Characterization of hospitalized patients with acute kidney injury associated with COVID-19 in Spain: renal replacement therapy and mortality. FRA-COVID SEN Registry Data.

BACKGROUND: Acute kidney injury (AKI) is common among hospitalized patients with COVID-19 and associated with worse prognosis. The Spanish Society of Nephrology created the AKI- COVID Registry to characterize the population admitted for COVID-19 that developed AKI in Spanish hospitals. The need of renal replacement therapy (RRT) therapeutic modalities, and mortality in these patients were assessed MATERIAL AND METHOD: In a retrospective study, we analyzed data from the AKI-COVID Registry, which included patients hospitalized in 30 Spanish hospitals from May 2020 to November 2021. Clinical and demographic variables, factors related to the severity of COVID-19 and AKI, and survival data were recorded. A multivariate regression analysis was performed to study factors related to RRT and mortality. RESULTS: Data from 730 patients were recorded. A total of 71.9% were men, with a mean age of 70 years (60-78), 70.1% were hypertensive, 32.9% diabetic, 33.3% with cardiovascular disease and 23.9% had some degree of chronic kidney disease (CKD). Pneumonia was diagnosed in 94.6%, requiring ventilatory support in 54.2% and admission to the ICU in 44.1% of cases. The median time from the onset of COVID-19 symptoms to the appearance of AKI (37.1% KDIGO I, 18.3% KDIGO II, 44.6% KDIGO III) was 6 days (4-10). A total of 235 (33.9%) patients required RRT: 155 patients with continuous renal replacement therapy, 89 alternate-day dialysis, 36 daily dialysis, 24 extended hemodialysis and 17 patients with hemodiafiltration. Smoking habit (OR 3.41), ventilatory support (OR 20.2), maximum creatinine value (OR 2.41), and time to AKI onset (OR 1.13) were predictors of the need for RRT; age was a protective factor (0.95). The group without RRT was characterized by older age, less severe AKI, and shorter kidney injury onset and recovery time (p < 0.05). 38.6% of patients died during hospitalization; serious AKI and RRT were more frequent in the death group. In the multivariate analysis, age (OR 1.03), previous chronic kidney disease (OR 2.21), development of pneumonia (OR 2.89), ventilatory support (OR 3.34) and RRT (OR 2.28) were predictors of mortality while chronic treatment with ARBs was identified as a protective factor (OR 0.55). CONCLUSIONS: Patients with AKI during hospitalization for COVID-19 had a high mean age, comorbidities and severe infection. We defined two different clinical patterns: an AKI of early onset, in older patients that resolves in a few days without the need for RRT; and another more severe pattern, with greater need for RRT, and late onset, which was related to greater severity of the infectious disease. The severity of the infection, age and the presence of CKD prior to admission were identified as a risk factors for mortality in these patients. In addition chronic treatment with ARBs was identified as a protective factor for mortality.

Prophylaxis against postcontrast acute kidney injury (PC-AKI): updates in the ESUR guidelines 10.0 and critical review. / Profilaxis de la lesión renal aguda poscontraste (LRA-PC). Actualización según la guía clínica ESUR 10.0 y revisión crítica.

The European Society of Urogenital Radiology (ESUR) updated its guidelines for prophylaxis against postcontrast acute kidney injury (PC-AKI) in 2018 (ESUR 10.0). These guidelines drastically reduce the indications for prophylaxis against PC-AKI after iodine-based contrast administration, lowering the cutoff for administering prophylaxis to glomerular filtration rates <30ml/min/1.73m2 and eliminating most of the prior risk factors. Moreover, in cases where prophylaxis is considered necessary, the periods of hydration are shorter than in the previous version. These guidelines have been approved by most radiological societies, although they have also been criticized for excessive relaxation regarding risk factors, especially by the nephrological community. In this article, we critically review the changes to the guidelines.

An update on tolvaptan for autosomal dominant polycystic kidney disease.

Tolvaptan is an orally active antagonist of vasopressin (antidiuretic hormone [ADH]) V2 receptors. By blocking water reabsorption in kidney collecting ducts, it prompts renal free-water excretion and has been used for the treatment of hyponatremia, both euvolemic due to the syndrome of inappropriate ADH secretion, and hypervolemic due to liver cirrhosis and congestive heart failure. In the past few years, it has been shown that vasopressin and its second messenger cyclic adenosine monophosphate (cAMP) play an important role in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). This has been the rationale for the use of tolvaptan to halt the progression of ADPKD, mainly through slowing kidney growth and decline in renal function. Two major randomized clinical trials have demonstrated the benefits of tolvaptan in slowing the progression of ADPKD in terms of kidney growth and decline in renal function at 1 and 3 years (REPRISE and TEMPO). However, the long-term effectiveness of treatment with tolvaptan remains to be determined.

Acute tubulointerstitial nephritis associated with atezolizumab, an anti-programmed death-ligand 1 (pd-l1) antibody therapy.

Direct stimulation of the antitumor activity of immune system through checkpoint inhibitors (ICIs) has demonstrated efficacy in the treatment of different cancer types. The activity of these antibodies takes place in the immunological synapse blocking the binding of the negative immunoregulatory proteins, thus leading to the finalization of the immune response. Despite having a favorable toxicity profile, its mechanism of action impedes the negative regulation of the immune activity which can potentially favor autoimmune attacks to normal tissues. Renal toxicity has been described in several ICI but not with atezolizumab, an IgG1 monoclonal antibody targeting PD-L1 (programmed death ligand 1), approved by FDA as a second-line therapy for advanced urothelial carcinoma. Here we present a patient with a single kidney and metastatic renal cell carcinoma treated with atezolizumab and bevacizumab combination, with biopsy-proven acute interstitial nephritis, who had a complete resolution of renal dysfunction after steroid therapy.

Factors associated with blood pressure control in diabetic patients treated in nephrology units. PRESDIAB Study.

BACKGROUND AND OBJECTIVE: Most hypertensive patients do not reach target blood pressure (BP), especially if they are diabetic. The objective of the study is to assess the percentage of tight BP control, defined as BP<130/80mm Hg and identify factors associated with it in diabetic type 2 (DM2) patients treated in nephrology units. PATIENTS AND METHODS: Observational and cross-sectional study; we included 526 patients with DM2 and arterial hypertension (AHT). We collected data on: demographics, anthropometrics, harmful habits, history of cardiovascular disease (CVD), blood pressure, kidney function, glycaemic control, lipid profile, and drug treatment, among others. RESULTS: The mean age (SD) was 66 (10.6) years, 61% were male, 12.8% were smokers, 39.4% had a history of CVD, 72% had hypercholesterolemia, and 44% were obese. Seventeen point five percent of patients had tight BP control (<130/80mm Hg) (95% confidence interval [CI]:14.3-21.0), while 36.9% had BP below 140/85mm Hg. Seventy-one percent of patients were prescribed two or more anti-hypertensive treatments. Several factors are associated with tight BP control not being achieved, and the logistic regression analysis revealed that LDL cholesterol levels were significantly associated (odds ratio [OR] 0.55; 95% CI:0.41-0.75 for one standard deviation increase). CONCLUSIONS: Of the DM2 patients that attended the nephrology units, less than 20% achieved a tight BP control. Cholesterol levels seem to be the main factor associated with unsatisfactory BP control within our study population.

[Endoscopic techniques in bronchogenic carcinoma. Changes in recent decades]. / Técnicas endoscópicas en carcinoma broncogénico. Cambios en las últimas décadas.

A 57-year old woman with arterial hypertension under treatment. She has smoked since she was 18 years old with an accumulated index of 70 years/pack. She was studied in our Respiratory Department due to constitutional syndrome, the X-ray showing an image of focal pulmonary lesion in the right upper lobe of more than 3cm of peripheral location. The computed tomography (CT) scan confirmed the existence of a 3.3cm mass in the upper right lobe and detected paratracheal and subcarinal mediastinal abnormal lymph nodes. A subsequent Positron Emission Tomography (PET) confirmed pathological uptake of the mass and both lymph node locations. Which additional studies do you consider to be indicated for a correct diagnosis and mediastinal staging? Do bronchoscopy techniques alone establish the final diagnosis and staging of this patient?

Bortezomib decreases Rb phosphorylation and induces caspase-dependent apoptosis in Imatinib-sensitive and -resistant Bcr-Abl1-expressing cells.

The use of c-abl-specific inhibitors such as Imatinib (IM) or Dasatinib has revolutionized the treatment of chronic myeloid leukemia (CML). However, a significant percentage of patients become resistant to IM. In this report, we have analyzed the possibility of using the proteasome as a molecular target in CML. Our results show that cells that express Bcr-Abl1 are more sensitive to the inhibition of the proteasome with Bortezomib (Btz) than control cells. This treatment reduces the proliferation of Bcr-Abl1-expressing cells, by inactivating NF-kappaB2 and decreasing the phosphorylation of Rb, eventually leading to an increase in caspase-dependent apoptosis. Furthermore, we show that Btz also induces cell-cycle arrest and apoptosis in cells expressing Bcr-Abl1 mutants that are resistant to IM. These results unravel a new molecular target of Btz, that is the Rb pathway, and open new possibilities in the treatment of CML especially for patients that become resistant to IM because of the presence of the T315I mutation.

Urinary albumin excretion is associated with true resistant hypertension.

Resistant (or refractory) hypertension (RH) is a clinical diagnosis based on blood pressure (BP) office measurements. About one third of subjects with suspected RH have indeed pseudo-resistant hypertension and 24-h ambulatory-blood pressure-monitoring aids to precisely identify them. Our aim was to determine those clinical, laboratory or echocardiographic variables that may be associated with subjects with sustained hypertension (namely true RH). We carried out a cross-sectional analysis of 143 patients consecutively enrolled with the clinical diagnosis of RH. All patients underwent clinical-demographic, laboratory evaluation, 2D-echocardiography and 24-h ambulatory-blood pressure-monitoring. Pseudo-resistant hypertension or white-coat RH was defined if office BP was > or =140 and/or 90 mm Hg and 24-h BP <130/80 mm Hg. One-hundred and three (72%) patients had true RH and 40 (28%) patients had white-coat RH. True RH patients had significantly higher diabetes prevalence and higher office-systolic blood pressure (SBP) levels. Regarding target organ damage, left ventricular mass index (LVMI) and 24-h urinary albumin excretion (UAE) were also higher in true RH after adjustment for possible confounders (P=0.031 and P=0.012, respectively). In a logistic regression analysis, only office-SBP (multivariate OR (95%CI): 1.030 (1.003-1.057), P=0.030) and UAE (multivariate OR (95% CI): 2.376 (1.225-4.608), P=0.010) were independently associated with true RH. We conclude that true resistant hypertension is associated with silent target organ damage, especially UAE. In patients with suspected RH, assessment of 24 h ambulatory BP is the most accurate way to detect a population with high risk for target-organ damage.

RhoE is spatiotemporally regulated in the postnatal mouse CNS.

Rnd proteins are a family of small GTPases that have been involved in axon path finding and CNS development by their control of actin cytoskeleton dynamics. Rnd proteins are constitutively activated and, subsequently, their functions determined by their localization and expression levels. In this work we have analyzed by Western blot and immunohistochemistry the levels and localization of Rnd3/RhoE during mouse postnatal development. CNS was found to be the main tissue for RhoE protein expression, which was detected in all regions of the adult brain and spinal cord, with the highest levels in the olfactory bulb and cortex. RhoE protein levels were considerably higher in all the regions of the CNS the first 2-3 weeks of postnatal development, undergoing later a decrease that led to low levels in the adult. Immunohistochemical detection of RhoE at postnatal day 21 showed an intense and widespread labelling throughout the CNS. RhoE immunoreactivity was detected in the granular and mitral cells and anterior olfactory nuclei of the olfactory bulb and in all cerebral layers. In the striatum, diencephalon, mesencephalon, pons, medulla oblongata and spinal cord, RhoE was widely distributed with higher intensity in the motoneurones and in some brainstem nuclei such as the red nucleus or the reticulotegmental nucleus. The pyramidal cells of CA1-3 and the polymorph layer, but not the granular cells of the dentate gyrus in the hippocampus were strongly labelled. At earlier stages the labelling was nearly similar; however, a prominent labelling was detected in the cells of the rostral migratory stream and in the external granule cells of the cerebellum. Our results suggest that RhoE can play important roles in the postnatal development and maturation of the CNS, especially in the migratory processes affecting the neurones.

[Profitability of the bronchoscopy in the diagnosis of focal pulmonary malignant lesions]. / Rentabilidad de la broncoscopia en el diagnóstico de lesiones pulmonares focales malignas.

INTRODUCTION: We define focal pulmonary lesion (FPL) as an intra-parenchymatous pulmonary lesion that is well circumscribed and completely surrounded by healthy lung. It is considered that the profitability of the fine needle aspiration puncture (FNAP) in FPL < or = 2 cm is better than that of the fibrobronchoscopy (FBC). OBJECTIVE: To analyze the diagnostic profitability of the FNAP in the malignant FPL and study if it varies according to site, size and histology. MATERIAL AND METHODS: We analyzed all the FBCs of our Unit between 01/2000 and 12/2001 in patients with solitary FLP < or = 6 cm with a definitive diagnosis of malignancy. The diagnostic profitability by size, site and histology was analyzed with Pearson's chi(2) statistics. RESULTS: 124 patients. Mean FBC per patient was 1.3. A total of 101 cases (82%) were diagnosed with FBC, 15 by thoracotomy and 8 by FNAP. Global diagnostic profitability of the FBC was 0.82 and the transbronchial biopsy 0.76. There are no diagnostic profitability differences by size (< or = 2 cm vs > 2 cm) (0.81 vs 0.82 p = 0.96), site (peripheral vs central) (0.79 vs 0.85 p = 0.41) and histology (epidermoid vs adenocarcinoma) (0.89 vs 0.75 p = 0.21). CONCLUSION: Profitability of the FBC in malignant FPL in our hospital is elevated without differences by size, site or histology. In our site, the initial diagnostic approach of the FLP is done with FBC.

Nephrogenic systemic fibrosis: a case series suggesting gadolinium as a possible aetiological factor.

Nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy is a rare fibrotic condition that presents in patients with a history of renal disease. The aetiology is unknown, but it has recently been proposed that gadolinium, a paramagnetic contrast agent, may be a trigger of this disease. We report three patients with NSF with a history of use of gadolinium in magnetic resonance angiography a few weeks before the onset of symptoms. In the future, gadolinium should probably be avoided as much as possible in renal insufficiency patients until its role in the development of NSF is clarified.

[Quality indicators in Hypertension Care Units: indicators of structure in the QUALIHTA study]. / Indicadores de calidad en unidades asistenciales de hipertensión arterial en España: indicadores de estructura en el estudio QUALIHTA.

AIM: To evaluate the minimum-required indicators of quality of care in Hypertension Units at two levels of delivered care (secondary and tertiary) in Spain. METHODS: A total of 51 quality indicators were included (N) in order to evaluate: architectural resources (8), material resources (12 on devices and 22 on supportive services) and human resources (9), which were presented as a formulary to the head of the corresponding Hypertension Unit. As a measure of the indicator, the accomplishment (yes/no) was registered. RESULTS: Data from 61 participating centers were collected and included in the analysis: 42 (68,9%) centers of tertiary level and 19 (31,1%) of secondary level. The degree of compliance of the different quality indicators in the global sample is (range): architecture, 60%-100%; material resources, 83.3%-100% (devices); 57.4-100% auxiliary services; 51.7% with respect to human resources and 69-100% with respect to continuing education and the dedication of the personnel. As expected, the differences between care levels were observed mainly in the availability of auxiliary services. CONCLUSIONS: The Hypertension Units in Spain comply with a series of structural indicators of care quality at an acceptable level. The degree of compliance in certain aspects of human resources, mainly percent of dedication, number and continuing education could be improved. The evaluation of these aspects of care quality could allow the Scientific Societies to define the recommendation in order to deliver the best quality of care in hypertension.

[Hypertension in hemodialysis: prevalence and associated factors in Catalonia. The PRESDIAL study]. / Prevalencia y factores asociados a hipertensión arterial en hemodiálisis en Cataluña. Estudio PRESIDIAL.

OBJECTIVE: To evaluate the prevalence of hypertension (HT) in prevalent hemodialysis (HD) patients in our region, and to analyze the associated clinical and biochemical variables. METHODS: Observational, cross-sectional and multicentric study including a representative sample of prevalent and stable (> 6 months) HD patients from all the HD centers (in and out of Hospitals) in Catalonia, Spain. Clinical and biochemical variables were recorded and predialysis blood pressure (BP) was determined (x3) in each dialysis session during 1 month, as well as the pre/post weight weekly. HT was defined as having at least one of these criteria: a mean (12 determinations) systolic BP > or = 140 mmHg or diastolic BP > or = 90 mmHg or antihypertensive treatment for at least 3 months. RESULTS: The sample comprised 387 patients from 32 of the 40 centers included, 231 of whom where men, with mean age of 63 +/- 14 years. The prevalence of HT in this sample was 67.4%, varying according to the etiology of End-Stage Renal Disease: diabetic 81%, vascular 81%, glomerulonephritis 61%, PKD 52%, unknown and others 64%. The prevalence of additional CV risk factors was 83%. One of each hypertensive 4 patients were treated, of whom 58% had systolic BP > or = 140 or dyastolic > or = 90, in contrast to 28% of untreated patients. The proportion of individuals according to the number of antihypertensive agents was 21% (no agents), 48% (1 agent), 20% (2 agents), 11% (3 agents). Blood pressure was higher among patients receiving higher number of antihypertensive agents. No differences according HT were found in age (64 +/- 13 in hypertensive patients versus 60 +/- 15 in normotensives), time on dialysis (4 +/- 4 vs 4 +/- 4 years), interdialysis weight gain (2.1 +/- 0.8 vs 2.1 +/- 0.8 kg), proportion of weight gain (3.3 +/- 1.4 vs 3.1 +/- 1.4%) or proportion of patients with > 5% weight gain with respect to dry weight (32.5 vs 27.3%). While 84% of hypertensive patients had an additional CV risk factor, this value was 67% in the patients without HT (p < 0.001). CONCLUSION: In HD patients HT has a high prevalence in our region and is poorly controlled. The causes of this poor control may be multiple, and weight gain parameters seem not to be a main factor in these stable patients. Due to the aggregation of risk factors in these patients, strategies in order to improve BP control in HD are mandatory.

[Baclofen-associated encephalopathy in a hemodialysis patient with hiccups]. / Encefalopatía asociada a baclofeno como tratamiento del hipo refractario en un paciente en hemodiálisis.

Baclofen is a centrally acting gamma-ammino butyric acid agonist that is used like muscular relaxant in disorders with spasticity and intractable hiccups. Although encouraging and safe results were provided 5 mg/day in hemodialysis patients, his pharmacokinetic and pharmacodinamic properties are not well known in end stage renal disease. We present here the case of a hemodialysis patient with intractable hiccups who developed baclofen-associated encephalopathy with this recommended dose.

A coding polymorphism in the 12-lipoxygenase gene is associated to essential hypertension and urinary 12(S)-HETE.

The arachidonic acid-derived metabolite 12-(S)hydroxyeicosatetraenoic acid (12(S)-HETE), catalyzed by 12-lipoxygenase (12-LOX, ALOX12), exhibits a variety of biological activities with implications in cardiovascular disease. Previous studies have shown higher urinary excretion of this metabolite in essential hypertension. The aim of this study was to analyze the association of polymorphisms in ALOX12 with hypertension and urinary levels of 12(S)-HETE. We studied 200 patients with essential hypertension (aged 56+/-1 years, mean+/-s.e.m., 97 males) and 166 matched controls (aged 54+/-1 years, 91 males). Out of six polymorphisms in the coding region of ALOX12, only R261Q determined a nonconservative amino-acid change and was evaluated by polymerase chain reaction and restriction digestion. Urinary 12(S)-HETE was measured in Sep-Pack-extracted samples using specific enzyme-linked immunosorbent assay. The distribution of genotypes of the R261Q polymorphism was significantly different between patients and controls: patients 92 (0.46) GG, 84 (0.42) GA, 24 (0.12) AA vs controls 56 (0.34) GG, 78 (0.47) GA, 32 (0.19) AA (P=0.030). On the contrary, no association was observed for two intronic polymorphisms. The urinary excretion of 12(S)-HETE (ng/mg creatinine) was significantly higher in GG homozygous patients (13.0+/-1.5) than in GA (8.2+/-1.8) or in AA (8+/-1.5) patients (P=0.018). These results indicate that a nonsynonymous polymorphism in ALOX12 is associated to essential hypertension and to urinary levels of 12(S)-HETE, thus suggesting a role for this gene in this disease.

Molecular basis of salt sensitivity in human hypertension. Evaluation of renin-angiotensin-aldosterone system gene polymorphisms.

We analyzed the association between salt sensitivity in essential hypertension and 8 genetic polymorphisms in 6 genes of the renin-angiotensin aldosterone system. Seventy-one patients with essential hypertension were classified as salt sensitive or salt resistant by means of the 24-hour ambulatory blood pressure (BP) change to high salt intake. The polymorphisms evaluated correspond to the following genes: ACE (I/D), angiotensinogen (M235T), angiotensin II type 1 receptor (A1166C), 11beta-Hydroxysteroid dehydrogenase type 2 (11betaHSD2) (G534A), aldosterone synthase (C-344T and Intron 2 conversion), and the mineralocorticoid receptor (G3514C and A4582C); all were determined using standard polymerase chain reaction methods. Thirty-five patients (49%) were classified as salt sensitive. We analyzed the BP response to high salt intake among genotypes and found a significant association for ACE I/D and 11betaHSD2 G534A polymorphisms. Patients homozygous for the insertion allele of the ACE gene (II) had a significantly higher BP increase with high salt intake than did patients homozygous for the deletion allele (DD). Heterozygous patients (ID) exhibited an intermediate response. The prevalence of salt-sensitive hypertension was also significantly higher (P=0.003) in II (68%) and DI patients (59%) compared with DD hypertensives (19%). With respect to 11betaHSD2 G534A, patients with the GG genotype had a significantly higher systolic BP increase with high salt intake than did GA patients. In addition, plasma renin activity suppression in response to high salt was significantly greater in GA patients than in GG patients. The prevalence of salt-sensitive hypertension was 14.3% in GA patients and 50.8% in GG patients (P=0.067). In conclusion, the I allele of ACE I/D polymorphism is significantly associated to salt-sensitive hypertension. The BP response to high salt intake was different among genotypes of ACE I/D and 11betaHSD G534A, suggesting that these polymorphisms may be potentially useful genetic markers of salt sensitivity.

Role of Sp1 in the induction of p27 gene expression in vascular smooth muscle cells in vitro and after balloon angioplasty.

-The abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an important role in atherosclerosis and restenosis. Although several studies have implicated the growth inhibitory protein p27(Kip1) (p27) in the control of myocyte growth and hypertrophy, little is known about the molecular mechanisms that regulate p27 expression in the cardiovascular system. In the present study, we demonstrate the interaction of the transcription factor Sp1 with 2 GC-rich sequences within the p27 promoter in cultured VSMCs. Importantly, point mutations that disrupted Sp1 binding markedly reduced p27 promoter activity, demonstrating that Sp1 is required for efficient p27 gene transcription in cultured VSMCs. Because p27 expression is upregulated after balloon angioplasty, we investigated Sp1 expression and activity in control and balloon-injured rat carotid arteries to assess the role of Sp1 as a physiological regulator of p27 expression. Although immunohistochemical analysis disclosed Sp1 protein expression in both control and balloon-injured arteries, a high level of Sp1 DNA-binding activity was found only in response to balloon angioplasty. Collectively, these results demonstrate that Sp1 is essential for maximum p27 promoter activity in VSMCs and suggest that posttranslational induction of Sp1 DNA-binding activity contributes to the induction of p27 expression and VSMC growth arrest at late time points after balloon angioplasty.

Increased levels of 12(S)-HETE in patients with essential hypertension.

The platelet-type 12-lipoxygenase (12-LO) catalyzes the transformation of arachidonic acid into 12-hydroperoxyeicosatetraenoic acid [12-(S)HPETE], which is reduced to 12-hydroxyeicosatetraenoic acid [12-(S)HETE]. These metabolites exhibit a variety of biological activities such as mediation of angiotensin II-induced intracellular calcium transients in cultured rat vascular smooth muscle cells. It has recently been reported that platelet 12(S)-HETE production is enhanced in the spontaneously hypertensive rat. The pronounced hypotensive effect of LO inhibition in SHR suggests that LO activity may play a role in this form of hypertension. The aim of this study was to determine the basal and thrombin-induced platelet 12(S)-HETE production and the urinary 12(S)-HETE excretion in essential hypertension. We studied 19 patients with this disease (57+/-2 years of age) and 9 normotensive control subjects (48+/-5 years of age) (P:=0.074). 12(S)-HETE was measured in Sep-Pack-extracted samples with specific ELISA and high-performance liquid chromatography. The platelet basal level of 12(S)-HETE was significantly higher in patients than in control subjects (3.56+/-1.22 versus 0.64+/-0.13 ng/10(6) platelets, P:<0.025). In contrast, there were no differences in thrombin-stimulated (1 U/mL) 12(S)-HETE generation: 7.66+/-2.14 in patients versus 4.87+/-1.46 in control subjects (P:=0.61). Platelet 12-LO protein levels, measured by Western blotting with a polyclonal antibody, were higher in the patients than in the control subjects. The urinary excretion of 12(S)-HETE was higher in patients than in control subjects: 36.8+/-7.24 versus 17.1+/-3.14 ng/mg creatinine (P:<0.01). These results indicate that 12(S)-HETE levels and 12-LO protein are increased in patients with essential hypertension, suggesting a role for this metabolite in human hypertension.