Nicolás Roberto Robles

Renin–Angiotensin System Blocking Drugs:

The two major classes of drugs that target the RAS are the angiotensin-converting enzyme (ACE) inhibitors and the selective AT1 receptor blockers (ARBs). Although both of these drug classes target angiotensin II, the differences in their mechanisms of action have implications for their effects on other pathways and receptors that may have therapeutic implications. Both ACEIs and ARBs are effective antihypertensive agents that have been shown to reduce the risk of cardiovascular and renal events. Direct inhibition of renin –the most proximal aspect of the RAS –became clinically feasible from 2007 with the introduction of aliskiren. This latter drug has been shown to be efficacious for the management of hypertension. Combined therapy of direct renin-inhibitors with ACEIs or ARBs has been tested in some clinical situations as congestive HF and proteinuria with diverse results. This article tries to offer an updated review of current knowledge on the use of RAS blocking drugs in clinical settings.

Microalbuminuria en pacientes diabéticos y en pacientes con hipertensión arterial: estudio de una cohorte de 979 pacientes

BACKGROUND AND OBJECTIVE: Microalbuminuria is a known complication of diabetes mellitus but it is also a cardiovascular risk factor commonly present among hypertensive (non diabetic) population. The prevalence of microalbuminuria is variable and it has been never estimated in our region. The aim of this study has been to determine the prevalence of microalbuminuria in hypertensive (non diabetic) and diabetic population in Extremadura (Spain). PATIENTS AND METHOD: The study included diabetic patients and non-diabetic hypertensive ones randomly selected. Microalbuminuria was measured in every patient using albumin/creatinin reactive stick in fasting first morning urine. Whenever possible microalbuminuria was confirmed in laboratory by microalbuminuria/creatinina coefficient in first morning urine samples. RESULTS: A total of 979 patients (mean age [SD], 67.9 [10.8] years; 409 men and 570 women, 505 diabetics) were studied. The presence of microalbuminuria was found in 12.4% of hypertensive patients and in 21.4% of diabetic patients (p < 0.001). Hypertensives and normotensive diabetics showed a similar prevalence of microalbuminuria (13.3%, not significant), but it tripled in hypertensive diabetics (33.8; p < 0.01). Glicemic control was not different for microalbuminuric diabetic patients and non microalbuminuric ones. The patients receiving rennin-angiotensin axis blocking drugs do not showed less prevalence of microalbuminuria (hypertensives 10.5%, diabetics 23.5%). Microalbuminuria was confirmed in 65.4% of patients. CONCLUSIONS: The prevalence of microalbuminuria in Extremadura seems to be high either in diabetics or non diabetic hypertensive patients. The finding of microalbuminuria in diabetics patients correlates with hypertension but do not with glicemic control. The prevalence of microalbuminuria is high in spite of using rennin-angiotensin axis blocking drugs.

Comparative Effects of Fosinopril and Irbesartan on Hematopoiesis in Essential Hypertensives

Objective. To compare the response of erythropoiesis to an angiotensin receptor blocker, irbesartan with an angiotensin conversing enzyme inhibitor, fosinopril, in essential hypertensive patients with normal renal function. Design and Methods. Thirty patients were randomized to receive either irbesartan (150 mg once daily) (n = 15, mean age 65.2 ± 8.7 years) or fosinopril (20 mg once daily) (n = 15, mean age 57.4 ± 11.5 years, difference is not significant) during 12 weeks. Plasma erythropoietin, hemoglobin (Hb) and hematocrit (Hc) levels were measured at start and monthly after receiving the treatment. All values are expressed as mean ± 1SD. Results. Irbesartan decreased erythropoietin levels (baseline 20.7 ± 1.3 vs. 18.1 ± 3.7 mU/mL, p = 0.019), but they remained unchanged with fosinopril (baseline 18.8 ± 1.3 vs. 18.6 ± 1.6 mU/mL). Hb levels lowered in irbesartan group (baseline 13.8 ± 1.2 vs. 13.5 ± 1.1 g/dL, p = 0.029), but they did not change in fosinopril‐treated patients (baseline 14.6 ± 1.3 vs. 14.5 ± 1.3 g/dL). Hc did not show any change neither in irbesartan group (baseline 40.9 ± 3.7 vs. 40.8 ± 3.3 %) nor in fosinopril group (baseline 14.6 ± 1.3 vs. 14.5 ± 1.3 %). Conclusions. Irbesartan lowered erythropoietin secretion and hemoglobin levels in essential hypertensives. Fosinopril can neither influence erythropoietin secretion nor decrease hemoglobin levels. Angiotensin receptor blockers seem to get higher efficacy for antagonism angiotensin effects. Safety of angiotensin receptor blockers in anemic hypertensive patients should be studied.

Non-Proteinuric Diabetic Nephropathy

Diabetic nephropathy patients traditionally show significant macroalbuminuria prior to the development of renal impairment. However, this clinical paradigm has recently been questioned. Epidemiological surveys confirm that chronic kidney disease (CKD) diagnosed by a low glomerular filtration rate (GFR) is more common in diabetic patients than in the non-diabetic population but a low number of patients had levels of proteinuria above that which traditionally defines overt diabetic nephropathy (>500 mg/g). The large number of patients with low levels of proteinuria suggests that the traditional clinical paradigm of overt diabetic nephropathy is changing since it does not seem to be the underlying renal lesion in most of diabetic subjects with CKD.

Cystatin c and blood pressure: Results of 24 h ambulatory blood pressure monitoring

BACKGROUND The relationship between kidney function and blood pressure (BP) components has been studied in chronic kidney disease patients. Whether cystatin C, a marker of kidney function, is associated in the normal range with systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) obtained using ambulatory blood pressure monitoring has not been previously studied. METHODS The sample subjects were 53 males and 34 females, mean age was 59.3+/-13.5 years. 76% were receiving antihypertensive drug treatment. Kidney function was evaluated by measuring serum cystatin C. Microalbuminuria was measured in a 24h urine collection. Glomerular filtration rate (GFR) was estimated using the abbreviated Modification of Diet in Renal Disease equations. The ambulatory BP was measured non-invasively for 24h by the Spacelab devices programmed to measure BP every 15 min during daytime and every 20 min during nighttime. RESULTS The highest quartile of cystatin C distribution showed an older age and worsel parameters of renal function (cystatin C, serum creatinine and GFR) than the other groups. No differences for gender or diabetes were found. 24h SBP and PP were higher in the fourth quartile compared to the fist one (p<0.01). 24h DBP was lower for the patients in the fourth quartile of cystatin C compared which any one of the other groups (p<0.001). The relationship between cystatin C, as well as GFR, with SBP and PP was statistically significant as renal function comes down. Contrariwise, as cystatin C increases DBP declines; but the correlation with GFR measured through MDRD 4 is not significant. In the same way, no correlation was found for GFR and microalbuminuria, but there was a statistically significant positive relationship between cystatin C and microalbuminuria severity (p<0.01). Multivariate regression analysis confirms these findings. CONCLUSIONS Both SBP and pulse pressure were significantly associated with kidney function. DBP was negatively correlated with cystatin C concentrations but not with GFR. Cystatin C shows a positive relationship with microalbuminura severity. Cystatin C might have cardiovascular effects beyond its use as a marker of the renal function.

Hematocrit, urea and gender: The Hematocrit, Urea and GEnder formula for prognosing progressive renal failure in diabetic nephropathy

OBJECTIVE Diabetic nephropathy is a common cause of end stage renal disease. Notwithstanding, wide inter-individual variations in the speed of progression of diabetic nephropathy are frequent. We have used the score of the HUGE formula to predict progression of kidney disease in a group of diabetic nephropathy patients. DESIGN AND METHODS The sample consisted of 84 type 2 diabetic patients. At treatment entry, the mean age was 62.1 ± 12.5 years and 59.5% were male. Blood pressure was measured at office at each visit. Serum creatinine, urea, hematocrit and 24h proteinuria were analyzed every 6 months. HUGE score was calculated from gender, urea and hematocrit. RESULTS Mean HUGE score was 0.99 ± 3.88. Using as cut off point 1.5, those patients who had a score equal or higher (n=31) showed a bigger increase in serum creatinine after one year (41.8 ± 62.1%) than those subjects with score<1.5 (n=53) (18.7 ± 38.6%, p=0.041). 5 patients with low HUGE score reached end stage renal failure (9.4%) and 10 patients in the high HUGE score group (32.3, p=0.008). When logistic regression analysis was performed only a HUGE score higher than 1.5 (p=0.003) and proteinuria higher than 2g/day (p=0.041) were independently associated to CRF progression (creatinine increment>25%). CONCLUSIONS In diabetic nephropathy patients the HUGE equation may be useful to detect the subjects prone to progressive renal failure. Wider samples will be needed to confirm this finding and, most important, its applicability to other kinds of nephropathy.

Symmetrical ambulatory arterial stiffness index: relationship with microalbuminuria and renal function.

OBJECTIVE The aim of this study was to investigate the arterial stiffness parameters derived from the proposed linear relationship between SBP and DBP obtained by ABPM, regarding its relationships with two markers of renal disease, microalbuminuria and renal function. DESIGN AND METHODS One hundred and sixty six patients were studied: 73 males and 93 females mean age 55.2+/-15.5 years. 36.2% were receiving antihypertensive drug treatment. Microalbuminuria was measured in 24-h urine collection as well as albumin to creatinine ratio (ACR) in first morning urine. The ambulatory BP was measured non-invasively for 24 h by the Spacelab devices. RESULTS Correlation test showed a significant relationship of Sym-AASI with age (p<0.001), serum creatinine (p=0.038), creatinine clearance (-0.423, p<0.001) and GFR (-0.263, p<0.001). On the other hand AASI was also correlated with age (p<0.001) and creatinine clearance (p=0.012), but not with the other parameters studied. 24-h albumin excretion rate was not correlated with Sym-AASI or AASI. Contrariwise, the albumin to creatinine ratio was correlated with Sym-AASI (p=0.013). As expected, AASI and Sym-AASI increase as severity of renal diseases grows. The patients in the highest quartile of Sym-AASI distribution showed an older age (p<0.001) and worse parameters of renal function (GFR, p<0.001; and creatinine clearance, p<0.008). CONCLUSIONS Sym-AASI, an improved method for detecting arterial stiffness, seems to get an independent relationship with these parameters of renal disease which could not be detected with AASI.

Cross-sectional survey of the prevalence of reduced estimated glomerular filtration rate, albuminuria and cardiovascular risk in a native Spanish population.

OBJECTIVES HERMEX is a population-based study which tries to evaluate the relative weight of cardiovascular risk factors in inhabitants of Extremadura, Spain. This report presents the data about chronic kidney disease (CKD) in a Spanish population sample. METHODS For an observational cross-sectional population-based study, 3,402 subjects were randomly selected from health care system records. The final sample included 2,813 participants (mean age 51.2 years, 53.5% women). Renal function was estimated from serum creatinine using the 4-variable Modification of Diet in Renal Disease (MDRD-4) Study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Individual renal risk was calculated using the Kidney Disease Improving Global Outcomes (KDIGO) table. RESULTS Using the CKD-EPI formula, 3.6% of participants had a glomerular filtration rate (GFR) <60 ml/min. MDRD-4 gave a result of 4.0%. Prevalence of albuminuria was 5.5%. Taken together, in patients with albuminuria and/or reduced GFR, the prevalence of renal disease was 8.1%. The KDIGO renal risk table suggested that 0.05% of patients were at high or very high risk of CKD progression and 1.6% at medium risk. CKD was more common in those who were obese, hypertensive, dyslipidemic or had diabetes. Multivariate analysis showed an independent negative association of CKD as dependent variable with systolic blood pressure and body mass index, but a positive correlation with diastolic blood pressure and male sex. CONCLUSIONS A low frequency of abnormal GFR was detected in a randomly selected sample of the Spanish general population. This finding agreed with the low rates of cardiovascular mortality and morbidity observed in Spain in spite of a high prevalence of classic cardiovascular risk factors.

Riesgo cardiovascular asociado a microalbuminuria en pacientes diabéticos y en pacientes con hipertensión arterial

BACKGROUND AND OBJECTIVE The MICREX Study has shown an high prevalence of microalbuminuria in Extremadura among diabetic patients and hypertensive population. It has been retrospectively evaluated the cardiovascular risk associated to microalbuminuria and/or diabetes mellitus. PATIENTS AND METHOD A total of 902 patients older than 18 years were studied (mean age, 68.7 [11.0] years; 370 men and 532 women; 469 were diabetics and 433 non diabetic hypertensives). Microalbuminuria was measured in every patient using albumin/creatinin reactive stick in fasting first morning urine. Anthropometric measures and previous cardiovascular diseases were recorded. RESULTS Odds ratio of cardiovascular disease for all patients with microalbuminuria was 1.91 (confidence interval [CI] 95%, 1.31-2.78; p = 0.001), for diabetic group it was 1.87 (CI 95%, 1.15-3.04; p = 0.01) and for non diabetic hypertensives 1.78 (CI 95%, 0.98-3.30; p = 0.06). The risk associated to all patients with diabetes mellitus (versus non diabetic hypertensives) showed an odds ratio = 1.59 (CI 95%, 1.19-2.14; p = 0.02). Hypertension in diabetic subjects rises odds ratio up to 2.13 (CI 95%, 1.30-3.48; p = 0.002). When hypertensives diabetics were compared to non diabetic hypertensives odds ratio was 1.88 (CI 95%, 1.37-2.57; p < 0.0001). CONCLUSIONS In a retrospective view microalbuminuria and diabetes mellitus were positively related to a higher risk of cardiovascular disease. Microalbuminuria and/or hypertension in diabetic patients were also associated to higher cardiovascular risk.

Prevalence of abnormal urinary albumin excretion in a population‐based study in Spain: results from the HERMEX Study

Eur J Clin Invest 2012; 42 (12): 1272–1277