Bellavere's scoring in chronic kidney disease: A study protocol

Saket Toshniwal; Sunil Kumar; Sourya Acharya

doi:10.12688/f1000research.140672.1

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Study Protocol

Bellavere's scoring in chronic kidney disease: A study protocol

[version 1; peer review: awaiting peer review]

Saket Toshniwal ¹, Sunil Kumar², Sourya Acharya³

PUBLISHED 25 Sep 2023

Author details Author details

¹ Post Graduate Resident, Department of General Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, 442001, India
² Professor, Department of General Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, 442001, India
³ Professor and Head, Department of General Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, 442001, India

Saket Toshniwal
Roles: Conceptualization, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing

Sunil Kumar
Roles: Conceptualization, Supervision, Writing – Review & Editing

Sourya Acharya
Roles: Conceptualization, Supervision, Writing – Review & Editing

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REVIEWER STATUS AWAITING PEER REVIEW

This article is included in the Datta Meghe Institute of Higher Education and Research collection.

Abstract

Background: Chronic kidney disease (CKD) refers to abnormalities in kidney structure and/or function for more than three months; cardiac autonomic neuropathy (CAN) is an indicator of cardiovascular death due to various abnormalities such as cardiac arrhythmias.

Heart rate variability (HRV) is an important component of CAN and has been shown to be related to CAN. This study aims to evaluate cardiac autonomic neuropathy at different stages of CKD with the Bellavere score and to correlate CAN with lipids, plasma, electrolytes and blood pressure in patients with CKD at different stages.

Methods: Consent of 95 patients who met the diagnosis of chronic kidney disease according to Modification of Diet in Renal Disease (MDRD) criteria were included in the study. All subjects will have blood tests for lipids, anaemia, and electrolytes. All participants' blood pressure will be monitored.

All subjects will also be scored based on the Bellevere scoring system, the Valsava ratio, and the 30:15 ratio. Data will be analyzed using SPSS version 21 and appropriate statistical tests will be used depending on the study objectives and the data collected.

Expected results: Based on the literature review and previous studies, the results of this study should demonstrate the relationship between CAN and CKD at this stage. The study also expects to find higher Bellavere scores in patients with different stages of CKD.

Keywords

Cardiac autonomic neuropathy, chronic kidney disease, bellavere’s score, heart rate variability, valsalva ratio, blood pressure, hemodialysis, end stage renal disease

Corresponding author: Saket Toshniwal

Competing interests: No competing interests were disclosed.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright: © 2023 Toshniwal S et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Toshniwal S, Kumar S and Acharya S. Bellavere's scoring in chronic kidney disease: A study protocol [version 1; peer review: awaiting peer review]. F1000Research 2023, 12:1206 (https://doi.org/10.12688/f1000research.140672.1) First published: 25 Sep 2023, 12:1206 (https://doi.org/10.12688/f1000research.140672.1) Latest published: 25 Sep 2023, 12:1206 (https://doi.org/10.12688/f1000research.140672.1)

Introduction

Structural or functional abnormalities of the kidneys present for more than three months is chronic kidney disease (CKD). Glomerular filtration rate (GFR) is generally considered the most common measure of kidney function. A GFR of less than 60 ml/min/1.73 m² indicates poor functioning of the kidneys; a GFR of less than 15 ml/min/1.73 m² indicates kidney failure. It can also be used to diagnose CKD. Proteinuria is another marker that can be used to diagnose CKD; of these, a urinary albumin excretion rate (AER) of more than 30 mg/24 hours and an albumin-creatinine ratio (ACR) of more than 30 is considered kidney disease. The prevalence of CKD in India has not been studied in longitudinal studies and only limited data are available from an Indian perspective.¹^–⁵

Cardiac autonomic neuropathy (CAN) is an important indicator of cardiovascular mortality from arrhythmia. CAN is divided into three stages: deep breathing itself causes heart failure, the intermediate stage presents as a Valsalva reaction, and the severe stage presents as orthostatic hypotension.⁴^–⁸ Extensive research in recent years has shown that both the pre-dialysis and dialysis stages of CKD are associated with increased cardiovascular risk and increased overall mortality. CKD is also associated with poor heart function. Heart rate variability (HRV) has been used to diagnose CAN, and HRV studies in patients with end-stage renal disease (ESRD) have shown that reduction in HRV is associated with mortality.⁹^–¹¹ CAN is also associated with various diseases such as myocardial ischemia, myocardial infarction, heart failure, diabetes, cardiac arrhythmias, and hypertension.

Many articles have been published on cardiac autonomic neuropathy and its impact on conditions such as type 2 diabetes, adult epilepsy, fibromyalgia, hypertension, metabolic syndrome, and prediabetes, but none on CKD correlating CAN using the Bellavere score.¹²^–¹⁶

Rationale

Animal models have shown that tolerance causes kidney damage. However, it is unclear how autonomic dysfunction predicts the development of CKD and ESRD in humans. Dysautonomia (sympathetic hyperactivity and/or parasympathetic depression) is a poorly studied renal injury. The results of several studies suggest that low self-efficacy may be an important risk factor for complications associated with ESRD and CKD, and these are the norm in these settings. Further research is needed on factors.¹⁷^–²⁰

Although autonomic dysfunction has been reported to cause renal injury in animal models, it is unclear how autonomic dysfunction predicts the development of CKD and ESRD in humans.²¹^,²² Dysautonomia (sympathetic hyperactivity and/or parasympathetic depression) is an under-researched renal injury.

Findings from several completed studies suggest that occupational inactivity may be an important risk factor for ESRD and CKD-related hospitalizations and encourage further research to identify mechanisms in these institutions.²¹^,²²

Some small studies show that people with CKD show lower HRV than healthy people. Although nephrosclerosis, which can lead to recurrent autonomic imbalances, may be the main cause of this link, it is not clear which autonomic imbalance existed before and could lead to the development of CKD.²¹^,²²

A cross-sectional study found that young adults with poor cardiovascular health were more likely to develop kidney disease. This group was followed longitudinally to elucidate the association between autonomic and renal failure and the impact of interventions in this population.²¹^,²² If abnormalities are insufficient before the onset of CKD, it can be used as a marker to identify patients at risk for ESRD.

In addition, the review described the effect and relationship between impaired kidney function, modification, and replacement.²² More research is needed to examine how renal failure and autonomic neuropathy may be related.²¹ Therefore, we are starting a prospective study to investigate the relationship between CKD and CAN. The aim of this study was to see if there is an association between CAN and CKD development, including increased albuminuria, decreased kidney function, and mixed outcomes, including ESRD, with a reduction in all-cause mortality and an estimated mortality GFR of at least 30% higher.

This study will be conducted in a group of CKD patients who will be followed up to identify risk factors for the development of CKD in the future.

Aims and objectives

1. Evaluation of cardiac autonomic neuropathy via Bellavere’s score in various stages of chronic kidney disease
2. To correlate cardiac autonomic neuropathy with lipid profiles like cholesterol, triglycerides, low density lipoprotein (LDL) and anemia, electrolytes, and blood pressure in all stages of CKD.
3. To compare CAN in patients of CKD with or without hemodialysis

Protocol

Methods

All patients who meet the diagnosis of CKD at Acharya Vinoba Bhave Rural Hospital (AVBRH), DMIHER (Datta Meghe Institute of Higher Education and Research) according to the Modification of Diet in Renal Disease (MDRD) criteria will be included in this study.

All patients meeting the inclusion and exclusion criteria will be included in this study after written informed consent has been obtained.

The information collected will be kept confidential. The data will be encoded and entered as a password-protected code. The patient’s name and other personal information will not be disclosed.

Patients who met CKD criteria and had informed consent, according to the National Kidney Foundation, were included. Patients who did not give consent had other conditions, refused the study, lost follow-up, died, and had missing data were excluded from the study.

Ethical considerations

This protocol has been approved by Institutional Ethical Committee of Datta Meghe Institute of Higher Education and Research on 27th June, 2022 (approval no. IEC20221088). Confidentiality will be ensured for all participants. Prior to taking part in the process, participant’s written consent will be obtained and they will be informed that they have the option to revoke their consent at any moment.

Inclusion criteria

• Patients satisfying the criteria of CKD according to the national kidney foundation
• Patients giving consent

Exclusion criteria

• Patients not consenting
• Patients with other comorbidities
• Patients refusing investigations
• Loss to follow-up, death and incomplete information
• Patients who are seriously ill

Bellavere’s scoring system, classification according to the total score of CAN and stages of CKD have been explained via Table 1, Table 2 and Table 3 respectively.¹³

Table 1. Bellavere’s scoring system.

(BP- Blood Pressure, VR- Valsalva Ratio).

COMPONENTS	SCORE
COMPONENTS	0 (Normal)	1 (Borderline)	2 (Abnormal)
Heart rate variability	>15	10–15	<10
VR	≥1.21	1.11–1.20	≤1.10
30:15 ratio	≥1.04	1.01–1.03	≤1.0
BP-standing	≥10	11–29	≥30
BP-hand grip	≥16	11–15	≤10

Table 2. Classification according to the total score of cardiac autonomic neuropathy.

Score	Interpretation
0–1	No neuropathy
2–4	Autonomic neuropathy
5–10	Severe autonomic neuropathy

Table 3. Stages of CKD (CKD- Chronic Kidney Disease, MDRD-Modification of Diet in Renal Disease, eGFR-estimated glomerular filtration rate).

Stages	Groups	e GFR by MDRD
Stage 1	GFR >90	111±26.2
Stage 2	GFR 60–90	77±23.8
Stage 3	GFR 30–59	39±9
Stage 4	GFR 15–29	21±6
Stage 5	GFR<15	13±4.5

Collection of blood sample

The skin over the median nerve of the cubital fossa will be disinfected with alcohol. A tourniquet will be used proximal to the fossa. The blood will be removed from the vein using a sterile standard venipuncture needle.

Measurement of blood pressure

Systolic blood pressure response to standing: systolic blood pressure will first be measured in a supine position and then the patient will be asked to stand and systolic blood pressure will be measured again 2 minutes later.¹⁴

The normal response is <10 mmHg decrease with an initial drop of 10–29 mmHg is considered borderline normal; abnormal is a drop of >30 mmHg with symptoms as shown in Table 1.

Diastolic blood pressure response to isometric exercise: The subject squeezes a handgrip dynamometer to establish a maximum reading. Grip is then squeezed at 30% maximum for 5 min. A normal response for diastolic blood pressure is a rise of > 16 mmHg in the opposite arm.

Heart rate variability

In this test, subjects are asked to take deep breaths six times per minute, inhale for five seconds per minute, and exhale for five seconds. The ECG will be recorded during a deep breath with a marker indicating the beginning of each inhalation and exhalation. The maximum and minimum R-R intervals in each respiratory cycle will be measured using a caliper and converted to beats per minute.¹³

Values equal to or less than 10 beats per minute are considered abnormal readings. A heart rate higher than 15 beats per minute is considered normal; however, anything below 10 bpm is abnormal.

Valsalva ratio

The ratio of the maximum R-R interval to the minimum R-R interval on the EKG is called the Valsalva ratio. In order to calculate this ratio, the subject is asked to breathe for 15 seconds into the mouth connected to the manometer while the mercury manometer is held at 40 mmHg pressure. The ECG will be recorded during and 45 seconds after this manoeuvre. The maximum and minimum R-R intervals will be recorded to calculate the Valsalva ratio. The ratio is less than or equal to 1.¹³

30:15 ratio

The longest R-R interval (measured at 30 beats) and the shortest R-R interval (measured at 15 beats) will be measured after 45 seconds of standing. The ratio of these two measurements is called the 30:15 ratio. A ratio less than or equal to 1 is considered abnormal.¹³

Sample size determination

N = Z 2 P (1 - P) / d 2

Z - Probability of type 1 error at 95% confidence interval (constant Value- 1.96)

P - Incidence of Cardiac autonomic neuropathy in CKD stage V (in this case 0.7242)

d - Precession level/Margin of error (constant value- 0.09)

On substituting these values in the formula, N = 95.

Therefore, the calculated sample size for this study is 95 at a 95% confidence interval and 5% probability of alpha error.

The investigation required for the study

Complete blood count, serum albumin, kidney function test, BMI, waist circumference, blood pressure, fasting lipid profile, 2D echocardiography, electrocardiography.

Expected outcome and results

This study intends to study the relationship between CKD and CAN based on variables like blood pressure, anaemia, electrolytes and lipid profile (cholesterol, triglycerides, LDL) in patients with CKD. Based on the literature review, it is anticipated that the results of this study will reveal a positive association between chronic kidney disease and cardiac autonomic neuropathy at all stages of CKD. The study is also expected to show higher Bellavere scoring in CKD patients at different stages. Finally, in the comparative analysis, the outcome of this study is expected to show that CAN is higher or more severe in CKD patients on hemodialysis as compared to CKD patients not on hemodialysis.

Dissemination

This study will be published in an indexed journal.

Study status

Data collection has not yet started.

Discussion

CKD is characterized by the presence or absence of kidney function for more than three months, regardless of the cause. CAN can damage weak blood vessels that supply the heart and blood vessels, leading to abnormalities in heart rate control and vascular dynamics. Few studies investigating the relationship between CKD and CAN have shown a strong association between the two conditions and a weak cardiac neuropathy observed in patients with different stages of CKD compared with those without CKD.⁷^,¹⁸^,²¹

Thapa L et al. in Nepal, differences in heart rate response to standing were observed in diabetic CKD patients compared with non-diabetic patients with CKD.

This study also found a positive correlation between the severity of autonomic dysfunction and the severity of CKD.²³

Malik S. et al. evaluated autonomic function in 67 patients with chronic renal failure. The five-point cardiovascular reflex test was used in their study. This study found a higher prevalence of cardiovascular autonomic disorders in patients with chronic renal failure.²⁴

Oliveira CA de et al. in a cross-sectional study, CKD patients were found to have lower sympathetic activity, higher parasympathetic activity, and lower sympathovagal balance compared to CAN patients. According to research, CKD patients not on dialysis have lower HRV, which can be an early sign of heart failure.²⁵ In a study examining the relationship between metabolic syndrome (MetS), CKD and CAN in the Chinese population, Zhang J et al. both factors were found to be positively associated with the development of CAN.²⁶

Conclusion

This prospective cross-sectional study aims at estimating the impact of CAN in different stages of CKD. Cardiovascular causes are a major contributor to mortality in CKD patients and hence a study correlating them is necessary. The Bellavere score for CAN in relation to CKD has not yet been published, and there are no such publications available in India.

This study aims to evaluate CAN in CKD patients via Bellavere’s scoring system and hence calculate the severity of CAN in different stages of chronic kidney disease. CAN is an established indicator of cardiovascular neuropathy and hence this study would help in establishing whether early diagnosis of CAN in CKD patients would help decrease cardiovascular morbidity and mortality in CKD patients.

Data availability

No underlying data associated with this protocol.

Acknowledgements

The corresponding author will be conducting the complete study as his thesis for his post-graduation in General Medicine. All authors have equally contributed to the conception, design and analysis of this protocol.

All authors confirm that they have read and agree to the contents of this manuscript. Also, the easily reproducible materials described in the manuscript are freely available to any researcher who wishes to use them for non-commercial purposes.

References

1. Hogg RJ, Furth S, Lemley KV, et al.: National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative clinical practice guidelines for chronic kidney disease in children and adolescents: evaluation, classification, and stratification. Pediatrics. 2003 Jun 1; 111(6): 1416–1421. PubMed Abstract | Publisher Full Text
2. Turner NN, Lameire N, Goldsmith DJ, et al.: Oxford textbook of clinical nephrology. Oxford University Press; 2015 Oct 29.
3. Levey AS, Eckardt KU, Tsukamoto Y, et al.: Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2005 Jun 1; 67(6): 2089–2100. PubMed Abstract | Publisher Full Text
4. Cockwell P, Fisher LA: The global burden of chronic kidney disease. Lancet. 2020 Feb 29; 395(10225): 662–664. Publisher Full Text
5. Varma PP: Prevalence of chronic kidney disease in India-Where are we heading? Indian J. Nephrol. 2015 May; 25(3): 133–135. PubMed Abstract
6. Memon A: Cardiac autonomic neuropathy in type 2 diabetes mellitus using Bellavere’s score system. Int. J. Health Sci. 2017 Nov; 5(5): 26. Publisher Full Text
7. Kasthuri AS, Yadav RP: Cardiac autonomic neuropathy in diabetes mellitus. Med. J. Armed Forces India. 1997 Jan 1; 53(1): 7–10. Publisher Full Text
8. Adebiyi AM, Komolafe MA, Idowu AO, et al.: Cardiac autonomic neuropathy in adult epilepsy patients in a tertiary hospital in South-Western Nigeria. Niger. J. Clin. Pract. 2020 Oct 1; 23(10): 1437–1442. Publisher Full Text
9. Kulshreshtha P, Deepak KK, Yadav RK, et al.: Cardiac autonomic neuropathy in fibromyalgia: Revisited. J. Back Musculoskelet. Rehabil. 2022 Jan 1; 35(1): 111–117. PubMed Abstract | Publisher Full Text
10. Gateva A, Kamenov Z: Cardiac Autonomic Neuropathy in Patients with Newly Diagnosed Carbohydrate Disturbances. Horm. Metab. Res. 2022 May; 54(05): 308–315. Publisher Full Text
11. Baheti A, Sarode R, Kumar S, et al.: Evaluation of Cardiovascular Autonomic Function in Prediabetics: Need of Tomorrow. Int. J. Cur. Res. Rev. 2021 Oct; 13(19): 149–154. Publisher Full Text
12. Ayad F, Belhadj M, Pariés J, et al.: Association between cardiac autonomic neuropathy and hypertension and its potential influence on diabetic complications. Diabet. Med. 2010 Jul; 27(7): 804–811. PubMed Abstract | Publisher Full Text
13. Venugopala D, Shyamala KV: Cardiovascular Autonomic Neuropathy scorings in chronic renal failure patients. Int. J. Adv. Res. 2013; 1(5): 614–617.
14. Williams SM, Eleftheriadou A, Alam U, et al.: Cardiac autonomic neuropathy in obesity, the metabolic syndrome and prediabetes: a narrative review. Diabetes Ther. 2019 Dec; 10(6): 1995–2021. PubMed Abstract | Publisher Full Text | Free Full Text
15. Doulgerakis D, Moyssakis I, Kapelios CJ, et al.: Cardiac autonomic neuropathy predicts all-cause and cardiovascular mortality in patients with end-stage renal failure: a 5-year prospective study. Kidney Int. Rep. 2017 Jul 1; 2(4): 686–694. PubMed Abstract | Publisher Full Text | Free Full Text
16. Curtis BM, O’Keefe JH Jr: Autonomic tone as a cardiovascular risk factor: the dangers of chronic fight or flight. Mayo Clinic Proceedings. Elsevier; 2002 Jan 1; (Vol. 77(1): pp. 45–54). Publisher Full Text
17. Levey AS, Coresh J, Greene T, et al.: Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin. Chem. 2007 Apr; 53(4): 766–772. PubMed Abstract | Publisher Full Text
18. Weinrauch LA, D’Elia JA, Gleason RE, et al.: Autonomic function in type I diabetes mellitus complicated by nephropathy a cross-sectional analysis in the presymptomatic phase. Am. J. Hypertens. 1995 Aug 1; 8(8): 782–789. PubMed Abstract | Publisher Full Text
19. Kurata C, Uehara A, Sugi T, et al.: Cardiac autonomic neuropathy in patients with chronic renal failure on hemodialysis. Nephron. 2000; 84(4): 312–319. Publisher Full Text
20. Agashe S, Petak S: Cardiac Autonomic Neuropathy in Diabetes Mellitus. Methodist Debakey Cardiovasc. J. 2018 Oct-Dec; 14(4): 251–256. PubMed Abstract | Publisher Full Text | Free Full Text
21. Brotman DJ, Bash LD, Qayyum R, et al.: Heart rate variability predicts ESRD and CKD-related hospitalization. J. Am. Soc. Nephrol. 2010 Sep 1; 21(9): 1560–1570. PubMed Abstract | Publisher Full Text | Free Full Text
22. Cho YH, Craig ME, Davis EA, et al.: Cardiac autonomic dysfunction is associated with high-risk albumin-to-creatinine ratio in young adolescents with type 1 diabetes in AdDIT (adolescent type 1 diabetes cardio-renal interventional trial). Diabetes Care. 2015 Apr 1; 38(4): 676–681. Publisher Full Text
23. Thapa L, Karki P, Sharma SK, et al.: Cardiovascular autonomic neuropathy in chronic kidney diseases. JNMA J. Nepal Med. Assoc. 2010 Apr-Jun; 49(178): 121–128. PubMed Abstract | Publisher Full Text
24. Malik S, Winney RJ, Ewing DJ: Chronic renal failure and cardiovascular autonomic function. Nephron. 1986; 43: 191–195. Publisher Full Text
25. de Oliveira CA , de Brito Junior HL , Bastos MG, et al.: Depressed cardiac autonomic modulation in patients with chronic kidney disease. Braz. J. Nephrol. 2014 Apr; 36: 155–162. (Braz. J. Nephrol., 2014 36 (2)). Publisher Full Text
26. Zhang J, Liu NJ, Zhang Y, et al.: The association and interaction analysis of metabolic syndrome and chronic kidney disease on cardiovascular autonomic neuropathy in the general Chinese population. Int. J. Clin. Exp. Med. 2015 Jun 15; 8(6): 9649–9657. PubMed Abstract | Free Full Text

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VERSION 1 PUBLISHED 25 Sep 2023

Author details Author details

¹ Post Graduate Resident, Department of General Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, 442001, India
² Professor, Department of General Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, 442001, India
³ Professor and Head, Department of General Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, 442001, India

Saket Toshniwal
Roles: Conceptualization, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing

Sunil Kumar
Roles: Conceptualization, Supervision, Writing – Review & Editing

Sourya Acharya
Roles: Conceptualization, Supervision, Writing – Review & Editing

Competing interests

No competing interests were disclosed.

Grant information

The author(s) declared that no grants were involved in supporting this work.

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Published: 25 Sep 2023, 12:1206

https://doi.org/10.12688/f1000research.140672.1

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© 2023 Toshniwal S et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Toshniwal S, Kumar S and Acharya S. Bellavere's scoring in chronic kidney disease: A study protocol [version 1; peer review: awaiting peer review]. F1000Research 2023, 12:1206 (https://doi.org/10.12688/f1000research.140672.1)

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[1] 1. Hogg RJ, Furth S, Lemley KV, et al.: National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative clinical practice guidelines for chronic kidney disease in children and adolescents: evaluation, classification, and stratification. Pediatrics. 2003 Jun 1; 111(6): 1416–1421. PubMed Abstract | Publisher Full Text

[2] 2. Turner NN, Lameire N, Goldsmith DJ, et al.: Oxford textbook of clinical nephrology. Oxford University Press; 2015 Oct 29.

[3] 3. Levey AS, Eckardt KU, Tsukamoto Y, et al.: Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2005 Jun 1; 67(6): 2089–2100. PubMed Abstract | Publisher Full Text

[4] 4. Cockwell P, Fisher LA: The global burden of chronic kidney disease. Lancet. 2020 Feb 29; 395(10225): 662–664. Publisher Full Text

[5] 5. Varma PP: Prevalence of chronic kidney disease in India-Where are we heading? Indian J. Nephrol. 2015 May; 25(3): 133–135. PubMed Abstract

[6] 6. Memon A: Cardiac autonomic neuropathy in type 2 diabetes mellitus using Bellavere’s score system. Int. J. Health Sci. 2017 Nov; 5(5): 26. Publisher Full Text

[7] 7. Kasthuri AS, Yadav RP: Cardiac autonomic neuropathy in diabetes mellitus. Med. J. Armed Forces India. 1997 Jan 1; 53(1): 7–10. Publisher Full Text

[8] 8. Adebiyi AM, Komolafe MA, Idowu AO, et al.: Cardiac autonomic neuropathy in adult epilepsy patients in a tertiary hospital in South-Western Nigeria. Niger. J. Clin. Pract. 2020 Oct 1; 23(10): 1437–1442. Publisher Full Text

[9] 9. Kulshreshtha P, Deepak KK, Yadav RK, et al.: Cardiac autonomic neuropathy in fibromyalgia: Revisited. J. Back Musculoskelet. Rehabil. 2022 Jan 1; 35(1): 111–117. PubMed Abstract | Publisher Full Text

[10] 10. Gateva A, Kamenov Z: Cardiac Autonomic Neuropathy in Patients with Newly Diagnosed Carbohydrate Disturbances. Horm. Metab. Res. 2022 May; 54(05): 308–315. Publisher Full Text

[11] 11. Baheti A, Sarode R, Kumar S, et al.: Evaluation of Cardiovascular Autonomic Function in Prediabetics: Need of Tomorrow. Int. J. Cur. Res. Rev. 2021 Oct; 13(19): 149–154. Publisher Full Text

[12] 12. Ayad F, Belhadj M, Pariés J, et al.: Association between cardiac autonomic neuropathy and hypertension and its potential influence on diabetic complications. Diabet. Med. 2010 Jul; 27(7): 804–811. PubMed Abstract | Publisher Full Text

[13] 13. Venugopala D, Shyamala KV: Cardiovascular Autonomic Neuropathy scorings in chronic renal failure patients. Int. J. Adv. Res. 2013; 1(5): 614–617.

[14] 14. Williams SM, Eleftheriadou A, Alam U, et al.: Cardiac autonomic neuropathy in obesity, the metabolic syndrome and prediabetes: a narrative review. Diabetes Ther. 2019 Dec; 10(6): 1995–2021. PubMed Abstract | Publisher Full Text | Free Full Text

[15] 15. Doulgerakis D, Moyssakis I, Kapelios CJ, et al.: Cardiac autonomic neuropathy predicts all-cause and cardiovascular mortality in patients with end-stage renal failure: a 5-year prospective study. Kidney Int. Rep. 2017 Jul 1; 2(4): 686–694. PubMed Abstract | Publisher Full Text | Free Full Text

[16] 16. Curtis BM, O’Keefe JH Jr: Autonomic tone as a cardiovascular risk factor: the dangers of chronic fight or flight. Mayo Clinic Proceedings. Elsevier; 2002 Jan 1; (Vol. 77(1): pp. 45–54). Publisher Full Text

[17] 17. Levey AS, Coresh J, Greene T, et al.: Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin. Chem. 2007 Apr; 53(4): 766–772. PubMed Abstract | Publisher Full Text

[18] 18. Weinrauch LA, D’Elia JA, Gleason RE, et al.: Autonomic function in type I diabetes mellitus complicated by nephropathy a cross-sectional analysis in the presymptomatic phase. Am. J. Hypertens. 1995 Aug 1; 8(8): 782–789. PubMed Abstract | Publisher Full Text

[19] 19. Kurata C, Uehara A, Sugi T, et al.: Cardiac autonomic neuropathy in patients with chronic renal failure on hemodialysis. Nephron. 2000; 84(4): 312–319. Publisher Full Text

[20] 20. Agashe S, Petak S: Cardiac Autonomic Neuropathy in Diabetes Mellitus. Methodist Debakey Cardiovasc. J. 2018 Oct-Dec; 14(4): 251–256. PubMed Abstract | Publisher Full Text | Free Full Text

[21] 21. Brotman DJ, Bash LD, Qayyum R, et al.: Heart rate variability predicts ESRD and CKD-related hospitalization. J. Am. Soc. Nephrol. 2010 Sep 1; 21(9): 1560–1570. PubMed Abstract | Publisher Full Text | Free Full Text

[22] 22. Cho YH, Craig ME, Davis EA, et al.: Cardiac autonomic dysfunction is associated with high-risk albumin-to-creatinine ratio in young adolescents with type 1 diabetes in AdDIT (adolescent type 1 diabetes cardio-renal interventional trial). Diabetes Care. 2015 Apr 1; 38(4): 676–681. Publisher Full Text

[23] 23. Thapa L, Karki P, Sharma SK, et al.: Cardiovascular autonomic neuropathy in chronic kidney diseases. JNMA J. Nepal Med. Assoc. 2010 Apr-Jun; 49(178): 121–128. PubMed Abstract | Publisher Full Text

[24] 24. Malik S, Winney RJ, Ewing DJ: Chronic renal failure and cardiovascular autonomic function. Nephron. 1986; 43: 191–195. Publisher Full Text

[25] 25. de Oliveira CA , de Brito Junior HL , Bastos MG, et al.: Depressed cardiac autonomic modulation in patients with chronic kidney disease. Braz. J. Nephrol. 2014 Apr; 36: 155–162. (Braz. J. Nephrol., 2014 36 (2)). Publisher Full Text

[26] 26. Zhang J, Liu NJ, Zhang Y, et al.: The association and interaction analysis of metabolic syndrome and chronic kidney disease on cardiovascular autonomic neuropathy in the general Chinese population. Int. J. Clin. Exp. Med. 2015 Jun 15; 8(6): 9649–9657. PubMed Abstract | Free Full Text

Bellavere's scoring in chronic kidney disease: A study protocol

Abstract

Keywords

Introduction

Rationale

Aims and objectives

Protocol

Methods

Ethical considerations

Inclusion criteria

Exclusion criteria

Table 1. Bellavere’s scoring system.

Table 2. Classification according to the total score of cardiac autonomic neuropathy.

Table 3. Stages of CKD (CKD- Chronic Kidney Disease, MDRD-Modification of Diet in Renal Disease, eGFR-estimated glomerular filtration rate).

Collection of blood sample

Measurement of blood pressure

Heart rate variability

Valsalva ratio

30:15 ratio

Sample size determination

The investigation required for the study

Expected outcome and results

Discussion

Conclusion

Data availability

Acknowledgements

References

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