Kidney Transplantation and "Sex Mismatch": A 10-Year Single-Center Analysis.

BACKGROUND The effect of a relative disproportion in the size of a transplanted kidney (KT) on graft function and survival is well documented. However, the importance of the H-Y antigen (male donor and female recipient) has not been unambiguously confirmed. MATERIAL AND METHODS Our retrospective analysis consists of 230 deceased donor/recipient pairs. The aim of the study was to determine the effect of sex mismatch between donors and recipients on the function of the graft and the graft and patient survival. RESULTS In the group of male donors, a statistically significantly lower value of the eGFR (estimated glomerular filtration rate) was recorded for female recipients in the fifth year after the KT (=0.0047). The male donor/female recipient group was an independent risk factor for: eGFR (<60 ml/min (CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration) in the third year after KT [HR 0.1618; (P=0.0004)], acute rejection in the first year after KT [HR 1.8992; (P=0.0387)], and the 5-year graft survival was significantly worse in this group. By adjusting the results for age and induction, this group was at significantly higher risk for decreased graft function (eGFR <30 ml/min) if the age of the donor was ≤50 years old and the recipient was >45 years old in the fifth year [HR 11.1676; (P=0.0139)], the age of the donor was ≤50 years old/recipient was ≤45 years old in the third year [HR 1.2500; (P=0.0050)], and also in the fifth year after KT [HR 8.1993; (P=0.0183)]. CONCLUSIONS Based on our analysis, the differences in the incidence of acute rejection episodes as well as in graft survival among the different groups of patients were confirmed. The group with the highest risk, in cases of an acute rejection episode, is a male donor/female recipient.

Role of sex in post-transplant diabetes mellitus development: Are men and women equal?

INTRODUCTION: Sex differences are defined as biology-linked differences between women and men that occur through the sex chromosomes and their effects on organ systems. MATERIAL AND METHODS: The objective of this prospective study was to determine risk factors for post-transplant diabetes mellitus (PTDM) in men and women. RESULTS: A total of 417 patients (271 men and 146 women) were included in the monitored group. Age at the time of kidney transplantation (KT) >60 years and hypovitaminosis D at the time of KT (<20 µg/l) were identified as independent risk factors for PTDM in both men and women. It was further confirmed as an independent risk factor for men a waist circumference at the time of KT >94 cm, C-peptide at the time of KT >5 ng/ml, HOMA-IR >2 and triacylglycerols at the time of KT >1.7 mmol/l. In case of women, the dominant factor was BMI at the time of KT >30 kg/m2 and menopause at the time of KT. A significant decrease in C-peptide was recorded in women with PTDM. CONCLUSION: It was confirmed that there are gender differences with regard to the development of PTDM after KT. Women show pancreas ß cell dysfunction, whereas insulin resistance and metabolic syndrome are dominant in men.

Leptin - A new marker for development of post-transplant diabetes mellitus?

INTRODUCTION: Obese patients have increased leptin production and selective resistance to its central anti-adipogenic effects, yet its pro-inflammatory immunostimulating effects persist. MATERIAL AND METHODS: In a group of 70 patients who underwent primary kidney transplantation (KT) we examined adiponectin and leptin levels at the time of KT and 6 months post-transplantation. Patients with diabetes mellitus type 1 or type 2 at the time of KT were excluded from the study. RESULTS: We found that leptin levels significantly increased during the post-transplant period (P = 0.0065). Overall, leptin levels were positively correlated with the level of triacylglycerols, post-transplant diabetes mellitus (PTDM) development and acute rejection (AR). We discovered that, in particular, high leptin levels were associated with AR [OR 2.1273; 95% CI 1.0130-4.4671 (P = 0.0461)] and PTDM development [OR 7.200; 95% CI 1.0310-50.2836 (P = 0.0465)], whereas, low adiponectin levels represent a risk factor for the development of insulin resistance [HR 38.6135; 95% CI 13.3844-67.7699 (P < 0.0001)] and obesity [HR 3.0821; 95% CI 0.8700-10.9192 (P = 0.0053)]. CONCLUSION: We found that a high serum concentration of leptin before KT is associated with both PTDM development and AR and merits further investigation in relation to KT.

Sensitivity of airway cough-related afferents is influenced by female sex hormones.

Chronic hypersensitivity cough syndrome affects mainly postmenopausal women; however, the pathogenesis of cough hypersensitivity in this demographic is not entirely understood. The role of sex hormones in cough has never been studied in detail; however, sex hormones seem to play an important role in the lung health of women. Our study was aimed to analyse the effect of female sex hormones (oestrogen - E2 and progesterone - Pg) on cough sensitivity measured by inhalation of capsaicin in follicular and luteal phases of menstrual cycle, characterized by significantly different concentrations of sex hormones. These data were compared with a matched group of women taking oral contraceptives. Cough sensitivity to capsaicin increased in luteal phase in subjects with normal menstrual cycle, and this functional change was not present in group with contraceptive pills. The cough sensitivity correlates with the Pg/E2 ratio, and relative lack of oestrogen in luteal phase is associated with higher cough sensitivity to capsaicin.

Role of gender in basic cough research.

Cough hypersensitivity affects mainly postmenopausal women. Pathogenesis remains unknown in their case; therefore, an optimal treatment is unavailable. Only male guinea pigs are used in basic cough research and exclusion of females leads to gender bias. Nowadays, the efforts of grant agencies aim to support projects which take gender into account and involve both sexes to reduce gender bias. The aim of our pilot study is to assess the suitability of female guinea pig model in cough research. Cough response to citric acid (0.4M) was obtained in female and male guinea pigs (n=12 each). Reproducibility of cough response was tested four times a week apart. The cough was detected from the airflow traces and cough sound analysis. Our initial results show that cough response of female guinea pigs is higher than in males. Variability of females is also higher than in males. Further investigations are necessary to validate this model in different conditions to achieve gender equality in cough studies.

TRPV4 antagonist GSK2193874 does not modulate cough response to osmotic stimuli.

Osmolarity changes of airway superficial fluid are associated with cough and are used in research. TRPV4 is calcium channel initially described as osmosensor. In the airways, it can play role in increasing cough reflex sensitivity. The aim of our study was to test whether cough to osmotic stimuli is mediated via TRPV4 channel. Cough response was measured in 12 male guinea pigs by inhalation of saline, distilled water, hypertonic solution and citric acid for 10min in whole-body plethysmograph. Data were obtained in naïve animals and after pre-treatment with selective TRPV4 antagonist GSK2193874 in doses 300µg/kg (GSK300) and 900µg/kg (GSK900). Cough response to all tested aerosols was significantly higher than to saline. Pre-treatment with GSK300 did not influence response to osmotic stimuli - only reduced cough to citric acid. GSK900 reduced cough response to hypotonic stimuli and citric acid. TRPV4 mediated activation of airway afferents does not seem to be the exclusive mechanism responsible for cough to osmotic stimuli.