Baroreflex dysfunction in chronic kidney disease

Table 1 Cardiovascular risk factors in chronic kidney disease

Traditional risk factors	Non-traditional factors
Sympathetic hyperactivity	Albuminuria
Hyperhomocysteinemia	Inflammation
Hypertension	Oxidative stress
High LDL cholesterol	Anemia
Low HDL cholesterol	Abnormal calcium/phosphate metabolism
Diabetes	Extracellular fluid volume overload
Smoking	Electrolyte imbalance
Physical inactivity	Malnutrition
Menopause	Sleep disturbances
Family history of CVD	Endothelial dysfunction

LDL: Low density lipoprotein; HDL: High density lipoprotein; CVD: Cardiovascular disease.

Table 2 Baroreflex sensitivity in chronic kidney disease

Ref.	Number of patientsStudy design	Method of BRS assessment	Results
Pickering et al[65]	32 patients on HD serially studied	Intra-venous bolus of phenylephrine	BRS was found to be low
			HD improved reflex sensitivity over the long term, but did not have any consistent immediate effect
Lazarus et al[64]	13 patients on HD and 5 controls	Intra-venous angiotensin and inhaled amyl nitrite	BRS lower in patients than controls for both pressor and depressor stimuli
	Cross- sectional
Tomiyama et al[78]	22 non-dialysed patients and controls	Intra-venous bolus of phenylephrine and inhaled amyl nitrite	Lower BRS in patients as compared to controls
Agarwal et al[62]	Cross- sectional	Intra-venous bolus of phenylephrine	Lower BRS in patients
	25 non-dialyzed patients and 8 controls		8 patients restudied after HD, BRS lower in hypotension-prone vs normotensive group
	8 patients reassessed after 6.6 +/- 1.0 wk of hemodialysis		12 patients restudied after RT, BRS improved
	12 patients were restudied 24 +/- 4.0 wk after renal transplantation
Gerhardt et al[67]	20 patients of HD, RT and controls each	Sequence analysis	Reduced BRS in CKD vs Controls
	Cross-sectional		Similar BRS in RT and controls
Gao et al[79]	17 ESRD patients and 29 controls	Sequence analysis	BRS was 62% lower in ESRD than controls
	Cross-sectional
Johansson et al[80]	216 hypertensive CKD patients with 43 age-matched controls	Spontaneous method	BRS was reduced by 51% in CKD patients as compared with controls
			Greater reductions in BRS noted in diabetic vs non-diabetic patients
Chan et al[32]	10 hypertensive ESRD patients receiving conventional hemodialysis were studied before and 2 mo after conversion to nocturnal hemodialysis	Spontaneous method	Improvement in BRS by nocturnal HD as compared to conventional HD
	Assessed BRS along with total arterial compliance		Increases in BRS correlated with increases in total arterial compliance
Bavanandan et al[81]	105 non-dialysis CKD patients	Spontaneous method	Nondialysis dependent CKD patients have impaired BRS
	Baseline and follow-up of 42 mo		BRS is related to decreasing GFR
	Studied relationship with increasing degrees of uremia		A trend towards poorer prognosis in patients with impaired BRS
	Recorded primary (death, dialysis, transplantation) and secondary (fatal and nonfatal cardiovascular events) outcome measures
Studinger et al[33]	Juvenile study group with 14 HD patients, 14 RT and 14 controls	Pharmacological and spontaneous method	BRS was markedly reduced in HD as compared to controls
	BRS with HRV and carotid artery stiffness		Carotid artery stiffness was higher in HD than controls and was inversely related to BRS
			HRV was also compromised in HD, and was directly related to BRS
			No significant differences in any of these variables between RT and controls
			Decreased baroreflex function in juvenile HD is partly due to loss of carotid artery elasticity and partly due to impaired heart rate variability. Renal transplantation may partly prevent impairment or improve compromised baroreflex function in young patients with ESRD
Chesterton et al[31]	40 HD patients	Spontaneous method	Reduced BRS in HD patients
	Assessed BRS with arterial calcification and arterial stiffness indices		Reduced BRS is associated with increased vascular calcification and arterial stiffness
Lacy et al[82]	55 non-dialysis non-diabetic CKD patients	Spectral method	BRS reduced as renal disease severity increases Reduced GFR was correlated with increased PWV and decreased cardiac BRS
	BRS relationship with arterial stiffness and GFR
			Non-dialysis non-diabetic CKD patients with decreasing GFR have reduced cardiac BRS and increased large artery stiffness
Rubinger et al[35]	52 HD, 44 RT and 41 controls	Spontaneous method	In HD patients, BPV was increased, while HRV and BRS were markedly decreased as compared to controls
	16 patients before and after transplant		RT was associated with normalization of BPV at short term ( ≤ 1 yr) and long term and with improvement of HRV at a long-term (> 1 yr) follow-up. After RT baroreceptor indices were significantly increased and returned to values similar to those of the control
	BRS with HRV and BPV
Chesterton et al[77]	34 chronic HD	Spontaneous method	Impaired BRS predicts intra-dialytic hypotension
	Cross-sectional
	Relation with intra-dialytic hypotension
Kaur et al[34]	23 ESRD patients studied prospectively before and at 3 and 6 mo after RT	Spontaneous method	RT normalizes BRS in ESRD patients by 6 mo which follows the improvement in the central arterial stiffness
	BRS with central arterial stiffness and HRV and BPV

HD: Hemodialysis; RT: Renal transplantation; CKD: Chronic kidney disease; ESRD: End stage renal disease; GFR: Glomerular filtration rate; HRV: Heart rate variability; BPV: Blood pressure variability; BRS: Baroreflex sensitivity.