A Randomized, Double-Blind, Placebo-Controlled Trial of Spironolactone on Carotid Intima-Media Thickness in Nondiabetic Hemodialysis Patients

Abstract

Background and objectives: Hemodialysis patients (HD) display high rates of cardiac diseases and mortality. In chronic kidney disease, vascular injury leads to coronary artery disease, heart failure, and stroke. Carotid intima-media thickness (CIMT) measurements are currently widely used in randomized controlled trials (RCTs) to study the efficacy of interventions. An RCT was designed for the assessment of the safety and effectiveness of spironolactone to inhibit the progression of CIMT in HD patients as a primary outcome. Secondary outcomes included measurements of plasma potassium.

Design, setting, participants, & measurements: HD patients were randomly assigned to receive 50 mg spironolactone or placebo thrice weekly after dialysis. In between dialysis sessions, plasma potassium concentrations were measured every month. Ultrasonographic measurements of CIMT were done at the beginning of the study and after 2 years.

Results: Fifty-three age- and sex-adjusted patients (30 with drug and 23 with placebo) successfully completed the trial. There were no significant differences between the two groups in all profiles studied at baseline. Measurements of CIMT after 2 years showed a progression in the placebo group, whereas in the spironolactone group a significant decrease or even reversed CIMT was observed. Progression rates (mm/yr) were: common carotid, placebo: 0.06 ± 0.07, spironolactone: 0.01 ± 0.04; carotid bifurcation, placebo: 0.15 ± 0.27, spironolactone: 0.0001 ± 0.01; internal carotid, placebo: 0.10 ± 0.12, spironolactone: −0.10 ± 0.15. No episodes of hyperkalemia were observed, but a slight increase in plasma potassium was found in the spironolactone group.

Conclusions: Fifty milligrams of spironolactone thrice weekly significantly reduced the progression of CIMT in HD patients.

Cardiovascular complications are the main cause of mortality in patients with ESRD (chronic kidney disease [CKD]). Dialyzed patients have a 10% to 20% higher risk of death compared with the general population (1–3). To date, the major effect in delaying the progression of CKD has been provided by the use of renin-angiotensin system (RAS) blockers. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have significantly reduced urinary protein excretion by 20% to 30% (4,5). In humans, RAS blockade results in “aldosterone escape,” an initial decrease in aldosterone levels followed by a subsequent increase despite continued treatment with ACEI or ARB therapy (6). Recent studies have added mineralocorticoid antagonist to angiotensin-blockers to reduce the progression of ESRD (7–9).

Evidence indicates that there is an increased incidence and accelerated worsening of atherosclerosis in patients on chronic hemodialysis (HD) (2). Among noninvasive diagnostic methods for atherosclerosis, ultrasonography of the carotid artery is useful for measuring intima-media thickness (IMT). Over the past years, many trials have been performed in which carotid intima-media thickness (CIMT) was used as an alternative end point for cardiovascular morbidity and mortality in the study of the efficacy of certain interventions (10–13). Increased CIMT is considered as an early phase of atherosclerosis and might be seen even in patients with mild hypertension and normal serum cholesterol. The European Society of Cardiology Guidelines suggested that IMT measurement can add incremental information to traditional risk factor assessment. Recent studies have shown increased IMT and arteriosclerosis as a contributing factor to mortality in CKD (14–17).

In the study presented here, we have evaluated the effects of spironolactone on the progression of CIMT as an indicator of atherosclerosis in HD patients. We selected nondiabetic HD patients without ACEI or ARB therapy to establish the direct participation of the mineralocorticoid receptor (MR).

The specific objectives of this placebo-controlled randomized clinical trial were to

1. Investigate the progression of IMT in HD patients and the potential protective action of spironolactone treatment for 2 years (50 mg thrice weekly, after dialysis).

2. Compare the chronic effects of spironolactone versus placebo on plasma potassium handling in HD patients.

Materials and Methods

Patient Population

The study was conducted in ESRD patients on HD treatment 3 times a week. Inclusion criteria were ESRD patients with at least 18 months on HD without residual renal function. Patients with any of the following diagnoses were excluded: diabetes mellitus; severe valvulopathy; cirrhosis and liver disease; cancer; poor diet adherence; serum potassium values ≥6 mEq/L; and patients on current spironolactone, β-agonists, β-blockers, insulin, ACEIs and ARB therapy. All other cardiovascular medications remained unchanged during the study. The local ethics research committee approved the study, and 66 patients provided written informed consent before enrollment. Subjects were randomized (double blind) to receive spironolactone or placebo for 24 months. They received a single dose of 50 mg spironolactone or placebo thrice weekly after dialysis.

Study Protocol

Patients underwent baseline carotid ultrasound for assessment of CIMT of the common carotid artery (CCA), carotid bifurcation (BIF), and internal carotid artery (ICA) with high-resolution B-mode ultrasonography. Carotid ultrasonography was repeated after 24 months. Blood samples were also collected for measurement of biochemical parameters, including hematocrit, parathyroid hormone (PTH), aldosterone, creatinine, liver function tests, lipid profile, and plasma glucose. Plasma potassium was measured every month and weekly during the first 2 months. All studies were performed the day after the mid-week HD. Pre- and postdialysis blood pressure (BP) was registered monthly. BP was measured with the patient in a sitting position for 5 minutes with the cuff selected for appropriate width (cuff bladder encircling ≥80% of the arm) on the non-HD fistula arm. Hypertension was diagnosed if the mean of three measurements of systolic BP was ≥140 mmHg and/or diastolic BP was ≥90 mmHg before or after HD.

CIMT

Carotid ultrasound studies were performed by a single operator, blinded to treatment group, at baseline and after 24 months. Measurements were made after the mid-week dialysis. Ultrasonography of the right and left CCA, BIF, and ICA were performed with a 4- to 7-MHz or 5- to 12-MHz linear-array transducer (ALT HDI 3000). On a longitudinal, two-dimensional ultrasound image of the artery, the anterior (near) and posterior (far) walls of the artery were displayed as two bright white lines separated by a hypoechogenic space. CIMT was defined as the distance between the leading edge of the first bright line and the leading edge of the second bright line. Careful search was performed for all interfaces of the near and far walls of the right and left CCA, BIF, and ICA. Measurements were taken over a 10-mm length. When an optimal longitudinal image was visualized, three longitudinal B-mode images at end diastole (onset of the R wave in the electrocardiogram) were recorded and printed in laser films and stored for subsequent processing and analysis. BIF was defined as the segment of the artery between the CCA and the tip of the flow divider. The ICA was defined as the segment of the artery after the tip of the flow divider between the ICA and the CCA. When an atherosclerotic plaque was present at the measurement site, it was included in the measurement of the CIMT. Plaques (defined as a protrusion into the lumen adding 50% to the thickness of the surrounding intima-media or maximal thickness of 1.5 mm in the BIF or along the carotid arterial tree) were documented. All ultrasonic examinations were printed in laser films and stored for subsequent processing and analysis by two separate physicians blinded to patient profile. CCA, BIF, and ICA were determined as the mean of the three maximum IMT measurements of the near and far walls, on the right- and left-side arteries. The difference between first and second blind measurements varied between 0.03 and 0.06 mm.

Statistical Analyses

Results are presented as mean ± SD for continuous variables and as percentages for categorical data. Differences in continuous variables between baseline and end of the study results were assessed using Wilcoxon signed-rank test and paired t test. Categorical variables were compared using Fisher exact test and logistic regression. Analyses of continuous variables between treatment groups were assessed using two-sample Wilcoxon rank-sum (Mann–Whitney) unpaired test and a t test for change by treatment group. Analysis of serum potassium evolution was assessed using a generalized estimating equation (GEE) population-averaged model.

P < 0.05 was considered to be statistically significant and all reported P values are two-sided. Statistical analysis was performed with STATA and Microsoft Office Excel 2007 software.

Results

Patients Characteristics

A total of 66 patients were screened for study participation according to the established protocol. However, at the end of the study, 53 patients took the assigned treatment for the 24-month follow-up: 30 with spironolactone and 23 with placebo. The main reasons for withdrawal are included in Figure 1. Fourteen patients were smokers in the spironolactone group; five patients were smokers in the placebo group. Three patients from each group had a positive family history of cardiovascular disease (CVD).

Figure 1.

Trial profile. The reason for patients withdrew is given in the frame boxes.

Baseline characteristics were similar in both groups that completed the study with respect to age, gender distribution, statin therapy, presence of cardiovascular risk factors, etc. (Table 1).

Table 1.

Patient characteristics at baseline

Characteristic	Placebo Group (n = 23)	Spironolactone Group (n = 30)
Age, years	55.6 ± 3.6	60.1 ± 5.2
Gender, n (%)
male	14 (61)	20 (66.7)
female	9 (39)	10 (33.3)
Time since ESRD diagnosis, years	10.3 ± 1.5	8.5 ± 1.5
Time in hemodialysis treatment, years	8.8 ± 1.2	7.9 ± 1.3
History of stroke, n (%)	2 (8.7)	3 (10)
ESRD cause, n (%)
hypertension	13 (56.5)	18 (60)
unknown	4 (17.4)	5 (16.7)
glomerulopathy	4 (17.4)	3 (10)
vesical urethral reflux	2 (8.7)	1 (3.3)
others	0 (0)	3 (10)
BP, mmHg
systolic	149.6 ± 4.8	149.3 ± 5
diastolic	84.3 ± 3.2	83 ± 3
Heart rate, beats/min	78.4 ± 2.3	77.7 ± 1.8
NYHA class, n (%)
I	20 (87)	21 (70)
II	2 (8.7)	6 (20)
III	1 (4.3)	3 (10)
IV	0 (0)	0 (0)
Left ventricular ejection fraction, %	62.5 ± 1.3	61.9 ± 1.5
Medications, n (%)
loop diuretics	1 (4.3)	1 (3.3)
calcium channel blockers	10 (43.5)	11 (36.7)
digitalis	0 (0)	1 (3.3)
aspirin	9 (39)	10 (33.3)
statins	1 (4.3)	1 (3.3)
nitrates	1 (4.3)	1 (3.3)
calcium	20 (87)	20 (66.7)
amiodarone	0 (0)	2 (6.7)
erythropoietin	5 (21.7)	6 (20)

BP and heart rate were measured before dialysis. Plasma potassium concentration was measured immediately before mid- week dialysis. NYHA, New York Heart Association. Mean ± SD.

Safety and Tolerability

None of the ESRD patients studied presented cardiovascular morbidity or mortality during the 24 months of follow-up. Study termination as a result of drug-related side effects was not reported. None of the HD patients treated with spironolactone or placebo presented hyperkalemic events during the 24 months of study. Two patients experienced slight breast tenderness.

After 2 years of follow-up, there were no statistical significant changes in hematocrit, serum phosphorous, calcium, and PTH, but there was an increase of alkaline phosphatase in the placebo group after 24 months (Table 2). Aldosterone plasma levels were elevated (>22 ng/dl) in half of all patients, with a similar distribution among groups (placebo 48% and spironolactone 49%).

Table 2.

Blood parameters at baseline in spironolactone and placebo groups

	Placebo	Spironolactone
Hematocrit (%)	31.3 ± 5.7	29.7 ± 6.1
Potassium (mEq/L)	4.71 ± 0.74	4.7 ± 0.87
Phosphate (mg/dl)	5.7 ± 2.0	5.3 ± 1.5
Calcium (mg/dl)	9.0 ± 1.0	9.2 ± 0.9
Alkaline phosphatase (IU/L)	235 ± 213.0	235 ± 166
Aspartate aminotransferase (IU/L)	15.1 ± 8.0	16.4 ± 6.7
Alanine aminotransferase (IU/L)	16.5 ± 11.2	18.4 ± 9.9
PTH (pg/ml)	635.5 ± 598.1	598.6 ± 798.4
Ca×P	51.57 ± 17.3	48.91 ± 13.9
Total cholesterol	174.2 ± 42.5	180.4 ± 31.6
Triglycerides	227.2 ± 173.4	178.3 ± 90.0
HDL cholesterol	37.1 ± 9.4	41.7 ± 13.9
Plasma glucose	101.4 ± 36.8	95.5 ± 20.8

No statistical significant differences were observed between groups. Values presented as mean ± SD.

BP

Pre- and postdialysis BP was measured monthly during the 24 months of treatment. Spironolactone treatment did not significantly change BP. Predialysis BP values were 149.3 ± 26.7/ 83 ± 16.4 mmHg at baseline and 147.6 ± 19.6/78.6 ± 13.1 at 24 months. Placebo predialysis BP values were 149.6 ± 22/84.3 ± 14.6 mmHg at baseline and 144.7 ± 19.0/80.3 ± 11.2 at 24 months.

CIMT Values

Baseline CIMT values were similar in spironolactone and placebo groups, with no statistical significant differences between the two groups, except for the left ICA in male patients and right CCA in female patients (in both cases the values were higher in the spironolactone than in the placebo patients). When the mean CIMT values at the beginning of the study were compared by sex, it was found that men had a significantly higher CIMT than female patients in all of the segments studied. In Table 3, baseline values are included for both groups as well as the results after 24 months of treatment. As shown in Table 3, a progression of carotid thickness was observed in the placebo group in all of the segments, whereas in spironolactone-patients no such tendency was seen. Changes from baseline in CIMT between spironolactone and placebo groups after 2 years of treatment are shown in Table 4. As shown in the table, significant differences were observed between both groups: Although placebo patients showed a significant progression in CIMT in all carotid segments after 24 months (P < 0.02), spironolactone-treated patients had minor CIMT increments and even in some segments a regression was observed. Calculated CIMT progression rate for left + right segments in the placebo group were 0.06 ± 0.07 mm/yr in CCA, 0.15 ± 0.27 mm/yr in the BIF, and 0.10 ± 0.12 mm/yr in the ICA, versus 0.01 ± 0.04 mm/yr in the CCA, 0.00 ± 0.00 mm/yr in the BIF and −0.10 ± −0.15 mm/yr in the ICA in the spironolactone group (P < 0.003; P < 0.02; P < 0.00001, respectively). Figure 2 includes the box plot for separated right and left segments, together with the power of the differences.

Table 3.

CIMT according to treatment with spironolactone versus placebo: 2 years of follow-up

		Placebo Group		Spironolactone Group
		Baseline	24 Months	Baseline	24 Months
Right CCA (mm)	Total	0.74 ± 0.26	0.86 ± 0.31a	0.81 ± 0.26	0.870 ± 0.30
	Male	0.84 ± 0.28	0.92 ± 0.28	0.84 ± 0.31	0.87 ± 0.36
	Female	0.60 ± 0.16	0.77 ± 0.33a	0.76 ± 0.12	0.76 ± 0.12
Right ICA (mm)	Total	0.59 ± 0.17	0.75 ± 0.23a	0.72 ± 0.31	0.72 ± 0.31
	Male	0.62 ± 0.18	0.79 ± 0.24a	0.76 ± 0.37	0.76 ± 0.37
	Female	0.53 ± 0.17	0.69 ± 0.21a	0.65 ± 0.15	0.65 ± 0.15
Right BIF (mm)	Total	1.09 ± 0.99	1.36 ± 1.02	1.12 ± 0.67	1.12 ± 0.67
	Male	1.39 ± 1.17	1.64 ± 1.20	1.22 ± 0.76	1.22 ± 0.76
	Female	0.63 ± 0.26	0.92 ± 0.42	0.93 ± 0.43	0.93 ± 0.43
Left CCA (mm)	Total	0.79 ± 0.37	0.90 ± 0.44a	0.91 ± 0.41	0.91 ± 0.41
	Male	0.86 ± 0.46	1.01 ± 0.54a	1.04 ± 0.45	1.03 ± 0.45
	Female	0.69 ± 0.11	0.72 ± 0.12	0.67 ± 0.11	0.67 ± 0.10
Left ICA (mm)	Total	0.57 ± 0.19	0.82 ± 0.45a	1.15 ± 0.81	0.84 ± 0.49a
	Male	0.61 ± 0.23	0.91 ± 0.55a	1.31 ± 0.87	0.84 ± 0.47a
	Female	0.52 ± 0.13	0.68 ± 0.17a	0.82 ± 0.57	0.82 ± 0.57
Left BIF (mm)	Total	0.84 ± 0.49	1.16 ± 0.68a	1.18 ± 0.83	1.18 ± 0.83
	Male	0.96 ± 0.52	1.28 ± 0.78a	1.31 ± 0.87	1.31 ± 0.87
	Female	0.64 ± 0.40	0.99 ± 0.48a	0.92 ± 0.72	0.93 ± 0.71

CIMT (mm) expressed as mean ± SD.

^aP < 0.05, calculated using Wilcoxon signed-rank test for median values.

Table 4.

Changes (Δ) from baseline in CIMT in placebo and spironolactone groups after 2 years of treatment

		ΔIMT Placebo Group	ΔIMT Spironolactone Group	Pbetween Groups
Right CCA (mm)	Total	0.1174 ± 0.22	0.0237 ± 0.13	0.002
	Male	0.0857 ± 0.21	0.0350 ± 0.15	0.04
	Female	0.1667 ± 0.23	0.0010 ± 0.00	0.02
Right ICA (mm)	Total	0.1636 ± 0.17	0.0007 ± 0.00	<0.0001
	Male	0.1692 ± 0.16	0.0005 ± 0.00	<0.0001
	Female	0.1556 ± 0.19	0.0010 ± 0.00	0.02
Right BIF (mm)	Total	0.2609 ± 0.82	0.0007 ± 0.00	0.02
	Male	0.2429 ± 1.01	0.0005 ± 0.00	NS
	Female	0.2889 ± 0.44	0.0010 ± 0.00	0.03
Left CCA (mm)	Total	0.1087 ± 0.18	0.0000 ± 0.00	0.001
	Male	0.1571 ± 0.21	−0.0005 ± 0.00	0.0005
	Female	0.0333 ± 0.09	0.0010 ± 0.00	NS
Left ICA (mm)	Total	0.2435 ± 0.42	−0.3097 ± 0.56	<0.0001
	Male	0.3000 ± 0.51	−0.4650 ± 0.63	0.0001
	Female	0.1556 ± 0.21	0.0010 ± 0.00	0.007
Left BIF (mm)	Total	0.3261 ± 0.41	0.0037 ± 0.02	<0.0001
	Male	0.3143 ± 0.50	0.0005 ± 0.00	0.01
	Female	0.3444 ± 0.26	0.0100 ± 0.03	NS

Changes in CIMT (mm) are expressed as mean ± SD. NS, not statistically significant.

Figure 2.

Progression rate in CIMT (mm) after 2 years of follow-up in HD patients. Analysis with t test for Δ by treatment group: (a) placebo, (b) spironolactone. A, right CCA (P < 0.03, power 0.56); B, right ICA (P < 0.0001, power 0.99); C, right BIF (P < 0.0001, power 0.92); D, left CCA (P < 0.0001, power 0.99); E, left ICA (P < 0.04, power 0.45); F, left BIF (P < 0.0001, power 0.98). The graph box plot represents median, interquartile range, and outer layer thickness.

Plasma Potassium Values

Plasma potassium values (measured every month during the 2-year period) are included in Figure 3. No significant differences were observed between the two groups, except for months 23 and 24. In the final analysis, using the GEE population-averaged model, it was observed that patients under spironolactone treatment had a tendency to increase their plasma potassium concentration by 0.012 mEq/L per month during treatment (P < 0.001), whereas such a trend was not observed in the placebo group.

Figure 3.

Plasma potassium values in each month during 24 months for patients with spironolactone (closed circles) or placebo (open circles). Values expressed as mean ± SD. *P < 0.05. Insert: GEE population-averaged model predicts a monthly increase in plasma potassium concentration of 0.018 mEq/L with spironolactone treatment.

Discussion

This study shows that spironolactone prevents the progression of carotid CIMT in HD patients. The protective effect of spironolactone was observed in the absence of RAS inhibitors. Atherosclerosis is accepted as a common mechanism underlying all CVDs and atherosclerotic CVD is a significant cause of morbidity and mortality in patients with ESRD (1–3). Prospective studies have shown an association between increased CIMT and the incidence of CVDs (16–18). In fact, CIMT is a well described surrogated marker for cardiovascular risk (10–14). A thickened CIMT correlates with the presence of myocardial infarction and stroke by cross-sectional analysis (13). In some countries, recommendations already suggest that carefully performed IMT measurement can add incremental information to traditional risk factor assessment (European Society of Cardiology Guidelines). The main advantage of using CIMT as an end point in a trial concerning morbidity and mortality is the considerable reduction in sample size and possibly shorter duration of follow-up. This is because CIMT reflects not only early atherosclerosis, but also nonatherosclerotic compensatory enlargement with largely medial hypertrophy as a result of smooth muscle cell hyperplasia and fibrocellular hypertrophy, secondary to hypertension and volume overload, two situations that are important and common in ESRD patients (14–17).

The reason for the rapid clinical progression of CVD in HD patients is not entirely understood (15). Several studies have focused on different strategies for slowing the progression of CKD, with special emphasis on controlling proteinuria. Aldosterone has been implicated as a key mediator of progressive cardiovascular and renal disease (18–20). As summarized in two recent meta-analyses, the addition spironolactone to ACEIs and/or ARBs reduces proteinuria in CKD (8,9). However, the beneficial cardiovascular effects of spironolactone have not been fully assessed in renal disease. In the study presented here, we have evaluated the direct effect of MR blockade in the progression of CIMT. Our purpose was to define the potential benefits and risks of spironolactone in treating HD patients in the absence of RAS blockers. To our knowledge, our findings are the first demonstration that spironolactone alone has an effect in vascular remodeling in humans. The data presented here are in agreement with previous experimental studies that have shown that MR blockade markedly reduced cardiac and renal damage in rats infused with high levels of angiotensin II (21).

CIMT measurements were done in 30 patients on HD at baseline and after 2 years; spironolactone treatment was maintained without RAS blockers. The results demonstrate that spironolactone significantly reduced the progression of CIMT and even reversed carotid thickness in some segments, indicative of a role of aldosterone in arterial atherosclerosis. We have compared each patient at baseline and after 24 months, and analysis was carried out separately for men, women, and for the whole group of patients with spironolactone or placebo.

Age and sex are two IMT independent variables to be considered in any study. As shown in the results, gender differences were observed: Men presented higher CIMT than women—a result that is consistent with a previous report (22), although the number of patients in our study is relatively small to obtain a definitive conclusion. We also observed that baseline IMT in all HD patients was higher than our normal population according to the Carmela Study, in which the mean normal value is defined as 0.70 mm in the male population and 0.68 mm in the female population between 55 and 64 years old (23). Therefore, our results confirm that atherosclerosis is accelerated in HD patients (24–26).

Several interventional approaches to reduce cardiovascular risk factors with RAS blockers, calcium antagonists, or β-blockers can result in a reduction in progression or even net regression of CIMT (2,3). The most potent agents to date are the statins, which have consistently shown effects on CIMT in nondiabetic patients with hypercholesterolemia and/or atherosclerotic disease (27). Differences in the concomitant use of statins are unlikely to account for the differences observed because only one patient in each group was on stable statin therapy. Here, we show that blocking MR has a direct effect on vascular remodeling and that the effect was independent of BP because 50 mg of spironolactone had no effect. Confirming our data, a recent study has shown that spironolactone improves the hypertensive vascular hypertrophy and remodeling in angiotensin-II-overproducing transgenic mice (28).

Changes in total cholesterol, LDL- and HDL-cholesterol, triglycerides, and serum concentrations of these lipids at study end did not differ significantly in either treatment group. Multivariate regression analyses were performed for lipid profile, Ca×P product, intact PTH, hematocrit, albumin, smoking, hypertension, and left ventricular hypertrophy recorded at baseline. These variables were not related with the presence and number of carotid plaques (data not shown).

To date, the major effect in delaying the progression of CKD has been provided by the use of RAS blockers (7–10). However, RAS blockade has demonstrated to be associated with hyperkalemia, particularly in the common clinical setting of reduced renal function (29–31). Previous studies from our group with a similar protocol have shown the effectiveness of the protocol used in the study presented here. In fact, measurements of genomic epithelial sodium channel expression in lymphocytes were returned to normal levels with the use of spironolactone (32). In the study presented here, we performed monthly plasma potassium analysis and we have not observed hyperkalemic episodes during the 2 years of spironolactone treatment. Nevertheless, it should be taken in account that peculiar situations such as dehydration, dietary incompliance, hyperglycemia, etc., may result in the possibility of hyperkalemia. Interestingly, using the GEE population-averaged model to further evaluate the effect of MR inhibition on plasma potassium levels, it was found that patients under spironolactone treatment had a slight tendency to increase the plasma potassium concentration 0.0118 mEq/L for every month of active treatment (P < 0.001). Although this increment is statistically significant, the potassium handling levels of the spironolactone group was in the safe range during the 2 years. The protocol presented here could be useful in selected HD patients (33,34).

In summary, our results demonstrate that spironolactone reduces the progression of CIMT, opening new perspectives in the challenge of preventing CVD in ESRD patients.

Disclosures

None.