The Effect of Visit-to-Visit Blood Pressure Variability on Renal Function in Geriatric Chronic Kidney Disease.

OBJECTIVE: The visit-to-visit variability (VVV) of blood pressure (BP) has been recognized as a risk factor for cardiovascular events and chronic kidney disease (CKD). The objective of this study is to valuate the association between the VVV of BP and changes in estimated glomerular filtration rate (eGFR) in elderly CKD patients at different stages of renal function. MATERIALS AND METHODS: For 60 months, we analyzed the medical records of 105 patients with and without diabetes and hypertension. Systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) were examined. A multivariable linear regression model was used to analyze the correlation between eGFR and the VVV of BP. RESULTS: No differences were demonstrated between the groups in the clinical characteristics. Mean SBP and DBP were not significant between the groups, and we observed no decrease in renal function. A significant negative correlation between PP and eGFR was observed in the total CKD population with a P of .010 (95% CI: -0.20, -0.03) and a correlation coefficient of -0.11. CONCLUSION: Our study shows no statistical significances in terms of the VVVs of BP in any of the geriatric groups, with no significant decreases in renal function. However, we observed a significant negative correlation between PP and eGFR. We demonstrated that if a VVV of BP does not occur, there is no decrease in eGFR.

Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for the Treatment of Anemia in Patients with CKD.

BACKGROUND AND OBJECTIVES: Roxadustat (FG-4592), an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis, regulates iron metabolism, and reduces hepcidin, was evaluated in this phase 2b study for safety, efficacy, optimal dose, and dose frequency in patients with nondialysis CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The 145 patients with nondialysis CKD and hemoglobin ≤10.5 g/dl were randomized into one of six cohorts of approximately 24 patients each with varying roxadustat starting doses (tiered weight and fixed amounts) and frequencies (two and three times weekly) followed by hemoglobin maintenance with roxadustat one to three times weekly. Treatment duration was 16 or 24 weeks. Intravenous iron was prohibited. The primary end point was the proportion of patients achieving hemoglobin increase of ≥1.0 g/dl from baseline and hemoglobin of ≥11.0 g/dl by week 17 (16 weeks of treatment). Secondary analyses included mean hemoglobin change from baseline, iron utilization, and serum lipids. Safety was evaluated by frequency/severity of adverse events. RESULTS: Of the 145 patients enrolled, 143 were evaluable for efficacy. Overall, 92% of patients achieved hemoglobin response. Higher compared with lower starting doses led to earlier achievement of hemoglobin response. Roxadustat-induced hemoglobin increases were independent of baseline C-reactive protein levels and iron repletion status. Overall, over the first 16 treatment weeks, hepcidin levels decreased by 16.9% (P=0.004), reticulocyte hemoglobin content was maintained, and hemoglobin increased by a mean (±SD) of 1.83 (±0.09) g/dl (P<0.001). Overall mean total cholesterol level was reduced by a mean (±SD) of 26 (±30) mg/dl (P<0.001) after 8 weeks of therapy, independent of the use of statins or other lipid-lowering agents. No drug-related serious adverse events were reported. CONCLUSIONS: In patients with nondialysis CKD who were anemic, various starting dose regimens of roxadustat were well tolerated and achieved anemia correction with reduced serum hepcidin levels. After anemia correction, hemoglobin was maintained by roxadustat at various dose frequencies without intravenous iron supplementation.

Analysis of clinical characteristics of dialysis patients at the University Hospital.

OBJECTIVES: The incidence and prevalence of Chronic Kidney Disease (CKD) patients treated with dialysis has continued to increase worldwide. These patients are at the highest risk of developing cardiovascular complications which contribute to their demise. The objective of this study was to describe the clinical and demographic characteristics of the patients on maintenance hemodialysis at the University Hospital, in San Juan Puerto Rico. METHODS: We reviewed a total of 55 active patients. Data was collected to identify the demographic and clinical characteristics. Co-morbid conditions such as diabetes mellitus, hypertension, and coronary artery disease (CAD) were noted as well as age, dialysis vintage and social and educational profiles. RESULTS: Patients were divided into two groups according to age (group 1 were less than 60 years and group 2 were more than 60 years). Average age was 42 years in group 1 with 17 females and 24 males and 78 years in group 2 with 6 females and 8 males. Diabetes mellitus was present in 17 (41%) of group 1 and 5 patients (35%) of group 2. Likewise hypertension was present in 26 (63%) of group 1 patients and 11(78%) of group 2 patients. CAD was present in 15 (36%) of group 1 patients and 7 (50%) of group 2 patients. There was an association between low annual income in both groups but not in the level of education. CONCLUSION: A relatively young population was identified in our descriptive analysis of hemodialysis patients at the University Hospital. The expected high incidence of diabetes mellitus observed in the general population of hemodialysis patients in our country was not present. Hypertension and CAD were major risk factors in these patients. In view of these findings we recommend better control of blood pressure, prevention and early detection of CAD in CKD patients before initiating dialysis.

Intradialytic Hypertension / Hypotension and Mortality in San Juan, Puerto Rico.

End Stage Renal Disease patients undergo profound hemodynamic changes during hemodialysis treatments which are now recognized as a marker for increased risk of morbidity and mortality. Development of intradialytic hypotension or hypertension are a common clinical problem in this population with an incidence of up to 20%. We performed a retrospective review of 49 Hispanic patients receiving ambulatory hemodialysis during a period of 6 months to ascertain the development of aforementioned intradialytic events. Clinical data examined the association of these events to mortality and their relationship to antihypertensive medications and cardiomegaly. The prevalence of intradialytic hypotension was 38.78%, hypertension 16.33% individually and both taking place 16.33%. Taken together, the prevalence of these intradialytic events was 71.43% in our Hispanic population. A significant association was found between mortality and Beta blockers (BB)(P=0.044), Calcium channel blockers (CCB) (P=0.023), cardiomegaly (P=0.044), and intradialytic events (P=0.035). Odds ratio of multiple variables dis- closed that dependent variable death decreased in probability with the use of BB by an estimate of 73% and with the use of CCB by 74.8%. On the other hand, odds of developing the dependent variable death increased by 74.5% if the patients developed intradialytic events. Similarly, the odds of developing cardiomegaly in the living group increased by 70%. A logistic regression of multiple variables found that the probability of developing the dependent condition of death increases by almost 2.896 times if intradialytic events are present and that there is a 58.9% inferred causality. It is concluded that intradialytic hyper- tension and hypotension are major risk factors for mortality in dialysis patients. The use of BB and CCB may be protetive to avoid the risk of mortality in these patients.

Longitudinal Observations on the Mineral Metabolism of Dialysis Patients at the University Hospital.

A retrospective review was performed from November 2011 through June 2012 in 49 stable patients receiving ambulatory hemodialysis at the dialysis unit of the University Hospital in San Juan. Measurements of serum phosphate, serum calcium (corrected to albumin levels), intact parathyroid hormone (PTH), and pulse pressure were obtained at 3-month intervals over the course of a 9-month observation period. These longitudinal observations assessed the efficiency of treatment, with the objective being to determine the nature of and then implement such changes as would improve the patients' outcomes. Thirty-three of the 49 patients appeared to have fairly good control of their PTH levels during the observation period. Sixteen patients had levels over 300 pg/ml, and, using Stata data analysis software, a linear relationship with phosphate levels was obtained (p = 0.021, R2 = 0.1037, adjusted R2 = 0.0855). Pulse pressure (PP) measurements obtained at each observation interval showed the following increases: 69% at 3 months, 65% at 6 months, and 57% at 9 months. Calcium-containing phosphate binders were used in one third of the population and vitamin D analogs in 50%. A trend towards a rise in PP was observed as calcium levels increased over 9.5 mg/dl. It is concluded that those patients experiencing that rise need close supervision to avoid the increasing morbidity and mortality associated with mineral metabolism derangement. Wide PPs were observed in these patients during the 9 months of observation, denoting persistent arterial stiffness suggestive of an increase in calcium balance.

Anemia management among hemodyalisis patients at the University Hospital in Puerto Rico.

End-stage renal disease is frequently complicated with anemia. Iron deficiency anemia occurs in most hemodialysis patients secondary to increased iron demand driven by the accelerated erythropoiesis that occurs when stimulating agents are administered as treatment of the anemia. The purpose of this study was to determine the prevalence of anemia and iron stores in patients undergoing hemodialysis at our unit; identify their treatment and effectiveness. Medical records of fifty-three patients undergoing ambulatory hemodialysis were evaluated for three months. Patient's hemoglobin, ferritin, iron, total iron binding capacity and percent transferrin saturation were recorded. 91% patients had arterial hypertension and 62% were diabetic. The prevalence of anemia was 34%, 57% and 47% during the three-month period respectively. Only 21% of the population had transferrin saturation less than 20% and none had ferritin below 200 ng/ml. Throughout the study, the majority of patients were managed with combination of iron and erythropoietin stimulating agents (ESAs). The prevalence of anemia remained elevated despite treatment with iron and ESAs. However, 56% of anemic patients throughout the three months showed an increase in hemoglobin levels by the end of the observation period. 53% of patients were treated with iron alone or with ESAs for the three consecutive month periods and only two had transferrin saturation less than 20%. In our population, ESAs low responsiveness is not related to iron deficiency but to the morbidity of their disease.

Predisposing factors for acute kidney injury in Hispanic patients treated with diuretics for decompensated heart failure.

OBJECTIVE: In patients with congestive heart failure (CHF), use of loop diuretic therapy may result in acute kidney insufficiency (AKI). We assessed the factors that contributed to the development of AKI in patients with CHF treated with loop diuretics in a sample of patients who attended the Cardiovascular Center of Puerto Rico and the Caribbean (CCPRC). METHODS: Medical records of 236 patients admitted between: January 1, 2008 to December 31, 2008 with the diagnosis of CHF were reviewed. Diagnosis of CHF based on symptoms and signs was confirmed by echocardiography. Twenty six (26) patients with significant valvular disease and four (4) patients who did not receive diuretics during hospitalization were excluded. Hospital course was observed until diuretic therapy was discontinued or patient was discharged. AKI was defined as a 25% increase in serum creatinine level after the start of diuretic therapy. The study sample was categorized in two groups: patients who developed AKI and those who did not. Variables associated with AKI (p<0.05) in the bivariate logistic regression models were included in the multivariate logistic regression models. RESULTS: In the multivariate logistic regression model, only a greater dose of diuretic therapy (>80 mg/dl) and history of diabetes mellitus were significantly (p<0.05) associated with AKI. CONCLUSION: Analysis of data shows that increased doses of diuretic therapy and history of diabetes mellitus were significantly associated with AKI in patients with CHF. This study highlights the importance of monitoring the doses of diuretic therapy during hospitalization, in this group of patients.

Aliskiren improves left ventricular dysfunction and reduces cardiac dilation in Syrian cardiomyopathic hamsters.

OBJECTIVE: Chronic activation of the renin-angiotensin-aldosterone system is a major contributing factor to the pathogenesis and progression of cardiovascular and renal diseases. METHODS: To evaluate the role of renin-angiotensin-aldosterone system blockade with aliskiren, a direct renin inhibitor, in the development and progression of dilated cardiomyopathy in the Syrian cardiomyopathic hamster (SCH) model, we treated 1-month-old SCH with aliskiren (10 mg·kg·d) over a 4-month period. For comparative purposes, we also evaluated the effects of the angiotensin receptor blocker valsartan (10 mg·kg·d) and the combination of both drugs. Age-matched golden hamsters were used as controls. Left ventricular end-diastolic volume and end-systolic volume, ejection fraction, and diastolic function were determined by echocardiography. Systolic blood pressure (SBP) was also measured in the left femoral artery by sphygmomanometry. RESULTS: Results indicate that at 2 months of age, SBP is higher in SCH than in controls, and administration for 1 month of aliskiren, valsartan, or the combination of these drugs normalized SBP in SCH to a similar extent. In 5-month-old SCH, aliskiren improved ejection fraction (from 48.6% ± 5.8% to 69.4% ± 3.2%, n = 5, P < 0.05), left ventricular end-systolic volume (from 0.28 ± 0.06 to 0.10 ± 0.01 mL/100 g body weight), left ventricular end-diastolic volume (from 0.61 ± 0.05 to 0.34 ± 0.02 mL/100 g body weight), and normalized diastolic function (E:A ratio increases from 0.93 ± 0.13 to 1.70 ± 0.03, n = 5, P < 0.05). Similar results were observed with valsartan or the combination of aliskiren and valsartan. CONCLUSIONS: Our results indicate that in this animal model, aliskiren is as effective as valsartan, or the combination of both drugs, in improving diastolic function and in preventing the development of dilated cardiomyopathy. These findings suggest that aliskiren may be used as a monotherapy in heart failure management. Clinical studies, however, are needed to assess the effectiveness of this drug in patients with heart failure.

Registry of kidney biopsy in a single center in Puerto Rico: university district hospital.

Glomerular diseases continue to be the leading cause of end-stage renal disease globally. Renal biopsy plays a fundamental role in the evaluation of glomerular diseases not only to establish an accurate diagnosis but also help deciding on appropriate treatment and assessing prognosis. The prevalence of glomerular disease and the clinical indications for kidney biopsies are poorly delineated in Puerto Rico. We undertook a retrospective analysis of the indications, clinical presentation and pathologic reports in renal biopsies performed at the University District Hospital in San Juan, Puerto Rico from the year 1995 to 2008. A total of 208 kidney biopsies showed a predominance of membranous nephropathy representing 20% of the studied population. Women were more frequently biopsied than men (57.2% vs. 42.7%). Lupus nephritis, a condition affecting mostly women was identified in 16.9% of the patients. Minimal change disease was reported in 13.6% of the patients, a condition that affects mostly children and adolescents. In contrast to other geographical areas IgAN was reported only in 6.3% and FSG in 0.9% of patients. In our biopsied patient population, membranous nephropathy is the most common primary glomerular disease and lupus erythematosus the most frequent secondary glomerular disease.

Kidney biopsy findings as prognostic factors of renal outcome in a case of ANCA-associated glomerulonephritis.

We present the case of a 29-year-old woman with twelve-years history of Wegener's granulomatosis and multiple relapses resulting in chronic kidney disease. The patient was referred to our center for kidney biopsy, after presenting with a relapse of Wegener's disease mainly manifested by rapid progressive glomerulonephritis. Kidney biopsy was obtained and she was treated with intravenous methylprednisolone and oral cyclophosphamide as initial therapy. Histopatological findings are described, followed by a discussion on how it can be used as a tool to established renal prognosis.

General concepts in the management of a kidney transplant.

The management of a kidney transplant patient is, in most cases, challenging and requires a multidisciplinary approach. For the physician caring for the patient it is imperative to have a broad knowledge regarding several concepts on their management, as they are increasingly faced with long-term care. Baseline rapport and accessibility provides a pivotal role in the treatment, monitoring and preventive measures in the kidney transplant patient. Currently, most aspects regarding patient management vary according to each transplant center. This article describes the importance of several medical issues directed towards the clinician aiming to improve awareness and expand knowledge, with the development of a systematic approach.

Influence of Hispanic ethnicity on blood pressure control and cardiovascular outcomes in women with CAD and hypertension: findings from INVEST.

BACKGROUND: Prospective data regarding blood pressure (BP) control and cardiovascular (CV) outcomes in Hispanic women are lacking. METHODS: We analyzed 5017 Hispanic and 4710 non-Hispanic white hypertensive women with coronary artery disease (CAD) in the INternational VErapamil SR/Trandolapril STudy (INVEST) to determine the impact of baseline characteristics and BP control on CV outcomes. RESULTS: At baseline, Hispanic women were younger and a had lower prevalence of most established CV risk factors than non-Hispanic white women. At 24 months, BP control (< 140/90 mm Hg) was achieved in 75% of Hispanic and 68% of non-Hispanic white women, (p < 0.001), with most women, regardless of ethnicity, requiring > or =2 antihypertensive agents. Following 26,113 patient-years of follow-up, the primary outcome (first occurrence of nonfatal myocardial infarction [MI], nonfatal stroke, or all cause death) occurred in 5.7% of Hispanic and 12.3% of non-Hispanic white women (adjusted HR = 0.84, 95% CI = 0.71-0.98, p = 0.03). There was no difference in outcome in either group of women comparing the randomized antihypertensive treatment strategies. CONCLUSIONS: Despite accounting for a lower risk profile, deployment of protocol-based antihypertensive treatment regimens resulted in superior BP control and fewer CV events in Hispanic women compared with non-Hispanic white women.

Blood pressure control and cardiovascular outcomes in high-risk Hispanic patients--findings from the International Verapamil SR/Trandolapril Study (INVEST).

BACKGROUND: People of Hispanic origin are the fastest growing ethnic minority in the United States and often have hypertension and other comorbidities which increase the risk associated with coronary artery disease (CAD). METHODS AND RESULTS: An analysis of the 8045 Hispanic patients enrolled in INVEST was conducted, and comparisons were made to the 14,531 non-Hispanic patients. INVEST was a prospective, randomized, open, blinded end point study in CAD patients with hypertension. After 61,835 patient-years of follow-up, treatment with either a verapamil sustained release (SR) or atenolol antihypertensive strategy resulted in greater blood pressure control in Hispanic patients, and Hispanic patients were at significantly lower risk of experiencing a nonfatal myocardial infarction, nonfatal stroke, or death (hazard ratio [HR] 0.87, 95% CI 0.78-0.97). Hispanic ethnicity was associated with an increase (HR 1.19, 95% CI 1.04-1.36), and randomization to the verapamil SR strategy was associated with a decrease (HR 0.85, 95% CI 0.76-0.95), in the risk of new-onset diabetes. Use of trandolapril in the verapamil SR strategy was associated with reduced risk of new-onset diabetes, whereas increasing doses of atenolol and hydrochlorothiazide in the atenolol strategy were associated with increased risk of new-onset diabetes. CONCLUSIONS: The Hispanic cohort of INVEST had better blood pressure control and lower risk of adverse cardiovascular outcomes compared with the non-Hispanic cohort. A verapamil SR strategy is an alternative to an atenolol strategy for the treatment of Hispanic patients with hypertension and CAD and can reduce the risk of new-onset diabetes.

Effect of intravenous iron sucrose in peritoneal dialysis patients who receive erythropoiesis-stimulating agents for anemia: a randomized, controlled trial.

Although iron therapy is essential to optimize use of erythropoiesis-stimulating agents (ESA), randomized, controlled trials have heretofore been unavailable to evaluate reliably the efficacy of intravenous iron as an adjuvant to ESA treatment in peritoneal dialysis (PD) patients. In a multicenter trial, patients who had anemia, PD-dependent chronic kidney disease, stable ESA therapy, and a broad range of iron status (ferritin < or = 500 ng/ml, transferrin saturation < or = 25%) were randomly assigned to receive either 1 g of iron sucrose intravenously in three divided doses (300 mg over 1.5 h on days 1 and 15, 400 mg over 2.5 h on day 29) or no supplemental iron. No serious adverse drug events occurred after intravenous iron administration. The primary end point, peak hemoglobin increase, was higher (1.3 +/- 1.1 versus 0.7 +/- 1.1, mean +/- SD; P = 0.0028), and anemia intervention (transfusion, increase in ESA dose, or intravenous iron therapy not called for in protocol) occurred later (P = 0.0137) and less often in intravenous iron-treated patients compared with untreated control subjects (one of 66 [1.3%] versus five of 30 [16.7%]). Among patients who did not require intervention, iron-treated patients showed a calculated net ESA dose decrease compared with untreated control subjects. Baseline iron status did not predict responsiveness to intravenous iron therapy. Intravenous iron sucrose is an effective adjunct to ESA therapy in anemic patients with PD-dependent chronic kidney disease and is administered safely as 300 mg over 1.5 h or 400 mg over 2.5 h. Evidence of iron deficiency at baseline is not required to demonstrate intravenous iron efficacy.

Characteristics of contemporary patients with hypertension and coronary artery disease.

BACKGROUND: Despite a high prevalence of hypertension in the population with CAD, there are limited data describing the clinical characteristics and treatments, as well as their interrelations in these patients. This is particularly true for black and Hispanic patients who have been underrepresented in randomized CAD trials. HYPOTHESIS: There exist racial and ethnic differences that define the characteristics of patients with both coronary artery disease (CAD) and hypertension. METHODS: This report describes the characteristics of Caucasian, Hispanic, and black patients enrolled in the International Verapamil SR/trandolapril Study (INVEST), a prospective trial undertaken exclusively in patients with CAD and hypertension. RESULTS: In all, 10,925 Caucasian, 8,045 Hispanic, and 3,029 black patients are described. An abnormal angiogram or documented myocardial infarction was observed more frequently in Caucasian patients (73%), while angina pectoris was more prevalent in Hispanic patients (87%). Diabetes and left ventricular hypertrophy were most common in black patients (33 and 29%, respectively), while hypercholesterolemia and prior revascularization (coronary artery bypass graft or angioplasty) were most common in Caucasian patients (64 and 41%, respectively). More than 60% of Hispanic and black patients were women--a unique characteristic for randomized CAD trials. Comparing race/ethnic cohorts, there were significant differences for all characteristics. More than 80% of patients in all race/ethnic groups were receiving antihypertensive therapy; however, only fewer than 25% had controlled blood pressure according to guidelines from the sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. CONCLUSIONS: This high-risk population of hypertensive patients with CAD has been undertreated and does not have well-controlled BP. Race/ethnic differences were observed for clinical characteristics and medication use.

A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial.

CONTEXT: Despite evidence of efficacy of antihypertensive agents in treating hypertensive patients, safety and efficacy of antihypertensive agents for coronary artery disease (CAD) have been discerned only from subgroup analyses in large trials. OBJECTIVE: To compare mortality and morbidity outcomes in patients with hypertension and CAD treated with a calcium antagonist strategy (CAS) or a non-calcium antagonist strategy (NCAS). DESIGN, SETTING, AND PARTICIPANTS: Randomized, open label, blinded end point study of 22 576 hypertensive CAD patients aged 50 years or older, which was conducted September 1997 to February 2003 at 862 sites in 14 countries. INTERVENTIONS: Patients were randomly assigned to either CAS (verapamil sustained release) or NCAS (atenolol). Strategies specified dose and additional drug regimens. Trandolapril and/or hydrochlorothiazide was administered to achieve blood pressure goals according to guidelines from the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) of less than 140 mm Hg (systolic) and less than 90 mm Hg (diastolic); and less than 130 mm Hg (systolic) and less than 85 mm Hg (diastolic) if diabetes or renal impairment was present. Trandolapril was also recommended for patients with heart failure, diabetes, or renal impairment. MAIN OUTCOME MEASURES: Primary: first occurrence of death (all cause), nonfatal myocardial infarction, or nonfatal stroke; other: cardiovascular death, angina, adverse experiences, hospitalizations, and blood pressure control at 24 months. RESULTS: At 24 months, in the CAS group, 6391 patients (81.5%) were taking verapamil sustained release; 4934 (62.9%) were taking trandolapril; and 3430 (43.7%) were taking hydrochlorothiazide. In the NCAS group, 6083 patients (77.5%) were taking atenolol; 4733 (60.3%) were taking hydrochlorothiazide; and 4113 (52.4%) were taking trandolapril. After a follow-up of 61 835 patient-years (mean, 2.7 years per patient), 2269 patients had a primary outcome event with no statistically significant difference between treatment strategies (9.93% in CAS and 10.17% in NCAS; relative risk [RR], 0.98; 95% confidence interval [CI], 0.90-1.06). Two-year blood pressure control was similar between groups. The JNC VI blood pressure goals were achieved by 65.0% (systolic) and 88.5% (diastolic) of CAS and 64.0% (systolic) and 88.1% (diastolic) of NCAS patients. A total of 71.7% of CAS and 70.7% of NCAS patients achieved a systolic blood pressure of less than 140 mm Hg and diastolic blood pressure of less than 90 mm Hg. CONCLUSION: The verapamil-trandolapril-based strategy was as clinically effective as the atenolol-hydrochlorothiazide-based strategy in hypertensive CAD patients.