Eugenia Espinel

Continuous positive airway pressure treatment in sleep apnea patients with resistant hypertension: a randomized, controlled trial.

Objectives This controlled trial assessed the effect of continuous positive airway pressure (CPAP) on blood pressure (BP) in patients with obstructive sleep apnea (OSA) and resistant hypertension (RH). Methods We evaluated 96 patients with resistant hypertension, defined as clinic BP at least 140/90 mmHg despite treatment with at least three drugs at adequate doses, including a diuretic. Patients underwent a polysomnography and a 24-h ambulatory BP monitoring (ABPM). They were classified as consulting room or ABPM-confirmed resistant hypertension, according to 24-h BP lower or higher than 125/80 mmHg. Patients with an apnea-hypopnea index at least 15 events/h (n = 75) were randomized to receive either CPAP added to conventional treatment (n = 38) or conventional medical treatment alone (n = 37). ABPM was repeated at 3 months. The main outcome was the change in systolic and diastolic BP. Results Sixty-four patients completed the follow-up. Patients with ABPM-confirmed resistant hypertension treated with CPAP (n = 20), unlike those treated with conventional treatment (n = 21), showed a decrease in 24-h diastolic BP (−4.9 ± 6.4 vs. 0.1 ± 7.3 mmHg, P = 0.027). Patients who used CPAP > 5.8 h showed a greater reduction in daytime diastolic BP {−6.12 mmHg [confidence interval (CI) −1.45; −10.82], P = 0.004}, 24-h diastolic BP (−6.98 mmHg [CI −1.86; −12.1], P = 0.009) and 24-h systolic BP (−9.71 mmHg [CI −0.20; −19.22], P = 0.046). The number of patients with a dipping pattern significantly increased in the CPAP group (51.7% vs. 24.1%, P = 0.008). Conclusion In patients with resistant hypertension and OSA, CPAP treatment for 3 months achieves reductions in 24-h BP. This effect is seen in patients with ABPM-confirmed resistant hypertension who use CPAP more than 5.8 h.

A randomized controlled study of CPAP effect on plasma aldosterone concentration in patients with resistant hypertension and obstructive sleep apnea.

Objective: The high prevalence of obstructive sleep apnea in patients with resistant hypertension could be mediated by an activation of the renin-angiotensin-aldosterone system. This study assessed the impact of continuous positive airway pressure (CPAP) treatment on plasma aldosterone concentration (PAC). Methods: One hundred and twenty-four patients with resistant hypertension were assessed, and those who fulfilled inclusion criteria (n = 116) underwent full night polysomnography, 24-h ambulatory blood pressure monitoring, and PAC measurement. Patients with an apnea–hypopnea index above 15 (n = 102) were randomized to CPAP (n = 50) or to conventional treatment (n = 52) for 3 months. Results: Seventy-eight patients completed the follow-up (36 CPAP, 42 conventional treatment); 58 had true resistant hypertension (74.3%), whereas 20 had white-coat resistant hypertension (25.6%). Most patients were men (70.7%), age 58.3 ± 9.4 years, and the mean apnea–hypopnea index was 50.1 ± 21.6. In patients with true resistant hypertension, CPAP achieved a significant decrease in most 24-h BP measurements and a nonsignificant decrease in PAC (25 ± 8.7 vs. 22.7 ± 9 ng/dl; P < 0.182). In patients with white-coat resistant hypertension, CPAP achieved a significant decrease in PAC (26.1 ± 11.2 vs. 18.9 ± 10.1 ng/dl; P < 0.041) and in night-time DBP. After adjustment, a weak but significant association was found between cumulative time spent with SaO2 below 90% (CT90%) and baseline PAC (P < 0.047, R2 0.019), and between changes in PAC and changes in office DBP (P < 0.020, R2 0.083) Conclusions: Night-time hypoxemia and changes in DBP showed an association with baseline and changes in PAC, respectively. CPAP achieved a significant reduction in PAC only in patients with white-coat resistant hypertension, although the CPAP effect on BP was highest in patients with true resistant hypertension.

Angiotensin‐Converting Enzyme I/D Polymorphism in Patients With Malignant Hypertension

The angiotensin‐converting enzyme (ACE) gene has been implicated in the manifestation of the phenotype of malignant hypertension (MH). In 1990 the ACE gene polymorphism characterized by the insertion or deletion of a 287‐base pair fragment in the 17q23 chromosome was identified. The DD genotype is associated with increased tissue and circulating ACE levels and elevated angiotensin II. ACE polymorphism was studied in 48 patients with MH, 25 patients with non‐MH, and a control group of 78 normotensive individuals by real‐time polymerase chain reaction using the LightCycler system (Roche Diagnostics Corporation, Indianapolis, IN). The DD genotype was found statistically more frequently in MH patients than controls (p=0.028; odds ratio, 2.5; confidence interval, 1.1–5.5). Presence of the DD genotype of the ACE gene is more frequent in MH patients than in controls, indicating that this genotype could be a significant risk factor and a predictor for the development of MH.

Renal Biopsy in Type 2 Diabetic Patients

The majority of diabetic patients with renal involvement are not biopsied. Studies evaluating histological findings in renal biopsies performed in diabetic patients have shown that approximately one third of the cases will show pure diabetic nephropathy, one third a non-diabetic condition and another third will show diabetic nephropathy with a superimposed disease. Early diagnosis of treatable non-diabetic diseases in diabetic patients is important to ameliorate renal prognosis. The publication of the International Consensus Document for the classification of type 1 and type 2 diabetes has provided common criteria for the classification of diabetic nephropathy and its utility to stratify risk for renal failure has already been demonstrated in different retrospective studies. The availability of new drugs with the potential to modify the natural history of diabetic nephropathy has raised the question whether renal biopsies may allow a better design of clinical trials aimed to delay the progression of chronic kidney disease in diabetic patients.

Hypertension in chronic kidney disease: the influence of renal transplantation.

Background Hypertension is one of the most prevalent cardiovascular risk factors in chronic kidney disease (CKD) and kidney transplants. The contribution of transplantation to hypertension in comparison to patients with CKD and similar renal function has not been characterized. Methods Ninety-two transplants and 97 CKD patients with an estimated glomerular filtration rate less than 60 mL/min/1.73 m2 not receiving dialysis were enrolled. At entry, office blood pressure (BP) and 24-hr ambulatory blood pressure monitoring (ABPM) were obtained. Results Office BP was not different between transplants and CKD patients (139.5±14.3 vs. 135.2±19.3, P=1.00, respectively). ABPM 24-hr systolic blood pressure (SBP) (133.9±14.3 vs. 126.2±16.1, P=0.014), awake SBP (135.6±15.2 vs. 128.7±16.2, P=0.042), and sleep SBP (131.2±16.2 vs. 120.2 ±17.9, P=0.0014) were higher in renal transplants. When patients were classified according to BP patterns associated with highest cardiovascular risk, the proportion of patients with both nocturnal hypertension and non-dipper pattern was higher in transplants (68.5% vs. 47.4%, P=0.03). In the multivariate regression analysis, transplantation was an independent predictor of 24-hr, awake, and sleep SBP. Conclusion Office BP is similar in kidney transplants and CKD patients with similar renal function. On the contrary, hypertension is more severe in kidney transplants when evaluated with ABPM mainly as a result of increased sleep systolic BP. Thus, precise evaluation of hypertension in kidney transplants requires ABPM.

Inflammation and Atherosclerosis Are Associated With Hypertension in Kidney Transplant Recipients.

The aim of the current study was to evaluate risk factors associated with hypertension in kidney transplant recipients. The authors recruited 92 consecutive kidney transplant recipients and 30 age‐matched patients with chronic kidney disease without history of cardiovascular events. Twenty‐four–hour ambulatory blood pressure monitoring, pulse wave velocity, and carotid ultrasound were performed. Serum levels of log‐transformed interleukin 6 (Log IL‐6), soluble tumor necrosis factor receptor 2, and intercellular adhesion molecule 1 were determined. Twenty‐four–hour systolic blood pressure (SBP) (P=.0001), Log IL‐6 (P=.011), and total number of carotid plaques (P=.013) were higher, while the percentage decline of SBP from day to night was lower in kidney transplant recipients (P=.003). Independent predictors of 24‐hour SBP were urinary protein/creatinine ratio and circulating monocytes (P=.001), while Log IL‐6, serum creatinine, and total number of carotid plaques (P=.0001) were independent predictors of percentage decline of SBP from day to night. These results suggest that subclinical atherosclerosis and systemic inflammation are associated with hypertension after transplantation.

Microalbuminuria and the Combination of MRI Markers of Cerebral Small Vessel Disease

Background: Kidney function has been related to the presence of individual markers of cerebral small vessel disease (CSVD), as lacunes, white matter hyperintensities (WMH) or microbleeds. We aimed at studying the relationship of kidney dysfunction with the combination of several markers of CSVD. Methods: Subjects are those included in the ISSYS cohort (Investigating Silent Strokes in hypertensives: a magnetic resonance imaging study). A scale ranging from 0 to 4 points was applied based on the presence (one point each) of lacunes, deep microbleeds, moderate to extensive basal ganglia enlarged perivascular spaces (EPVS), and periventricular or deep WMH. We determined the creatinine-based glomerular filtration rate and the urinary albumin-to-creatinine ratio (UACR) as markers of kidney function and studied their association with the scale of CSVD in univariate and ordinal logistic regression analyses. Results: Among the 975 patients included, 28.2% presented one or more CSVD markers, being the most prevalent marker (either alone or in combination) basal ganglia EPVS. The UACR was elevated at increasing the scores of the CSVD scale and remained as independent predictor of the combination of markers (common OR per natural log unit increase in UACR: 1.23, 1.07-1.41) after controlling per age, gender, cardiovascular risk, antihypertensive treatment and hypertension duration. In contrast, no associations were found between the CSVD scores and the creatinine-based estimated glomerular filtration rate. Conclusions: A significant proportion of stroke-free hypertensives present at least one imaging marker of CSVD. UACR but not creatinine-based glomerular filtration rate is associated with the combination of markers of CSVD.

Múltiples quistes parapiélicos en la enfermedad de Fabry

Fabry disease is an inherited, X-linked lysosomal storage disorder caused by deficiency of the enzyme alpha galactosidase A (alpha-GLA A), which leads to glycosphingolipid accumulation, mainly globotriaosylceramide, in tissues. Disease prevalence and the index of suspicion are both low, which tends to result in delayed diagnosis and treatment. We present the case of a male Fabry disease patient who manifested no angiokeratoma lesions but presented multiple parapelvic cysts and renal failure. The genetic study revealed an alpha-GLA A gene mutation that had not been recorded in the mutations registry. The de novo mutation was not found in his relatives and it was not transmitted to his offspring. The large number and peculiar appearance of the parapelvic cysts led to the diagnosis.

[OP.1B.07] CAROTID ATHEROSCLEROSIS PROGRESSION AND REVERSE DIPPER PATTERN IN KIDNEY TRANSPLANTATION

Objective: Presence of subclinical atherosclerosis constitutes a risk factor for cardiovascular events. The aim is to describe the prevalence of subclinical carotid plaques in stable renal transplants and evaluate the variables associated with its progression. Design and method: Between June and September 2011, consecutive kidney transplants with an estimated glomerular filtration rate (e-GFR) <60 ml/min/1.73 m2 and without previous cardiovascular events were included. At entry, carotid ultrasound and 24 h ambulatory blood pressure monitoring (ABPM) were performed and a serum sample to determinate interleukin 6 (IL-6), soluble tumor necrosis factor receptor 2 (sTNFR2) and intercellular adhesion molecule 1 (ICAM-1) levels was obtained. At 18 months of follow up, carotid ultrasound was repeated. Results: A total of 100 kidney transplants were included. Demographic characteristics are summarized in table 1. Five patients were lost to follow up. In the basal and follow up carotid ultrasound there were 54% and 61% of patients showing at least one carotid plaque, respectively (p = 0.320). The number of carotid plaques increased during follow up in 27 out of 95 patients (28.4%). The mean number of carotid plaques per patient increased from 1.12 ± 1.44 to 1.43 ± 1.64 (p = 0.0001) and the progression of the number of carotid plaques was 0.2 ± 0.4 plaque/year. Recipient age (HR: 1.090, 95% CI: 1.009–1.177, p = 0.029) and reverse dipper pattern (HR: 5.757, 95%CI: 1.261–26.284, p = 0.024) were independent predictors of the presence of plaques at basal carotid ultrasound. Reverse dipper pattern (p = 0.003), 24 h SBP (p = 0.001) and basal IMT (p = 0.001) were independent predictors of progression of the number of carotid plaques at 18 months follow-up. Conclusions: Hypertension and reverse dipper pattern evaluated by ABPM are predictors of presence and progression of carotid plaques in kidney transplants recipients.