Test |
Normal |
Borderline |
Abnormal |
Valsalva ratio |
? 1.21 |
1.11 – 1.20 |
? 1.10 |
E:I |
? 1.21 |
1.11 – 1.20 |
? 1.10 |
30:15 |
? 1.04 |
1.01 – 1.03 |
? 1 |
Fall in SBP |
? 10 mmHg |
11 – 29 mmHg |
? 30 mmHg |
Rise in DBP |
? 16 mmHg |
11 – 15 mmHg |
? 10 mmHg |
The results are categorized into following groups:6
- Normal
- Early parasympathetic damage with results of one of the three tests of parasympathetic function abnormal;
- Definite parasympathetic damage with results of at least two of the tests of parasympathetic function abnormal;
- Combined parasympathetic and sympathetic damage, where in addition to abnormal parasympathetic test results findings in one or both of the sympathetic tests are abnormal. For the purpose of the above mentioned classification, the borderline tests were interpreted as normal.
Study Design and Statistical Analysis:
It is a cross sectional study in which the statistical analysis was done by using the SPSS Software version 20.
Statistical analysis done by Unpaired Student’s t-test.
P value < 0.05 was taken as significant.
Results:
Table 2: Parasympathetic function tests of controls and patients of CKD on dialysis:
Variables |
Controls Mean±SD (n=30) |
CKD on Dialysis Mean±SD (n=40) |
t value |
P value |
||
Valsalva ratio |
1.48±0.226 |
1.42±0.344 |
|
|
||
E:I ratio |
1.57±0.185 |
1.15±0.184 |
9.429 |
< 0.0001 |
||
30:15 ratio |
1.4±0.174 |
1.17±0.163 |
5.6758 |
<0.0001 |
The above table shows that the difference in Valsalva ratio between the above two groups is not statistically significant and the difference in E:I ratio and 30:15 ratio is statistically significant.
CKD on dialysis |
|
Normal |
08(20%) |
Early parasympathetic dysfunction |
00(0%) |
Definite parasympathetic dysfunction |
08(20%) |
Combined autonomic dysfunction |
20(50%) |
Only sympathetic dysfunction |
04(10%) |
Total |
40(100%) |
Table 3: Sympathetic function tests of controls and patients of CKD on dialysis:
Variables |
Controls Mean±SD (n=30) |
CKD on Dialysis Mean±SD (n=40) |
t value |
P value |
Significance |
Fall in SBP immediately after standing |
5.2±1.54 |
10.3±8.564 |
3.2173 |
0.002 |
HS |
Rise in DBP on sustained handgrip |
17.27±1.92 |
9.8±5.761 |
6.8132 |
<0.0001 |
VHS |
The above table shows that the difference in fall in SBP immediately after standing and rise in DBP on sustained handgrip is statistically significant between the above two groups.
Thirty two (80%) out of forty patients of CKD on dialysis had one or more abnormal autonomic function tests.
Among the five tests, the two most abnormal tests were the heart rate variation during deep breathing(70%) and the blood pressure response to hand grip exercise(60%).
Table 4: Number of patients with different patterns of autonomic dysfunction
8 subjects (20%) had definite parasympathetic dysfunction and 20 subjects (50%) had combined autonomic dysfunction.
Discussion:
Combined form of autonomic dysfunction was seen in 50% subjects. Among 80% of patients of CKD on dialysis who had one or more abnormal autonomic function tests, 20% had definite parasympathetic dysfunction, 50% had combined autonomic dysfunction and 10% had only sympathetic dysfunction. Combined form of autonomic dysfunction was observed in 50% of the cases clearly suggesting involvement of both the divisions of autonomic nervous system. This is in concordance with study by Stamboulis E et al,7 where 62% of chronic heamodialysis patients had combined autonomic dysfunction. These results are also in concordance with studies by Sahin M et al, 8 Sanya EO, 9 Solders G,10 Heidbreder,11 Thapa L et al,12 Vita G et al. 13
Among the five tests, the two most abnormal tests were the heart rate variation during deep breathing (70%) and the blood pressure response to hand grip exercise (60%). According to previous studies parasympathetic dysfunction occurs much earlier than sympathetic dysfunction.3In this study 20 out of 24 subjects (83%) who had abnormal blood pressure response to sustained hand grip also had one or more abnormal parasympathetic test. So the blood pressure response to sustained hand grip test can alone be used to diagnose the autonomic neuropathy in patients of CRF on HD.
In patients with renal failure on hemodialysis (HD) cardiovascular disease is a major cause of death.13 Bleyer et al. estimate approximately 42% of death on dialysis is of cardiovascular etiology, of which 22.4% are related to cardiac arrest or arrhythmia.14 The autonomic nervous system (ANS) controls a variety of fundamental physiological processes in the human body including regulation of breathing, heart rate, blood pressure, temperature, gastrointestinal motility15, bladder, and sexual function.
The autonomic and peripheral nervous system dysfunction is a well-known complication of chronic uremia and nearly 70 % of uremic patients fulfill electrodiagnostic criteria for polyneuropathy including autonomic neuropathy (AN). 4Cardiac autonomic nervous system dysfunction (CAND) leading to depressed arterial baroreflex sensitivity (BRS) has been associated with an increased risk of ventricular arrhythmias and sudden death in patients with CKD on maintenance hemodialysis (MHD). Autonomic dysregulation, which is common among patients on HD even without diabetes, may contribute to dysrhythmias and an increased risk of sudden death.4
Among the five tests, the two most abnormal tests were the heart rate variation during deep breathing and the blood pressure response to handgrip exercise. Sahin M, et al.17 also found these two tests to be abnormal in his study suggesting that performing only one test instead of all five tests has a high sensitivity and is more practicable in terms of determining autonomic neuropathy.
References:
- Best and Taylor’s Physiological basis of medical practice, thirteenth edition; pg 1145-1156.
- Varughese S, Abraham G. Chronic Kidney Disease in India A Clarion Call for Change. Clinical Journal of the American Society of Nephrology. 2018 May 7;13(5):802-4.
- Salman IM. Cardiovascular autonomic dysfunction in chronic kidney disease: a comprehensive review. Current hypertension reports. 2015 Aug 1;17(8):59.
- S. Acharya and W. Ahmed: Autonomic System Evaluation in Non Diabetic ESRD. Department of Nephrology, ShaikhZayed Hospital, Lahore. S.Z.P.G.M.I.2012;26(2)75-80.
- Kidney International Supplements (2017)7,8.
- Ewing DJ, Clarke BF. Diagnosis and management of diabetic autonomic neuropathy. British medical journal (Clinical research ed.). 1982 Oct 2;285(6346):916.
- Stamboulis E, Voumvouraki K, Zambelis T, Andrikopoulou A, Vlahakos D, Tsivgoulis A, Rallis D, Tsivgoulis G. There is no association between cardiovascular autonomic dysfunction and peripheral neuropathy in chronic hemodialysis patients. Journal of Clinical Neurology. 2010 Sep 1;6(3):143-7.
- Sahin M, Kayatas M, Urun Y, Sennaroglu E, Akdur S. Performing only one cardiovascular reflex test has a high positive predictive value for diagnosing autonomic neuropathy in patients with chronic renal failure on hemodialysis. Renal failure. 2006 Jan 1;28(5):383-7.
- Sanya EO, Ogunniyi A. Cardiovascular autonomic neuropathy in non-diabetic Nigerian patients with chronic renal failure. West African journal of medicine. 2004;23(1):15-20.Solders G, Persson A, Gutierrez A. Autonomic dysfunction in non-diabetic terminal uraemia, Acta Neurologica Scandinavica.1985 Apr;71(4):321-7.
- Solders G, Persson A, Gutierrez A. Autonomic dysfunction in non-diabetic terminal uraemia. Acta neurologica scandinavica. 1985 Apr;71(4):321-7.
- Heidbreder E, Schafferhans K, Heidland A. Autonomic neuropathy in chronic renal insufficiency. Nephron. 1985;41(1):50-6.
- Thapa L, Karki P, Sharma SK, Bajaj BK. Cardiovascular autonomic neuropathy in chronic kidney diseases. Journal of Nepal Medical Association.2010 Apr-Jun;49(178):121-8.
- Vita G, Bellinghieri G, Trusso A, Costantino G, Santoro D, Monteleone F, Messina C, Savica V. Uremic autonomic neuropathy studied by spectral analysis of heart rate. Kidney international. 1999 Jul 1;56(1):232-7.
- Underwood CF, Hildreth CM, Wyse BF, Boyd R, Goodchild AK, Phillips JK. Uraemia: an unrecognized driver of central neurohumoral dysfunction in chronic kidney disease?. Acta Physiologica. 2017 Jan;219(1):305-23.
- Jassal SV, Douglas JF, Stout RW. Prevalence of central autonomic neuropathy in elderly dialysis patients. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association-European Renal Association. 1998 Jul 1;13(7):1702-8.