis. LIMITATIONS: Retrospective uncontrolled study, small number of kidney biopsies. CONCLUSIONS: This series describes cases of AKI with prior exposure to hair-straightening treatments. Acute oxalate nephropathy was the dominant finding on kidney biopsies, which may be related to absorption of glycolic acid derivatives and their metabolism to oxalate. This case series suggests a potential underrecognized cause of AKI in the young healthy population. Further studies are needed to confirm this association and to assess the extent of this phenomenon as well as its pathogenesis.

Exposure to tacrolimus trough levels below 6 ng/ml during the first year is associated with inferior kidney graft survival.

BACKGROUND: Accumulating data indicate that sub-therapeutic levels of tacrolimus are associated with long-term kidney graft loss. However, elevated doses increase the risk of infection and drug toxicity, which also threaten graft and patient longevity. We sought to determine the minimal tacrolimus level required to maintain graft survival. METHODS: We conducted a single-center historical cohort study. The first-year post-transplant exposure time was calculated for each of the five tacrolimus trough level intervals. This measure was adjusted to the exposure time below a given interval level, allowing us to define the threshold for the optimal tacrolimus level as the upper limit of the interval. We then determined the association between the adjusted exposure time at each tacrolimus level interval and our primary outcome, death-censored graft loss. RESULTS: One thousand four hundred and seventeen patients with a median follow-up of 5.3 years were included in the final cohort. The tacrolimus level interval of 5-6 ng/ml was the highest interval, which demonstrated a statistically significant association between adjusted exposure time and increased risk of graft loss (HR 1.58, per log days, p = .002). Cumulative exposure time above 14 days with a tacrolimus level below 6 ng/ml was associated with an increased rate of graft loss in most studied subgroups, except for recipients with pre transplant diabetes. CONCLUSIONS: Maintaining tacrolimus levels above 6 ng/ml during the first-year post-transplant might improve kidney graft survival.

Multi-phasic eGFR trajectory during follow up and long-term graft failure after kidney transplantation.

BACKGROUND: The prevailing assumption is that following kidney transplantation the pattern of kidney function decline is consistent. Nevertheless, numerous factors leading to graft loss may emerge, altering the trajectory of kidney function. In this study, we aim to assess alterations in estimated glomerular filtration rate (eGFR) trajectory over an extended period of follow-up and examine its correlation with graft survival. METHODS: We calculated eGFR using all creatinine values available from 1-year post transplantation to the end of follow-up. For pattern analysis, we used a piecewise linear model. RESULTS: Nine hundred eighty-eight patients were included in the study. After a median follow-up of 5.2 years, 297 (30.1%) patients had a multi-phasic eGFR trajectory. Change in eGFR trajectory was associated with increased risk for graft failure (HR 7.15, 95% CI 5.17-9.89, p < .001), longer follow-up time, younger age, longer cold ischemia time, high prevalence of acute rejection, longer hospitalization and a lower initial eGFR. Of the 988 patients included in the study, 494 (50.0%) had a mono-phasic stable trajectory, 197 (19.9%) had a mono-phasic decreasing trajectory, 184 (18.6%) had bi-phasic decreasing trajectory (initial stability and then decline, 46(4.7%) had a bi-phasic stabilized (initial decline and then stabilization) and 67(6.8%) had a more complex trajectory (tri-phasic). Out of the total 144 patients who experienced graft loss, the predominant pattern was a bi-phasic decline characterized by a bi-linear trajectory (66 events, 45.8%). CONCLUSIONS: Changes in eGFR trajectory during long-term follow-up can serve as a valuable tool for assessing the underlying mechanisms contributing to graft loss.

Second pregnancy following kidney transplantation is not associated with an increased risk of graft loss in a single center retrospective cohort study.

INTRODUCTION: Previous studies on first pregnancy following kidney transplantation (KT) show no association with decreased graft survival. This study examined patients with multiple gestations compared to a single pregnancy following KT and evaluated the risk of graft function deterioration. METHODS: A retrospective cohort study on fertile female kidney transplant recipients (KTRs) from Rabin Medical Center between January 2001 and December 2017 was performed. Data were collected on patients' comorbidities, pregnancy complications, graft loss, mortality, and lab results. Time-varying COX analysis was performed - second pregnancy being the time-related variable. RESULTS: Fifty-two KTRs split into 30 single pregnancy and 22 multiple pregnancy patients following KT. Single pregnancy patients were older during their first pregnancy and had a higher caesarian section rate. During a median follow-up period of 5.6 years, multiple pregnancies, compared to a single pregnancy, were not associated with an increased rate of graft loss. No significant difference was seen between first and second pregnancy in gestational age, birth weight, graft function, and proteinuria rates. CONCLUSIONS: Second pregnancy following KT was not shown to be associated with a decreased graft survival. In addition, obstetrical, maternal, and fetal complication rates are not increased in second compared to first pregnancy following KT.

Absence of hemoglobin increase is associated with reduced graft survival after kidney transplantation.

BACKGROUND: Anemia is prevalent following kidney transplantation and is associated with reduced graft survival. The association between temporal changes in hemoglobin (Hb) level at the early post-transplant period and graft survival is unknown. PATIENTS AND METHODS: The study cohort included consecutive patients included in a single center transplantation registry between January 2002 and December 2016. Temporal changes in Hb values during the first 90 days after the transplantation were evaluated by piecewise linear regression model. Significant Hb increase rate was defined as an increase of .5 gram/deciliter/month. Patients were divided into groups according to the presence of significant Hb increase. The primary outcome was death-censored graft failure. RESULTS: Of 946 patients included in the study cohort, 831 (87.8%) had at least one interval of Hb increase, and 115 (12.2%) had no Hb increase. The absence of Hb increase was associated with an elevated risk of death censored graft failure by univariate (HR 2.9, 95% CI 1.88-4.49, P < .001) and multivariate (HR 2.47, 95% CI 1.48-4.12, P = .001) analyses. The timing and rate of Hb increase had no association with the main outcome. CONCLUSIONS: Lack of Hb increase during the early post-transplant period is associated with an increased risk of graft loss.

Novel Protein to Phosphorous Ratio Score Predicts Mortality in Hemodialysis Patients.

OBJECTIVE: Lowering serum phosphorus in people on hemodialysis may improve their survival. However, prior studies have shown that restricting dietary protein intake, a major source of phosphorus, is associated with higher mortality. We hypothesized that a novel metric that incorporates both these values commensurately can improve survival prediction. METHODS: We used serum phosphorous and normalized protein catabolic rate (nPCR), a surrogate of dietary protein intake, to form a new metric R that was used to examine the associations with mortality in 63,016 people on hemodialysis (HD) of one year after treatment initiation. Survival models were adjusted for case-mix, malnutrition-inflammation cachexia syndrome (MICS), and residual kidney function (RKF). RESULTS: Individuals treated with hemodialysis were divided into five groups in accordance with R value. Group 1 included sick individuals with high phosphorous and low nPCR. Group 5 included individuals with low phosphorous and high nPCR. After 1-year follow-up, survival difference between the groups reflected R value, where an increase in R was associated with improved survival. The association of R with mortality was strengthened by adjustment in demographic variables and attenuated after adjustment to MICS. Mortality associations in accordance with R were not influenced by residual kidney function (RKF). CONCLUSION: The novel protein to phosphorus ratio score R predicts mortality in people on dialysis, probably reflecting both nutrition and inflammation state independent of RKF. The metric enables better phosphorus monitoring, although adequate dietary protein intake is ensured and may improve the prediction of outcomes in the clinical setting.

Post-transplantation erythrocytosis in kidney transplant recipients-A retrospective cohort study.

OBJECTIVES: To characterize risk factors for the development of post-transplant erythrocytosis (PTE), and its long-term effect on mortality, graft failure, and thrombosis. METHODS: Retrospective study including all kidney transplant recipients in Rabin Medical Center (RMC) during the years 2005-2014. The primary outcome was a composite outcome of all-cause mortality or graft failure at the end of follow-up. Secondary outcomes included death censored graft loss, venous thromboembolism, major adverse cardiovascular events, and mortality. A matched control group was also evaluated. Univariate and multivariate time-varying Cox model analyses were conducted for outcome evaluation. RESULTS: A total of 1304 patients were included, 169 of whom were diagnosed with PTE (12.9%). PTE was associated with male gender, higher glomerular filtration rate (GFR), and polycystic kidney disease. PTE was found to be associated with a reduced risk of the primary outcome (HR 0.355, CI 95% 0.151-0.89, P = .027) in a univariate time-varying Cox analysis, but was not associated with the composite outcome in a multivariate analysis. There was no difference in the primary outcome when the PTE group was compared with the matched control. CONCLUSION: PTE was not found to be associated with long-term outcomes of graft failure and poor survival.

Apixaban Level and Its Influence on Immunosuppression and Graft Outcome in Kidney Transplant Recipients With Atrial Fibrillation.

BACKGROUND: Currently, there is limited information on the level of apixaban in kidney transplant (KT) patients with atrial fibrillation and the influence of apixaban therapy on the level of immunosuppression and graft function. METHODS: This was a cross-sectional prospective study of 19 KT patients treated with apixaban. The levels of apixaban were measured using a chromogenic assay calibrated for apixaban and compared with those predicted by the manufacturer. Mean immunosuppression trough levels before and after apixaban treatment initiation were calculated using 3 consecutive measurements. Apixaban levels were compared with a historical control group comprising of 20 nontransplant patients with atrial fibrillation who were treated with the standard 5-mg bid apixaban dosage. RESULTS: All KT patients should have been treated with the standard 5-mg bid apixaban dosage according to the clinical parameters; however, 7 were inappropriately treated with a reduced dosage (2.5-mg bid). There was no significant difference in apixaban level between KT patients treated with the 5-mg bid dosage and nontransplant patients. No KT patient administered the standard dose had out-of-range levels. Peak GM level was significantly lower in KT patients administered an inappropriately reduced dose (P = 0.05). Two patients had below-range peak levels. Apixaban treatment initiation had minimal influence on the level of immunosuppression. Furthermore, it had no adverse impact on graft function. CONCLUSIONS: Similar to nontransplant patients, KT patients administered the standard 5-mg bid dosage had apixaban levels that were well within the recommended manufacturers' expected ranges. In addition, this dosage had minimal influence on immunosuppression and no effect on graft function.

Short versus prolonged antibiotic treatment for complicated urinary tract infection after kidney transplantation.

There is no consensus regarding the optimal duration of antibiotic therapy for urinary tract infection (UTI) following kidney transplantation (KT). We performed a retrospective study comparing short (6-10 days) versus prolonged (11-21 days) antibiotic therapy for complicated UTI among KT recipients. Univariate and inverse probability treatment weighted (IPTW) adjusted multivariate analysis for composite primary outcome of all-cause mortality or readmissions within 30 days and relapsed UTI 180 days were performed. Overall, 214 KT recipients with complicated UTI were included; 115 short-course treatment (median 8, interquartile range [IQR] 6-9 days), 99 prolonged course (median 14, IQR 12-21 days). The composite outcome occurred in 33 (28.6%) in the short-course group and 30 (30%) in the prolonged-course group; relapsed UTI occurred in 19 (16.5%) vs. 21 (21%), respectively. Duration of antibiotic treatment was not associated with any of these outcomes. The only risk factor for mortality/readmissions in multivariate analysis was deceased donor. No differences between groups were demonstrated for length of hospital stay, rates of bacteraemia, resistance development, and serum creatinine at 30 and 90 days. In conclusion, we found no difference in clinical outcomes between KT recipients treated for complicated UTI with short-course antibiotic (6-10 days) versus longer course (11-21 days).

The significance of acute kidney injury in Clostridioides difficile infection.

OBJECTIVE: Clostridioides difficile infection (CDI) may present as sepsis with acute kidney injury (AKI). Herein, we aimed to evaluate the clinical outcomes of patients with AKI complicating CDI. METHODS: All consecutive adult patients hospitalized in Rabin Medical Center between 1 January 2013 and 31 December 2018 with laboratory confirmed CDI, were included in the study. Subjects were divided into two groups: patients with AKI and controls. Primary outcome was all-cause mortality at 30 days after the CDI episode. Secondary outcomes included number of patients with deteriorating renal functions at 90 days, 90-day all-cause mortality, length of hospital stay and readmission rates. A multivariable analysis adjusted for other risk factors for mortality and renal function deterioration was conducted. An analysis of subgroups based on baseline kidney function and AKI stage was also performed. Results are reported as odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: A total of 527 patients were included, amongst them 140 patients with AKI and 387 controls. Patients with AKI were significantly older, had more comorbidities, and more of them had chronic kidney disease (CKD) at any stage at baseline. On multivariable analysis, 30 days all-cause mortality was significantly higher in patients with AKI, OR 1.67, 95% CI 1.05-2.66. Mortality was also significantly associated with advanced age and baseline CKD. Among patients alive at 90 days, deterioration of renal function was significantly more common in patients with AKI (27/63 (42.8%) vs 22/191 (11.5%), P = .000). In a multivariable analysis, deterioration of renal function at 90 days was associated with AKI at presentation (OR 4.67, 95% CI 1.05-20.6). Early (at discharge) renal function recovery was not associated with protection from further deterioration of renal function at day 90. CONCLUSIONS: CDI patients with AKI have an increased risk of mortality and further deterioration of renal function. Early renal function recovery does not infer protection from further deterioration of renal function at 3 months. Caution and nephrology follow-up should be considered after discharge for all patients who developed AKI during CDI, regardless of discharge creatinine levels.

Occlusive Mesenteric Ischemia in Chronic Dialysis Patients.

BACKGROUND: Among dialysis patients, occlusive mesenteric vascular disease has rarely been reported. OBJECTIVES: To report on the experience of one center with regard to diagnosing and treating this complication. METHODS: The retrospective case-series involved six patients (3 females, 3 males; age 52-88 years; 5/6 were smokers) on chronic hemodialysis at a single center. All patients with symptoms suggestive of occlusive mesenteric disease and a subsequent angiographic intervention were included. Demographic, clinical, and laboratory data were collected from patient charts for the period before and after angioplasty and stenting of the mesenteric vessels. A Wilcoxon signed-rank test was used to compare the relevant data before and after the intervention. RESULTS: All participants had variable co-morbidities and postprandial abdominal pain, food aversion, and weight loss. CT angiography was limited due to heavy vascular calcifications. All underwent angioplasty with stenting of the superior mesenteric artery (4 patients) or the celiac artery (2 patients). All procedures were successful in resolving abdominal pain, malnutrition, and inflammation. Weight loss before was 15 ± 2 kg and weight gain after was 6 ± 2 kg. C-reactive protein decreased from 13.4 ± 5.2 mg/dl to 2.2 ± 0.4 mg/dl (P < 0.05). Serum albumin increased from 3.0 ± 0.2 g/dl to 3.9 ± 0.1 g/dl (P < 0.05). Two patients underwent a repeat procedure (4 years, 5 months, respectively). Follow-up ranged from 0.5-7 years. CONCLUSIONS: Occlusive mesenteric ischemia occurs among dialysis patients. The diagnosis requires a high degree of suspicion, and it is manageable by angiography and stenting of the most involved mesenteric artery.

Risk factors for high-dose methotrexate associated acute kidney injury in patients with hematological malignancies.

High dose methotrexate (HDMTX)-induced acute kidney injury (AKI) is a well-known adverse event in hemato-oncology patients. Our purpose was to define factors and setup cut-offs that may help better identify patients at-risk for developing AKI following HDMTX. All consecutive patients who received MTX dose ≥1 g were retrospectively reviewed. We compared patients with or without renal toxicity. We used a logistic regression model to define baseline variables associated with AKI. Overall survival (OS) was estimated by the Kaplan-Meier method employing log-rank test. Between 2012 and 2017, 160 patients were included with a total of 265 courses. Indications included: primary central nervous system (CNS) lymphoma, CNS prophylaxis in other lymphoma types, acute lymphatic leukemia and others. Median age at diagnosis was 58 years (range, 18-84), 54% were males, median MTX dose was 1941 mg/m2 (range, 743-5442) and AKI developed in 9% of drug administrations (n = 24). In univariate analysis: age > 40, LDH > 380 units/L, eGFR < 112 mL/min, albumin <3.6 mg/dL at baseline and Charlson comorbidity index (CCI) were associated with AKI. In multivariable analysis, only LDH > 380 units/L (OR = 4.1, 95% confidence interval [CI] 1.04-20.9, P = .04) and albumin levels <3.6 g/dL (OR = 4.17, 95% CI 1.04-6.5, P = .04) remained significant. In patients with AKI, median drug elimination was longer (8 days vs 5 days). In 80% of cases, the creatinine levels returned to normal within 1 month. Yet, the median survival of patients who developed AKI was 37 months, compared to 145 months in patients without AKI (Log rank = 0.015). In conclusion, LDH > 380 units/L and albumin <3.6 g/dL were the strongest factors associated with AKI in patients receiving HDMTX. Although the rise in creatinine levels was almost uniformly reversible, AKI was associated with increased mortality rates.

Immunosuppression reduction in kidney transplant recipients during bacterial infection-A retrospective study.

BACKGROUND: Immunosuppression reduction is a common practice in the management of bacterial infection among kidney transplant recipients (KTRs). This practice, however, is based on limited evidence. METHODS: Retrospective study comparing clinical outcomes of KTRs whose antimetabolite was discontinued vs continued during hospitalization due to bacterial infection, considering calcineurin inhibitors (CNI) levels. Primary outcome was a composite of clinical failure at day 5; all-cause mortality; and/or re-hospitalization at 90 days. Multivariable analysis of risk factors for the primary outcome was performed using a propensity-matched cohort. RESULTS: We included 183 KTRs hospitalized with bacterial infection. Neither discontinuation of antimetabolites nor lower levels of CNI at infection onset were associated with a significant decrease the composite primary outcome. No significant difference in graft loss or rejection was demonstrated between patients with low vs high CNI levels or discontinuation vs continuation of antimetabolite. In multivariable analysis, CNI levels and management of antimetabolite were not significantly associated with adverse outcome. CONCLUSIONS: Immunosuppression reduction in hospitalized KTRs with bacterial infection did not offer a clinical advantage in terms of mortality, re-hospitalization, or clinical success. An interventional study evaluating continuation of immunosuppression vs reduction should be considered.

Long-term results of desensitization protocol with and without rituximab in sensitized kidney transplant recipients.

BACKGROUND: Desensitization protocols have been developed in order to overcome the immunological barrier of donor-specific anti-HLA antibodies (DSA). METHODS: During 2006-2012, we implemented a program for desensitizing sensitized (positive DSA, negative NIH-CDC crossmatch) living-donor recipients. The long-term outcome of 36 sensitized recipients, treated with IVIG and plasmapheresis (PP), with or without rituximab (added when > 7500 MFI), was compared to 252 non-sensitized living-donor recipients. RESULTS: Median peak DSA level before desensitization was 7223 (range 3567-16 000) MFI. During a mean follow-up of 121.9 months, graft loss occurred in 6/36 (17%) of the sensitized and 15/251 (6%) of the non-sensitized recipients (P = 0.021). Five-year and 10-year death-censored graft survival rates were 85% and 81% compared to 95% and 92%, respectively, for the non-sensitized recipients. There was no difference in recipients' survival. Slightly more episodes of acute rejection occurred in the sensitized group but had not influence on graft survival. At the last follow-up, 28 recipients had functioning graft; seventeen (47%) did not have detectable DSA. Eleven recipients had excellent graft function despite having detectable DSA. CONCLUSION: The long-term outcomes of sensitized recipients who underwent desensitization are encouraging. Adding rituximab to PP + IVIG in candidates with very high titers may result in improved outcome.

Immunosuppression reduction in liver and kidney transplant recipients with suspected bacterial infection: A multinational survey.

BACKGROUND: There is no consensus on the optimal management of immunosuppression during bacterial infections among solid organ transplant recipients. METHODS: A multicenter, cross-sectional survey, of high-volume kidney and liver transplant centers across US and Europe. Structured questionnaires including six multiple-choice questions concerning the management of immunosuppression during infection were distributed among 381 centers. RESULTS: A total of 124 (33%) centers fully completed the questionnaire: 67 liver, 57 kidney centers. Participating centers reported heterogenous approaches to immunosuppression management for all types of immunosuppressive drugs. Notably, kidney centers reported similar frequencies of either discontinuation (19%), continuation (19%), or dose reduction (17.5%) of antimetabolites; discontinuation only for life-threatening infection (17.5%) or case by case decisions (27%). Calcineurin inhibitors (CNI) management was heterogenous mostly among liver centers, with 8% discontinuing the CNI, 18% continuing, and 22% reducing dose. Heterogenous approaches to management of steroids and inhibitors of the mammalian target of rapamycin were also demonstrated. CONCLUSIONS: Immunosuppression management during bacterial infection is heterogenous in US and European centers. Immunosupression reduction (ISR) during infection is a common practice, though supported by limited evidence. Demonstrating high heterogeneity in the approach to ISR, together with the equivocal results of clinical studies, support consideration of an interventional clinical trial.

Iron Deficiency Anemia in Chronic Kidney Disease.

Iron deficiency anemia is a common complication of chronic kidney disease (CKD). CKD patients suffer from both absolute and functional iron deficiency. Absolute iron deficiency is defined by severely reduced or absent iron stores, while functional iron deficiency is defined by adequate iron stores but insufficient iron availability for incorporation into erythroid precursors. This is due to increased levels of hepcidin. Anemia in CKD is associated with an increased risk of morbidity and mortality. The association between anemia and mortality may be related to the severity of anemia. All CKD patients should be screened for anemia during the initial evaluation for CKD. Criteria used to define iron deficiency are different among CKD compared to normal renal function. Among CKD patients, absolute iron deficiency is defined when the transferrin saturation (TSAT) is ≤20% and the serum ferritin concentration is ≤100 ng/mL among predialysis and peritoneal dialysis patients or ≤200 ng/mL among hemodialysis patients. Functional iron deficiency, also known as iron-restricted erythropoiesis, is characterized by TSAT ≤20% and elevated ferritin levels. Iron supplementation is recommended for all CKD patients with anemia. There is general agreement according to guidelines that intravenous (i.v.) iron supplementation is the preferred method for CKD patients on dialysis (CKD stage 5D) and either i.v. or oral iron is recommended for patients with CKD ND (CKD stages 3-5). In this review we discuss the evidence base for these recommendations.