Effect of Renal Transplantation on Gonadal Hormones in Male Patients with End Stage Renal Disease

INTRODUCTION

Hypogonadism, or testosterone (T) levels below assay reference ranges, is widespread in people with end-stage renal disease (ESRD), with prevalence rates ranging from 50 to 70% in different studies. Low testosterone has been associated to an increased risk of morbidity and mortality in males with ESRD¹. Primary gonadal failure, hypothalamic–pituitary–gonadal axis dysfunction, and maybe a change in oestrogen homeostasis ²can all contribute to hypogonadism in ESRD.

Many men with renal failure experience pituitary and gonadal changes, which disrupt the hypothalamic-pituitary-gonadal axis and contribute to hypogonadism. Renal failure is linked to a decrease in luteinizing hormone (LH) synthesis in the gonadal axis, which can lead to hypogonadism. Renal failure is linked to a reduction in luteinizing hormone (LH) synthesis as well as a reduction in prolactin clearance. Hyperprolactinemia is caused by a

reduction in prolactin clearance, which can limit LH production and, as a result, testosterone production ³.

Renal transplantation significantly improved the eugonadal phenotype in at least some patients, with plasma testosterone levels tripling. A closer look found an increase in testosterone, as well as decreases in LH, FSH, and prolactin⁴.

PATIENTS AND METHODS

This was a prospective comparative study directed on 90 patients (30 male chronic kidney disease patients (CKD) stage 4, 30 male ESRD patients on regular hemodialysis and 30 male patients with post renal transplantation), at Maadi Military Medical Complex during the period from January 2020 to July 2021.

Inclusion criterion: Male < fifty years.

Exclusion criteria: Age more than fifty years or less than 18 years, patients with primary hypogonadism, hemochromatosis, patients on cancer treatment (chemotherapy and radiotherapy), pituitary tumors, hypopituitarism of any etiology, and inflammatory diseases such as tuberculosis and sarcoidosis.

All participants were informed about the study's purpose and laboratory or radiological procedures. All participants signed a consent form. All patients were informed of the results of the examinations performed at the conclusion of the study and received appropriate advice and therapy. This research was carried out in conformity with the World Medical Association's Code of Ethics (Declaration of Helsinki) for human studies.

Patient’s randomization:Group 1: 30 male chronic kidney disease patients (CKD) stage 4,Group 2: 30 male ESRD patients on regular hemodialysis three sessions per week and four hours per session for at least 6 months,Group 3: 30 male patients with post renal transplantation and gonadal hormones was investigated at 1, 3, 6 and 12 months after renal transplantation.

All patients were subjected to:Full medical history,Through medical examination includes (Body mass index and waist circumference, measurement of blood pressure),Laboratory investigation:Complete blood count,Renal functions tests (blood urea and serum creatinine),Liver function test (Aspartate Aminotransferase, Alanine Aminotransferase),Serum calcium, phosphorus and parathyroid hormone (PTH),C- reactive protein (CRP), ESR, Serum albumin, Total protein and ferritin,Free testosterone, LH, FSH, prolactin, Free T4 and TSH by LIAISON.

Statistical Methodology:

MedCalc version 18.11.3 was used for data entry, processing, and statistical analysis (MedCalc, Ostend, Belgium). We employed Kruskal-Wallis, Friedman's, factorial ANOVA, Spearman's correlation, and ROC Curve analysis to determine significance. Data were supplied, and appropriate analysis was performed for each variable based on the kind of data (parametric and non-parametric). For parametric numerical data, mean, standard deviation (SD), and range are used, while for non-parametric numerical data, median and inter-quartile range (IQR) are used. Non-numerical data frequency and proportion Significant was defined as a P value of less than 0.05.

RESULTS

Table 1: Comparison between the 3 groups as regards baseline laboratory data using Kruskal-Wallis test.

Comparative study between the 3 groups revealed; highly significant increase in baseline hemoglobin, platelets, Ca, albumin, ferritin, in post-renal transplantation group-3; compared to other groups (p < 0.01 respectively). Comparative study between the 3 groups revealed; highly significant decrease in baseline urea, creatinine, Po4, PTH, in post-renal transplantation group-3; compared to other groups (p < 0.01 respectively). Comparative study between the 3 groups revealed non-significant difference as regards baseline TLC, ALT, AST, T. proteins, ESR, CRP, free T4 and TSH (p > 0.05) (Table 1).

Table 2: Comparison between the 3 groups as regards baseline gonadal hormone profile using Kruskal-Wallis test.

In a comparison of the three groups, post-renal transplantation group-3 showed a highly significant rise in baseline free and total Testosterone, LH, and FSH when compared to the other groups (p 0.01 correspondingly). In a comparative analysis of the three groups, it was discovered that post-renal transplantation group-3 had a highly significant decrease in baseline Estradiol and Prolactin when compared to the other groups (p 0.01 correspondingly) (Table 2).

ANOVA: analysis of variance, 3-F: 3-factor study. #logarithmic transformation was done to non-parametric data.

Table 3: Comparison between the 3 groups of patients as regards serial laboratory measurements using repeated measures ANOVA test (2-Factor study).

During the serial baseline and follow-up assessments, there was an increase in free Testosterone in post-renal transplantation group-3 compared to the other groups (p 0.01). During the serial baseline and follow-up assessments, there was an increase in total Testosterone in post-renal transplantation group-3 compared to the other groups (p 0.01). During the serial baseline and follow-up assessments, there was a decrease in Estradiol in post-renal transplantation group-3 compared to the other groups (p 0.01). During the serial baseline and follow-up assessments, there was an increase in LH in post-renal transplantation group-3 compared to the other groups (p 0.01). During the serial baseline and follow-up assessments, there was an increase in FSH in post-renal transplantation group-3 compared to the other groups (p 0.01). During serial baseline and follow-up measurements, there was a decrease in prolactin in post-renal transplantation group-3 when compared to the other groups (p 0.01). (Table 3).

rho: Spearman's rho (correlation coefficient).

Table 4: Spearman's correlation analysis for baseline Factors associated with 12-months T. testosterone level.

Spearman's correlation analysis shows that; baseline hemoglobin, platelets, Ca, albumin and ferritin, had a highly significant positive correlation with 12-months T. testosterone level (p < 0.01 respectively). Spearman's correlation analysis shows that; age, baseline urea, creatinine, Po4 and PTH, had a highly significant negative correlation with 12-months T. testosterone level (p < 0.01 respectively) (Table 4).

ROC (Receiver operating characteristic), AUC= Area under curve, SE= Standard Error.

Table 5: Roc-curve of renal transplantation to predict 12-months T. testosterone level increase.

By using ROC-curve analysis, renal transplantation predicted 12-months T. testosterone level increase, with perfect (100%) accuracy, sensitivity= 100% and specificity= 100% (p < 0.001) (Table 5).