A STUDY OF THE IMPACT OF REMOTE ISCHAEMIA PRECONDITIONING ON THE REDUCTION OF MYOCARDIAL INJURY IN CHRONIC KIDNEY DISEASE PATIENTS UNDERGOING MAINTENANCE HAEMODIALYSIS.

Introduction:

Individuals undergoing long-term haemodialysis(HD) treatment are  already prone to several anatomical and functional problems that can cause  myocardial ischemia.  Renal insufficiency often leads to the development of  left ventricular hypertrophy. Myocardial stunning, a condition characterised by  protracted but reversible left ventricular dysfunction caused by temporary  myocardial ischaemia, has been observed during HD. HD can cause a significant decrease in myocardial blood flow leading to the development of myocardial ischemia. Episodes of ischaemia  caused by HD have the potential to contribute to the development of heart  failure and act as a trigger for cardiac arrhythmias. Hence, it would be  advantageous to focus on minimising HD-induced ischaemia as a treatment  objective. Research conducted by Jongha Park et al. demonstrated  that ischaemic preconditioning provides a safeguarding effect against HD-induced schemia. Several further investigations have also demonstrated the cardioprotective function of remote ischemia preconditioning(RIPC). Remote ischaemia preconditioning is a potentially more convenient and cost-effective method that may decrease myocardial injury during HD; hence reducing morbidity and death in affected populations. The objective of this study is to determine the impact of remote ischaemia preconditioning on  minimizing myocardial injury during conventional HD.

Methods:

This is a prospective randomised open controlled study done among patients undergoing maintenance hemodialysis from Government medical college Kozhikode. Patients were randomised into control and intervention arm. Patients in the intervention group were subjected to remote ischemic preconditioning for 12 consecutive hemodialysis session. Each session consisting of 3 cycles with each cycle comprising of 5 minute period of ischemia and reperfusion. Patients’ clinical and dialysis parameters were recorded. Troponin I levels were done at the beginning of study, after one week and at the end of study. Mann Whitney U test used to assess the statistical significance of RIPC in reducing troponin level at the end of study

Results:

We screened a total of 194 hemodialysis patients and randomly assigned 173 patients to the intervention and control groups. The intervention group consisted of 87 patients, while the control group included 86 patients. 21 patients had screening failures, primarily due to the short dialysis vintage. 

Among the total of 173 patients, 120 were males and 53 were females. The study population's mean age is 52.78. The majority of patients were in the age group of 51 to 60.Diabetic kidney disease was the most common cause of renal failure, followed by chronic tubulointerstitial disease and chronic glomerulonephritis (figure 1).

80% of patients received their dialysis via AV fistula. Few patients used tunneled catheters, and 7% used jugular catheters.The study population's mean dialysis vintage was 3.46 years. However, the majority of patients had a duration of less than one year(figure 2). 

Baseline characteristics of control and intervention arm were comparable( figure 3 - 8).

An increase in troponin I level was considered a marker of cardiac damage in patients on hemodialysis. The mean troponin I in the study population was 21.06 ng/L. The intervention arm had 17.7 ng/L, while the control arm had 24.4 ng/L.We analysed multiple patient, laboratory, and dialysis parameters to find an association between their baseline troponin levels. Some factors showed a positive correlation, whereas others had a negative correlation. The study revealed that the studied predictors can explain 41% of the variance in troponin I. The following table (figure 9 and figure 10) displays some of the studied factors. However, we obtained statistically significant associations for sex, average ultrafiltration removed, and serum calcium levels.

There was significantly higher baseline troponin I levels in females compared to males(30.02 vs 17.02 ng/L).Mean troponin levels were lower in younger age groups and higher mean troponin I levels were seen in patients older than 50 years(  figure 11).

Patients diagnosed with hypertensive kidney disease exhibited a higher mean troponin I value, while those with chronic tubulointerstitial disease displayed lower troponin levels. The differences in troponin levels between groups were statistically significant but didn’t provide a statistically significant result when combined with other predictors(figure 12).

No significant difference in mean troponin levels were seen between patients with previous cardiac illness and those with cardiac disease. Mean troponin I level in patients with cardiovascular disease was 18.0 ng/L and those without cardiovascular disease had mean troponin value of 21.5 ng/L.

Difference in troponin level between baseline and end of study: 

1) Control arm – -1.8 

2) Intervention arm - -6.41.

 Study showed a significant reduction of troponin level from baseline in intervention arm (p value = 0.05)(figure 13).

No significant difference in troponin levels were obtained after one week on RIPC maneuver. Difference between day 7 and day 28 were significant(figure 14).

We analyzed multiple factors to determine their impact on preconditioning for remote ischemia. The use of alpha-2 agonists and those with normocalcemia yielded significant positive impacts.The type of kidney disease or the dialysis parameters had no effect on the impact of RIPC in reducing troponin levels.Patients with a higher BMI and haemoglobin tend to do better at reducing troponin levels with intervention. Patients with higher baseline troponin levels showed a greater decrease in troponin level with intervention ( figure 15 and 16).

We conducted subgroup analyses based on their baseline troponin levels and assessed the mean difference in troponin levels at day 28. Results are shown in figure 17.

Patients with higher baseline troponin levels showed a greater decrease in troponin level with intervention.The effect of RIPC seems to be better in patients with normal serum calcium levels, which was statistically significant. Anaemia, hypoalbuminemia, a low body mass index, and a hypervolemic state were factors that attenuated the effect of ischemia preconditioning( figure 18).

Conclusions:

Remote ischemia preconditioning is an effective and safe procedure for reducing myocardial injury in patients on hemodialysis. Malnutrition, hypocalcemia, greater ultrafiltration removal, and female sex are risk factors for myocardial injury in patients on hemodialysis. Troponin I levels were lower in younger age group patients compared to older people. No significant difference in troponin I levels were seen between patients with or without prior cardiac illness. ACEI/ARB had no role in reducing myocardial injury in patients on hemodialysis. Remote ischemia preconditioning is not beneficial in patients with a high sensitivity troponin I level below 10ng/L. Anaemia, hypoalbuminemia, low body mass index, and hypervolemic states attenuate the effect of remote ischemic preconditioning.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.