Female Kidney Research Articles

High dose of liraglutide impairs renal function in female hypertensive rats.

Glucagon-like peptide-1 (GLP-1) receptor agonists exhibit beneficial cardiovascular effects. However, the renal effects of different doses of liraglutide in an essential hypertension model have not yet been investigated. SHR female rats were treated for 30 days, twice a day, with saline (control) or liraglutide at low (0.06 mg/kg, LL) and high (0.6 mg/kg, LH) doses. Volume intake and excretion were monitored for a period of 24h. In renal tissue, nitrite-NO2-, nitrate-NO3-, advanced protein oxidation products-AOPP, collagen deposition, creatinine (Cr), urea (U), sodium, and potassium were analyzed. liraglutide reduced body weight gain in both groups. However, in the high dose, it increased urinary volume excretion and sodium/potassium ratio. Both doses reduced the urinary U/Cr ratio and LH increased the serum U/Cr ratio. AOPP was reduced only in LL. LH augmented collagen and early markers of kidney injury (blood urea nitrogen-BUN, BUN/Cr). LH increased NO3-, reduced NO2-, and caused an aberrant increase in GFR. Both doses' effects were independent of blood pressure and glycemic control. liraglutide appears to have distinct effects on the hypertensive female kidney depending on the dose, with higher doses impairing kidney function.

Optimizing renal transporter immunodetection: consequences of freeze-thaw during sample preparation.

Renal transporters (cotransporters, channels, and claudins) mediate homeostasis of fluids and electrolytes and are targets of hormonal and therapeutic regulators. Assessing renal transporter abundance with antibody probes by immunoblotting is an essential tool for mechanistic studies. Although journals require authors to demonstrate antibody specificity, there are no consensus guidelines for kidney sample preparation leading to lab-to-lab variability in immunoblot results. In this study, we determined the impact of sample preparation, specifically freeze-thawed (Frozen) versus freshly processed (Fresh) kidneys (female and male rats and mice) on immunoblot signal detection of 15 renal transporters and the impact of protease inhibitors during homogenization. In female Sprague-Dawley rat kidneys homogenized with aprotinin, Na2EDTA, PMSF, and phosphatase inhibitors, immunodetection signals were ∼50% lower in Frozen versus Fresh samples for most transporters. Inclusion of additional inhibitors (Roche cOmplete Protease Inhibitor, "+") only partially increased transporter immunoblot signals to near Fresh levels. In male Sprague-Dawley rats, immunoblot signal density was lower in Frozen+ versus Fresh+ despite additional inhibitors. In C57BL/6 male mice, immunoblot signals from proximal tubule transporters were lower in Frozen versus Fresh by ∼25-50% and greater in Frozen+. In contrast, immunodetection signal was equivalent in female Frozen+ versus female Fresh+ for claudin 2, villin, AQP1, NKCC2, NCC, ENaCβ, ENaCɣ, claudin 7, AQP2, NKAα1, and NKAβ1. Thus, kidney sample preparation variables, including freeze-thaw and protease inhibition, have substantial transporter-specific effects on quantification of renal transporter abundance by immunoblot. These findings underscore the critical importance of assessing and reporting the impact of sample preparation protocols on transporter recovery to ensure robust rigor and reproducibility. NEW & NOTEWORTHY Freeze-thawing kidneys before homogenization is widely accepted in renal research. This study demonstrates that if kidneys are freeze-thawed just once before homogenization, immunoblot signals are reduced in a transporter-specific manner in rats and mice dependent on sex and that immunoblot signals can be partially recovered by adding additional protease inhibitors. These findings underscore the critical importance of assessing the impact of sample preparation, including freeze-thaw versus fresh, to ensure robust rigor and reproducibility.

Pregnancy outcomes in patients with kidney transplant-A retrospective snapshot

Pregnancy in renal transplantation is a sensitive issue since fertility improves shortly after transplantation and the prevalence of pregnancy-related complications in these patients are more in comparison to non-transplanted matched cohorts. Our study aimed at assessing the outcomes of pregnancy in our transplant patients. Methods: This study was designed as a questionnaire based retrospective cross-sectional study wherein the authors contacted all their patients who underwent kidney transplantation under our care and now being followed with us or 4 other hospitals. Results: Total of 20 females conceived unplanned, out of 130 females of child bearing age who underwent kidney transplant. single pregnancy ended up in elective abortion at 4th month after transplant, rest of the pregnancies were successful and uneventful. Conclusion: Fertility related issues should be included in the counselling of kidney transplant females for planned pregnancy. Successful outcome is quite possible. There is a critical need for comprehensive support systems, including counseling, education, and resources, to empower female kidney transplant recipients in their reproductive journeys and to address the gaps in understanding family planning and contraceptive methods in the post-transplant period.

Azoospermia and multi-organ damage in juvenile rats exposed to α-Terpineol from weaning to sexual maturity

This study aimed to evaluate the repeated oral administration of α-terpineol in juvenile Wistar rats over a 70-day period. The objective was to assess the potential systemic and reproductive toxicity of α-terpineol when administered by gavage at doses of 75, 150, and 300 mg/kg/day to juvenile Wistar rats for 70 days from postnatal day 24. The control group received corn oil for 70 days. During the study, various parameters were evaluated, including clinical signs, body weight, food intake, neurobehavioral observations, haematology, serum biochemistry, organ weights, steroidogenic gene expression, and histopathological examination. No toxicity-related changes were observed in body weight, food intake, neurobehavioral observations, or steroidogenic gene expression. However, sperm evaluation revealed a complete absence of sperm and delayed sexual maturation. Total cholesterol was significantly elevated in both sexes, and serum testosterone was reduced at the 150 and 300 mg/kg doses. Microscopic examination showed severe pathological changes in the testes, epididymis, liver, and kidneys of both males and females. After the 14-day recovery period, total cholesterol levels returned to the normal range, but no recovery was observed in the other organs. The no-observed-adverse-effect level was 75 mg/kg/day for male rats based on the histopathological findings in the testes, liver, and kidneys, and for female rats based on the kidney and liver histopathology.

Sex-dependent metabolic remodeling of kidneys revealed by arteriovenous metabolomics.

Sex is a fundamental biological variable important in biomedical research, drug development, clinical trials, and prevention approaches. Among many organs, kidneys are known to exhibit remarkable structural, histological, and pathological differences between sexes. However, whether and how kidneys display distinct metabolic activities between sexes is poorly understood. By developing kidney-specific arteriovenous (AV) metabolomics combined with transcriptomics, we report striking sex differences in both basal metabolic activities and adaptive metabolic remodeling of kidneys after a fat-enriched ketogenic diet (KD), a regimen known to mitigate kidney diseases and improve immunotherapy for renal cancer. At the basal state, female kidneys show highly accumulated aldosterone and various acylcarnitines. In response to the KD, aldosterone levels remain high selectively in females but the sex difference in acylcarnitines disappears. AV data revealed that, under KD, female kidneys avidly take up circulating fatty acids and release 3-hydroxybutyrate (3-HB) whereas male kidneys barely absorb fatty acids but consistently take up 3-HB. Although both male and female kidneys take up gluconeogenic substrates such as glycerol, glutamine and lactate, only female kidneys exhibit net glucose release. Kidney transcriptomics data incompletely predict these sex differences, suggesting post-transcriptional/translational regulation mechanisms. This study provides foundational insights into the sex-dependent and diet-elicited metabolic flexibility of the kidneys in vivo, serving as a unique resource for understanding variable disease prevalence and drug responses between male and female kidneys.

Morphometric study of ostrich kidneys Struthio camelus Linnaeus, 1758

In recent years, avian medicine has advanced in the recognition of kidney diseases, but little is known about the morphology and renal morphometry of the common ostrich Struthio camelus Linnaeus, 1758. This study aimed to describe the morphometry and location of kidneys in the common ostrich. Twenty-six cadavers, aged one to seven days, which died of natural causes on a farm in the municipality of Magé, state of Rio de Janeiro, Brazil, were donated to the Department of Animal and Human Anatomy at the Universidade Federal Rural do Rio de Janeiro (UFRRJ). The specimens were identified, sexed, and fixed in a 10% aqueous solution of formaldehyde. The kidneys and renal divisions were measured using a precision digital caliper. The kidneys of S. camelus are elongated, and lobular, and have three renal divisions (cranial, middle, and caudal). The average length of the right kidney was 6.69 ± 0.83 cm, and the left kidney was 6.87 ± 0.81 cm. The body length correlated positively and significantly with the lengths of the right kidney (r = 0.8273, p = 0.0017) and left kidney (r = 0.8534, p = 0.0008) in females. The renal cranial limit was observed at the eighth lumbar vertebra (L8) in 22 kidneys (42.3%), and the caudal limit, at the eighth sacrocaudal vertebra (Sc8) in 11 kidneys (21.2%), and the second caudal vertebra (C2) in 11 kidneys (21.2%). The morphometric dimensions and skeletopy of the ostrich kidney contribute to the field of comparative avian anatomy and assist in the interpretation of imaging techniques.

Abstract P148: Loss of Ovarian Estrogen Downregulates Renal Steroidogenesis

Hypertension impacts half of US adults and importantly is more prevalent in men than premenopausal women. Sex hormones, particularly estrogen, have been implicated in this sex-difference. Recently we showed renal medullary estrogenic signaling via the G protein-coupled estrogen receptor 1 promotes sodium excretion in female, but not male, Sprague Dawley (SD) rats which implicates estrogen as a possible female-specific natriuretic factor. This led us to question whether the kidney could produce its own steroids, including estrogen, to respond to salt load changes locally. Evidence in cultured COS-7 and fetal kidney cells indicates the expression and activity of steroidogenic enzymes. Recently, we showed the outer medulla of the female SD rat kidney expresses key enzymes and metabolites involved in sex steroid biosynthesis. It is unknown how ovarian estrogen regulates steroidogenesis in the kidney. We hypothesize that ovarian estrogen stimulates the intrarenal capacity to biosynthesize sex steroids. To test this, we measured mRNA expression of several steroidogenic enzymes in the renal outer medulla of gonadally-intact female or ovariectomized SD rats (N=6). Cholesterol is the initial substrate for steroid synthesis. Thus, we first measured HMG-CoA reductase (HMGCR), the key synthesizing enzyme for cholesterol and steroidogenic acute regulatory protein (StAR), which helps commit cholesterol to steroid synthesis. Ovariectomy (OVX) reduced mRNA expression of both when compared to intact females (HMGCR: 63.5 ± 6.2 vs 100.0 ± 10.7 P=0.0169; StAR: 66.6 ± 12.4 vs 100.0 ± 6.4 P=0.0298). Although not significantly different, OVX seemed to reduce the expression of hydroxysteroid 3-β Dehydrogenase, which converts several intermediate steps in androgen and estrogen synthesis, compared to intact females (73.4 ± 13.3 vs 100.0 ± 9.7 P=0.1283). Hydroxysteroid 17-β Dehydrogenase (17β-HSD) 1, which converts estrone to estradiol, was unchanged in OVX compared to intact females (107.6 ± 13.2 vs 100.0 ± 10.1 P=0.6537). OVX reduced expression of 17β-HSD2 (28.34 ± 7.8 vs 100.0 ± 12.85 P=0.0008) and 17β-HSD3 (71.1 ± 7.5 vs 100.0 ± 5.7 P=0.0097) which interconvert androstenedione and testosterone compared to intact females. Combined these data suggest that ovariectomy blunts the intrarenal machinery for steroidogenesis. Additional experiments are required to test whether menopause downregulates renal sex steroid biosynthesis and predisposes postmenopausal women to hypertension.

Abstract Mo129: Elevation in male sex hormone metabolites with increased risk factors for inflammation and clotting in female kidneys following chronic binge drinking

Background: Binge drinking is a major systemic health concern. Binge drinking could alter renal metabolome and induce markers of injury as per our previously published work. Further investigation into the top regulated pathways revealed alterations sex hormone biosynthesis pathway was altered in a sex specific manner following 6 weeks of binge drinking. Our goal is to unveil individual metabolite mediators belonging to sex hormone biosynthesis pathway and to investigate the connecting link to cardiorenal health in both sexes following chronic binge drinking. Materials and Methods: For this work, n=3 male and female mice belonging to either control (water fed) or ethanol (20% fed in water) treatment groups were included. At the age of 8- 10 weeks, mice underwent water or binge (20% ethanol) drinking from Monday to Thursday for 4 hours, in dark cycle. This cycle was repeated for 6 weeks. Renal tissues from our experimental groups were collected at the end of 6 weeks and subjected to untargeted metabolomics. In brief, Ultra Performance Liquid Chromatography (UPLC) with Time-of-flight Mass Spectrometry (ESI-TOF-MS) followed by Mass spectrometry based separation was used to identify significantly altered metabolites. Results: Steroid hormone biosynthesis was the one among the top regulated pathways. Metabolites belonging to male hormone biosynthesis were the significantly altered one but specifically in females. Dehydroepiandrosterone, and it’s downstream 11-hydroxytestosterone were upregulated only in females and not in males. Female binge drinking group demonstrated an increase of 4.24 (fold) and 2.21 (fold) for dehydroepiandrosterone, and 11-hydroxytestosterone respectively as per the Log 2 Fold change values with a statistical significance of P<0.05 . Interestingly, this increase in male hormone metabolites we observed in females were also accompanied by an increase in metabolites of proinflammatory and prothrombotic mediators, thromboxane B3 and 5- Oxo- 12 HETE, of 2.3 (fold) and over 1.6 (fold) respectively as per Log 2 Fold change values and with a statistical difference of P<0.05 . Conclusion: Our data clearly demonstrate a sex specific effect following chronic binge drinking, where females have an increase in male hormones accompanied by an increase in prothrombotic and proinflammatory factors.

Sex-specific differences in SLE – Significance in the experimental setting of inflammation and kidney damage in MRL-Faslpr mice

Animal models are an important tool in the research of chronic autoimmune diseases, like systemic lupus erythematosus (SLE). MRL-Faslpr mice are one of different lupus models that develop spontaneously an SLE-like disease with autoantibodies and immune complex deposition that leads into damage of different organs. In contrast to human SLE, both sexes of MRL-Faslpr mice develop a similar autoimmune disease. Due to the sex bias in human and the delayed disease progression in male MRL-Faslpr mice, the majority of studies have been performed in female mice. To determine the suitability of male MRL-Faslpr mice for SLE research, especially with regard to the 3 R-principle and animal welfare, analyses of phenotype, inflammation and damage with focus on kidney and spleen were performed in mice of both sexes. Female mice developed lymphadenopathy and skin lesions earlier as males. At an age of 3.5 month, more immune cells infiltrated kidney and spleen in females compared to males. At the age of 5 months, however, substantially less sex-specific differences were detected. Since other studies have shown differences between both sexes on other manifestations like autoimmune pancreatitis and Sjögren syndrome in MRL-Faslpr mice, the use of male mice as part of 3 R-principle and animal welfare must be carefully considered.

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.

Worsening of Diabetes Control Measures and Decreased Kidney Function in Pre-Diabetic Kidney Donors Compared to Non-Diabetic Donors Whose BMI Before Kidney Donation was Above 30

The incidence of end-stage renal disease has increased dramatically over the past two decades. Kidney transplantation is the best treatment option for individuals with end-stage renal disease, and living donor kidney transplantation has significant advantages over deceased donor kidney transplantation. Although there are criteria for assessing living kidney donors, different medical centers handle certain medical problems differently. The aim of this study is to investigate how kidney donation affects renal biochemical indicators, blood pressure measurements, and glucose control in healthy young female adults without diabetes compared to a pre-diabetic group. A prospective cohort study recruited 142 female kidney donors, who were divided into two cohorts based on their diabetic history (pre-diabetic and non-diabetic). The participants were monitored for seven years after kidney donation. Key clinical and biochemical markers were measured before and after donation. The pre-diabetic group had higher mean values for blood pressure readings, body mass indices, Oral Glucose Tolerance Test, HbA1c (DCCT) (%), serum creatinine levels, proteinuria, and lower e-GFR compared to those in the non-diabetic group. All these findings were statistically significant. Pre-diabetic donors are at an increased risk for many adverse clinical and biochemical outcomes, including hypertension, glucose tolerance, and worsening kidney function tests and should be advised that their condition may worsen over time and can result in end-organ complications. If the donors decide to proceed, they should be closely and frequently monitored during both the short- and long-term periods.

FOXP3 splice variant expression in males and females in healthy populations and in kidney transplant recipients

The forkhead box P3 (FOXP3) transcript is essential for tolerance of alloantigens. Here, we describe the expression of FOXP3 mRNA variants in healthy females and males, and in kidney transplant recipients (KTR). We measured FOXP3 in peripheral blood mononuclear cells from healthy kidney donors (N = 101), and in blood from KTRs (N = 248) before and after transplantation. FOXP3 was measured with quantitative polymerase chain reaction, and differentiated between pre-mature mRNA FOXP3, Total mature FOXP3, FOXP3 in which exon two is spliced, and full length FOXP3. We found similar levels of FOXP3 in healthy female and male kidney donors. We confirmed this result in a publicly available cohort (N = 33) of healthy individuals (GSE97475). Homogenously, female and male KTR FOXP3 levels were similar pre-transplantation, one day post-transplantation and 29 days post-transplantation. This may suggest that kidney transplantation and related immunosuppressive treatments do not influence FOXP3 expression differently in females and males. Finally, fold difference analysis revealed that KTRs express lower levels of mature FOXP3 and higher levels of pre-mature FOXP3 mRNA pre-transplant compared to healthy individuals. This finding may suggest higher pre-mRNA synthesis, lower pre-mRNA degradation, lower spliceosome efficiency or higher degradation of mature FOXP3 mRNA in kidney transplant candidates.

#745 Age and gender specific reference values for renal volume and association with risk factors for chronic kidney disease in a general population

Abstract Background and Aims Renal volume (RV) is associated with renal function and with a variety of cardiovascular risk factors (CVRF). We analyzed RV by magnetic resonance imaging (MRI) in a large population-based study (Study of Health in Pomerania; SHIP-TREND) and tested the influence of age, sex, smoking status, BSA, systolic and diastolic blood pressure, type 2 diabetes, HDL-C, LDL-C, estimated glomerular filtration rate (eGFR) and uric acid on RV. Method 1,815 participants without kidney disease (930 women) aged 21-81 years were included in our study. Right and left RV with and without body surface area (BSA) indexation were compared among three age groups (22-39 years, 40-59 years, 60-81 years) by median and interquartile range and tested separately in women and men. Results eGFR, uric acid, right and left RV were higher in men compared to women (all p < 0.001). Left kidney were larger than right kidneys (both sexes). With age, RV showed a continuously decreasing trend in women and an upside down U-shape relation in men. In multivariable linear regression models, current smoking (β = 14.96, 95% CI 12.12; 17.79), BSA (β = 97.66, 95% CI 90.4; 104.93), diastolic blood pressure (β = 0.17, 95% CI 0.01; 0.32), and eGFR (β = 0.57, 95% CI 0.50; 0.65) were positively associated with both left and right renal volume whereas uric acid (β = −0.03, 95% CI −0.05; −0.01) showed an inverse association with RV. Interestingly, the same eGFR correlated with higher RV in men compared to women. Conclusion Reference values for RV are different for age-groups and sex. For any given age, female kidneys are smaller than male kidneys. RV associates positively with eGFR, but for any chosen eGFR, renal volume in females is lower compared to males. RV decreases with age, but in men, RV first increases in the age group 40-59 years before finally decreasing with a faster decline after 60 years. This may reflect hyperfiltration and glomerular hypertrophy associated with the presence of CVRF.

#2057 Sex differences in bioimpedance-spectroscopy-derived fluid status and body composition of maintenance hemodialysis patients

Abstract Background and Aims Bioimpedance-spectroscopy-(BIS)-derived estimates of fluid status and body composition are associated with mortality in patients undergoing maintenance hemodialysis (HD). Previously, thresholds for improved survival were identified for volume overload (VO, <2.5 L), VO relative to extracellular water (VO/ECW, <15%), lean tissue index (LTI, 15-20 kg/m2) and fat tissue index (4-15 kg/m2). However, these thresholds did not distinguish between sexes. Considering current efforts to untangle differences between male and female kidney disease patients, we aimed to analyze BIS data stratified by sex. Method We retrospectively evaluated pre-HD BIS measurements using the whole-body “Body Composition Monitor” device (Fresenius Medical Care). Measurements were conducted at the “Vienna Dialysis-Center”, a large tertiary dialysis center in Vienna, Austria. Continuous variables were described as medians and interquartile ranges and compared between sexes using Wilcoxon tests. Differences in proportions of males and females within the above-mentioned target ranges of body composition parameters were tested using Chi-Square tests and Fisher's exact tests. Results In November 2022, the Vienna Dialysis-Center cared for 304 patients, 159 of whom underwent BIS measurements. A total of 137 patients remained for analysis after excluding erroneous results (62% male, 38% female). The median [interquartile range] age among analyzed male and female patients was 60.0 years [48.0; 72.0] and 65.5 years [57.8; 75.3], and the median dialysis vintage was 28.9 months [12.1; 52.7] and 27.2 months [14.8; 61.9], respectively. VO (2.7 vs 1.9 L, p = 0.025), LTI (13.4 vs. 11 kg/m2, p < 0.001) and FTI (11.1 vs. 14.2 kg/m2, p = 0.036) differed significantly between males and females but VO/ECW did not (14.3 vs. 12%, p = 0.4). 27.1% of males (n = 23) were within 15-20 kg/m2 LTI compared to 7.7% of females (n = 4, p = 0.007). Differences in the proportions of male and female patients within optimal ranges of VO (43.5% vs. 61.5%, p = 0.062) and FTI (67.9% vs. 50.0%, p = 0.058) were close to reaching statistical significance. Conclusion We discovered relevant differences in fluid status and body composition among patients undergoing maintenance HD not only in absolute numbers, but also in the proportion of patients within the optimal range of LTI. Considering sex differences in body composition but (on average) equal mortality among HD patients, optimum target ranges of BIS measurements may differ between sexes. Our findings from this relatively small cohort call for large-scale sex-specific analyses of fluid status, body composition and outcomes in maintenance HD patients.

#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.

Przypadek nieszczelności zespolenia wywołanej zakażeniem <i>Candida albicans</i> u 64-letniej pacjentki po przeszczepieniu nerki, leczonej w trybie nagłym poprzez wszczepienie pomostu biodrowo-udowego z dostępu nadłonowego

IntroductionVascular complications are a rare but important risk factor for failure and loss of kidney graft, increasing the mortality of renal graft recipients.Case reportWe present the case of massive haemorrhage due to the rupture of the arterial anastomosis caused by <i>Candida albicans</i> infection in a 64-year old female kidney graft recipient managed with suprapubic iliofemoral bypass during emergency life-saving graft nephrectomy performed in our unit. The postoperative period was complicated by femoral vein thrombosis and intraabdominal fluid collection. After 33 days, with a well-functioning iliofemoral bypass, the patient was discharged to the nephrology unit. At the 12-month follow-up, the patient is functioning well, receiving nephrological care and haemodialysis treatment.ConclusionsRoutine fungal cultures of graft preservation fluid and radiological follow-up in high-risk patients after transplantation may be helpful in the prevention of fatal complications in the high-risk patient group – especially if digestive tract injury occurred during organ harvesting. Nevertheless, histological examination remains the gold standard for the detection of fungal arteritis. Negative culture samples from the preservation fluid, blood and urine before the transplantation do not exclude the risk of fungal infection. Urgent allograft nephrectomy with resection and reconstruction of changed vessels seems to be the safest approach in ruptured anastomotic pseudoaneurysm, as shown in our case.

Profound Sex Differences in the Kidney Expression of Mitochondria-Related Genes in Endothelin-1 Receptor B (ETB) Deficient Rats Fed a High Salt Diet

Elevated levels of endothelin-1 (ET-1), overactivation of the ETA receptor and oxidative stress are critical in the development of hypertensive kidney disease. Females are more resistant than males to kidney damage; however, it is unclear if overactivation of the ETA receptor disrupts mitochondrial homeostasis similarly in both sexes. With these studies we aimed to determine if overactivation of the ET-1/ETA axis has a differential effect on mitochondrial homeostasis in the male and female kidney during high salt consumption. Male and female ETB deficient (ETB def) and transgenic (TG) control rats were placed on a high salt diet (4.0% NaCl) for 3 weeks. Kidneys were collected and the expression of 84 mitochondria-related genes in renal cortex and outer medulla was assessed with qRT-PCR arrays. In response to high salt, male ETB def rats displayed cortical overexpression of 13 genes when compared to male TG controls, while only 7 genes were upregulated in cortex of female ETB def rats compared to female TG controls. Genes upregulated in male ETB def rats are involved in apoptosis, mitochondrial biogenesis and transport, energy metabolism and ROS handling (selected genes, male ETB def vs. TG controls, n=3/group: Ucp1 (19-fold increase, p=0.03), Bnip3 and Scl25a21 (6-fold, p=0.003 and p=0.004, respectively), and Mfn1 (5-fold, p=0.03). Genes upregulated in females are involved in apoptosis, ROS handling and mitochondrial transport (selected examples, female ETB def vs. TG control, n=3/group: 2-fold increase in Sod1 (p=0.03), Akt1 (p=0.003) and Grpel1 (p=0.019). No common genes were changed between the sexes. When comparisons were made in the outer medulla, we found that deficiency of the ETB receptor in males resulted in a ≥30% reduction in the expression of 29 genes involved in apoptosis, mitochondrial biogenesis and transport, energy metabolism, ROS handling and other mitochondrial functions (p<0.05). On the other hand, the expression of 8 genes involved in mitochondrial transport and apoptosis was reduced by ≥80% in the female ETB def rat outer medulla vs. TG controls, while 3 genes involved in mitochondrial transport and energy metabolism had a 2-fold overexpression (p<0.05). Altogether, our results demonstrate that salt-sensitive hypertension affects mitochondrial homeostasis differentially in distinct regions of the kidney, and that the male and female kidney respond to salt in a disparate manner: with overactivation of the ET-1/ETA axis resulting in greater dysregulation of mitochondria-related genes in the male versus the female kidney during a high salt diet. Funded by UAB-UCSD O’Brien Center Summer Research Pathway for Students P30 DK079337 and KURE R25 DK115353 to BSM, NIGMS UAB CORD BBRT to GJC, and NIH K01HL145324 and Sapphire North America Return to Science Research grant to CDM. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sex-Specific Mitochondrial Bioenergetics Differences in Heart and Kidney Cortex

Rationale: Mitochondrial bioenergetics of different tissues have been studied widely, but their sex-specific differences have not been systematically studied. The goal of this study was therefore to investigate the sex-specific differences in mitochondrial respiration (oxygen consumption rate; OCR) and membrane potential (Δψ) in the heart and kidney cortex and to explore underlying mechanisms responsible for any observed differences. Methods: Mitochondria were isolated from adult male and female Sprague-Dawley rat heart and kidney cortex and were used to study their bioenergetics responses. Three different substrate combinations, namely, pyruvate+malate (PM), glutamate+malate (GM), and succinate in the presence of complex I inhibitor rotenone (SR) were used. This was followed by two different ADP addition protocols to determine how different substrates influence mitochondrial OCR and Δψ to ADP perturbations during oxidative phosphorylation (OxPhos) in male and female heart and kidney cortex. In one, a single saturated dose of ADP, while in the other, sequentially increasing doses of ADP were added to mitochondria in the presence of different substrates. Mitochondrial OCR was measured using a dual chamber Oroboros Oxygraph-2k Instrument and Δψ was measured using a spectrofluorometer and rhodamine-123 dye. From these measurements, OCR and Δψ alterations under different respiratory states and as functions of added ADP concentration were determined for different substrates and for both male and female rats. Results: Male and female mitochondria exhibited distinct respiratory patterns in the kidney cortex and heart with different substrates. In the kidney cortex, male mitochondria showed significantly higher OCR than female mitochondria when fueled with PM or SR. However, no significant sex differences in the OCR were observed when GM were used as substrates. In contrast, heart mitochondria exhibited negligible sex differences in the OCR for PM and SR, but significant differences emerged with GM, where female mitochondria displayed higher OCR than their male counterparts. Interestingly, sex-specific variations of Δψ in ADP-stimulated respiration were not apparent for either tissue or substrate when a single saturated dose of ADP was used. Instead, a trend similar to the OCR emerged when ADP was administered in gradually increasing concentrations. Conclusion: Heart and kidney cortex mitochondrial Δψ for males and females did not differ conclusively with the two ADP addition protocols. However, there were significant differences in the OCR of mitochondria from the heart and kidney cortex of males and females, depending on the respiratory substrate utilized. Males were found to have enhanced OCR in the kidney cortex, whereas females exhibited higher OCR in the heart. These observed sex-specific differences in the OCR could be attributed to differential regulation of mitochondrial metabolic pathways by respiratory substrates and sex hormones. NIH R01-HL151587. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sex Differences in T Cell Migration from the Spleen to the Kidney in Mice at Baseline and in Response to Angiotensin II Infusion

Decades of research has indicated that T cells contribute to the development of hypertension and target organ damage. There is a critical role of spleen-derived T cells in angiotensin II-mediated hypertension and kidney damage in mice. Splenectomy abolished sex differences in the development of hypertension in spontaneously hypertensive rats, suggesting sex differences in the spleen-kidney immune axis. It is well-appreciated that immune cells migrate from different tissues to infiltrate organs. However, whether there are sex differences in T cell migration from the spleen to the kidney remained unexplored. Thus, we hypothesized that male mice would show higher immune cell migration from the spleen to the kidney at baseline and in response to angiotensin II infusion when compared to female mice. To quantify T cell migration in male and female mice, we utilized Kikume Green-Red (KikGR) transgenic mice that ubiquitously express the kikume green protein in all cells throughout the body, and this protein can be stably photoconverted to kikume red with exposure to 405 nm blue light. We specifically photoconverted mouse spleens with 10-minute exposure to blue light and infused angiotensin II via mini-pump implantation (490 ng/kg*min) in half of the photoconverted mice. After 3 days post-photoconversion, all mice were sacrificed, and both kidneys were removed for analysis via spectral flow cytometry to determine spleen-derived infiltrating immune cells (CD45+, KikRed+ cells) as well as spleen-derived T cells (CD45+, KikRed+, CD3+) in the kidney. There were no differences in the immune cell profiles found between left and right kidneys within each sex (p = 0.8 [male kidneys] and 0.8292 [female kidneys], n = 6-10 kidneys per group). At baseline, we found significantly increased spleen-derived immune cells in the kidneys of male compared to female mice (P = 0.0173, n = 3-5 per group). In addition, sex was a significant factor in spleen-derived T cell percentages within the kidney (Two-Way ANOVA, P = 0.029, n = 3-5 mice). In response to 3 days of angiotensin II infusion, spleen-derived immune cells were significantly higher in the kidneys of males compared to females (P = 0.0499, n = 3-5 mice). We conclude that there is reduced immune cell migration to the kidney from the spleen at baseline and in response to angiotensin II infusion in female mice, which may contribute to the lower blood pressure and kidney damage observed in female mice. NIH TL1 DK139566 to LNB, NIH R01 DK134562 to JSP. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.