Female Kidney Transplant Recipients Research Articles

Contraceptive Counselling and Uptake Among Female Kidney Transplant Recipients in Ethiopia

ABSTRACTBackgroundContraceptive counselling and utilization for kidney transplant patients is a vital component of their kidney transplant care. The use of standardized information on contraceptive methods to prevent unplanned post‐transplant pregnancies in Africa in general is less studied. This study aimed to describe contraceptive counselling and uptake among kidney transplant recipients at a kidney transplant centre in Ethiopia.MethodsA descriptive study on contraceptive counselling and uptake among female Ethiopian kidney transplant recipients was conducted at St. Paul's Hospital Millennium Medical College (Ethiopia) from April 15 to July 15, 2023. Data on women's sociodemographic, renal transplantation and contraceptive counselling and use were collected through interviewing the participants using a structured questionnaire. Data were analyzed on SPSS 23 using simple descriptive analysis. Percentages and frequencies were used to present the results.ResultsA total of 60 participants were included in the final analysis. The mean age of the participants was 33.7 ± 8.4 years. The median duration from the time of renal transplant was 19 months. Most (49/60, 81.7%) of the participants reported that they did not receive family planning counselling on contraceptive methods in the early post‐transplant phase. The rate of contraceptive uptake was 8.3% (5/60) with two patients being copper IUD users, and Implanon, tubal ligation and combined oral contraceptives each utilized by a single kidney transplant patient.ConclusionContraceptive counselling and uptake rates among female kidney transplant recipients in this study were very low, which is consistent with findings from previous studies. Increasing female kidney transplant patients’ awareness on safe and effective contraceptive use through adequate contraceptive counselling is essential.

#2425 A change in deceased donor allocation policy may provide gender equality in kidney transplantation

Abstract Background and Aims Overcoming gender disparity in access to kidney transplantation is a well-established universal challenge. The SRTR data showed a greater proportion of males than females for kidney transplant waitlists (61% vs 39%). Similarly, of 831 deceased donor kidney transplants (DDKT) conducted between 1997 and 2018 at IKDRC-ITS, 68% have been male and 32% female recipients while majority of donors in living donor kidney transplants (LDKT) were females. Prior to 2020, there duration on transplantation waitlist was the only criteria for deceased donor kidney allocation. In January 2020, SOTTO Gujarat was formed which implements a point system based deceased donor allocation policy including HLA mismatch, Panel Reactive Antibody, Donor Specific Antibody, age and duration on dialysis, amongst others. 2 additional points are allocated to female recipients in this allocation system. The aim is to study the impact of change in DDKT allocation policy on gender disparity. Method This is a retrospective, single-center, observational study. Number of male and female kidney transplant recipients was collected from the medical records held by the department of nephrology between January 2014 to December 2023. The data was categorized as before and after implementation of SOTTO Gujarat guidelines and analyzed. Results A total of 3182 kidney transplants were conducted at our centre over the study period, 2231 were LDKT while only 951 were DDKT. We found the percentage of female LDKT recipients to have remained disproportionately low as compared to male DDKT throughout the study period, while there was a gradually progressive increase in the percentage of female DDKT recipients with almost a doubling of female DDKT recipients from 27.57% in 2019 to 54.19% in 2023. This may be attributed to the compounding effect of allocating points to DSA, PRA, age of patient and gender as female patients tend to have higher PRA and DSA level after sensitization. Conclusion This study provides new insights into steps that can be taken to bridge the gender gap in DDKT. It shows that implementing a point based system for DDKT allocation policy with extra points for female recipients may increase the number of kidney transplants in them. Similar policy may be undertaken by other transplant centers as a bridge to achieve temporary solution till underlying factors leading to gender disparity are better understood and ways to overcome them are formed. Action should be taken to provide for equitable access to females at all stages, from diagnosis to treatment such as intensive and timely counselling. Policies for social empowerment of women must be formed including literacy, better maternal and child healthcare and financial independence. Raising awareness and education at a grassroot level must remain the key component to change public attitude regarding organ donation and ensure equitable access to transplantation for all.

#1590 Human papilloma virus vaccination rates in kidney transplant recipients

Abstract Background and Aims Kidney transplant recipients are predisposed to chronic infections and malignancies because they receive chronic immunosuppressive therapy. Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide. HPV is a significant cause of cervical, vaginal, vulvar, penile, anal, and head and neck cancers in kidney transplant recipients. HPV vaccine prophylaxis has an important role in preventing HPV-related diseases in renal transplant patients, with a 70-100% rate. Vaccine prophylaxis is recommended before or after kidney transplantation. In our country, HPV vaccination in kidney transplant recipients seems to be a neglected issue. We first determined the HPV vaccination level of the transplant recipients we follow. We compared it with the current guidelines. We aimed to evaluate the adequacy of pretransplant and/or post-transplant vaccinations. Method Our study is a cross-sectional survey study. Between March 15 and April 15, 2023, 170 patients who applied to Ankara City Hospital Kidney Transplant outpatient clinic were included in our study. The questionnaire form structured by the researchers was applied to the patients by face-to-face interviews. The questionnaire consisted of questions about the sociodemographic characteristics of the patients, their level of knowledge about human papillomavirus vaccines and their vaccination rates. Data analysis was performed using SPSS 22, with statistical significance set at p < 0.05. Results 170 patients participated in our study. Participants were between the ages of 18-43 years. 51.8% were male and 48.2% were female. 72.9% were married and 27.1% were single. 78.8% of the patients had an income below 9,000 TL. 34.7% had high school education or higher. The most common reason for transplantation was hypertension with 30.5%. 75.9% of the patients stated that they did not know the necessity of HPV vaccine. Again, 80% of the patients stated that they did not receive information about HPV vaccine before or after transplantation. Among these, 130 patients did not want to get vaccinated, with 79 of them mentioning the cost as the reason for not getting vaccinated. Only 4.1% of the patients had received HPV vaccination before or after transplantation. More than half of those who were vaccinated (57.1%) reported having received the quadrivalent vaccine and had received two doses. It was found that the mean age of patients who received HPV vaccine (32.0 ± 6.83) was statistically significantly younger than the mean age of those who did not (47.3 ± 12.69) (p = 0.034). Those with an education level of high school and above received HPV vaccination at a significantly higher rate than those with a lower education level (p = 0.037). Similarly, in the question about the necessity of HPV vaccination and in the question about whether they received information about HPV vaccines, the rate of those with high school and above education level (32.3%) who answered yes to the question was statistically significantly higher than those with secondary school education level (13.5%) (p = 0.004). Conclusion Our study found that both male and female kidney transplant recipients lacked sufficient knowledge about HPV and HPV vaccines, with very low vaccination rates. We believe that the vaccine's age-specific administration in two or three doses, its high cost, and the necessity of payment have negatively affected HPV vaccination rates. HPV, causes various infections and cancers, making it crucial to raise awareness about HPV vaccines. Especially primary health care services should be used more effectively, education programs should be organized and individuals should be directed to vaccination.

Uterine Artery Pulsatility Index in Pregnant Kidney or Liver Recipients and Its Impact on Perinatal Outcome

The uterine artery pulsatility index (UtA PI) is associated with blood flow to the placenta. Its increased values imply impaired placentation. This study aimed to evaluate UtA PI measurements in first-trimester ultrasound in pregnancies after kidney (KTx) or liver transplantation (LTx) and its relationship with perinatal outcome. A retrospective analysis of 72 pregnancies in female kidney (35) or liver (37) transplant recipients between 2017 and 2023 was performed. Data concerning UtA PI were available for 17 kidney and 19 liver recipients. Statistical analysis of variables between KTx and LTx groups and the correlation with perinatal outcomes was performed using Student's t test and Pearson's correlation with P < .05 considered statistically significant. The mean UtA PI results were similar, and there were no statistical differences between the group of pregnant kidney and liver recipients with mean values of 1.46 (SD 0.44] and 1.73 (SD 0.51] respectively (P = .10). The mean neonate birth weight was lower in KTx group (2158 g ([SD 723 g]) compared with the LTx group (2780 g [SD 754g]; P =.02). In the KTx and LTx groups, mean UtA PI was in negative correlation with Apgar score in the first minute (P = .04, P = .01 respectively). Uterine artery Doppler is useful in predicting perinatal outcomes in the general population and organ recipient pregnancies, even in the early stages of pregnancy, as we observed the correlation between UtA PI and Apgar score. Pregnant kidney recipients remain at higher risk for complications and more unpredictable outcomes than liver recipients.

The combinatorial effect of age and biological sex on alloimmunity and transplantation outcome.

Both age and biological sex affect transplantation outcomes. We have recently shown in a large volume clinical analysis utilizing the SRTR data that graft survival is inferior in young female kidney transplant recipients. In this multi-factorial analysis, older female recipients presented with a trend towards improved transplant outcomes compared to both young female recipients and male recipients of any age. Those data supported by reports of those of others suggest that sex and age impact alloimmune responses both, individually and synergistically. Biological sex and hormone levels change throughout a lifetime with recognized effects on longevity in addition to an impact on the development and course of several disease preconditions. Detailed mechanisms of those sex and age-specific aspects have thus far been studied outside of transplantation. Effects on alloimmunity are largely unknown. Moreover, the combinatorial impact that both, biological sex and age have on transplant outcomes is not understood. Here, we summarize available data that analyze how age in combination with biological sex may shape alloimmune responses and affect transplant outcomes.

Sex Differences among Overweight/Obese Kidney Transplant Recipients Requiring Oxygen Support Amid the COVID-19 Pandemic.

Background and Objectives: Overweight/obesity puts individuals at greater risk for COVID-19 progression and mortality. We aimed to evaluate the impact of overweight/obesity on oxygen (O2) requirement outcomes of male and female kidney transplant recipients (KTRs) during the COVID-19 pandemic. Materials and Methods: We conducted a retrospective analysis of a cohort of KTRs diagnosed with COVID-19. Participants were stratified based on BMI categories, and data on the need for O2 therapy outcome were collected and analyzed separately for male and female KTRs. Results: In total, 284 KTRs (97 males and 187 females) were included in the study. Overweight/obesity was observed in 60.6% of male KTRs and 71% of female KTRs. Strikingly, overweight/obese women had a significantly higher requirement for supplemental O2 (63.3% vs. 41.7%, OR = 2.45, p = 0.03), particularly among older individuals (OR = 1.05, p = 0.04), smokers (OR = 4.55, p = 0.03), those with elevated lactate dehydrogenase (LDH) levels (OR = 1.01, p = 0.006), and those with lower admission and basal estimated glomerular filtration rate (eGFR) levels. Within this cohort, the necessity for O2 supplementation was correlated with more unfavorable outcomes. These included heightened mortality rates, transfers to the intensive care unit, employment of invasive mechanical ventilation, and the emergence of acute kidney injury requiring hemodialysis. On the other hand, although overweight/obese male KTRs had a higher prevalence of hypertension and higher fasting blood glucose levels, no significant association was found with COVID-19-related outcomes when compared to lean male KTRs. Conclusions: Overweight/obesity is highly prevalent in KTRs, and overweight/obese women demonstrated a higher need for supplemental O2. Therefore, the early identification of factors that predict a worse outcome in overweight/obese female KTRs affected by COVID-19 contributes to risk stratification and guides therapeutic decisions.

Thyroid, Gonadal and Adrenal Dysfunction in Kidney Transplant Recipients: A Review for the Clinician

While chronic kidney disease-associated mineral and bone disorders (CKD-MBD) prevail in the endocrinological assessment of CKD patients, other endocrine abnormalities are usually overlooked. CKD is associated with significant thyroid, adrenal and gonadal dysfunction, while persistent and de novo endocrinological abnormalities are frequent among kidney transplant recipients (KTR). Low T3 levels prior to transplantation may help identify those at risk for delayed graft function and are often found in KTR. Thyroid surveillance after kidney transplantation should be considered due to structural anomalies that may occur. Despite the rapid recovery of gonadal hormonal secretion after renal transplantation, fertility is not completely restored. Testosterone may improve anemia and general symptoms in KTR with persistent hypogonadism. Female KTR may still experience abnormal uterine bleeding, for which estroprogestative administration may be beneficial. Glucocorticoid administration suppresses the hypothalamic-pituitary–adrenal axis in KTR, leading to metabolic syndrome. Patients should be informed about signs and symptoms of hypoadrenalism that may occur after glucocorticoid withdrawal, prompting adrenal function assessment. Clinicians should be more aware of the endocrine abnormalities experienced by their KTR patients, as these may significantly impact the quality of life. In clinical practice, awareness of the specific endocrine dysfunctions experienced by KTR patients ensures the correct management of these complications in a multidisciplinary team, while avoiding unnecessary treatment.

Plasma Copper Concentration Is Associated with Cardiovascular Mortality in Male Kidney Transplant Recipients.

Kidney transplant recipients (KTR) are at increased risk of cardiovascular mortality. We investigated whether, in KTR, post-transplantation copper status is associated with the risk of cardiovascular mortality and potential effect modification by sex. In this cohort study, plasma copper was measured using mass spectrometry in extensively-phenotyped KTR with a functioning allograft >1-year. Cox regression analyses with the inclusion of multiplicative interaction terms were performed. In 660 KTR (53 ± 13 years old, 56% male), the median baseline plasma copper was 15.42 (IQR 13.53-17.63) µmol/L. During a median follow-up of 5 years, 141 KTR died, 53 (38%) due to cardiovascular causes. Higher plasma copper was associated with an increased risk of cardiovascular mortality in the overall KTR population (HR 1.37; 95% CI, 1.07-1.77 per 1-SD, p = 0.01). Sex was a significant effect modifier of this association (Pinteraction = 0.01). Among male KTR, higher plasma copper concentration was independently associated with a two-fold higher risk of cardiovascular mortality (HR 2.09; 95% CI, 1.42-3.07 per 1-SD, p < 0.001). Among female KTR, this association was absent. This evidence offers a rationale for considering a sex-specific assessment of copper's role in cardiovascular risk evaluation. Further studies are warranted to elucidate whether copper-targeted interventions may decrease cardiovascular mortality in male KTR.

Sodium bicarbonate for kidney transplant recipients with metabolic acidosis in Switzerland: a multicentre, randomised, single-blind, placebo-controlled, phase 3 trial

Metabolic acidosis is common in kidney transplant recipients and is associated with declining graft function. Sodium bicarbonate treatment effectively corrects metabolic acidosis, but no prospective studies have examined its effect on graft function. Therefore, we aimed to test whether sodium bicarbonate treatment would preserve graft function and slow the progression of estimated glomerular filtration rate (GFR) decline in kidney transplant recipients. The Preserve-Transplant Study was a multicentre, randomised, single-blind, placebo-controlled, phase 3 trial at three University Hospitals in Switzerland (Zurich, Bern, and Geneva), which recruited adult (aged ≥18 years) male and female long-term kidney transplant recipients if they had undergone transplantation more than 1 year ago. Key inclusion criteria were an estimated GFR between 15 mL/min per 1·73 m2 and 89 mL/min per 1·73 m2, stable allograft function in the last 6 months before study inclusion (<15% change in serum creatinine), and a serum bicarbonate of 22 mmol/L or less. We randomly assigned patients (1:1) to either oral sodium bicarbonate 1·5-4·5 g per day or matching placebo using web-based data management software. Randomisation was stratified by study centre and gender using a permuted block design to guarantee balanced allocation. We did multi-block randomisation with variable block sizes of two and four. Treatment duration was 2 years. Acid-resistant soft gelatine capsules of 500 mg sodium bicarbonate or matching 500 mg placebo capsules were given at an initial dose of 500 mg (if bodyweight was <70 kg) or 1000 mg (if bodyweight was ≥70 kg) three times daily. The primary endpoint was the estimated GFR slope over the 24-month treatment phase. The primary efficacy analyses were applied to a modified intention-to-treat population that comprised all randomly assigned participants who had a baseline visit. The safety population comprised all participants who received at least one dose of study drug. The trial is registered with ClinicalTrials.gov, NCT03102996. Between June 12, 2017, and July 10, 2019, 1114 kidney transplant recipients with metabolic acidosis were assessed for trial eligibility. 872 patients were excluded and 242 were randomly assigned to the study groups (122 [50%] to the placebo group and 120 [50%] to the sodium bicarbonate group). After secondary exclusion of two patients, 240 patients were included in the intention-to-treat analysis. The calculated yearly estimated GFR slopes over the 2-year treatment period were a median -0·722 mL/min per 1·73 m2 (IQR -4·081 to 1·440) and mean -1·862 mL/min per 1·73 m2 (SD 6·344) per year in the placebo group versus median -1·413 mL/min per 1·73 m2 (IQR -4·503 to 1·139) and mean -1·830 mL/min per 1·73 m2 (SD 6·233) per year in the sodium bicarbonate group (Wilcoxon rank sum test p=0·51; Welch t-test p=0·97). The mean difference was 0·032 mL/min per 1·73 m2 per year (95% CI -1·644 to 1·707). There were no significant differences in estimated GFR slopes in a subgroup analysis and a sensitivity analysis confirmed the primary analysis. Although the estimated GFR slope did not show a significant difference between the treatment groups, treatment with sodium bicarbonate effectively corrected metabolic acidosis by increasing serum bicarbonate from 21·3 mmol/L (SD 2·6) to 23·0 mmol/L (2·7) and blood pH from 7·37 (SD 0·06) to 7·39 (0·04) over the 2-year treatment period. Adverse events and serious adverse events were similar in both groups. Three study participants died. In the placebo group, one (1%) patient died from acute respiratory distress syndrome due to SARS-CoV-2 and one (1%) from cardiac arrest after severe dehydration following diarrhoea with hypotension, acute kidney injury, and metabolic acidosis. In the sodium bicarbonate group, one (1%) patient had sudden cardiac death. In adult kidney transplant recipients, correction of metabolic acidosis by treatment with sodium bicarbonate over 2 years did not affect the decline in estimated GFR. Thus, treatment with sodium bicarbonate should not be generally recommended to preserve estimated GFR (a surrogate marker for graft function) in kidney transplant recipients with chronic kidney disease who have metabolic acidosis. Swiss National Science Foundation.

Impairment of endothelial progenitor cells in women after kidney transplantation.

The long-term survival of kidney transplant patients has substantially improved. However, there is a higher risk for cardiovascular events after transplantation, partly due to immunosuppression. A diminished number of endothelial progenitor cells (EPCs), which play an important role in angiogenesis and the repair of endothelial damage, is associated with an increased cardiovascular risk. The aim of this study was to evaluate whether kidney transplantation affects EPCs in women. Twenty-four healthy women and 22 female kidney transplant recipients were recruited. The ratio of angiogenic and non-angiogenic circulating progenitor cells (CPCs) was determined by multicolor flow cytometry and related to clinical parameters. Cord blood-derived endothelial colony-forming cells (ECFCs), a proliferative subgroup of endothelial progenitor cells, were treated with pooled sera from transplant patients or healthy controls and tested for their functional integrity using in vitro models. Kidney transplant recipients displayed a reduced ratio of angiogenic and non-angiogenic CPCs compared to healthy controls. Differences were especially pronounced in premenopausal women. Exposure to sera of transplanted women led to a significant impairment of ECFC proliferation, migration and angiogenesis ability. Alterations of EPC populations may contribute to the higher cardiovascular risks after organ transplantation and should be considered in therapeutic strategies.

Comparison of P-glycoprotein function in peripheral blood mononuclear cells ex vivo in stable Black and White male and female kidney transplant recipients.

Kidney allograft survival remains poorer in Black compared to White recipients due to racial differences in calcineurin inhibitor (CNI) pharmacology. P-glycoprotein (P-gp), an ABC efflux transporter expressed in peripheral blood mononuclear cells (PBMCs), modulates CNI pharmacokinetics and intracellular pharmacology. This study investigated P-gp function in PBMC ex vivo at 0 (trough), 4, 8, and 12 h in stable Black and White male and female kidney transplant recipients (n=67) receiving tacrolimus and mycophenolic acid. Tacrolimus doses were adjusted to troughs of 4-10ng/ml. P-gp function was quantified with flow cytometric measurement of cyclosporine (CYA; 2.5μM)-reversible efflux of P-gp substrate, 3,3'-Diethyloxacarbocyanine iodide by determining the percentage change of mean fluorescent intensity (MFI) with CYA (% ΔMFI). The composite parameter of area under the concentration versus time (AUC)0-12h % ΔMFI estimated P-gp function. Data analysis examined race, sex, and race-sex associations to P-gp function. A secondary aim analyzed ABCB1 genotypes: 1236C>T (rs1128503), 2677G>T/A (rs2032582), 3435C>T (rs1045642), and P-gp function. P-gp function (% ΔMFI) was higher in White patients at troughs (p=0.031) compared to Black counterparts with similar trends at 4 and 8h. Reduced AUC0-12h % ΔMFI was noted in Black recipients (N=32) compared with Whites (N=35, p=0.029) with notable pairwise adjusted differences between Black and White women (p=0.021). Higher AUC0-12h % ΔMFI was associated with ABCB1 2677 TT compared to GG variants (p=0.035). The AUC0-12h % ΔMFI was greater in White than Black subjects. P-gp function was higher at troughs in White subjects and differed between race-sex groups. P-gp function in PBMC may influence intracellular tacrolimus exposure and inter-relating pharmacodynamic responses which may support race and sex pharmacologic differences.

Concurrent Epstein Barr virus-associated smooth muscle tumor and myeloid sarcoma of the liver and acute myeloid leukemia in a patient post kidney transplant: a case report and review of the literature

Epstein Barr virus-associated smooth muscle tumors (EBV-SMT) are rare neoplasms that can occur in immunocompromised individuals. The native or transplanted liver is the most commonly involved site in post transplant patients. Systemic therapies have been utilized in EBV-SMT with modest activity. We describe a 23-year-old female kidney transplant recipient who presented with acute myeloid leukemia (AML) and hepatic myeloid sarcoma (MS). Although it was not recognized initially, her liver biopsy revealing MS at diagnosis was posthumously found to have synchronous EBV-SMT. She underwent anthracycline based induction and achieved a complete remission of her AML by bone marrow biopsy. Due to a persistent hepatic mass, she was given salvage chemotherapy including fludarabine, etoposide, cytarabine, decitabine, and venetoclax for presumed refractory MS. Re-biopsy of the liver revealed the absence of MS and presence of EBV-SMT, which subsequently grew rapidly and precluded her from a liver tumor resection. The patient underwent sirolimus mammalian target of rapamycin (mTOR) therapy with palliative intent, but the patient's EBV-SMT progressed shortly after. At time of autopsy, the patient remained in complete remission from AML/MS, but was found to have multifocal progressive metastatic EBV-SMT. To our knowledge this is the first reported case of synchronous AML/MS and post transplant hepatic EBV-SMT that underwent treatment for AML/MS. Our report suggests that the chemotherapeutic agents utilized for AML/MS may have poor efficacy against EBV-SMT.

The Selective Estrogen Receptor Modulator, Raloxifene, Is Protective Against Renal Ischemia-reperfusion Injury.

There is increasing evidence that estrogen is responsible for improved outcomes in female kidney transplant recipients. Although the exact mechanism is not yet known, estrogen appears to exert its protective effects by ameliorating ischemia-reperfusion injury (IRI). In this study, we have examined whether the beneficial effects of exogenous estrogen in renal IRI are replicated by therapy with any one of several selective estrogen receptor modulators. C57BL/6 adult mice underwent standardized warm renal ischemia for 28 min after being injected with the selective estrogen receptor modulators, raloxifene, lasofoxifene, tamoxifen, bazedoxifene, or control vehicle (dimethyl sulfoxide), at 16 and 1 h before IRI. Plasma concentrations of blood urea nitrogen and creatinine were assessed 24, 48, 72, and 96 h post-IRI. Tissue was collected 30 d postischemia for fibrosis analysis using Sirius Red staining. Raloxifene treatment in female mice resulted in significantly lower blood urea nitrogen and creatinine after IRI and significantly lower fibrosis 30 d following IRI. Raloxifene is protective against both acute kidney injury and fibrosis resulting from renal IRI in a mouse model.

Graft survival differences in kidney transplants related to recipient sex and age.

BackgroundIn recent years, there has been increasing interest in studying differences in recipient sex in renal disease treatment, access to renal replacement therapy, and subsequent outcomes. Our aim was to find out whether there are differences in outcomes after renal transplantation between female and male kidney transplant recipients in our series, particularly in adults under 60 years of age during long-term follow-up.MethodsThis was a retrospective study of our kidney transplant series (n = 1,101) to compare graft survival depending on the sex of the recipient in the entire series and patients < 60 years of age (n = 687) during long-term follow-up.ResultsWe observed no association between recipient sex and graft survival throughout the series, regardless of recipient sex. However, adult female recipients under 60 years of age had lower graft survival than male recipients (p = 0.040). Pre-transplant sensitization (HR 2.438, p = 0.002) and donor age (HR: 1.021, p = 0.017) were the independent variables associated with graft failure.ConclusionFemale recipients younger than 60 years of age had lower graft survival than male recipients, although there were no gender differences in graft or patient survival in the overall study population. Recipient sex per se was not related to graft failure, but the greater immunological risk in women and more frequent use of expanded criteria donors in female recipients under 60 years of age were the main factors related to their poorer graft survival. Further studies and new strategies are needed to identify these differences and develop the best approach to address them.

Infection with high-risk genotypes of human papillomavirus and cervical cytological findings among kidney transplant recipients in Kenya: a single centre experience.

High-risk human papillomavirus (hrHPV) infection is linked with uterine cervix premalignant lesions and invasive carcinoma of the uterine cervix. Descriptive cross sectional study carried out among female kidney transplant (KTx) recipients in Kenyatta National Hospital, Nairobi-Kenya. We studied the risk factors for acquisition of hrHPV, examined cervical cytology and assayed for 14 hrHPV DNA using Cervista® HPV HR test and Cervista® MTA (Hologic®) automated platforms. The 14-hrHPV genotypes assayed were 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 and the prevalence rate was 31.25 % (10/32). Abnormal cervical cytology was noted in 4/32 (12.5%) and included low-grade squamous intraepithelial lesion (2/32), atypical squamous cells of undetermined significance (1/32) and atypical glandular cells (1/32). The average age was 41.9 years with mean age at first coitus being 20.4 years. Majority of the women 20(62.5%) were married while 8(25%) were single. About 18(56.3%) had only one sexual partner. About 20% of women were nulliparous and 4(12.5%) had a parity of five. Duration since transplantation ranged between 1-21 years. The burden of hrHPV and abnormal cervical cytology in our study seemed lower than that reported elsewhere and even in general population. This study may form basis for further studies about HPV infections and carcinoma of the uterine cervix among the kidney allograft recipients in our setting.

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

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. 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. 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. 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.

Herpes simplex virus hepatitis in a renal transplant recipient seronegative pre-transplant.

BACKGROUND: Herpes simplex virus (HSV) is a rare cause of acute viral hepatitis but has high mortality rates and primarily affects immunocompromised hosts. We report a case of HSV hepatitis in a 20-year-old female kidney transplant recipient who had 1000-fold elevations in transaminases on post-transplant day 14, and the strategies employed for diagnoses and treatment. METHODS: Routine laboratory, serological, and molecular viral testing was completed, and she underwent a bone marrow biopsy given initial suspicion of hemophagocytic lymphohistiocytosis (HLH). HSV serologic results and high transaminases triggered a liver biopsy. RESULTS: The patient presented with elevated transaminases (ALT 1731 U/L and AST 1400) and ferritin (1431 μg/L). Transaminases and ferritin peaked with an ALT of 6609 U/L, AST of 6525 U/L, and ferritin >50000 μg/L. Bone marrow biopsy revealed no definitive HLH. HSV-DNA PCR of blood was positive, and she was empirically started on intravenous acyclovir 10 mg/kg 3 times per day. Liver biopsy confirmed the histological diagnosis of HSV hepatitis. CONCLUSIONS: Given the high mortality rates associated with HSV hepatitis, it is crucial to determine pre-transplant HSV status, initiate appropriate antiviral prophylaxis, and to have a low threshold for investigating for HSV hepatitis and initiating treatment in patients with a suspected diagnosis.

645. Rapid Diagnosis of Disseminated Mycobacterium kansasii infection in Renal Transplant Recipients Using Plasma Microbial Cell Free DNA Next Generation Sequencing

BackgroundDisseminated Mycobacterium kansasii infection is rare in kidney transplant recipients. The diagnosis may not be suspected readily due to non-specific clinical presentation. The diagnosis and treatment can be further delayed due to poor sensitivity of culture (especially of extra-pulmonary sites) and slow growth in culture media. Accurate and rapid diagnosis of disseminated M. kansasii infections in transplant recipients is important for antimicrobial management.MethodsTwo cases of disseminated M. kansasii infections with unusual presentation in which rapid diagnosis was made using the Karius test (KT) are presented. The KT is a CLIA certified/CAP-accredited next-generation sequencing (NGS) plasma test that detects microbial cell-free DNA (mcfDNA). After mcfDNA is extracted and NGS performed, human reads are removed, and remaining sequences are aligned to a curated database of >1400 organisms. Organisms present above a statistical threshold are reported.ResultsCase 1: A 31-year female kidney transplant recipient presented with a thyroglossal duct cyst, as well as swelling of her right metacarpophalangeal joint and left 3rd finger. AFB culture of the thyroglossal cyst aspiration done on post admission day (PAD) 2 took 27 days to be identified as M. kansasii (on PAD 29) whereas plasma sent for KT on PAD 5 reported a positive test for M. kansasii at 284 molecules/microliter (MPM) in 4 days (on PAD 9). Case 2: A 59-year male kidney transplant recipient presented with generalized weakness, arthralgia, pericardial effusion, cytopenia, weight loss and intermittent fevers. Plasma sent for KT on PAD 12 was reported positive for M. kansasii at 1314 MPM in 3 days (on PAD 15). PET CT done simultaneously was consistent with an infection of an old AV graft in the left upper extremity. The AFB culture of the resected graft was confirmed as M. kansasii in 22 days on PAD 36. After the KT was available (before confirmation of M. kansasii on culture), the first patient underwent modification of empiric treatment and the second patient was started on specific treatment for M. kansasii.Table of M. kansasii cases Rapid diagnosis of disseminated M. kansasii infectionConclusionOpen-ended NGS plasma testing for mcfDNA identified disseminated M kansasii infection much earlier than standard microbiology and thus helped in initiation and modification of pathogen directed treatment.Disclosures All Authors: No reported disclosures

Treatment of Mixed Dyslipidemia With Alirocumab in a Kidney Transplant Recipient: A Case Report

Dyslipidemia is common in kidney transplant recipients owing to the disturbance of lipid metabolism caused by chronic kidney disease and the effect of immunosuppression on lipid metabolism. Patients receiving treatment with mammalian target of rapamycin inhibitors show more prominent lipid disorders, which are attributed mainly, but not only, to adipocyte lipid uptake disruption, lipolysis promotion and lipogenic gene expression enhancement. Dyslipidemias in kidney transplant recipients predispose these patients to an increased risk of developing cardiovascular disease; thus, current guidelines recommend treatment initiation with a statin, regardless of low-density lipoprotein cholesterol (LDL-C) concentration, with ezetimibe as a secondary option for patients who do not tolerate such therapy or for those with inadequate response. Treatment with pro-protein convertase subtilisin/kexin type 9 inhibitors such as alirocumab, although effectively reducing LDL-C in patients with chronic kidney disease, has not been evaluated in kidney transplant recipients. In this case report, we present a case of a female kidney transplant recipient who developed substantial dyslipidemia after everolimus initiation. This case was resistant to treatment with simvastatin/ezetimibe combination, and the patient subsequently received alirocumab. Our patient showed a mean reduction of 46.6% in LDL-C during an 18-month period after alirocumab initiation, which is comparable to the results of studies on patients with or without renal impairment. Furthermore, treatment with alirocumab proved to be well tolerated without adverse effects or interactions with the immunosuppression regimen.

Sex differences in ambulatory blood pressure levels, control, and phenotypes of hypertension in kidney transplant recipients.

Ambulatory blood pressure (BP) control is worse in men compared with women with chronic kidney disease (CKD) and this may partially explain the faster CKD progression in men. This is the first study investigating possible sex differences in prevalence, control and phenotypes of hypertension in kidney transplant recipients (KTRs) with office-BP and 24-h ambulatory BP monitoring (ABPM). This cross-sectional study included 136 male and 69 female stable KTRs who underwent office-BP measurements and 24-h ABPM. Hypertension thresholds for office and ambulatory BP were defined according to the 2017 ACC/AHA and 2021 KDIGO guidelines for KTRs. Age, time from transplantation, eGFR and history of major comorbidities did not differ between groups. Office SBP/DBP levels were insignificantly higher in men than women (130.3 ± 16.3/77.3 ± 9.4 vs. 126.4 ± 17.8/74.9 ± 11.5 mmHg; P = 0.118/0.104) but daytime SBP/DBP was significantly higher in men (128.5 ± 12.1/83.0 ± 8.2 vs. 124.6 ± 11.9/80.3 ± 9.3 mmHg; P = 0.032/P = 0.044). No significant between-group differences were detected for night-time BP. The prevalence of hypertension was similar by office-BP criteria (93.4 vs. 91.3%; P = 0.589), but higher in men than women with ABPM (100 vs. 95.7%; P = 0.014). The use of ACEIs/ARBs and CCBs was more common in men. Office-BP control was similar (43.3 vs. 44.4%, P = 0.882), but 24-h control was significantly lower in men than women (16.9 vs. 30.3%; P = 0.029). White-coat hypertension was similar (5.1 vs. 7.6%; P = 0.493), whereas masked hypertension was insignificantly more prevalent in men than women (35.3 vs. 24.2%; P = 0.113). BP levels, hypertension prevalence and control are similar by office criteria but significantly different by ABPM criteria between male and female KTRs. Worse ambulatory BP control in male compared with female KTRs may interfere with renal and cardiovascular outcomes.