Evaluation and treatment of resistant hypertension

Hypertension is a major cause and contributor to stroke, heart and kidney disease. Despite the development of an arsenal of medication to treat hypertension over the past half-century, adequate treatment continues to be a major problem in the United States. The Third National Health and Nutrition Examination Survey (NHANES-III) shows that only 29% of hypertensive patients reach a blood pressure less than 140/90 mm Hg. Resistant hypertension is defined as a blood pressure greater than 140/90 mm Hg despite a rational combination of three or more blood pressure medications including a diuretic. The prevalence of true resistant hypertension in hypertension clinics is only about 11-13%. Higher prevalence rates are evident in populations with evidence of end-organ disease such as cardiac or renal disease where lower blood pressure targets have now been established. Ascertaining the possible cause(s) for resistant hypertension is a challenge to all clinicians, but critical in eventual determination of a therapeutic solution. The following review will hopefully help guide clinicians in their discernment of causes and potential treatments for resistant hypertension. The diagnosis and treatment of the more common secondary causes will be described and treatment options for patients with resistant hypertension are discussed. Newer options, some still under clinical investigation, will be described and their future utility will be discussed. (Cardiol J 2007; 14: 329-339

Diagnostyka i leczenie nadciśnienia opornego

Nadciśnienie tętnicze jest jedną z głównych przyczyn udarów mózgu, chorób serca i nerek. Mimo że w ciągu ostatniego półwiecza opracowano wiele leków hipotensyjnych, odpowiednie leczenie nadciśnienia pozostaje dużym problemem. W badaniu NHANES III wykazano, że tylko u 29% pacjentów z nadciśnieniem tętniczym w Stanach Zjednoczonych uzyskuje się ciśnienie mniejsze niż 140/90 mm Hg. Nadciśnienie oporne definiuje się jako ciśnienie utrzymujące się na poziomie powyżej 140/90 mm Hg pomimo stosowania racjonalnego połączenia 3 lub więcej leków hipotensyjnych, w tym diuretyku. Częstość występowania rzeczywistego nadciśnienia opornego w specjalistycznych ośrodkach leczenia nadciśnienia tętniczego wynosi jedynie około 11-13%. Większą częstość występowania stwierdza się w populacjach osób z powikłaniami narządowymi, takimi jak choroby serca lub nerek, u których przyjęto obecnie niższe docelowe wartości ciśnienia. Określenie możliwej przyczyny (lub przyczyn) nadciśnienia opornego jest wyzwaniem dla wszystkich klinicystów, ale ma zasadnicze znaczenie w ostatecznym wyborze rozwiązania terapeutycznego. Celem niniejszej pracy jest ułatwienie klinicystom wykrywania przyczyn i określania potencjalnych sposobów terapii nadciśnienia opornego. Przedstawiono diagnostykę i leczenie częstszych postaci wtórnego nadciśnienia, a także możliwości terapii nadciśnienia opornego. Uwzględniono również nowsze metody, z których część jest wciąż w fazie badań klinicznych i omówiono ich przydatność w przyszłości. (Folia Cardiologica Excerpta 2007; 2: 511-523

Icodextrin Versus Glucose Solutions for the Once-Daily Long Dwell in Peritoneal Dialysis: An Enriched Systematic Review and Meta-analysis of Randomized Controlled Trials

Rationale & Objective The efficacy and safety of icodextrin versus glucose-only peritoneal dialysis (PD) regimens is unclear. The aim of this study was to compare once-daily long-dwell icodextrin versus glucose among patients with kidney failure undergoing PD. Study Design Systematic review of randomized controlled trials (RCTs), enriched with unpublished data from investigator-initiated and industry-sponsored studies. Setting & Study Populations Individuals with kidney failure receiving regular PD treatment enrolled in clinical trials of dialysate composition. Selection Criteria for Studies Medline, Embase, CENTRAL, Ichushi Web, 10 Chinese databases, clinical trials registries, conference proceedings, and citation lists from inception to November 2018. Further data were obtained from principal investigators and industry clinical study reports. Data Extraction 2 independent reviewers selected studies and extracted data using a prespecified extraction instrument. Analytic Approach Qualitative synthesis of demographics, measurement scales, and outcomes. Quantitative synthesis with Mantel-Haenszel risk ratios (RRs), Peto odds ratios (ORs), or (standardized) mean differences (MDs). Risk of bias of included studies at the outcome level was assessed using the Cochrane risk-of-bias tool for RCTs. Results 19 RCTs that enrolled 1,693 participants were meta-analyzed. Ultrafiltration was improved with icodextrin (medium-term MD, 208.92 [95% CI, 99.69-318.14] mL/24 h; high certainty of evidence), reflected also by fewer episodes of fluid overload (RR, 0.43 [95% CI, 0.24-0.78]; high certainty). Icodextrin-containing PD probably decreased mortality risk compared to glucose-only PD (Peto OR, 0.49 [95% CI, 0.24-1.00]; moderate certainty). Despite evidence of lower peritoneal glucose absorption with icodextrin-containing PD (medium-term MD, −40.84 [95% CI, −48.09 to −33.59] g/long dwell; high certainty), this did not directly translate to changes in fasting plasma glucose (−0.50 [95% CI, −1.19 to 0.18] mmol/L; low certainty) and hemoglobin A1c levels (−0.14% [95% CI, −0.34% to 0.05%]; high certainty). Safety outcomes and residual kidney function were similar in both groups; health-related quality-of-life and pain scores were inconclusive. Limitations Trial quality was variable. The follow-up period was heterogeneous, with a paucity of assessments over the long term. Mortality results are based on just 32 events and were not corroborated using time-to-event analysis of individual patient data. Conclusions Icodextrin for once-daily long-dwell PD has clinical benefit for some patients, including those not meeting ultrafiltration targets and at risk for fluid overload. Future research into patient-centered outcomes and cost-effectiveness associated with icodextrin is needed

The association of functional status with mortality and dialysis modality change : results from the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS)

BACKGROUND: Little is known about the prevalence of functional impairment in peritoneal dialysis (PD) patients, its variation by country, and its association with mortality or transfer to hemodialysis. METHODS: A prospective cohort study was conducted in PD patients from 7 countries in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) (2014 - 2017). Functional status (FS) was assessed by combining self-reports of 8 instrumental and 5 basic activities of daily living, using the Lawton-Brody and the Katz questionnaires. Summary FS scores, ranging from 1.25 (most dependent) to 13 (independent), were based on the patient's ability to perform each activity with or without assistance. Logistic regression was used to estimate the odds ratio (OR; 95% confidence interval [CI]) of a FS score < 11 comparing each country with the United States (US). Cox regression was used to estimate the hazard ratio (HR; 95% CI) for the effect of a low FS score on mortality and transfer to hemodialysis, adjusting for case mix. RESULTS: Of 2,593 patients with complete data on FS, 48% were fully independent (FS = 13), 32% had a FS score 11 to < 13, 14% had a FS score 8 to < 11, and 6% had a FS score < 8. Relative to the US, low FS scores (< 11; more dependent) were more frequent in Thailand (OR = 10.48, 5.90 - 18.60) and the United Kingdom (UK) (OR = 3.29, 1.77 - 6.08), but similar in other PDOPPS countries. The FS score was inversely and monotonically associated with mortality but not with transfer to hemodialysis; the HR, comparing a FS score < 8 vs 13, was 4.01 (2.44 - 6.61) for mortality and 0.91 (0.58 - 1.43) for transfer to hemodialysis. CONCLUSION: Regional differences in FS scores observed across PDOPPS countries may have been partly due to differences in regional patient selection for PD. Functional impairment was associated with mortality but not with permanent transfer to hemodialysis

Implementing core outcomes in kidney disease: report of the Standardized Outcomes in Nephrology (SONG) implementation workshop

There are an estimated 14,000 randomized trials published in chronic kidney disease. The most frequently reported outcomes are biochemical endpoints, rather than clinical and patient-reported outcomes including cardiovascular disease, mortality, and quality of life. While many trials have focused on optimizing kidney health, the heterogeneity and uncertain relevance of outcomes reported across trials may limit their policy and practice impact. The international Standardized Outcomes in Nephrology (SONG) Initiative was formed to identify core outcomes that are critically important to patients and health professionals, to be reported consistently across trials. We convened a SONG Implementation Workshop to discuss the implementation of core outcomes. Eighty-two patients/caregivers and health professionals participated in plenary and breakout discussions. In this report, we summarize the findings of the workshop in two main themes: socializing the concept of core outcomes, and demonstrating feasibility and usability. We outline implementation strategies and pathways to be established through partnership with stakeholders, which may bolster acceptance and reporting of core outcomes in trials, and encourage their use by end-users such as guideline producers and policymakers to help improve patient-important outcomes

Normalization of lithium-induced hypercalcemia and hyperparathyroidism with cinacalcet hydrochloride

An underrecognized side effect of long-term lithium carbonate therapy is hyperparathyroidism with associated hypercalcemia and hypocalciuria. Because cessation of lithium carbonate therapy usually does not correct the hyperparathyroidism and associated hypercalcemia, parathyroidectomy frequently is necessary. This is the initial report of 2 patients with lithium carbonate-induced hyperparathyroidism treated with cinacalcet hydrochloride (HCl), which normalized serum calcium levels and reduced intact parathyroid hormone (iPTH) secretion. The patients, both with bipolar disease and a 15- to 30-year history of lithium carbonate therapy, were evaluated for stage 3 chronic kidney disease, persistent hypercalcemia, and hyperparathyroidism. A 67-year-old woman was administered cinacalcet HCl, 30 mg/d, for 11 months. Mean serum calcium level decreased from 10.8 +/- 0.4 mg/dL (2.69 +/- 0.10 mmol/L) to 9.9 +/- 0.4 mg/dL (2.47 +/- 0.10 mmol/L; P \u3c 0.001), and iPTH level decreased from 139 +/- 31 pg/mL (139 +/- 31 ng/L) to 114 +/- 39 pg/mL (114 +/- 39 ng/L; P = not significant). A 63-year-old man was administered 30 mg/d of cinacalcet HCl for 8 months, then 60 mg/d for another 2 months. Mean serum calcium and iPTH levels decreased from 11.0 +/- 0.5 mg/dL (2.74 +/- 0.12 mmol/L) to 10.3 +/- 0.4 mg/dL (2.57 +/- 0.10 mmol/L; P \u3c 0.001) and 138 +/- 10 pg/mL (138 +/- 10 ng/L) to 73 +/- 7 pg/mL (73 +/- 7 ng/L; P = 0.03), respectively. Urinary fractional excretion of calcium was low for both patients before (\u3c0.026 and \u3c0.015) and after (0.026 and 0.008) treatment with cinacalcet HCl. These findings suggest that cinacalcet HCl can provide an alternative nonsurgical means to control this disorder in patients with hypercalcemia of variable severity for whom surgical treatment is not a consideration because of perceived mildness of disease or unsuitability of the patient for surgical intervention