Sex Differences in Chronic Kidney Disease

2.1 Description and analysis of sex-specific differences in hemodialysis patients and the associated male-to-female mortality in Austria

Hypothesis:

There are sex-specific differences in hemodialysis incidence/prevalence and mortality among hemodialysis patients in Austria.

There are differences in male-to-female mortality among hemodialysis patients as compared to the general population in Austria.

Methodology:

Data extraction will be performed from the Austrian Dialysis registry which holds complete longitudinal entries of all Austrian hemodialysis patients since 197040 and contains data of all patients undergoing hemodialysis in Austria since the year 1965.

Demographic data, laboratory values, clinical characteristics and hemodialysis specific data will be collected for every patient registered in the Austrian Dialysis registry between 1865 and 2015.

Male and female population structure and mortality data of the Austrian general population will be retrieved from the ´Statistik Austria´ registry

Statistics:

Standard descriptive statistics will be used for tabulations of patient characteristics by sex and decade, of the Austrian hemodialysis population versus general population by sex and age group over time. The unadjusted male-to-female mortality rate ratio in the hemodialysis population will be compared with that of the Austrian general population. Adjusted hazard ratios for the male-to-female mortality risk in hemodialysis patients, by region will be performed using Cox regression analysis. Statistical modeling will closely follow a previously published study of hemodialysis data, analyzed by sex and country/region.4 All obtained p-values will be considered exploratory in nature.

2.2 Description and analysis of sex-specific differences in treatment and outcomes in patients with chronic kidney disease.

Hypothesis:

There are sex-specific differences in treatment, length of hospitalization, mortality and dialysis initiation in patients with chronic kidney disease admitted to internal medicine wards.

Methodology:

Patients hospitalized at internal medicine wards of the Krankenanstaltsverbund (KAV) between Jan 1st 2015 and Dec 31st 2015 with eGFR <60 mL/min/1.73m will be included.

Primary study endpoints are length of hospital stay, death within hospitalization and dialysis initiation. Secondary endpoints are renal function parameters (eGFR, serum creatinine, blood urea nitrogen) and proteinuria during hospital stay. Laboratory data will be extracted from the KAV laboratory database and patient characteristics will be derived from the KAV patient management database.

Statistics:

Descriptive statistics will be used for presentation of demographic and clinical patient characteristics and prevalence of chronic kidney disease in women as compared to men.

Further statistical methods will be chosen according to data availability and quality: The present plans include logistic regression to calculate the male-to-female odds of reaching one of the endpoints, conditional logistic regression for pair-matched data or logistic regression with propensity scoring.

2.3 Descriptive analysis of decision-making by doctors and patients with regards to renal replacement therapy initiation

Hypothesis

There are sex-specific differences in decision-making of doctors and patients with end-stage renal disease with regards to renal replacement therapy initiation.

Methodology

Questionnaires will be sent to every Austrian chronic kidney disease outpatient clinic willing to participate. Doctors and patients will complete the questionnaire anonymously and questionnaires will be sent back after a 3 months-time period of data collection /questionnaire completion.

The following questions will be included in the questionnaire:

Doctor level:

In your chronic kidney disease clinic

1. How many men (a) and how many women (b) were registered in the year 2016?

2. According to the first lab result that was taken in 2016, how many men (a) and how many women (b) were in chronic kidney disease stage 4, 3a, 3b, and 2?

3. How many times did the registered men (a) and the registered women (b) have their labs checked and saw the doctor during the year 2016? Please subdivide also by chronic kidney disease stage.

4. How many men (a) and how many women (b) have you informed they will likely need renal replacement therapy (RRT) in the next 12 months?

5. How many men (a) and how many women (b) already have a fistula, and how many have a graft for vascular access?

6. How many men (a) and how many women (b) have you informed about pre-emptive transplantation as an option for RRT?

7. How many men (a) and how many women (b) have you informed about peritoneal dialysis as an option for RRT?

8. How many men (a) and how many women (b) have you informed about hemodialysis as an option for RRT?

9. How many men (a) and how many women (b) ended up on RRT (HD, PD or preemptive transplantation) during the year 2016?

10. How many men (a) and how many women (b) did you consider end stage and thus in need of undergoing RRT in 2016?

11. How many men (a) and how many women (b) refused RRT in 2016 despite your advice?

12. Among those whom you considered end stage in the year 2016, in how many men (a) and how many women (b) was the decision to withhold or not do RRT mutual (taken by doctor and patient together)?

13. How many men (a) and how many women (b) started RRT in 2016 against your advice?

14. How would you judge your own decision making regarding RRT initiation

1. Influenced by patient sex, with men more likely to start RRT

2. Influenced by patient sex, with women more likely to start RRT

3. Not influenced by patient sex

To obtain adequate data, a reimbursement based on the number of patients seen by the center will be offered to the medical director of the outpatient clinic in December 2016. A specific plan on how to arrive at answering the questions correctly must be submitted; in principle, this plan should encompass several meetings with the outpatient clinic doctors in early 2017, in order to obtain an answer from all of them together (only question 14 must be individually answered).

Patient level:

1. I am a man (a), a woman (b).

2. My age is … years.

3. My nationality is Austrian (a), Non-Austrian (b).

4. My native language is German (a), not German (b).

5. I am married (a), living with my partner (b), separated or divorced (c), single (d), widowed (e).

6. My highest level of education is less than high school.

7. I know the reason (a), don't know the reason (b) why my kidneys are weak or failing.

8. The most important reason why my kidneys are weak or failing, to the best of my knowledge is hypertension (a), diabetes (b), glomerulonephritis (c), polycystic kidney disease (d); another reason not mentioned here (e).

9. I come to the clinic seldom [once a year at the most] (a), frequently [at least 3 times a year] (b) in order to check my labs and/or discuss treatment and progression of my disease.

10. A doctor at this clinic has told me (a) has not told me (b) that I will likely need renal replacement therapy (RRT) within the next 12 months.

11. I already have (a) / don't yet have (b) a fistula or graft for vascular hemodialysis access.

12. A doctor at this clinic has informed me (a) has not informed me (b) about the possibility to undergo pre-emptive transplantation as an option for RRT.

13. A doctor at this clinic has informed me (a) has not informed me (b) about peritoneal dialysis as an option for RRT.

14. A doctor at this clinic has informed me (a) has not informed me (b) about the possibility to undergo hemodialysis as an option for RRT.

1. I consider myself end stage and thus in need of undergoing RRT within the next 12 months.

15. RRT is not an option for me. I would rather die than go on dialysis. 16. I suffer from nausea/vomiting (a), fatigue/tiredness (b), edema (c), dyspnea (d).

17. I can take care (a), cannot take care (b) of my household.

Methodological Note: The questionnaire will be handed out to all patients coming to the outpatient clinic in the year 2017 by non-medical (administrative) personnel. The number of returned questionnaires will be counted and compared to the number of questionnaires that was handed out. Only the sex of the patient receiving the questionnaire will be recorded. The return of the questionnaire will be anonymous, by placing a box in the patient waiting area.

Statistics:

Data will be entered into an IBM SPSS statistics database. Descriptive analysis and graphical illustrations will be performed.