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Daprodustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) being investigated for the treatment of anemia of CKD. In this noninferiority trial, we compared daprodustat administered three times weekly with epoetin alfa (epoetin) in patients on prevalent hemodialysis switching from a prior erythropoiesis-stimulating agent (ESA).Patients on hemodialysis with a baseline hemoglobin of 8-11.5 g/dl receiving an ESA were randomized 2:1 to daprodustat three times weekly (Daprodustat three times weekly was noninferior to epoetin for mean change in hemoglobin (model-adjusted mean treatment difference [daprodustat-epoetin], -0.05; 95% confidence interval, -0.21 to 0.10). During the evaluation period, mean (SD) hemoglobin values were 10.45 (0.55) and 10.51 (0.85) g/dl for daprodustat and epoetin groups, respectively. Responders (defined as mean hemoglobin during the evaluation period in the analysis range of 10 to 11.5 g/dl) were 80% in the daprodustat group versus 64% in the epoetin group. Proportionately fewer participants in the daprodustat group versus the epoetin group had hemoglobin values either below 10 g/dl or above 11.5 g/dl during the evaluation period. Mean monthly intravenous iron use was not significantly lower with daprodustat versus epoetin. The effect on BP was similar between groups. The percentage of treatment-emergent adverse events was similar between daprodustat (75%) and epoetin (79%).Daprodustat was noninferior to epoetin in hemoglobin response and was generally well tolerated.Anemia Studies in Chronic Kidney Disease: Erythropoiesis

Antihypertensive drug therapy is one of the most efficient medical interventions for preventing disability and death globally. Most of the evidence supporting its benefits has been derived from outcome trials with morning dosing of medications. Accumulating evidence suggests an adverse prognosis associated with night-time hypertension, nondipping blood pressure (BP) profile and morning BP surge, with increased incidence of cardiovascular events during the first few morning hours. These observations provide justification for complete 24-h BP control as being the primary goal of antihypertensive treatment. Bedtime administration of antihypertensive drugs has also been proposed as a potentially more effective treatment strategy than morning administration. This Position Paper by the International Society of Hypertension reviewed the published evidence on the clinical relevance of the diurnal variation in BP and the timing of antihypertensive drug treatment, aiming to provide consensus recommendations for clinical practice. Eight published outcome hypertension studies involved bedtime dosing of antihypertensive drugs, and all had major methodological and/or other flaws and a high risk of bias in testing the impact of bedtime compared to morning treatment. Three ongoing, well designed, prospective, randomized controlled outcome trials are expected to provide high-quality data on the efficacy and safety of evening or bedtime versus morning drug dosing. Until that information is available, preferred use of bedtime drug dosing of antihypertensive drugs should not be routinely recommended in clinical practice. Complete 24-h control of BP should be targeted using readily available, long-acting antihypertensive medications as monotherapy or combinations administered in a single morning dose.

Kidney international 103(2), 391-402 (2022). doi:10.1016/j.kint.2022.09.017, Published by Elsevier, New York, NY

IntroductionAlthough studies have examined the utility of clinical decision support tools in improving acute kidney injury (AKI) outcomes, no study has evaluated the effect of real-time, personalised AKI recommendations. This study aims to assess the impact of individualised AKI-specific recommendations delivered by trained clinicians and pharmacists immediately after AKI detection in hospitalised patients.Methods and analysisKAT-AKI is a multicentre randomised investigator-blinded trial being conducted across eight hospitals at two major US hospital systems planning to enrol 4000 patients over 3 years (between 1 November 2021 and 1 November 2024). A real-time electronic AKI alert system informs a dedicated team composed of a physician and pharmacist who independently review the chart in real time, screen for eligibility and provide combined recommendations across the following domains: diagnostics, volume, potassium, acid–base and medications. Recommendations are delivered to the primary team in the alert arm or logged for future analysis in the usual care arm. The planned primary outcome is a composite of AKI progression, dialysis and mortality within 14 days from randomisation. A key secondary outcome is the percentage of recommendations implemented by the primary team within 24 hours from randomisation. The study has enrolled 500 individuals over 8.5 months. Two-thirds were on a medical floor at the time of the alert and 17.8% were in an intensive care unit. Virtually all participants were recommended for at least one diagnostic intervention. More than half (51.6%) had recommendations to discontinue or dose-adjust a medication. The median time from AKI alert to randomisation was 28 (IQR 15.8–51.5) min.Ethics and disseminationThe study was approved by the ethics committee of each study site (Yale University and Johns Hopkins institutional review board (IRB) and a central IRB (BRANY, Biomedical Research Alliance of New York). We are committed to open dissemination of the data through clinicaltrials.gov and sharing of data on an open repository as well as publication in a peer-reviewed journal on completion.Trial registration numberNCT04040296.

Argentina is the third most populated country in South America with an estimated population of 44,494,502. Despite having an area of 2,780,400 km2 (eighth largest in the world), 90% of the population resides in urban areas, with the majority concentrated in and around Buenos Aires. Life expectancy is 79.7 years in women and 73.6 years in men, with cardiovascular disease as the leading cause of mortality. Argentina spends approximately 10% of its gross domestic product on health care (1). There are 3.94 physicians and 4.5 hospital beds per 1000 inhabitants in Argentina (2). The physician-patient ratio is similar to that of Australia, Italy, Spain, and Switzerland, and is double than Brazil and almost four times than Chile and Peru. Argentina has a multitiered, decentralized health care system that is plagued by fragmented management and financing. There are national, provincial, and municipal government–sponsored health care insurances, which together with union-sponsored insurances, provide health care coverage to nearly 22 million people. An additional approximately 10% of the population has private health insurance, leaving nearly 36% of the population without health care coverage or the financial means to pay for private insurance. These individuals are cared for at cost-free public hospitals and community facilities (1,2). The first hemodialysis (HD) treatment in Argentina dates back to 1955. Five years later in 1960, the Argentine Society of Nephrology was founded (3). The incidence and prevalence of CKD and ESKD have been growing steadily, most likely because of increasing rates of diabetes and obesity as well as an aging population. Indeed, CKD is now the seventh leading cause of mortality in Argentina, and CKD-related deaths have increased by 15% between 2007 and 2017 (4). The National Transplantation Institute (INCUCAI) supports a National Dialysis and Transplant Registry (5,6). Patient …

Cardiovascular diseases are the leading cause of mortality and morbidity in the Region of the Americas, and hypertension is one of the main risk factors. In 2018, Argentina began implementing the HEARTS Initiative in five primary health care centers, through the National Plan for the Prevention and Control of Arterial Hypertension. This study presents the impact its implementation has had on the indicators of effective coverage, treatment, combination therapy, and control. The HEARTS Initiative has multiple components; these include training health teams, reassigning tasks based on the transfer of clinical competencies, providing automatic and clinically validated blood pressure measurement devices, and using a single standardized treatment protocol. A longitudinal data model (generalized estimating equation analysis) was used, and the information from the five health centers was grouped using weighted averages according to the size of the population under coverage. Analysis of the results was stratified into two time periods delimited by the imposition of restrictions due to COVID-19. During the first period of 18 months, significant improvement was observed in treatment (5.9%; p0.01) and combination therapy (13.4%; p0.01), with no significant change in coverage (8.4%; p=0.87) and with a paradoxical decrease in control (-3.3%; p=0.02). When the period of restrictions was compared to the previous period, a generalized reduction was observed in all indicators, particularly coverage (-23.6%; p0.01) and control (-12.5%; p0.01). However, treatment and combination therapy levels remained above baseline values (1.7%; p0.01 and 5.4%; p0.01, respectively).As doenças cardiovasculares são a principal causa de morbimortalidade, e a hipertensão, seu principal fator de risco. Em 2018, a Argentina começou a implementar a Iniciativa HEARTS em 5 centros de atenção primária à saúde por meio do Plano Nacional de Prevenção e Controle da Hipertensão Arterial. Este estudo apresenta o impacto de sua implementação nos indicadores de cobertura efetiva, tratamento, tratamento combinado e controle. A Iniciativa HEARTS inclui vários componentes. Entre eles, se destacam a capacitação das equipes de saúde, a reorganização das tarefas com base na transferência de competências clínicas, a disponibilização de aparelhos automáticos e clinicamente validados para aferição da pressão arterial e a utilização de um único protocolo padronizado de tratamento. Foi utilizado um modelo de equações de estimativas generalizadas para a análise de dados longitudinais, e as informações dos 5 centros de saúde foram agrupadas por meio de médias ponderadas de acordo com o tamanho da população coberta. A análise dos resultados foi estratificada em dois períodos de tempo delimitados pela irrupção das restrições em virtude da COVID-19. Durante os primeiros 18 meses, houve melhora significativa no tratamento (5,9%; p0,01) e no tratamento combinado (13,4%; p0,01), sem mudança significativa na cobertura (8,4%; p=0,87) e com uma diminuição paradoxal no controle (−3,3%; p=0,02). Durante as restrições e em relação ao período anterior, verificou-se redução generalizada em todos os indicadores, principalmente na cobertura (−23,6%; p0,01) e no controle (−12,5%; p0,01). No entanto, os níveis de tratamento e tratamento combinado persistiram acima dos valores basais (1,7%; p0,01 e 5,4%; p0,01, respectivamente).

PURPOSE OF REVIEW: Isolated diastolic hypertension (IDH) is a frequent hypertension phenotype. We review IDH pathophysiology, risk stratification, and therapeutic decisions. RECENT FINDINGS: Recent guidelines lowering blood pressure cutoff levels have increased IDH prevalence and likely decreased associated cardiovascular risk. Long-term cardiovascular risk and pharmacological intervention in IDH are controversial. Narrow pulse pressure and other physiological and epidemiological characteristics are shared with a systodiastolic hypertension (SDH) subgroup. We propose that IDH be incorporated into a broader category, predominantly diastolic hypertension (PDH), defined by pulse pressure ≤ 45 mmHg and includes IDH and SDH with a narrow pulse pressure. SUMMARY: IDH-PDH is associated with cardiovascular risk in the long term, especially in young patients. Standardization of the IDH definition and population may contribute to future research to understand genetics, pathophysiology, and eventually therapy in this important subgroup of hypertensive patients.

Key Messages About 1/4th of adults have high blood pressure which is the single most important risk for death (including heart disease and stroke). There are effective policies that could facilitate people making healthy choices to prevent raised blood pressure, and if fully implemented, could largely prevent hypertension from occurring. Hypertension is easy to screen and treat for BUT only about 50% of adults with hypertension are aware of their condition and only about 1 in 7 is adequately treated. Preventing and controlling high blood pressure is the major mechanism for NCD prevention and control and a model for other NCD risks. Effective lifestyle and drug treatments could prevent and control hypertension in most individuals if systematically applied to the population, simple interventions are feasible in all settings, and can be used to enhance primary care. Urgent sustained action is needed is needed for effective public polcies and health system changes to prevent and control hypertension

See related article, pp e13–e115 Global high blood pressure control and prevention is a major goal of the World Hypertension League (WHL), which strives to support and promote population strategies for the reduction in risks of hypertension-related outcomes. The implementation of hypertension management protocols and recommendations based on evidence from clinical studies is associated with the risk reduction in stroke, as well as cardiovascular and renal disease.1 The impact of the structured hypertension guidelines can be seen in the Figure where the risks of elevated blood pressure identified in the 1920s and the benefit of blood pressure reduction from the Veterans Administration studies was associated with declines in population stroke mortality.2–5 As evidence in the Table, the decline in stroke mortality coincides with the reduction of population blood pressure pressures which was consistent with the lowered blood pressure thresholds and targets described in the sequential recommendations from the Guidelines.6–12 View this table: Table. Mean and 90th …

Key Points Renin–angiotensin–aldosterone system (RAAS) blockade with an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker provides a 20% relative risk reduction for the progression of established cardiorenal disease compared with other non-RAAS blocking therapiesThe RAAS is an endocrine, paracrine and autocrine system that regulates blood pressure homeostasis through effects on a variety of target organs, as well as having a role in the responses to vascular injury and repairThe RAAS is a complex system with a variety of sites suitable for pharmacological interventionNovel molecules that alter the production of various RAAS peptides or that alter receptor density, function or responsiveness to these peptides could have an important influence on haemodynamics and vascular structure and function Supplementary information The online version of this article (doi:10.1038/nrendo.2015.6) contains supplementary material, which is available to authorized users., The renin–angiotensin–aldosterone system (RAAS) regulates blood pressure homeostasis via multiple mechanisms that act on a variety of organs. The development of drugs that target RAAS components is an active area of research. The authors of this Review discuss current and future therapeutic manipulation of the RAAS and its promise in improving the care of patients with hypertension. Supplementary information The online version of this article (doi:10.1038/nrendo.2015.6) contains supplementary material, which is available to authorized users., The renin–angiotensin–aldosterone system (RAAS) regulates blood pressure homeostasis and vascular injury and repair responses. The RAAS was originally thought to be an endocrine system critically important in regulating blood pressure homeostasis. Yet, important local forms of the RAAS have been described in many tissues, which are mostly independent of the systemic RAAS. These systems have been associated with diverse physiological functions, but also with inflammation, fibrosis and target-organ damage. Pharmacological modulation of the RAAS has brought about important advances in preventing morbidity and mortality associated with cardiovascular disease. Yet, traditional RAAS blockers such as angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) only reduce the risk of disease progression in patients with established cardiovascular or renal disease by ∼20% compared with other therapies. As more components of the RAAS are described, other potential therapeutic targets emerge, which could provide improved cardiovascular and renal protection beyond that provided by an ACE inhibitor or ARB. This Review summarizes the present and future pharmacological manipulation of this important system. Supplementary information The online version of this article (doi:10.1038/nrendo.2015.6) contains supplementary material, which is available to authorized users.

Hypertension is a leading risk factor for disease burden globally. An unresolved question is whether grade 1 hypertension (140-159/90-99. mm. Hg) with low (cardiovascular mortality

The main aim of the study was to determine the prevalence of vascular calcifications in patients with chronic kidney disease on dialysis in our population assessed by X-ray. The secondary objectives were to determine the cardiovascular risk factors associated with the presence of vascular calcifications and to evaluate the complementary use of the echocardiogram in a cross-sectional, observational, multicentric study. We included patients with chronic kidney disease on dialysis, age =18 years with at least 3 months of renal replacement therapy in 8 dialysis centres in Argentina. The degree of vascular calcification was determined using Adragao and Kauppila scores. The presence of valvular calcifications was established through a trans-thoracic doppler echocardiogram. Univariate and multivariate analysis were undertaken, considering the degree of vascular calcification as the dependent variable; 443 adult patients were evaluated at 8 centres across 5 provinces in Argentina. The prevalence of vascular calcifications by the X-rays was 63%, while 73% presented calcifications in hands and pelvis, with an Adragao score > 3, and 60% presented calcifications in the abdominal aorta with a Kauppila score > 4. The prevalence of valvular calcifications: 28%. We have shown a higher rate of vascular calcifications with the use of plain X-rays when compared to the prevalence of valvular calcifications obtained with echocardiograms. In this regard, valvular calcifications were present particularly in those patients with a severe level of radiological vascular calcification

Patients with resistant hypertension belong to a very high cardiovascular risk group and have a high prevalence of target organ damage. Microalbuminuria and low estimated glomerular filtration rate are associated with resistant hypertension, and could be a cause and/or complication of hypertension. In this review, we explore the relationship between these 2 markers of kidney disease and the prevalence of resistant hypertension. We identified different phenotypes of resistant hypertension that associate with microalbuminuria and/or low estimated glomerular filtration rate. These phenotypes suggest that high sympathetic activity associated with fluid overload and endothelial dysfunction may contribute differently to the development of resistant hypertension.

Hypertension complicates most cases of chronic kidney disease. While the prevalence and severity of hypertension increase as glomerular filtration rate falls, hypertension is often observed in patients with structural kidney disease while renal function is normal, in particular those with polycystic kidney disease or proteinuric glomerular diseases. On the other hand, even severe reductions in renal function may not result in hypertension, especially if there is effective control of extracellular fluid volume. Recent clinical and experimental data indicate that proteinuria may mediate sodium retention and hypertension via plasmin-mediated activation of the epithelial sodium channel. Current evidence supports the notion that chronic kidney disease is a cause of chronic hypertension, even in the absence of detectable changes in glomerular filtration rate.

The ability to reliably evaluate the impact of interventions and changes in hypertension prevalence and control is critical if the burden of hypertension-related disease is to be reduced. Previously, a World Hypertension League Expert Committee made recommendations to standardize the reporting of population blood pressure surveys. We have added to those recommendations and also provide modified recommendations from a Pan American Health Organization expert meeting for "performance indicators" to be used to evaluate clinical practices. Core indicators for population surveys are recommended to include: (1) mean systolic blood pressure and (2) mean diastolic blood pressure, and the prevalences of: (3) hypertension, (4) awareness of hypertension, (5) drug-treated hypertension, and (6) drug-treated and controlled hypertension. Core indicators for clinical registries are recommended to include: (1) the prevalence of diagnosed hypertension and (2) the ratio of diagnosed hypertension to that expected by population surveys, and the prevalences of: (3) controlled hypertension, (4) lack of blood pressure measurement within a year in people diagnosed with hypertension, and (5) missed visits by people with hypertension. Definitions and additional indicators are provided. Widespread adoption of standardized population and clinical hypertension performance indicators could represent a major step forward in the effort to control hypertension.

Background: Fabry disease is caused by an X-linked recessive inborn error of glycosphingolipid metabolism with deficient activity of a lysosomal enzyme, alpha-galactosidase A (α-GalA). Case Presentation: A 46 year-old man with progressive kidney disease showed on kidney biopsy electron microscopic evidence of Fabry disease. The patient had no systemic manifestations of Fabry disease, despite residual α-GalA activity, therefore genetic testing was done by direct DNA sequencing, demonstrating a new GAL A gene mutation (C174G-exon 3). After three years of enzyme replacement therapy (agalsidase beta) treatment, a second biopsy was done. Although there was demonstrable clearance of intracellular inclusions, remarkable podocyte activation was evident. Conclusions: This report represents an unusual renal variant of Fabry disease and provides histologic data on long-term follow up after enzyme replacement therapy.

To evaluate the evidence supporting the use of renin inhibitors to control hypertension, limit kidney disease progression, and decrease cardiovascular risk in patients with chronic kidney disease (CKD).The literature on the subject is still limited. Most of the studies have used aliskiren as the study drug. Animal models show improved survival and decreased renal injury in animals receiving aliskiren. Human studies in patients with normal renal function show effective blood pressure control alone or in combination with different agents. There are no studies focusing on blood pressure control in patients with CKD, though the drug has been safely used in CKD. In a randomized clinical trial, aliskiren decreased albuminuria when added to losartan in patients with early diabetic nephropathy. Ongoing studies are evaluating the role of renin inhibitors in the prevention of cardiovascular events and slowing of kidney disease progression in CKD.Renin inhibitors, specifically aliskiren, effectively decrease albuminuria. Their role in improving hard renal endpoints and decreasing cardiovascular events in CKD still remains to be established.

Aliskiren is a novel drug with the ability to lower plasma renin activity, reducing proteinuria in hypertension and in diabetic nephropathy. In primary and secondary glomerular diseases, important causes of endstage kidney disease, proteinuria is a hallmark. Moreover, urinary protein is a marker of renal disease progression. The renin angiotensin-aldosterone system is generally activated in these patients. A complete blockade with the use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers with or without aldosterone receptor blockers is not easy to achieve, and side effects are not uncommon. Plasma renin activity is even increased in patients with this approach. Aliskiren should be considered as a new therapeutic option to be assessed in glomerular diseases, as plasma renin activity can be reduced and a better control of the renin-angiotensin system could be achieved with the consequent reduction in the amount of urinary protein excretion.

To evaluate the spectrum of hemodynamic patterns in patients with isolated diastolic hypertension-predominantly diastolic hypertension, we re-analyzed a previously reported cohort of 189 non-medicated hypertensive individuals that were assessed by impedance cardiography. We selected 46 patients who were less than 50 years old and had pulse pressure less or equal than 45 mm Hg confirmed by ambulatory blood pressure monitoring. The selected cohort had a mean age of 39.7 years and was 47% men. Three distinct groups were identified: a high cardiac index (CI) "hyperdynamic" group, with normal to near normal systemic vascular resistance (SVR); an intermediate CI and SVR group; and a "vasotonic" group, with low CI and high SVR. Heart rate was similar among the three groups. Stroke volume index (SVI) was significantly higher in the hyperdynamic group (61.8, 49.7, and 39.7 mL/m(2) in the high, intermediate, and low CI groups, respectively). The hyperdynamic group had greater total arterial compliance index than the vasotonic group (1.3 ± 0.3 vs 0.92 ± 0.2 mL/m(2) mm Hg for high vs low CI, respectively; P < .001). In conclusion, isolated diastolic hypertension-predominantly diastolic hypertension patients can have diverse hemodynamic patterns that cannot be predicted based on peripherally measured blood pressure and heart rate alone. This hemodynamic complexity must be taken into account when considering the genetic and pathophysiologic mechanisms of hypertension.

INTRODUCTION: Uremic pruritus is common among dialysis patients. Effective treatments are not readily available. Early evidence with antihistamines and gabapentin indicate variable effects. OBJECTIVE: To compare the efficacy and side effects of gabapentin and desloratadine in patients with dialysis pruritus. METHODS: Prospective, open-label, cross-over clinical trial in 22 patients on chronic hemodialysis with sustained pruritus over a period of at least 60 days. After a one-week run-in period, we assigned patients to three weeks of either gabapentin 300 mg thrice weekly or desloratadine 5 mg thrice weekly. After a one-week washout period, each patient crossed-over to the alternate regimen for three more weeks. The primary endpoint of the study was the change in the visual analogue pruritus score (VAS). RESULTS: Nineteen subjects completed the two treatment blocks and were available for analysis. VAS scores decreased with both treatments (5.95 to 4.6 with gabapentin, p = 0.07; 5.89 to 3.4 with desloratadine, p = 0.004), but only desloratadine reached statistical significance. There were no differences when comparing the final pruritus score with gabapentin and desloratadine (4.6 versus 3.4, p = 0.16) Excessive sedation was common with gabapentin. Desloratadine was well tolerated. CONCLUSION: Desloratadine provides significant relief of uremic pruritus compared with no therapy. gabapentin has marginal efficacy. Desloratadine is better tolerated than gabapentin. INTRODUÇÃO: Prurido urêmico é comum entre pacientes em diálise. Tratamentos eficazes não estão disponíveis até o momento. Provas recentes com anti-histamínicos e gabapentina indicam vários efeitos. OBJETIVO: Comparar a eficiência e os efeitos colaterais da gabapentina e da desloratadina em pacientes com prurido na diálise. MÉTODOS: Estudo prospectivo, aberto e comparativo com 22 pacientes em hemodiálise crônica com prurido constante durante um período de pelo menos 60 dias. Após uma semana, submetemos os pacientes a três semanas de gabapentina 300 mg, três vezes por semana, ou desloratadina 5 mg três vezes por semana. Após um período de eliminação de uma semana, os pacientes trocaram de regime por mais três semanas. O objetivo primário do estudo foi a mudança na escala visual analógica (EVA) de prurido. RESULTADOS: Dezenove indivíduos completaram os dois tratamentos e foram submetidos à análise. Os escores da EVA caíram com ambos os tratamentos (5,95 para 4,6 com gabapentina, p = 0,07; 5,89 para 3,4 com desloratadina, p = 0,004), mas somente a desloratadina teve significância estatística. Nenhuma diferença foi observada ao comparar o escore final do prurido com gabapentina e desloratadina (4,6 versus 3,4, p = 0,16). Excesso de sedação foi comum com gabapentina. A desloratadina teve alto nível de tolerância. CONCLUSÃO: A desloratadina dá alívio significante do prurido urêmico quando comparada a nenhum tratamento. A gabapentina tem eficiência marginal. A desloratadina tem maior nível de tolerância em relação à gabapentina.

J Clin Hypertens (Greenwich). © 2010 Wiley Periodicals, Inc. The study of genes and mechanisms associated with hypertension is hampered by the heterogeneity of hypertensive patients. Refining the definition of hypertension is a potential means of improving the clarity of mechanistic studies, but the lack of intermediate phenotypes hinders the assessment of causal relationships. Looking at younger individuals and hemodynamic subsets of hypertension is one such refinement. The authors argue that the separate analysis of patients with isolated diastolic hypertension, predominantly diastolic hypertension, and isolated systolic hypertension in the young in combination with common biomarkers may be an initial step to decrease heterogeneity within patient subsets, thus providing new avenues for genetic and pathophysiological studies.

The development of nephrology has been greatly influenced by the performance of procedures. For example, kidney biopsies have elicited substantial knowledge, thereby linking kidney afflictions with their respective histopathologies, which consequently governed the course of therapy. Further, the growth of nephrology has been marked by the implementations of advanced forms of renal replacement therapy. Moreover, there is now the acute acknowledgement that the success of any modality of renal replacement therapy is contingent upon the integrity of its associated peritoneal or vascular access. Consequently, the concept of nephrologist as interventionalist has garnered broad appeal. In fact, the American Society of Diagnostic and Interventional Nephrology and the International Society of Nephrology promote this concept. Notably, these groups have already demonstrated successful outreach programs that have been replicated at local, regional, and national levels throughout the globe.

Background. The insertion/deletion (I/D) angiotensin-converting enzyme (ACE) polymorphism has been established as a cardiovascular risk factor in some populations, but the association with essential hypertension is controversial. Predominantly diastolic hypertension (PDH), or narrow pulse pressure hypertension, has been shown to have increased peripheral resistance. Because a DD genotype has been associated with higher plasma ACE levels and angiotensin II activity, we genotyped PDH patients for ACE I/D polymorphism. Methods. Ninety-three patients with systolic blood pressure (BP) < 140 mmHg systolic and diastolic BP > 90 mmHg, or BP > 140/90 mmHg with a pulse pressure < 45 mmHg, were defined as PDH. The II, ID and DD genotype variants of ACE were characterised by the triple primer nested-PCR method. Results were compared to 75 normotensive control individuals. Statistical significance was assessed by the Chi square test. Results. The genotype distribution among PDH patients was II=20 (21.5%), ID=34 (36.5%), DD=39 (42%), while the distribution among normotensive controls was II= O 16 (21.4%), ID=42 (56%), DD=17 (22.6%).The difference in genotype distribution between PDH patients and controls was significant (p Conclusion. These results suggest an association between ACE genotype DD and predominantly diastolic hypertension.

Ambulatory blood pressure monitoring (ABPM) has been increasingly used in hemodialysis (HD) practice and research; however, no study has evaluated the reproducibility of ABPM in this population. To address this question, we performed 48-hour interdialytic ABPM on 21 HD patients (mean age, 53 ± 16 years; 7 women) on two different occasions 68 ± 34 days (range, 30 to 154 days) apart. To qualify for the protocol, patients had to be at the same dry weight and on the same vasoactive drug regimen at both monitoring periods. BP was analyzed according to three different methods: isolated pre-HD and post-HD values, average pre-HD and post-HD values for the five HD sessions surrounding each monitoring period, and 48-hour interdialytic ABPM. Reproducibility was determined by analysis of the SD of the differences (SDD) between the two monitoring periods and the coefficient of variation of each method of BP determination. Our results show better reproducibility of ABPM (SDD, 10.6/6.6 mm Hg; coefficient of variation, 7.5%/8.1%) compared with isolated pre-HD BP (SDD, 24.4/11.3 mm Hg; coefficient of variation, 16.7%/14.1%) or post-HD BP (SDD, 16.8/14.5 mm Hg; coefficient of variation, 11.7%/17.8%), and averaged pre-HD BP (SDD, 14.7/7.2 mm Hg; coefficient of variation, 10.1%/9.1%) or post-HD BP (SDD, 12.4/8.7 mm Hg; coefficient of variation, 8.9%/11.1%). The reproducibility of the decrease in BP during sleep was poor, with up to 43% of the subjects changing dipping category within or between interdialytic periods. We conclude that ABPM is the most accurate method to study BP in HD patients over time. However, variability is significant, and there is poor reproducibility of the nocturnal decline in BP, Fil: Peixoto, Aldo. Universidad Católica de Córdoba. Facultad de Ciencias de la Salud; Argentina, Fil: Santos, Sergio F.F. Universidad Católica de Córdoba. Facultad de Ciencias de la Salud; Argentina, Fil: Mendes, Roger. Universidad Católica de Córdoba. Facultad de Ciencias de la Salud; Argentina, Fil: Crowley, Susan. Universidad Católica de Córdoba. Facultad de Ciencias de la Salud; Argentina, Fil: Maldonado, Rafael. Universidad Católica de Córdoba. Facultad de Ciencias de la Salud; Argentina, Fil: Orias, Marcelo. Universidad Católica de Córdoba. Facultad de Ciencias de la Salud; Argentina, Fil: Mansoor, George A. Universidad Católica de Córdoba. Facultad de Ciencias de la Salud; Argentina, Fil: White, William B. Universidad Católica de Córdoba. Facultad de Ciencias de la Salud; Argentina

Our laboratory previously cloned a novel rabbit gene ( Kcn1), expressed in kidney, heart, and aorta, and predicted to encode a protein with 58% amino acid identity with the K channel Shaker Kv1.3 (Yao X et al. Proc Natl Acad Sci USA 92: 11711–11715, 1995). Because Kcn1 did not express well (peak current in Xenopus laevis oocytes of 0.3 μA at +60 mV), the human homolog (KCNA10) was isolated, and its expression was optimized in oocytes. KCNA10 mediates voltage-gated K+currents that exhibit minimal steady-state inactivation. Ensemble currents of 5–10 μA at +40 mV were consistently recorded from injected oocytes. Channels are closed at the holding potential of −80 mV but are progressively activated by depolarizations more positive than −30 mV, with half-activation at +3.5 ± 2.5 mV. The channel displays an unusual inhibitor profile because, in addition to being blocked by classical K channel blockers (barium tetraethylammonium and 4-aminopyridine), it is also sensitive to inhibitors of cyclic nucleotide-gated (CNG) cation channels (verapamil and pimozide). Tail-current analysis shows a reversal potential shift of 47 mV/decade change in K concentration, indicating a K-to-Na selectivity ratio of at least 15:1. The phorbol ester phorbol 12-myristate 13-acetate, an activator of protein kinase C, inhibited whole cell current by 42%. Analysis of single-channel currents reveals a conductance of ∼11 pS. We conclude KCNA10 is a novel human voltage-gated K channel with features common to both K-selective and CNG cation channels. Given its distribution in renal blood vessels and heart, we speculate that KCNA10 may be involved in regulating the tone of renal vascular smooth muscle and may also participate in the cardiac action potential.

Phosphate intoxication, manifested by hypocalcemic tetany and acute renal failure, may complicate bowel-cleansing preparations which contain phosphate. These preparations are commonly used to prepare patients for various gastrointestinal procedures. Often, patients who receive these regimens are at increased risk of phosphate intoxication from diseases which slow gastrointestinal transit or decrease renal excretion (renal insufficiency). We present a patient who developed oliguric acute renal failure from severe phosphate intoxication associated with a phosphate-containing bowel-cleansing regimen.

The K-selective channel, TOK1, recently identified in yeast, displays the unusual structural feature of having two putative pore regions, in contrast to all previously cloned K channels. Using the TOK1 pore regions as probes, we identified a human kidney cDNA encoding a 337-amino acid protein (hKCNK1) with four transmembrane segments and two pore regions containing the signature sequence of K channels. Amino acid identity to TOK1 is only 15% overall but 40% at the pores. Northern analysis indicates high expression of a 1.9-kb message in brain > kidney >> heart. Nephron segment localization, carried out in rabbit by reverse transcription-polymerase chain reaction, reveals that KCNK1 is expressed in cortical thick ascending limb, connecting tubule, and cortical collecting duct. It was not detected in the proximal tubule, medullary thick ascending limb, distal convoluted tubule, and glomerulus. We conclude that KCNK1 is a unique, double-pore, mammalian K channel, distantly related to the yeast channel TOK1, that is expressed in distal tubule and is a candidate to participate in renal K homeostasis.

Potassium (K) channels are important components of virtually all cells, and they play critical roles in many cellular functions. KCNA10 represents a new class of K channel specifically regulated by cGMP and postulated to mediate the effects of substances that increase intracellular cGMP. Since KCNA10 has the potential to be useful in candidate gene analysis of inherited diseases, the human gene for KCNA10 was characterized. Fluorescence in situ hybridization indicates that human KCNA10 maps to chromosome 1 at p13.1--p22.1. Finer mapping of the gene was achieved by PCR of a set of CEPH YAC clones that spanned the region of interest. We found that YAC 818b9 contains human KCNA10. These data indicate human KCNA10 maps to 1p13.1 and resides within the genetic interval defined by microsatellite loci D1S2809 and D1S2726. That region of chromosome 1 contains another K channel gene, KCNA3.