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Unilateral renal artery stenosis (RAS) leads to atrophy of the stenotic kidney and compensatory enlargement of the contralateral kidney. Although the two-kidney, one-clip (2K1C) model has been extensively used to model human RAS, the cellular responses in the stenotic and contralateral kidneys, particularly in the murine model, have received relatively little attention. We studied mice 2, 5, and 11 wk after unilateral RAS. These mice became hypertensive within 1 wk. The contralateral kidney increased in size within 2 wk after surgery. This enlargement was associated with a transient increase in expression of phospho-extracellular signal-regulated kinase (p-ERK), the proliferation markers proliferating cell nuclear antigen and Ki-67, the cell cycle inhibitors p21 and p27, and transforming growth factor-β, with return to baseline levels by 11 wk. The size of the stenotic kidney was unchanged at 2 wk but progressively decreased between 5 and 11 wk. Unlike the contralateral kidney, which showed minimal histopathological alterations, the stenotic kidney developed progressive interstitial fibrosis, tubular atrophy, and interstitial inflammation. Surprisingly, the stenotic kidney showed a proliferative response, which involved largely tubular epithelial cells. The atrophic kidney had little evidence of apoptosis, despite persistent upregulation of p53; expression of cell cycle regulatory proteins in the stenotic kidney was persistently increased through 11 wk. These studies indicate that in the 2K1C model, the stenotic kidney and contralateral, enlarged kidney exhibit a distinct temporal expression of proteins involved in cell growth, cell survival, apoptosis, inflammation, and fibrosis. Notably, an unexpected proliferative response occurs in the stenotic kidney that undergoes atrophy.

Hypertension during pregnancy (HDP) increases the risk of future coronary heart disease (CHD), but it is unknown whether this association is mediated by renal injury. Reduced renal function is both a complication of HDP and a risk factor for CHD.Logistic regression models were fit to examine the association between a history of HDP and the presence and extent of coronary artery calcification (CAC), a measure of subclinical coronary artery atherosclerosis, in 498 women from the Epidemiology of Coronary Artery Calcification Study (mean age 63.3 +/- 9.3 years).Fifty-two (10.4%) women reported a history of HDP. After adjusting for age at time of study participation, HDP was associated with increased serum creatinine later in life (p = 0.014). HDP was positively associated with the presence of CAC after adjusting for age at time of study participation (OR = 2.7, 95% CI 1.4-5.4). This association was slightly attenuated with adjustment for body size and blood pressure (OR = 2.4, 95% CI 1.2-4.9) but was not further attenuated with adjustment for serum creatinine and urinary albumin/creatinine ratio (OR = 2.6, 95% CI 1.3-5.3). Results were similar for CAC extent.HDP may increase a woman's risk of future CHD beyond traditional risk factors and renal function. Women with a history of HDP should be monitored for potential increased risk of CHD as they age.

Medications are a major source of acute kidney injury, especially in critically ill patients. Medication-induced renal injury can occur through a number of mechanisms. We present two cases of acute kidney injury (AKI) where inactive cytochrome P450 (CYP) polymorphism may have played a role. The first patient developed a biopsy-proven allergic interstitial nephritis following urethrotomy. Genetic testing revealed the patient to be heterozygous for an inactivating polymorphism CYP2C9*3 and homozygous for an inactivating polymorphism CYP2D6*4. Patient had received several doses of promethazine, which is metabolized by CYP2D6*4. Another patient developed AKI on several occasions after exposure to lansoprazole and allopurinol. CYP testing revealed the patient to be homozygous for inactivating polymorphism CYP2C19*2, which is responsible for the metabolism of lansoprazole. These are the first two cases of AKI associated with non-functional polymorphisms of cytochrome P450 superfamily. While the exact mechanism has not been worked out, it introduced the possibility of a new source of kidney injury.

The objective of this study was to determine the impact of lupus nephritis disease activity on maternal and foetal outcomes in pregnant patients with systemic lupus erythematosus (SLE). Medical records of all pregnant patients with SLE treated at our institution between 1976 and 2007 were reviewed. All patients met American College of Rheumatology classification criteria for SLE. Demographic data, history of lupus nephritis, nephritis disease activity and maternal and foetal outcomes of pregnancy were abstracted. Active lupus nephritis was defined as the presence of proteinuria >0.5 g/day and/or active urinary sediment with or without an elevation in serum creatinine (Cr). Quiescent lupus nephritis was confirmed in the presence of proteinuria

© 2009 Mayo Foundation for Medical Education and Research A 25-year-old nonsmoking male tire technician presented to the emergency department with a 3-week history of macroscopic hematuria and flank pain. He had previously been feeling well and was taking no regular medications; however, he had seen his primary care physician 10 days previously for left flank pain and was empirically treated for pyelonephritis with oral ciprofloxacin. On presentation, the patient was not passing clots through the urethra, denied recent trauma, and rated his flank pain as 6 on a severity scale of 10, described as constant, bilateral, nonradiating, and pleuritic with no relieving factors. He had no nausea, vomiting, diarrhea, fevers, chills, or rigors. He denied recent travel, animal contacts, occupational exposures, use of over-the-counter medications, or illegal drug use. On examination, the patient appeared clinically well without evidence of distress, pallor, or jaundice. His temperature was 36.8 C, blood pressure was 118/72 mm Hg, pulse rate was 74/min, and oxygen saturation was 95% while breathing room air. Findings on cardiovascular and respiratory examinations were noncontributory. The abdomen was soft, nondistended, and nontender without masses or organomegaly. No costovertebral angle tenderness, suprapubic tenderness, or renal bruits were appreciated. There was no evidence of rash or musculoskeletal abnormality. Laboratory tests yielded the following results (reference ranges provided parenthetically): a normal white blood cell count with no evidence of peripheral eosinophilia; creatinine, 1.5 mg/dL (0.9-1.4 mg/dL); C-reactive protein, 99.2 mg/L ( 8.0 mg/L); and erythrocyte sedimentation rate, 111 mm/h (0-22 mm/h). The estimated glomerular filtration rate (eGFR) was 57 mL/min per 1.73m2 and the international normalized ratio was 1.0. Urinalysis by dipstick showed trace ketones, protein 3+, bilirubin 1+, and occult blood 3+. Initial urinalysis showed reddish urine, a protein concentration of 3100 mg/dL, and a large amount of hemoglobin. Microscopic examination showed more than 100 red blood cells per high power field, with more than 25% dysmorphic red blood cells and no evidence of urinary eosinophils. Chest radiography showed mild bilateral pleural effusions and atelectasis at the left base behind the heart. Computed tomography (CT) of the abdomen and pelvis was performed according to the renal stone protocol; findings were negative for kidney stones.

Background— Hypertensive pregnancy disorders have been associated with subjective cognitive complaints or brain white-matter lesions 5 to 10 years after the hypertensive pregnancy. The long-term effects of hypertensive pregnancies on brain structure and cognitive function remain unknown. Methods and Results— This study included 1279 women who participated in the Family Blood Pressure Project Genetic Epidemiology Network of Arteriopathy (GENOA) study. As part of the ancillary Genetics of Microangiopathic Brain Injury (GMBI) study, a neurocognitive battery was administered; 1075 also had a brain magnetic resonance imaging. A history of a hypertensive pregnancy disorder was obtained by a self-report using a validated questionnaire. Linear models fit with generalized estimating equations were used to assess the association between hypertensive pregnancy disorders and cognition, adjusting for age, race, education, body mass index, smoking, current hypertension, hypertension duration, and family history of hypertension. Regression models for the brain magnetic resonance imaging outcomes also were adjusted for total intracranial volume. Women with histories of hypertensive pregnancy disorders performed worse on all measures of processing speed (Digital Symbol Substitution Test [mean score, 41.2 versus 43.4; P =0.005], Trail Making Test Part A [mean seconds, 45.1 versus 42.2; P =0.035], and Stroop [mean score, 173.9 versus 181.0; P =0.002]) and had smaller brain volumes compared with women with histories of normotensive pregnancies (286 versus 297; P =0.023). Conclusions— Hypertensive pregnancy disorders are associated with worse performance on tests of processing speed and smaller brain volumes decades later. Population-based studies are needed to provide critical insight as to the contribution of hypertensive pregnancies to risk of cognitive decline and dementia.

Thrombotic microangiopathies (TMAs) comprise a heterogeneous set of conditions linked by a common histopathologic finding of endothelial damage resulting in microvascular thromboses and potentially serious complications. The typical clinical presentation is microangiopathic hemolytic anemia accompanied by thrombocytopenia with varying degrees of organ ischemia. The differential diagnoses are generally broad, while the workup is frequently complex and can be confusing. This statement represents the joint recommendations from a multidisciplinary team of Mayo Clinic physicians specializing in the management of TMA. It comprises a series of evidence- and consensus-based clinical pathways developed to allow a uniform approach to the spectrum of care including when to suspect TMA, what differential diagnoses to consider, which diagnostic tests to order, and how to provide initial empiric therapy, as well as some guidance on subsequent management.

Increasing evidence indicates that hypertension in pregnancy is an under-recognized risk factor for cardiovascular disease (CVD). Compared with women who have had normotensive pregnancies, those who are hypertensive during pregnancy are at greater risk of cardiovascular and cerebrovascular events and have a less favorable overall risk profile for CVD years after the affected pregnancies. One factor that might underlie this relationship is that hypertensive disorders of pregnancy (pre-eclampsia, in particular) and CVD share several common risk factors (e.g. obesity, diabetes mellitus and renal disease). Alternatively, hypertension in pregnancy could induce long-term metabolic and vascular abnormalities that might increase the overall risk of CVD later in life. In both cases, evidence regarding risk-reduction interventions specific to women who have had hypertensive pregnancies is lacking. While awaiting results of large-scale studies, hypertensive disorders of pregnancy should be screened for during assessment of a woman's overall risk profile for CVD. Women at high risk must be monitored closely for conventional risk factors that are common to both CVD and hypertensive disorders of pregnancy and treated according to current evidence-based national guidelines.

Pre-eclampsia is a pregnancy-specific disorder that causes a high degree of maternal and fetal morbidity and mortality. Despite many recent advances in the field, the diagnosis, treatment and prevention of pre-eclampsia remain elusive. The current patent application provides evidence for a marker of pre-eclampsia, a 26.6-kDa polypeptide, which is present in pre-eclamptic women and absent in normal controls. The prospect of developing a laboratory test for the diagnosis of pre-eclampsia is exciting, as is the possibility for risk-stratification and potential therapies.

Background/Aims: Restenosis following percutaneous transluminal renal angioplasty (PTRA) remains a concern even in the era of adjuvant stenting. The optimal form of therapy, and particularly the role of repeat PTRA in the treatment of recurrent hypertension associated with renal artery restenosis, is largely unknown. The aims of this study were to determine the risk factors for restenosis and to evaluate the blood pressure outcomes of patients who underwent repeat PTRA. Methods: Clinical and procedural characteristics of 32 patients who developed recurrent hypertension and renal artery restenosis were compared to a control group of patients who maintained renal artery patency and adequate blood pressure control after the first procedure. The groups were matched for sex and initial procedure date. Results: The restenosis group had a mean age of 71 ± 12 years, a female/male ratio of 24/8, an average blood pressure of 179/87 mm Hg, despite three antihypertensive medications, and a serum creatinine level of 1.5 ± 0.4 mg/dl. Repeat PTRA performed for clinically significant restenosis was 10.7 ± 8 months after the first procedure, and 17 of the 32 patients had a measurable blood pressure benefit at last follow-up (177 ± 119 weeks). The development of restenosis was positively associated with body weight (p = 0.003) and body mass index (p = 0.008), but independent of diabetes mellitus, hyperlipidemia, or statin therapy. Of the 15 patients who failed the second procedure, 4 went on to have third PTRA, none of whom had sustained benefit. Conclusions: An increased body mass index is associated with restenosis following initial PTRA. Patients with restenosis can be treated successfully with repeat PTRA which provides sustained improvement in blood pressure control in approximately half of these patients.

Hypertensive pregnancy disorders complicate 10% of all pregnancies and cover a spectrum of conditions, namely preeclampsia, eclampsia, and chronic and gestational hypertension. Preeclampsia is a pregnancy‐specific disorder clinically characterized by hypertension and proteinuria that occurs after 20 weeks of gestation. It remains a leading cause of both fetal and maternal morbidity and mortality worldwide. Traditionally, hypertensive pregnancy disorders were considered not to have any long‐term impact on mothers' cardiovascular health; however, recent studies consistently have supported the role of hypertension in pregnancy as a risk factor for cardiovascular disease later in life. Therefore, improved screening, and preventive and treatment strategies may not only optimize management of hypertensive pregnancy disorders, but may have a long‐term impact on women's cardiovascular events and outcomes years after the affected pregnancies. This article will provide a brief review of hypertensive pregnancy disorders and important recent discoveries regarding their pathogeneses, while focusing on current diagnostic and treatment strategies.

Uvod: Sindrom HELLP, težak oblik preeklampsije kojega klinički karakterizira hemoliza, povišeni jetreni enzimi, te mali broj trombocita, prvi je put opisan 1982. godine. Materijali i metode: Kako bismo procijenili utjecaj identificiranja ovoga sin-droma na ishode liječenja rodilja i fetusa, proveli smo retrospektivnu studiju i pregledali dokumentaciju bolesnica s preeklampsijom liječenih u Klinici Mayo prije i nakon 1982. godine. Načinili smo retrospektivnu dijagnozu sindroma HELLP u 11 od 146 bolesnica liječenih zbog preeklampsije prije 1982. godine. Usporedili smo ishode trudnoće u nasumce odabranoj skupini 24 žene sa sin-dromom HELLP koje su liječene u Klinici Mayo između 1986. i 1994. godine. Rezultati: Nismo zapazili statistički značajnu razliku među demografskim podatcima o rodiljama ili dijagnostičkim laboratorijskim nalazima. Smrtnost fetusa je bila značajno viša prije 1982. godine. Pojavnost i težina akutnog zatajenja bubrega i drugih skupnih komplikacija kod rodilja (uključujući plućni edem, pleuralni izljev, perikardijski izljev, unutarmoždano krvarenje, konvulzi-je, hepatičku nekrozu, te odignuće mrežnice) bili su značajno veći prije 1982. godine. Nakon te godine vrijeme od dijagnoze do porođaja bilo je značajno kraće (2,5 u odnosu na 14 dana), a za bolesnice je bilo vjerojatnije da će pri-miti profilaksu protiv konvulzija magnezijevim sulfatom. Zabilježena je i tendencija većega broja carskih rezova i poticanja trudova u žena liječenih nakon 1982. godine. Zaključci: Navedena zapažanja ukazuju da je prepoznavanje sindroma HELLP kao zasebnoga kliničkog sindroma dovelo do poboljšanih ishoda trudnoće vjerojatno zbog pravodobnije dijagnoze i ranijeg završetka trudnoće., Background: HELLP syndrome, a severe form of preeclampsia clinically characterized by hemolysis, elevated liver enzymes, and low platelet count, was first described in 1982. Materials and Methods: To assess the impact of recognition of this syndrome on fetal and maternal outcomes, we conducted a retrospective study and reviewed the records of patients with preeclampsia treated at Mayo Clinic before and after 1982. We made a retrospective diagnosis of HELLP in 11 of 146 patients treated for preeclampsia prior to 1982. We compared pregnancy outcomes to a randomly selected group of 24 women with HELLP syndrome treated at Mayo Clinic between 1986 and 1994. Results: We did not observe a statistically significant difference in maternal demographics or diagnostic laboratory findings. Priorto 1982, fetal mortality was significantly higher. The incidence and severity of acute renal failure and other cumulative maternal complications (including pulmonary edema, pleural effusion, pericardial effusion, intracerebral hemorrhage, seizure, hepatic necrosis, and retinal detachment) were significantly higher priorto 1982. After 1982, the time from diagnosis to delivery was significantly shorter (2.5 vs. 14 days), and patients were more likely to receive seizure prophylaxis with magnesium sulfate. There was a trend towards more Caesarian sections and labor induction in women treated after 1982. Conclusions: These observations suggest that recognition of HELLP as a distinct clinical syndrome has led to improved outcomes of pregnancies, probably due to more timely diagnosis and earlier termination of pregnancy.

The management of lupus nephritis in pregnancy presents a diagnostic and therapeutic challenge for providers. Pregnancy creates a series of physiologic changes in the immune system and kidney that may result in an increased risk of disease flare and adverse maternal and fetal outcomes, such as preeclampsia, fetal loss, and preterm delivery. Conception should be delayed until disease is in remission to ensure the best pregnancy outcomes. Maternal disease activity and fetal well-being should be monitored closely by an interdisciplinary team, including obstetricians, rheumatologists, and nephrologists throughout pregnancy. Careful attention must be paid to the dosing and potential teratogenicity of medications.

Hypertension in pregnancy is a risk factor for future hypertension and cardiovascular disease. This may reflect an underlying familial predisposition or persistent damage caused by the hypertensive pregnancy. We sought to isolate the effect of hypertension in pregnancy by comparing the risk of hypertension and cardiovascular disease in women who had hypertension in pregnancy and their sisters who did not using the dataset from the Genetic Epidemiology Network of Arteriopathy study, which examined the genetics of hypertension in white, black, and Hispanic siblings. This analysis included all sibships with at least one parous woman and at least one other sibling. After gathering demographic and pregnancy data, BP and serum analytes were measured. Disease-free survival was examined using Kaplan-Meier curves and Cox proportional hazards regression. Compared with their sisters who did not have hypertension in pregnancy, women who had hypertension in pregnancy were more likely to develop new onset hypertension later in life, after adjusting for body mass index and diabetes (hazard ratio 1.75, 95% confidence interval 1.27-2.42). A sibling history of hypertension in pregnancy was also associated with an increased risk of hypertension in brothers and unaffected sisters, whereas an increased risk of cardiovascular events was observed in brothers only. These results suggest familial factors contribute to the increased risk of future hypertension in women who had hypertension in pregnancy. Further studies are needed to clarify the potential role of nonfamilial factors. Furthermore, a sibling history of hypertension in pregnancy may be a novel familial risk factor for future hypertension.

Objective Cardiac changes of hypertensive pregnancy include left ventricular hypertrophy (LVH) and diastolic dysfunction. These are thought to regress postpartum. We hypothesised that women with a history of hypertensive pregnancy would have altered LV geometry and function when compared with women with only normotensive pregnancies. Methods In this cohort study, we analysed echocardiograms of 2637 women who participated in the Family Blood Pressure Program. We compared LV mass and function in women with hypertensive pregnancies with those with normotensive pregnancies. Results Women were evaluated at a mean age of 56 years: 427 (16%) had at least one hypertensive pregnancy; 2210 (84%) had normotensive pregnancies. Compared with women with normotensive pregnancies, women with hypertensive pregnancy had a greater risk of LVH (OR: 1.42; 95% CI 1.01 to 1.99, p=0.05), after adjusting for age, race, research network of the Family Blood Pressure Program, education, parity, BMI, hypertension and diabetes. When duration of hypertension was taken into account, this relationship was no longer significant (OR: 1.19; CI 0.08 to 1.78, p=0.38). Women with hypertensive pregnancies also had greater left atrial size and lower mitral E/A ratio after adjusting for demographic variables. The prevalence of systolic dysfunction was similar between the groups. Conclusions A history of hypertensive pregnancy is associated with LVH after adjusting for risk factors; this might be explained by longer duration of hypertension. This finding supports current guidelines recommending surveillance of women following a hypertensive pregnancy, and sets the stage for longitudinal echocardiographic studies to further elucidate progression of LV geometry and function after pregnancy. Clinical trial registrations GENOA- NCT00005269; HyperGEN- NCT00005267; Sapphire- NCT00005270; GenNet- NCT00005268.

Figures in scientific publications are critically important because they often show the data supporting key findings. Our systematic review of research articles published in top physiology journals (n = 703) suggests that, as scientists, we urgently need to change our practices for presenting continuous data in small sample size studies. Papers rarely included scatterplots, box plots, and histograms that allow readers to critically evaluate continuous data. Most papers presented continuous data in bar and line graphs. This is problematic, as many different data distributions can lead to the same bar or line graph. The full data may suggest different conclusions from the summary statistics. We recommend training investigators in data presentation, encouraging a more complete presentation of data, and changing journal editorial policies. Investigators can quickly make univariate scatterplots for small sample size studies using our Excel templates., A systematic review of research articles reveals widespread poor practice in the presentation of continuous data. The authors recommend training for investigators and supply templates for easy use.

Background A 26-year-old primigravida, with no history of hypertension, presented at 20 weeks of gestation with severe pre-eclampsia. A pelvic ultrasound revealed intrauterine fetal death, probably caused by placental abruption. The pregnancy was terminated by induction with oxytocin, followed by a vaginal breech delivery. The patient remained hypertensive for 8 weeks after delivery. Investigations Physical examination, laboratory investigation, renal angiogram and renal-vein renin sampling. Diagnosis An atrophic right kidney secondary to an occluded right renal artery, probably caused by dissected fibromuscular dysplasia; a contralateral high-grade stenosis secondary to fibromuscular dysplasia. Management Right nephrectomy and angioplasty of the left renal artery.

Seven single gene mutations are known to cause hypertension, generally by affecting electrolyte transport in the distal nephron, or synthesis or activity of mineralocorticoid hormones. These relatively uncommon disorders should be considered when young patients with a family history of high blood pressure present with severe or refractory hypertension. This article guides clinicians through identification of these defects, their associated laboratory findings, and recommended treatments. Hypertension is an important public health problem affecting more than 50 million individuals in the US alone. The most common form, essential hypertension, results from the complex interplay between genetic predisposition and environmental influences. In contrast, monogenic (mendelian) forms of hypertension are caused by single gene mutations that are influenced little, if at all, by environmental factors. Most monogenic forms of hypertension affect either electrolyte transport in the distal nephron, or the synthesis or activity of mineralocorticoid hormones, leading to the common pathogenic mechanisms of increased distal tubular reabsorption of sodium and chloride, volume expansion and hypertension. In young patients with a family history of hypertension who present with severe or refractory hypertension and characteristic hormonal and biochemical abnormalities, the differential diagnosis should include monogenic forms of hypertension. Genetic testing, which is increasingly available, can facilitate timely diagnosis and treatment of these relatively uncommon disorders, such that the underlying defect can be corrected or ameliorated and the long-term consequences of poorly controlled hypertension prevented.

We report a case of a healthy 24-year-old man who presented with acute renal failure and proteinuria while taking creatine and multiple other supplements for bodybuilding purposes. A renal biopsy showed acute interstitial nephritis. The patient recovered completely after he stopped taking the supplements. Creatine is a performance-enhancing substance that has gained widespread popularity among professional as well as amateur athletes. It is legal and considered relatively safe. Recently there have been case reports of renal dysfunction, including acute interstitial nephritis, associated with its use. Further studies are needed to evaluate the safety of creatine supplementation. It may be prudent to include a warning of this possible side effect in the product insert.

Dietary Na+ intake influences β2-adrenergic receptor (β2AR) responsiveness. While receiving a normal Na+ diet (150 mmol day−1), subjects homozygous for glycine at amino acid 16 (Gly16) have greater forearm β2AR-mediated vasodilatation than subjects homozygous for arginine (Arg16), an effect that is mediated by endothelial NO. We tested the hypothesis that dietary Na+ restriction eliminates genotype differences in forearm and systemic β2AR-mediated dilatation in these groups. We measured heart rate, mean arterial pressure and cardiac output (CO, acetylene breathing) responses to administration of intravenous terbutaline (TRB) before and after 5 days of low dietary Na+ intake (10 mmol day−1) in healthy Gly16 (n= 17; age, 31 ± 7 year) and Arg16 homozygotes (n= 15; age, 29 ± 8 year). After the low-Na+ diet, a catheter was placed in the brachial artery to measure forearm blood flow (FBF, plethysmography) responses to administration of isoprenaline (isoproterenol) before and after NO inhibition with NG-mono-methyl-l-arginine (l-NMMA). In the Gly16 group, the low-Na+ diet decreased baseline CO from 6.4 ± 1.4 to 5.5 ± 1.2 l min−1 (P= 0.003, paired t test), tended to decrease stroke volume from 97.0 ± 20.6 to 86.9 ± 21.7 ml (P= 0.06) and increased peripheral resistance from 1106 ± 246 to 1246 ± 222 dynes s cm−5 (P= 0.02); significant effects of the low-Na+ diet were not observed in Arg16 subjects. In a repeated measures ANOVA, the responses of all cardiovascular measures to systemic administration of TRB were not influenced by genotype or diet. Additionally, the FBF response to incremenetal doses of isoprenaline did not differ between genotype groups before or after administration of l-NMMA. We conclude that dietary Na+ restriction blunted the increased forearm NO-mediated β2AR responsiveness in Gly16 homozygotes observed in a previous study after normal dietary Na+ intake, while baseline CO decreased and peripheral resistance increased in this group. This study provides evidence that dietary Na+ modulates effects of the Arg16Gly polymorphism on cardiovascular function.

There is considerable controversy about how to test for renovascular hypertension and, with the development of percutaneous transluminal renal angioplasty (PTRA) and stenting, how to treat it. Which noninvasive diagnostic test should be considered, and when is renal angiography called for? Which patients will benefit from conservative medical therapy, and when is PTRA appropriate?

Hypertension produced by renal artery occlusive disease is an important secondary form of hypertension. Clinicians commonly encounter forms of renal arterial disease of varying severity, many of which are of little hemodynamic significance when first detected. Experimental studies emphasize that transient activation of the renin-angiotensin-aldosterone system is necessary for initiation of renovascular hypertension. At some point, angiotensin II activates additional mechanisms responsible for sustained increased blood pressure including sodium retention, endothelial dysfunction, and vasoconstriction related to production of reactive oxygen species. Widespread application of agents that block the renin-angiotensin system, including angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers, render many patients with unilateral renal arterial disease manageable primarily by medical means for many years. In the setting of high a priori likelihood of renovascular disease, recognizing the potential for disease progression during medical therapy and individually evaluating the risks and benefits of renal revascularization are important tasks. Recent prospective studies show limited, but real, benefit regarding blood pressure control for patients with atherosclerotic disease. Whether earlier renal revascularization offers benefits regarding improved morbidity and mortality from cardiovascular end point reduction is an important question to be addressed in multicenter, prospective, randomized trials. Our paradigm stresses the fact that patients with renovascular hypertension require intensive blood pressure control and cardiovascular risk factor intervention, both before and after revascularization. Hence, management of such patients requires close attention and periodic review regarding restenosis and progression of vascular disease.

Contrast nephropathy after coronary angiography is associated with considerable morbidity and mortality. We discuss the incidence, definition, and pathologic mechanisms of contrast nephropathy; provide an overview of risk factors; highlight proven preventive interventions; clarify which interventions have shown no benefit; and discuss future possibilities. The prevention of contrast nephropathy is crucial for the care of patients undergoing coronary angiography and should be possible with an understanding of risk factors and proven management strategies.

Maternal placental syndromes (MPS) occur as a consequence of abnormal placental vessel formation, and refer to hypertensive pregnancy disorders (HPDs) and related placental abnormalities, such as placental abruption and infarction.1 In the affected pregnancies, adverse pregnancy outcomes, including preterm delivery, foetal growth retardation and intrauterine foetal demise, are common. HPDs complicate about 5–10% of pregnancies worldwide2 and cover a spectrum of conditions. Most notable among these is preeclampsia, a multisystem pregnancy-specific disorder clinically characterised by hypertension and proteinuria, and which remains a leading cause of foetal and maternal morbidity and mortality. Evidence suggests that preeclampsia is associated with the release of antiangiogenic factors by an ischaemic placenta, which, in turn, may lead to maternal endothelial dysfunction.3 ,4 In 1927, Corwin and Herrick reported an association between ‘hypertensive toxemia of pregnancy’, as pre-eclampsia was once called, and chronic cardiovascular disease.5 Since then, there have been multiple epidemiological studies that confirm these authors' observation. HPDs have been associated with chronic hypertension, ischaemic heart disease, stroke, venous thromboembolism and cardiovascular death6 ,7; evidence suggests that other features of the metabolic syndrome are present as well.8 Similarly, the development of an MPS has been shown to double the risk of development of cardiovascular disease later on in life.1 However, studies evaluating an association between HPDs and future arrhythmias and heart failure are limited. In this issue of Heart Ray9 discusses these specific cardiovascular outcomes, heart failure and arrhythmias, in the context of a previous history of MPSs (see page 1136) . In this unique retrospective cohort study, using a large administrative database in Ontario, Canada, the authors evaluate the frequency of these two outcomes in women with previous MPSs, defined as placental abruption, …

Secondary causes of hypertension can affect over 10% of those patients diagnosed with hypertension, and the workup can encompass a wide variety of pathologies. Here we present a case of secondary hypertension found in a young physician who, fortunately, had both of these two entities diagnosed via fortuitous imaging performed for non-diagnostic reasons. This case involves a relatively common cause of secondary hypertension (renovascular) and a more obscure cause (paraganglioma). We outline evidencebased surgical and perioperative management of paragangliomas, as well as the medical management of renovascular hypertension. This case is unique in that it involves both elements of secondary hypertension and presents difficult management decisions.

To determine whether autosomal dominant polycystic kidney disease (ADPKD) is associated with adverse fetal outcomes and maternal complications.We identified a cohort of 146 patients seen for pregnancy and cystic kidney disease at Mayo Clinic from 1975 to 2010. From this cohort, 54 patients met the ultrasound diagnostic criteria for ADPKD (ADPKD group), while the other 92 patients were diagnosed as "Simple Cyst" (control group). We compared the fetal and maternal outcomes of pregnancy and long-term maternal prognoses between these two groups.Overall, the fetal complication rates were similar between the ADPKD and control groups. Rates of spontaneous abortion (15.1% versus 14%, p = 0.77) and premature birth (11.1% versus 6.8%, p = 0.44) were comparable between groups, while the rate of fetal distress (3.4% versus 0.7%, p 0.01) was increased in the ADPKD group. The rate of preeclampsia in the patients with simple cysts (2%) was similar to that of the general population. In contrast, the pregnant ADPKD patients had higher risks for hypertension, proteinuria, edema, urinary tract infection, renal dysfunction and preeclampsia during their pregnancies.ADPKD is associated with increased maternal complications during pregnancy, but only has a slight potential of increased rates of fetal complications.

A 23-year-old man presented with a 3-year history of untreated hypertension. He was an accomplished horse rider who had fallen several times during his teenage years. Three years earlier, he sustained an injury to the left flank while playing college football, with subsequent flank pain, ecchymoses, and a systolic blood pressure level between 150 and 170 mm Hg. He sought evaluation for blood pressure management. The patient denied having headaches, hematuria, weight change, dyspnea, chest pains, flushing, or decreased libido. This young man used no tobacco, nonsteroidal anti-inflammatory drugs, illicit drugs, or alcohol. His family history was unremarkable for hypertension. Physical examination revealed a healthy-looking man in no distress. His blood pressure level was 170/110 mm Hg in each arm, his heart rate was 68 beats/min, and he was afebrile. Cardiovascular examination findings were normal. The lungs sounded clear bilaterally, the abdomen was without bruits or masses, lower extremity pulses were symmetrical with no pulse lag, and the funduscopic examination findings were normal. The initial laboratory test results are shown in Table 1. Chest radiographic findings were normal without rib notching, and an electrocardiogram suggested no left ventricular hypertrophy.

Objective Mechanisms and interactions among intravascular cells contributing to development of subclinical atherosclerosis are poorly understood. In women, both menopausal status and pregnancy history influence progression of atherosclerosis. This study examined activation and interactions among blood elements with subclinical atherosclerosis in menopausal women with known pregnancy histories. Methods Carotid intima-media thickness (CIMT), as a marker of subclinical atherosclerosis, was measured using B-mode ultrasound in age- and parity-matched women [40 with and 40 without a history of preeclampsia] 35 years after the index pregnancy. Interactions among intravascular cells (38 parameters) were measured by flow cytometry in venous blood. Data analysis was by principal component which retained 7 independent dimensions accounting for 63% of the variability among 38 parameters. Results CIMT was significantly greater in women with a history of preeclampsia (P = 0.004). Platelet aggregation and platelet interactions with granulocytes and monocytes positively associated with CIMT in postmenopausal women independent of their pregnancy history (ρ = 0.258, P< 0.05). However, the association of the number of platelets, platelet activation and monocyte-platelet interactions with CIMT differed significantly depending upon pregnancy history (test for interaction, P

An 18-year-old girl, 15 weeks pregnant, presented to our hospital for the evaluation of headache. Her history was significant for immunoglobulin A (IgA) nephropathy, with a baseline serum creatinine of 1.8 mg/dl. She had been diagnosed with IgA nephropathy at 11 years of age after presenting with an elevated creatinine and microscopic hematuria. Her renal biopsy at the time showed mild mesangial proliferation with mesangial IgA deposits. The patient was not undergoing any therapy for her IgA nephropathy before her pregnancy.

Few clinical problems raise more controversy and debate among clinicians than the identification and treatment of renal artery stenosis and related syndromes, namely, renovascular hypertension and ischemic nephropathy. This field has rapidly evolved since Goldblatt's seminal findings in the 1930s that hypertension may be induced by partial occlusion of the renal arteries in animal models. On the clinical side, and short of efficacious antihypertensive medications at that time, these findings served as experimental evidence that optimal treatment should rely on surgical revascularization, aimed at improving blood pressure control and preserving renal function. Since then, our understanding of the underlying mechanisms of renovascular hypertension has advanced, particularly with respect to the role of the reninangiotensin-aldosterone system. In addition, new drug therapies have been devised (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and, more recently, renin inhibitors) that specifically target renin-angiotensin-aldosterone system, which have improved our ability to control renovascular hypertension, thus making the preservation of renal function a leading indication for revascularization. Furthermore, several diagnostic tests have been developed that may identify accurately either an anatomical renal artery lesion or a functional consequence of hemodynamically significant renal artery stenosis. Finally, less invasive interventional techniques have emerged, such as percutaneous transluminal renal angioplasty and renal artery stents, which allow

Evaluation of: Kanasaki K, Palmsten K, Sugimoto H et al. Deficiency in catechol-O-methyltransferase and 2-methoxyoestradiol is associated with pre-eclampsia. Nature 453 (7198), 1117–1121 (2008).Despite recent advances in the understanding of dysregulation of placenta-derived anti-angiogenic factors in preeclampsia, the etiology and pathogenesis of this disorder remain elusive. Catechol-O-methyltransferase (COMT) generates 2-methoxyestradiol (2-ME) in the human placenta and has been shown to have decreased activity in the placenta in severe preeclampsia. Kanasaki and colleagues performed a series of experiments in a Comt-/- mouse model, showing that decreased COMT activity and subsequent decreased 2-ME levels resulted in the clinical, histologic and molecular changes characteristic of preeclampsia. Furthermore, both the preeclampsia-like clinical features and characteristic angiogenic abnormalities completely resolved in rescue experiments with 2-ME. In addition, circulating levels of 2-ME were lower in ei...

Objective This study was undertaken to validate a self-administered questionnaire in verifying the diagnosis of preeclampsia, eclampsia, or toxemia in a group of women with a greater than 20-year history of preeclampsia. Study Design Questionnaires were mailed to a random sample of 144 women who received a diagnosis of any of these 3 conditions and 158 women who had normotensive pregnancies at Mayo Clinic, Rochester, Minnesota, from 1960-1979. Results A previous diagnosis of preeclampsia, eclampsia, or toxemia was verified with 80% sensitivity and 96% specificity. Conclusion Our validated questionnaire may be a useful research tool in identifying women with a previous history of preeclampsia. Women with a history of preeclampsia had a higher prevalence of future hypertension than those with a history of normotensive pregnancy.

Hypertensive disorders represent major causes of pregnancy related maternal mortality worldwide. Similar to the non-pregnant population, hypertension is the most common medical disorder encountered during pregnancy and is estimated to occur in about 6–8% of pregnancies [1]. A recent report highlighted hypertensive disorders as one of the major causes of pregnancy-related maternal deaths in the United States, accounting for 579 of the 4693 (12.3%) maternal deaths that occurred between 1998 and 2005 [2]. In low-income and middle-income countries, preeclampsia and its convulsive form, eclampsia, are associated with 10–15% of direct maternal deaths [3]. The optimal timing and choice of therapy for hypertensive pregnancy disorders involves carefully weighing the risk-versus-benefit ratio for each individual patient, with an overall goal of improving maternal and fetal outcomes. In this review we have compared and contrasted the recommendations in different treatment guidelines and we have outlined some newer perspectives on management. We have aimed to provide a clinically orientated guide to the drug treatment of hypertension in pregnancy.

Background: Urinary podocyte excretion (podocyturia) may function as a more specific marker of ongoing glomerular damage. This study sought to analyze the relationship between proteinuria and podocyturia in cancer patients treated with antivascular endothelial growth factor (anti-VEGF) agents. Methods: Thirty-seven patients treated with anti-VEGF medications were analyzed in a single-institution, cross-sectional study. Podocyte cultures were performed on random urine collections (50-100 ml), and podocytes were identified by positive podocin staining. The corresponding urine samples were analyzed for protein and creatinine (Cr) measurements. Results: Proteinuria ≥0.5 g/g Cr was found in 30% of the patients (median, 0.12; interquartile range, 0.04-0.86), and 62% had podocyturia. There was a significant difference in the amount of podocyturia between patients with proteinuria ≥0.5 g/g Cr and those with a value Discussion: Ongoing podocyte loss may be mechanistically related to the onset and severity of proteinuria in patients treated with anti-VEGF agents.

Objective Studies have shown that podocyturia, i.e., urinary loss of viable podocytes (glomerular epithelial cells), is associated with proteinuria in preeclampsia. We postulated that urinary podocyte loss may persist after preeclamptic pregnancies, thus resulting in renal injury. This may lead to future chronic renal injury. In addition, we compared the postpartum levels of the angiogenic factors, which previously have been associated with preeclampsia, between normotensive versus preeclamptic pregnancies. Study Design The diagnosis of preeclampsia was confirmed using standard clinical criteria. Random blood and urine samples were obtained within 24 hours prior to delivery and 5 to 8 weeks postpartum. Urine sediments were cultured for 24 hours to select for viable cells and staining for podocin was used to identify podocytes. Serum samples were analyzed for the levels of angiogenic markers using ELISA (enzyme-linked immunosorbent assay) methodology. Results At delivery, preeclamptic patients (n = 10) had significantly higher proteinuria (p = 0.006) and podocyturia (p

Hypertensive pregnancy disorders (HPD) are important causes of maternal and fetal morbidity and mortality worldwide. In addition, a history of HPD has been associated with an increased risk for maternal cardiovascular disease later in life, possibly because of irreversible vascular and metabolic changes that persist beyond the affected pregnancies. Therefore, treatment of HPD may not only improve immediate pregnancy outcomes, but also maternal long-term cardiovascular health. Unlike the recommendations for hypertension treatment in the general population, treatment recommendations for HPD have not changed substantially for more than 2 decades. This is particularly true for mild to moderate hypertension in pregnancy, defined as a blood pressure of 140-159/90-109 mm Hg. This review focuses on the goals of therapy, treatment strategies, and new developments in the field of HPD that should be taken into account when considering blood pressure targets and pharmacologic options for treatment of hypertension in pregnant women.

Hypertension is the most common medical disorder encountered during pregnancy, affecting up to 10 % of all pregnancies. Hypertensive disorders are one of the major causes of pregnancy-related maternal deaths in the United States. Hypertension in pregnancy includes a spectrum of conditions, including preeclampsia-eclampsia, preeclampsia superimposed on chronic hypertension, chronic hypertension, and gestational hypertension. Unlike other hypertensive pregnancy disorders, preeclampsia is a multisystem disease, its distinctive feature being either sudden onset or worsening of preexisting proteinuria. Despite significant advances in our understanding of preeclampsia, the etiology of this condition remains elusive, resulting in a failure to develop specific screening, preventive, and treatment strategies. Delivery remains the mainstay of therapy for severe forms and anticipated life-threatening complications. The most important reason for the initiation of antihypertensive treatment in these patients is to prevent maternal cerebrovascular and cardiac complications. The optimal timing and choice of therapy for hypertensive pregnancy disorders involves carefully weighing the risk-versus-benefit ratio for each individual patient, with an overall goal of improving maternal and fetal outcomes. Finally, over the past decades, it has become increasingly clear that women with a history of preeclamptic compared to normotensive pregnancies are at increased risk for cardiovascular disease later in life. In this chapter, we summarize the mechanisms thought to be involved in hypertensive pregnancy disorders, review the current treatment guidelines, and outline some newer perspectives on management, including postpartum monitoring and treatment of conventional cardiovascular risk factors in the affected women.

Multiple glomerular diseases may affect women of childbearing age. The relationship between glomerular disease and pregnancy is complex and should be approached from two major standpoints: the effects of pregnancy on maternal disease activity and progression and effects of the disease and related medical therapy on the developing fetus. Glomerular disease may be active or quiescent at conception, may flare during pregnancy, or may occur de novo during pregnancy.

Commentary on Wang IK, Muo CH, Chang YC, et al. Association between hypertensive disorders during pregnancy and end-stage renal disease: a population-based study. CMAJ 2013;185:207–13.[OpenUrl][1][Abstract/FREE Full Text][2] To date, case–control and registry-based cohort studies have suggested that women with histories of hypertensive pregnancy disorders and pre-eclampsia in particular, are at risk for future cardiovascular disease (CVD).1 ,2 Limited data have suggested that women with pre-eclampsia are at risk for microalbuminuria,3 CKD and ESRD years after their affected pregnancies.4 The limitations of the available evidence … [1]: {openurl}?query=rft.jtitle%253DCMAJ%26rft_id%253Dinfo%253Adoi%252F10.1503%252Fcmaj.120230%26rft_id%253Dinfo%253Apmid%252F23339156%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=cmaj&resid=185/3/207&atom=%2Febnurs%2F17%2F2%2F35.atom

Objective: To compare genome-wide methylation profiles in maternal leukocyte DNA between normotensive and preeclamptic pregnant women at delivery. Methods: Age, body mass index matched case-control comparison of methylation at 27,578 cytosine— guanine sites in 14,495 genes in maternal leukocyte DNA in women with preeclampsia (PE; n ¼ 14) and normotensive controls (n ¼ 14). Results: PE was associated with widespread differential methylation favoring hypermethylation. Pathway analysis identified the best matched process as a neuropeptide signaling pathway (p510 � 5 ); best matched disease as eclampsia (p59.97 � 10 � 20 ). Significantly differentially methylated genes (GRIN2b, GABRA1, PCDHB7, and BEX1) are associated with seizures. Conclusion: Altered maternal leukocyte DNA methylation is associated with PE at delivery, and differential methylation of certain neuronal genes may explain the risk for eclampsia.

An ankle-brachial index (ABI) (the ratio of ankle to brachial artery systolic blood pressure) value ≤0.9 identifies patients with peripheral arterial disease (PAD) and elevated cardiovascular event risk. This study examined whether women with a history of hypertension in pregnancy are more likely to have an ABI ≤0.9 decades after pregnancy.ABI was measured in nulliparous women (n = 144), and women with a history of normotensive (n = 1272) or hypertensive (n = 281) pregnancies who participated in the Genetic Epidemiology Network of Arteriopathy (GENOA) study [non-Hispanic white (39%) and black (61%) women, 60 (mean) ± 10 (SD) years of age]. Relationships between PAD and pregnancy history were examined by logistic regression. Compared to women with a history of normotensive pregnancy, women with a history of hypertensive pregnancy had greater odds of PAD (1.61 (odds ratio); 1.04-2.49 (95% confidence interval), p = 0.03, adjusted for age, race, height and heart rate). Additional adjustment for ever smoking, hypertension, diabetes, dyslipidemia, a family history of hypertension or coronary heart disease, body mass index and education did not attenuate this relationship (1.63; 1.02-2.62, p = 0.04). PAD risk did not differ between women with a history of normotensive pregnancy and nulliparous women (1.06; 0.52-2.14, p = 0.87).Hypertension in pregnancy is an independent risk factor for PAD decades after pregnancy after adjusting for race, age, height, heart rate, ever smoking, hypertension, diabetes, dyslipidemia, a family history of hypertension or coronary heart disease, body mass index and education.

This 58-year-old female with a 5-year history of hyper-tension was referred to our institution for furtherevaluation of a possible pheochromocytoma. Onemonth prior to her visit, she experienced the onset ofepisodic blood pressure elevations associated withheadaches, dizziness, sweating and palpitations. Herphysical examination was normal and her blood

Podocyturia, the shedding of live podocytes, is present at delivery in women with preeclampsia. The aim of this study was to test whether podocyturia is present earlier in pregnancy and predicts for preeclampsia. We also aimed to compare test characteristics of podocyturia with those of angiogenic factors previously implicated in the pathogenesis of this disorder. We prospectively enrolled 315 women who provided blood and urine samples at the end of the second trimesters of their pregnancies (median, 27 gestational weeks) and within 24 hours of their deliveries (median, 39.5 gestational weeks). Blood samples were analyzed for angiogenic markers, including placental growth factor, the soluble receptor fms-like tyrosine kinase receptor-1 for vascular endothelial growth factor, and endoglin. The urine sediments were analyzed for podocytes, identified by staining for podocin after culturing the urinary sediments for 24 hours. This analysis included all women who developed preeclampsia (n=15), gestational hypertension (n=15), and a subsample of women who remained normotensive throughout pregnancy (n=44), matched for maternal age and number of previous pregnancies to those who developed preeclampsia. At the second trimester collection, all women who developed preeclampsia had podocyturia, compared with none of those who remained normotensive or were diagnosed with gestational hypertension. Podocyturia in the second trimester had a significantly greater sensitivity and specificity for the subsequent diagnosis of preeclampsia than any single angiogenic marker or a combination thereof. Screening for podocyturia at the end of the second trimester may allow for accurate identification of pregnant women at risk for preeclampsia.

Renal artery stenosis (RAS) is an important cause of chronic renal dysfunction. Recent studies have underscored a critical role for CCL2 (MCP-1)-mediated inflammation in the progression of chronic renal damage in RAS and other chronic renal diseases. In vitro studies have implicated p38 MAPK as a critical intermediate for the production of CCL2. However, a potential role of p38 signaling in the development and progression of chronic renal disease in RAS has not been previously defined. We sought to test the hypothesis that inhibition of p38 MAPK ameliorates chronic renal injury in mice with RAS. We established a murine RAS model by placing a cuff on the right renal artery and treated mice with the p38 inhibitor SB203580 or vehicle for 2 wk. In mice treated with vehicle, the cuffed kidney developed interstitial fibrosis, tubular atrophy, and interstitial inflammation. In mice treated with SB203580, the RAS-induced renal atrophy was reduced (70% vs. 39%, P < 0.05). SB203580 also reduced interstitial inflammation and extracellular matrix deposition but had no effect on the development of hypertension. SB203580 partially blocked the induction of CCL2, CCL7 (MCP-3), CC chemokine receptor 2 (CCR2), and collagen 4 mRNA expression in the cuffed kidneys. In vitro, blockade of p38 hindered both TNF-α and TGF-β-induced CCL2 upregulation. Based on these observations, we conclude that p38 MAPK plays a critical role in the induction of CCL2/CCL7/CCR2 system and the development of interstitial inflammation in RAS.

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Background An increased number of podocyte-derived extracellular vesicles (pEVs) may reflect podocyte injury in renal disease. Elevated glomerular pressure and other insults may injure podocytes, yet it remains unclear whether the numbers of pEVs are altered in hypertensive patients. We tested the hypothesis that urinary pEV levels would be elevated in patients with renovascular hypertension (RVH) compared with essential hypertension (EH) or healthy volunteers (HVs). Methods We prospectively enrolled patients with EH ( n = 30) or RVH ( n = 31) to study renal blood flow (RBF) and cortical perfusion using multidetector computed tomography under controlled condition (regulated sodium intake and renin-angiotensin blockade). After isolation from urine samples, pEVs (nephrin and podocalyxin positive) were characterized by flow cytometry. Fourteen RVH patients were studied again 3 months after stenting or continued medical therapy. HVs ( n = 15) served as controls. Results The fraction of pEV among urinary EVs was elevated in RVH compared with HVs and EH (11.4 ± 6.4, 6.8 ± 3.4 and 6.3 ± 3.7%, respectively; P < 0.001) and remained unchanged after 3 additional months of therapy and after controlling for clinical parameters. However, eGFR- and age-adjusted pEV levels did not correlate with any clinical or renal parameters. Conclusions In hypertensive patients under controlled conditions, urinary pEV levels are elevated in patients with RVH and low eGFR compared with patients with EH and relatively preserved renal function. These pEVs may reflect podocyte injury secondary to kidney damage, and their levels might represent a novel therapeutic target.