Restoration of baroreflex function in patients with end-stage renal disease after renal transplantation
04 Dec 2008-Nephrology Dialysis Transplantation (Oxford University Press)-Vol. 24, Iss: 4, pp 1305-1313
TL;DR: The data show that renal transplantation improves blood pressure and HRV and restores baroreflex function to near normal range on the long-term follow-up and these effects may contribute to the improvement of blood pressure control and survival after successful transplantation.
Abstract: Background. Renal transplantation improves the uraemic autonomic dysfunction and heart rate variability (HRV). The effects of successful transplantation on blood pressure variability (BPV) and baroreflex function are not well defined. Methods. BPV, HRV and baroreceptor indices were determined in (1) 52 non-diabetic chronic haemodialysis patients, (2) 44 transplanted patients, 24 in the first year after renal transplantation (≤I year) and 20 at least 1 year (>1 year) after renal transplantation, and (3) 41 control individuals with normal renal function, age-matched to (1) and (2). Power spectrum analysis of interbeat intervals (IBI) and systolic blood pressure (SBP) was performed in the low-frequency (LF 0.04-0.15 Hz) and the high-frequency (HF 0.15-0.40 Hz) bands. Spontaneous baroreceptor sensitivity (BRS) was determined by the sequence (slope) and spectral (a coefficient) techniques. Results. In haemodialysis patients, BPV was increased, while HRV, BRS slope and LF a and HF a coefficients were markedly decreased as compared to control individuals. Renal transplantation was associated with normalization of BPV at short term (≤1 year) and long term and with improvement of HRV at a long-term (> 1 year) follow-up. In patients with long-standing functioning grafts (>1 year), baroreceptor indices were significantly increased and returned to values similar to those of the control subjects. Conclusions. Our data show that renal transplantation improves blood pressure and HRV and restores baroreflex function to near normal range on the long-term follow-up. These effects may contribute to the improvement of blood pressure control and survival after successful transplantation.
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TL;DR: The risk of cardiovascular disease in patients with chronic renal disease appears to be far greater than in the general population as mentioned in this paper, even after stratification by age, gender, race, and the presence or absence of diabetes.
1,165 citations
TL;DR: IgAN emerged as an independent predictor of worse graft outcome in the long-term in renal transplanted patients with IgA nephropathy and recurrence of IgAN seems to progressively reduce in transplants performed from 1981 to 2010.
Abstract: Background Few data are available on allograft survival at 15 years, the impact and the predictors of recurrence of the original disease in renal transplanted patients with IgA nephropathy (IgAN). Methods In this retrospective study, we compared the long-term outcome of renal transplant in 190 patients with IgAN with that of 380 non-diabetic controls and evaluated the impact of recurrence of IgAN on the graft outcome. Results At 15 years, the patient survival was 88.3% in IgAN patients and 82.6% in controls (P = 0.12), while the death-censored graft survival was 62.6 and 72.4%, respectively (P = 0.038). IgAN had a higher cumulative incidence of graft failures in comparison with controls even considering death as a competing risk (P = 0.025). At multivariate analysis, IgAN [relative risk (RR) = 1.468, P = 0.026], delayed graft function recovery (RR = 2.394, P = 0.000) and acute rejection (RR = 2.51, P = 0.000) were predictive of graft loss. IgAN recurred in 42 grafts (22.1%), of them, 12 were lost for recurrence and in another 6 recurrence was considered a concomitant cause of graft loss. The 15-year death censored graft survival was 68.3% in non-recurrent and 51.2% in recurrent patients (P = 0.069). Pure graft survival of non-recurrent IgAN patients was similar to that of controls (P = 0.406). At Cox analysis, the recurrence of IgAN significantly reduced from 1981 to 2010 (P = 0.0065, RR = 0.936). Conclusions IgAN emerged as an independent predictor of worse graft outcome in the long-term. Recurrence of IgAN seems to progressively reduce in transplants performed from 1981 to 2010.
88 citations
Cites background or result from "Restoration of baroreflex function ..."
...Significant improvement in baroreflex function was found in the RT patients with a well-functioning kidney for at least 1 year [6]....
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...On the other hand, although improvement in parasympathetic activity has been reported after RT [1], parasympathetic dysfunction was found to be common >1 year after RT [6, 13]....
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...Moreover, normalization of baroreflex indices was observed in their RT recipients only after partial correction of HRV alterations [6], which is in agreement with our results....
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...However, at a relatively early stage (1–3 months after RT), all autonomous nervous system (ANS) parameters were found to be similar to pre-RT levels [8, 9], while improvements were reported from 6 to 24 months after RT [1, 5, 6, 9, 10]....
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...Several studies have shown an improvement in baroreflex function following RT [1, 4, 6, 31]....
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TL;DR: Optization of HD treatment, pharmacological interventions, and renal sympathetic denervation are several approaches targeting sympathetic overactivity to improve cardiovascular morbidity and mortality in HD patients.
Abstract: Adequate sympathetic nervous system activation is essential for the compensatory mechanisms of blood pressure maintenance during the hemodialysis (HD) procedure. Chronic sympathetic nervous system overactivity, however, may lead to the development of hypertension and cardiovascular disease in HD patients. The present review focuses on recent findings on the sympathetic nervous system activity in these patients. Sympathetic overactivity has been demonstrated directly by muscle sympathetic nerve activity recordings (MSNA) in chronic renal disease, but only rarely in HD patients. In the latter, sympathetic activity has mostly been assessed using indirect methodology. Decreased heart rate variability, increased blood pressure variability (BPV), and suppressed baroreflex function are believed to represent chronic sympathetic overactivity in HD patients. The HD procedure and ultrafiltration are associated with enhanced sympathetic activity and baroreflex activation. During most episodes of intradialytic hypotension, the baroreflex is adequately activated; sympathetic withdrawal with bradycardia, however, has been reported during excessive hypovolemia. Sympathetic overactivity is also believed to be a mechanism associated with intradialytic hypertensive episodes and refractory hypertension. While successful renal transplantation is associated with improvement of heart rate variability (HRV), improvement and restoration of baroreflex function, persistent sympathetic overactivity has been documented in transplanted patients using MSNA recordings. Decreased HRV and baroreflex function have been reported to be associated with increased mortality and morbidity in HD patients. The predictive value of sympathetic outflow assessed by MSNA has yet to be determined. Optimization of HD treatment, pharmacological interventions, and renal sympathetic denervation are several approaches targeting sympathetic overactivity to improve cardiovascular morbidity and mortality.
80 citations
Cites background or methods or result from "Restoration of baroreflex function ..."
...A key finding in this study was the restoration of baroreflex function in transplanted patients at long-term follow-up, noted after at least partial correction of HRV (48)....
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...Furthermore, reversal of HRV alterations and improvement of baroreceptor function, and also increased sympathetic MSNA activity (15,48), have been reported after successful renal transplantation....
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...In contrast to the decrease in HRV, BPV in both LF (LF SBP) and HF (HF SBP) bands is increased in HD patients; in these patients, there is also a significant decrease in baroreflex function (48)....
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...Even though the baseline baroreceptor function is lower in dialysis patients, especially in elderly (48) and in those with a history of hemodynamic instability (81), the above data do not support the premise that intradialytic hemodynamic instability and hypotension are caused mainly by TABLE 1....
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...In a longitudinal study (48), BPV, HRV, and baroreflex function were studied in 52 nondiabetic chronic HD patients and in 44 transplanted patients and compared with those of 41 control individuals with normal renal function....
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TL;DR: In this article, the role of current interventional and therapeutic strategies in ameliorating autonomic deficits associated with chronic renal dysfunction, and identifies gaps in our knowledge of neural mechanisms driving cardiovascular disease in CKD.
Abstract: Cardiovascular autonomic dysfunction is a major complication of chronic kidney disease (CKD), likely contributing to the high incidence of cardiovascular mortality in this patient population. In addition to adrenergic overdrive in affected individuals, clinical and experimental evidence now strongly indicates the presence of impaired reflex control of both sympathetic and parasympathetic outflow to the heart and vasculature. Although the principal underlying mechanisms are not completely understood, potential involvements of altered baroreceptor, cardiopulmonary, and chemoreceptor reflex function, along with factors including but not limited to increased renin–angiotensin–aldosterone system activity, activation of the renal afferents and cardiovascular structural remodeling have been suggested. This review therefore analyzes potential mechanisms underpinning autonomic imbalance in CKD, covers results accumulated thus far on cardiovascular autonomic function studies in clinical and experimental renal failure, discusses the role of current interventional and therapeutic strategies in ameliorating autonomic deficits associated with chronic renal dysfunction, and identifies gaps in our knowledge of neural mechanisms driving cardiovascular disease in CKD.
59 citations
TL;DR: The increased cardiorespiratory fitness by exercise training was associated with an improved BRS function and a modification of the sympathovagal control of HRV towards a persistent increase in parasympathetic tone, which may lead to a better cardiovascular prognosis in RT recipients.
Abstract: Background. There are conflicting data regarding the effects of renal transplantation (RT) on uraemic autonomic dysfunction. Moreover, no study has examined the impact of physical training on the cardiac autonomic function in RT patients. Thus, we studied the effects of exercise training on heart rate variability (HRV) and arterial baroreflex sensitivity (BRS), which are sensitive markers of cardiac autonomic outflow, in RT recipients. Methods. Eleven patients (Exercise group—aged 52.1 ± 5.6 years) were studied before and after 6 months of exercise training. Twelve age- and sex- matched RT patients (Sedentary) and 12 healthy sedentary individuals (Healthy), who remained untrained, served as controls. At baseline and follow-up, all the subjects underwent cardiopulmonary exercise testing for the evaluation of peak oxygen consumption (VO2peak), a tilt test for the evaluation of BRS and baroreflex effectiveness index (BEI) and an ambulatory 24-h Holter monitoring for time- and frequency-domain measures of HRV. Results. In the exercise group, VO2peak increased by 15.8% (P < 0.05) and all depressed HRVand BRS indices were significantly improved after training. Specifically, the standard deviation of all normal-to-normal (NN) intervals (SDNN) significantly increased by 92.5%, the rootmean-square of the differences between consecutive NN intervals by 45.4%, the percentage value of NN50 count by 58.2%, the high-frequency by 74.8% and lowfrequency spectral power by 41.6%, BRS by 43.7% and BEI by 57.3%. None of the variables studied was altered over time in either control group. Conclusions. The increased cardiorespiratory fitness by exercise training was associated with an improved BRS function and a modification of the sympathovagal control of HRV towards a persistent increase in parasympathetic tone. These alterations may lead to a better cardiovascular prognosis in RT recipients.
52 citations
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TL;DR: It is the opinion that rhythms and neural components always interact, just like flexor and extensor tones or excitatory and inhibitory cardiovascular reflexes, and that it is misleading to separately consider vagal and sympathetic modulations of heart rate.
Abstract: A consistent link appears to exist between predominance of vagal or sympathetic activity and predominance of HF or LF oscillations, respectively: RR variability contains both of these rhythms, and their relative powers appear to subserve a reciprocal relation like that commonly found in sympathovagal balance. In this respect, it is our opinion that rhythms and neural components always interact, just like flexor and extensor tones or excitatory and inhibitory cardiovascular reflexes, and that it is misleading to separately consider vagal and sympathetic modulations of heart rate. In humans and experimental animals, functional states likely to be accompanied by an increased sympathetic activity are characterized by a shift of the LF-HF balance in favor of the LF component; the opposite occurs during presumed increases in vagal activity. In addition, LF oscillation evaluated from SAP variability appears to be a convenient marker of the sympathetic modulation of vasomotor activity. Although based on indirect markers, the exploration in the frequency domain of cardiovascular neural regulation might disclose a unitary vision hard to reach through the assemblage of more specific but fragmented pieces of information.
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TL;DR: The ATRAMI study as discussed by the authors provides clinical evidence that after myocardial infarction the analysis of vagal reflexes has significant prognostic value independently of LVEF and ventricular arrhythmias and that it significantly adds to the prognosis value of heartrate variability.
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