Factors Associated with Anemia and Iron Deficiency during Pregnancy: A Prospective Observational Study in Japan.

Gestational anemia (GA) is a global health concern with a remarkably high prevalence in Japan, which is associated with various maternal and neonatal outcomes. This study aimed to explore whether GA and non-anemic iron deficiency (NAID) during the third trimester is associated with maternal characteristics, nutrient intake, low birth weight (LBW), and preterm birth. Participants were categorized into GA, NAID, and normal groups, based on serum ferritin and hemoglobin levels. Nutrient intake was assessed using the Brief Diet History Questionnaire. Data from 317 pregnant women were analyzed, including 110 (34.7%), 151 (47.6%), and 56 (17.6%) women in the GA, NAID, and normal groups, respectively. Factors associated with GA included being multipara (p < 0.001) and not taking any type of iron supplements in the third trimester (p = 0.043). The normal group had a significantly higher proportion of preterm birth and LBW than the GA and NAID groups. The GA group had a significantly higher energy intake than the normal group (p = 0.044). Overall, energy and micronutrient intake were significantly below the estimated average requirement in the dietary reference intakes for Japanese. Health care professionals need to consider nutritional advice that can prevent GA by focusing on overall micronutrients, not just energy intake.

Association of Eicosapentaenoic and Docosahexaenoic Acid Intake with Low Birth Weight in the Second Trimester: The Japan Pregnancy Eating and Activity Cohort Study.

This study examined the association of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake during the second trimester with low birth weight (LBW) in pregnant Japanese women and was conducted in conjunction with the Japan Pregnancy Eating and Activity Cohort (J-PEACH) study. The study included 504 pregnant women from four Japanese sites. During the second trimester (14-27 weeks), the participants filled out a self-administered questionnaire assessing the frequency of DHA and EPA supplement intake in the past month, as well as a brief-type self-administered diet history questionnaire (BDHQ). The analysis involved data from two time points: responses to the BDHQ and infant data at birth. In total, 471 and 33 participants were classified into the normal birth weight and LBW groups, respectively. The participants were divided into high-, medium-, and low-intake groups based on their total dietary and EPA and DHA supplementary intakes. The Cochran-Armitage trend test was used to analyze the data; the prevalence of LBW was higher in the low-intake group (p = 0.04). There was no significant sex-based trend (p = 0.27 and p = 0.35). In Japanese women, low dietary and supplementary EPA and DHA intake until the second trimester were risk factors for LBW.

Dietary Intake and Its Association with Birth Outcomes in Women with Nausea and Vomiting during the Second Trimester of Pregnancy: A Prospective Cohort Study in Japan.

Nausea and vomiting in pregnancy (NVP) is a common symptom. Although the influence of NVP during the first trimester on dietary intake and birth outcomes has been revealed, no study has focused on NVP during the second trimester. This study aimed to reveal whether NVP severity during the second trimester is associated with dietary intake, gestational weight gain (GWG), birth weight, and delivery week. Participants completed a questionnaire at 18-27 gestational weeks. NVP severity was assessed using the modified Pregnancy-Unique Quantification of Emesis and Nausea scale in the questionnaire. Dietary habits were assessed using a brief-type diet history questionnaire. In total, 825 responses were analyzed: 202 (24.5%), 135 (16.4%), and 8 (1.0%) women reported mild, moderate, and severe NVP, respectively; 480 (58.2%) women did not have NVP during the second trimester. No significant association was observed between energy and nutrient intake and no/mild and moderate/severe NVP. Women with moderate/severe NVP had lower total GWG than those with no/mild NVP (p = 0.007). There was no significant difference in low birth weight and preterm birth rates (p = 0.246 and p = 0.604). This is the first study to investigate whether NVP severity during the second trimester is associated with dietary intake and birth outcomes.

The crucial role of CTCF in mitotic progression during early development of sea urchin.

CCCTC-binding factor (CTCF), an insulator protein with 11 zinc fingers, is enriched at the boundaries of topologically associated domains (TADs) in eukaryotic genomes. In this study, we isolated and analyzed the cDNAs encoding HpCTCF, the CTCF homolog in the sea urchin Hemicentrotus pulcherrimus, to investigate its expression patterns and functions during the early development of sea urchin. HpCTCF contains nine zinc fingers corresponding to fingers 2-10 of the vertebrate CTCF. Expression pattern analysis revealed that HpCTCF mRNA was detected at all developmental stages and in the entire embryo. Upon expressing the HpCTCF-GFP fusion protein in early embryos, we observed its uniform distribution within interphase nuclei. However, during mitosis, it disappeared from the chromosomes and subsequently reassembled on the chromosome during telophase. Moreover, the morpholino-mediated knockdown of HpCTCF resulted in mitotic arrest during the morula to blastula stage. Most of the arrested chromosomes were not phospholylated at serine 10 of histone H3, indicating that mitosis was arrested at the telophase by HpCTCF depletion. Furthermore, impaired sister chromatid segregation was observed using time-lapse imaging of HpCTCF-knockdown embryos. Thus, HpCTCF is essential for mitotic progression during the early development of sea urchins, especially during the telophase-to-interphase transition. However, the normal development of pluteus larvae in CRISPR-mediated HpCTCF-knockout embryos suggests that disruption of zygotic HpCTCF expression has little effect on embryonic and larval development.

Recurrent bilateral adrenal infarction with myelodysplastic/myeloproliferative neoplasm-unclassifiable (MDS/MPN-U): a case report.

BACKGROUND: Bilateral adrenal infarction is rare and only a small number of cases have been reported so far. Adrenal infarction is usually caused by thrombophilia or a hypercoagulable state, such as antiphospholipid antibody syndrome, pregnancy, and coronavirus disease 2019. However, adrenal infarction with myelodysplastic/myeloproliferative neoplasm (MDS/MPN) has not been reported. CASE PRESENTATION: An 81-year-old man with a sudden severe bilateral backache presented to our hospital. Contrast-enhanced computed tomography (CT) led to the diagnosis of bilateral adrenal infarction. Previously reported causes of adrenal infarction were all excluded and a diagnosis of MDS/MPN-unclassifiable (MDS/MPN-U) was reached, which was considered to be attributed to adrenal infarction. He developed a relapse of bilateral adrenal infarction, and aspirin administration was initiated. Partial primary adrenal insufficiency was suspected as the serum adrenocorticotropic hormone level was persistently high after the second bilateral adrenal infarction. CONCLUSION: This is the first case of bilateral adrenal infarction with MDS/MPN-U encountered. MDS/MPN has the clinical characteristics of MPN. It is reasonable to assume that MDS/MPN-U may have influenced bilateral adrenal infarction development, considering the absence of thrombosis history and a current comorbid hypercoagulable disease. This is also the first case of recurrent bilateral adrenal infarction. It is important to carefully investigate the underlying cause of adrenal infarction once adrenal infarction is diagnosed, as well as to assess adrenocortical function.

Maternal lifestyle and nutrient intakes during pregnancy and exclusive breastfeeding in relation to risk factors for breast cancer: The Japan Environment and Children's Study.

Breastfeeding has many benefits for infant growth and maternal health, such as reducing breast cancer risk. However, data on maternal factors influencing breastfeeding are insufficient. To clarify the associations between maternal lifestyle and diet during pregnancy and exclusive breastfeeding (EBF), we conducted a prospective study of pregnant women within the framework of the Japan Environment and Children's Study (a nationwide birth cohort study). Of 97,413 pregnant women recruited between January 2011 and March 2014, 27,775 with a singleton first live birth whose dietary data during pregnancy and lactation data were complete were eligible. Using logistic regression, we evaluated the associations between lifestyle factors including smoking and prepregnancy body mass index and intake of nutrients (macronutrients, isoflavones, and dietary fiber), some of which are known risk factors of breast cancer, and EBF for one month postpartum (initiation of EBF). To investigate the associations of these factors with EBF for 6 months (continuation of EBF), 9582 women who had successfully completed one-month EBF were further followed up. Smoking and prepregnancy obesity were inversely associated with the initiation and continuation of EBF. Intakes of protein, fat, isoflavone, and dietary fiber were positively associated (p trend = 0.0001 for dietary fiber), and carbohydrate intake was inversely associated with the initiation of EBF. Dietary fiber intake was also associated with the continuation of EBF (p trend = 0.048). These findings indicate that maternal lifestyles during pregnancy affect lactation performance. Lifestyle adjustments during pregnancy may have favorable effects on maternal and children's health through successful breastfeeding.

A hyperaldosteronism subtypes predictive model using ensemble learning.

This study aimed to develop a machine-learning algorithm to diagnose aldosterone-producing adenoma (APA) for predicting APA probabilities. A retrospective cross-sectional analysis of the Japan Rare/Intractable Adrenal Diseases Study dataset was performed using the nationwide PA registry in Japan comprised of 41 centers. Patients treated between January 2006 and December 2019 were included. Forty-six features at screening and 13 features at confirmatory test were used for model development to calculate APA probability. Seven machine-learning programs were combined to develop the ensemble-learning model (ELM), which was externally validated. The strongest predictive factors for APA were serum potassium (s-K) at first visit, s-K after medication, plasma aldosterone concentration, aldosterone-to-renin ratio, and potassium supplementation dose. The average performance of the screening model had an AUC of 0.899; the confirmatory test model had an AUC of 0.913. In the external validation, the AUC was 0.964 in the screening model using an APA probability of 0.17. The clinical findings at screening predicted the diagnosis of APA with high accuracy. This novel algorithm can support the PA practice in primary care settings and prevent potentially curable APA patients from falling outside the PA diagnostic flowchart.

Effect of Intraprocedural Cortisol Measurement on ACTH-stimulated Adrenal Vein Sampling in Primary Aldosteronism.

Context: Adrenocorticotropin (ACTH) loading is used to increase the success rate of adrenal vein sampling (AVS). Objective: We aimed to determine the effect of intraprocedural cortisol measurement (ICM) on ACTH-stimulated AVS (AS-AVS) owing to a lack of reliable data on this topic. Methods: This multicenter, retrospective, observational study took place in 28 tertiary centers in Japan. Among 4057 patients enrolled, 2396 received both basal AVS (B-AVS) and AS-AVS and were divided into 2 groups according to whether ICM was used. The effect of ICM on AS-AVS was measured. Results: In patients who underwent both AVS procedures, the ICM group had significantly higher success rates for both B-AVS and AS-AVS than the non-ICM group did. However, the probability of failure of AS-AVS after a successful B-AVS and the probability of success of AS-AVS after a failed B-AVS were not significantly different in the 2 groups. For subtype diagnosis, propensity-score matching revealed no significant difference between the 2 groups, and the discrepancy rate between B-AVS and AS-AVS for subtype diagnosis was also not significantly different. Conclusion: ICM significantly increased the success rate of B-AVS and AS-AVS in protocols in which both AVS procedures were performed and had no effect on subtype diagnosis. However, in protocols in which both AVS procedures were performed, the results suggest ICM may not be necessary when performing AS-AVS if ICM is used only when B-AVS is performed. Our study suggests that ICM during AVS plays an important role and should be recommended.

Isolation and characterization of a heavy metal- and antibiotic-tolerant novel bacterial strain from a contaminated culture plate of Chlamydomonas reinhardtii, a green micro-alga.

Background:Chlamydomonas reinhardtii, a green micro-alga, is normally cultured in laboratories in Tris-Acetate Phosphate (TAP), a medium which contains acetate as the sole carbon source. Acetate in TAP can lead to occasional bacterial and fungal contamination. We isolated a yellow-pigmented bacterium from a Chlamydomonas TAP plate. It was named Clip185 based on the Chlamydomonas strain plate it was isolated from. In this article we present our work on the isolation, taxonomic identification and physiological and biochemical characterizations of Clip185. Methods: We measured sensitivities of Clip185 to five antibiotics and performed standard microbiological tests to characterize it. We partially sequenced the 16S rRNA gene of Clip185. We identified the yellow pigment of Clip185 by spectrophotometric analyses. We tested tolerance of Clip185 to six heavy metals by monitoring its growth on Lysogeny Broth (LB) media plates containing 0.5 mM -10 mM concentrations of six different heavy metals. Results: Clip185 is an aerobic, gram-positive rod, oxidase-negative, mesophilic, alpha-hemolytic bacterium. It can ferment glucose, sucrose and mannitol. It is starch hydrolysis-positive. It is very sensitive to vancomycin but resistant to penicillin and other bacterial cell membrane- and protein synthesis-disrupting antibiotics. Clip185 produces a C50 carotenoid, decaprenoxanthin, which is a powerful anti-oxidant with a commercial demand. Decaprenoxanthin production is induced in Clip185 under light. NCBI-BLAST analyses of the partial 16S rRNA gene sequence of Clip185 revealed a 99% sequence identity to that of Microbacterium binotii strain PK1-12M and Microbacterium sp. strain MDP6. Clip185 is able to tolerate toxic concentrations of six heavy metals. Conclusions: Our results show that Clip185 belongs to the genus Microbacterium. In the future, whole genome sequencing of Clip185 will clarify if Clip185 is a new Microbacterium species or a novel strain of Microbacterium binotii, and will reveal its genes involved in antibiotic-resistance, heavy-metal tolerance and regulation of decaprenoxanthin biosynthesis.

Age-stratified comparison of clinical outcomes between medical and surgical treatments in patients with unilateral primary aldosteronism.

Although adrenalectomy (ADX) is an established treatment for unilateral primary aldosteronism (uPA), the influence of age on the surgical outcomes is poorly understood. Therefore, we aimed to elucidate how age affects the clinical outcomes after treatments. We analyzed 153 older (≥ 65 years) and 702 younger patients (< 65 years) with uPA, treated either with ADX or mineralocorticoid receptor antagonist (MRA) in the Japan PA Study, and compared the estimated glomerular filtration rate (eGFR) or blood pressure over a 36-month period after treatments. ADX-treated patients showed severer biochemical indicators than MRA-treated patients. During 6 and 36 months, the eGFR decreased more prominently in older but not in younger patients with ADX than in those with MRA, which remained significant after adjustment with the inverse probability of treatment weighting (IPTW). There was a significant interaction between the age-groups and the treatment choices in the change of the eGFR with IPTW-adjusted analysis. The post-treatment dose of antihypertensive medication was lower in younger and higher in older patients with ADX than those with MRA. The clinical benefit of ADX differed between younger and older patients with uPA. These findings indicate the need for further validation on whether ADX can benefit older patients with uPA.

Sex Differences in Renal Outcomes After Medical Treatment for Bilateral Primary Aldosteronism.

A higher incidence of bilateral primary aldosteronism in women is reported. Treatment of bilateral primary aldosteronism usually involves mineralocorticoid receptor antagonists. However, the impact of sex on renal outcomes is unknown. We compared renal outcomes between the sexes after mineralocorticoid receptor antagonist initiation by analyzing data obtained from 415 female and 313 male patients with bilateral primary aldosteronism who were treated with spironolactone or eplerenone in the JPAS (Japan Primary Aldosteronism Study). Over the course of 5 years, the temporal reduction in the estimated glomerular filtration rate was greater in women than in men (P<0.001). Systolic blood pressure levels were equal between the sexes, despite higher doses of antihypertensive drugs in men. The mean of the annual decline in estimated glomerular filtration rate during what we termed the late phase, or 6 to 60 months after mineralocorticoid receptor antagonist initiation, was larger in women than in men after adjusting for patient characteristics (-1.33 mL/min per 1.73 m2 per year versus -1.04 mL/min per 1.73 m2 per year, P<0.01). Female sex was a significant predictor of greater annual decline during the late phase in patients taking spironolactone but not in those taking eplerenone. Spironolactone use and diabetes were independent predictors of a greater annual decline in estimated glomerular filtration rate during the late phase in women. These findings suggest that female sex is associated with poorer renal outcomes in patients receiving mineralocorticoid receptor antagonist for bilateral primary aldosteronism.

Associations Between Changes in Plasma Renin Activity and Aldosterone Concentrations and Changes in Kidney Function After Treatment for Primary Aldosteronism.

INTRODUCTION: Greater reduction in estimated glomerular filtration rate (eGFR) after specific treatment for primary aldosteronism (PA) reflects improvement in glomerular hyperfiltration associated with PA and leads to better patient outcomes. However, little is known regarding the mechanisms underlying eGFR reduction after treatment for PA. METHODS: We analyzed data from the nationwide PA registry in Japan. Patients were assigned to adrenalectomy (n = 438) and mineralocorticoid receptor (MR) antagonist (n = 746) groups. We assessed associations between changes in blood pressure (BP), plasma renin activity (PRA) and plasma aldosterone concentrations (PAC), and eGFR before and 6 months after treatment for both groups. RESULTS: In a multivariable linear regression, the adjusted ß values (95% confidence interval [CI]) for change in eGFR after treatment were -2.76 (-4.29, -1.22) ml/min per 1.73 m2 for PRA (per 3.2 ng/ml per hour), and 1.97 (1.08, 2.85) ml/min per 1.73 m2 for PAC (per 236.1 pg/ml) in the adrenalectomy group; and -0.45 (-0.89, -0.01) ml/min per 1.73 m2 for PRA and -0.72 (-1.62, 0.18) ml/min per 1.73 m2 for PAC in the MR antagonist group. Change in mean arterial pressure after treatment was not significantly associated with change in eGFR in either group. Changes in PRA and PAC but not BP before and 6 months after treatment for PA were associated with greater reductions in eGFR. CONCLUSION: Post-treatment improvements in glomerular hyperfiltration may be attributable to decreased MR activity in the kidneys, but not to reductions in systemic BP.

Obesity predicts persistence of resistant hypertension after surgery in patients with primary aldosteronism.

OBJECTIVE: Primary aldosteronism (PA) is considered a major cause of resistant hypertension (RHT). The prevalence of RHT has been recently reported to reach 18% in general hypertension. However, little is known about the prevalence and the outcomes after adrenalectomy of RHT in PA. Therefore, we aimed to clarify the prevalence and surgical outcomes in patients with both PA and RHT. PATIENTS AND DESIGN: Among 550 patients who underwent adrenalectomy for unilateral PA in the Japan PA Study, RHT was defined as an uncontrolled blood pressure (≥140/90 mm Hg) despite treatment with at least any three antihypertensives or hypertension controlled with at least four drugs. Surgical outcome was assessed by the biochemical and clinical outcome. RESULTS: Although 40 (7.3%) patients fulfilled the criteria for preoperative RHT, this should be underestimated because only 36% of patients with postoperative RHT were classified as having preoperative RHT. The prevalence of preoperative RHT was approximately 20% when estimated using the total number of patients with postoperative RHT and the ratio of postoperative RHT in patients with preoperative RHT. Although an improvement in hypertension was achieved in approximately 80% of patients with preoperative RHT, 20% of these exhibited persistent RHT. These patients were more obese than those for whom RHT improved after surgery. Notably, body mass index of ≥25 kg/m2 was an independent predictor of postoperative RHT. CONCLUSIONS: The prevalence of RHT in PA was lower than expected even with the adjustment for underestimation. Furthermore, obesity is an independent factor predicting the postoperative persistence of RHT.

Effect of cosyntropin during adrenal venous sampling on subtype of primary aldosteronism: analysis of surgical outcome.

OBJECTIVES: We investigated the clinical significance of ACTH stimulation during adrenal venous sampling (AVS) by surgical outcome of primary aldosteronism (PA). DESIGN: Multicenter retrospective study by Japan PA study. METHOD: We allocated 314 patients with both basal and ACTH-stimulated AVS data who underwent adrenalectomy to three groups: basal lateralization index (LI) ≥2 with ACTH-stimulated LI ≥4 on the ipsilateral side (Unilateral (U) to U group, n = 245); basal LI <2 with ACTH-stimulated LI ≥4 (Bilateral (B) to U group, n = 15); and basal LI ≥2 with ACTH-stimulated LI <4 (U to B group, n = 54). We compared surgical outcomes among the groups using the Primary Aldosteronism Surgical Outcome (PASO) criteria. RESULTS: Compared with U to U group, U to B group had poor clinical and biochemical outcomes and low rates of adrenal adenoma as pathological findings (P = 0.044, 0.006, and 0.048, respectively), although there were no significant differences between U to U and B to U groups. All patients in U to B group with clinical and biochemical benefits, however, had adrenal adenoma as pathological findings and could be well differentiated from those with poor surgical outcomes via basal LI (>8.3), but not ACTH-stimulated LI. These results were similar even when we defined each group based on a cut-off value of 4 for basal LI. CONCLUSIONS: Although PA patients in U to B group had worse surgical outcomes than did those in U to U group, basal LI could discriminate among patients with better surgical outcomes in U to B group.

Historical changes and between-facility differences in adrenal venous sampling for primary aldosteronism in Japan.

Primary aldosteronism (PA) is a common curable cause of hypertension. Adrenal venous sampling (AVS) is recommended for subtype diagnosis but is a difficult procedure. Recently, an increased prevalence of PA was reported, creating a greater demand for treatment of the condition in clinical facilities. The aim of the present study was to identify the historical changes over time and the differences between facilities in the success rate and subtype diagnosis of PA. The database of the PA registry developed by the Japan PA Study (JPAS) was used. A total of 2599 patients with PA who underwent AVS were evaluated. The overall success rate of AVS was 88%. The bilateral subtype was the dominant subtype, comprising 69% of cases. During the period 2004-2011 to 2011-2017, there were significant changes in the total number of AVS procedures (from 562 to 1732), ratio of ACTH administration with AVS (75 to 97%), success rate (79 to 90%), and proportion with bilateral subtype diagnosis (53 to 72%). There were also significant inter-facility differences in the number of AVS procedures (6 to 322), success rate (59 to 97%), and proportion with the bilateral subtype (44 to 86%). The principal enrolled department was Endocrinology (86%), and the ratio of unilateral PA was significantly higher in this department than in others (32% vs. 25%). In conclusion, the number of AVS procedures performed, the success rate, and the proportion with the bilateral subtype increased over time after normalizing the centre difference. Significant differences were observed between the centres.

Continuous Catheter Irrigation for the Treatment of Purulent Tenosynovitis during Two-Stage Flexor Tendon Reconstruction.

Two-stage flexor tendon reconstruction with a silicone rod is useful for restoring the tendon and tendon sheath but sometimes results in infection after the first-stage operation. We experienced a case in which we maintained the reconstructed tendon sheath by replacing an infected silicone rod with a polyvinyl chloride tube, followed by continuous catheter irrigation until the infection subsided. This procedure can effectively deal with infection of a silicone rod during two-stage flexor tendon reconstruction.

Predictors of Clinical Success After Surgery for Primary Aldosteronism in the Japanese Nationwide Cohort.

CONTEXT: Aldosterone-producing adenomas are a curable subtype of primary aldosteronism (PA); however, hypertension persists in some patients after adrenalectomy. OBJECTIVE: To identify factors associated with, and develop prediction models for, blood pressure (BP) normalization or improvement after adrenalectomy. DESIGN: Retrospective analysis of patients treated between 2006 and 2018, with a 6-month follow-up. SETTING: A nationwide, 29-center Japanese registry encompassing 15 university hospitals and 14 city hospitals. PATIENTS: We categorized 574 participants in the Japan Primary Aldosteronism Study, who were diagnosed with PA and underwent adrenalectomy, as BP normalized or improved, on the basis of their presentations at 6 months postsurgery. MAIN OUTCOME MEASURE: The rate of complete, partial, and absent clinical success. Predictive factors related to BP outcomes after PA surgery were also evaluated. RESULTS: Complete clinical success was achieved in 32.6% and partial clinical success was achieved in 53.0% of the patients at 6 months postsurgery. The following five variables were independent predictors for BP normalization: ≤7 years of hypertension, body mass index ≤25 kg/m2, no more than one antihypertensive medication, absence of medical history of diabetes, and female sex. The area under the receiver operator characteristic curve was 0.797 in the BP normalization model. CONCLUSION: We established models that predicted postoperative BP normalization in patients with PA. These should be useful for shared decision-making regarding adrenalectomy for PA.

Association Between Acute Fall in Estimated Glomerular Filtration Rate After Treatment for Primary Aldosteronism and Long-Term Decline in Renal Function.

Primary aldosteronism causes renal structural damage after glomerular hyperfiltration, and primary aldosteronism-specific treatment leads to an acute fall in estimated glomerular filtration rate (eGFR). We investigated whether this change affected the long-term eGFR slope in a retrospective cohort from the multicenter Japan Primary Aldosteronism Study. We allocated patients with primary aldosteronism to the adrenalectomy (n=202) and MR (mineralocorticoid receptor) antagonist (n=303) groups based on their treatment history and analyzed the association between the initial eGFR fall and long-term eGFR slope. The increased age, low serum potassium levels, high eGFR, and high plasma aldosterone levels were independent predictors for a large initial eGFR fall in both groups. Our analysis of tertiles based on the initial eGFR fall revealed that in the MR antagonist group, patients with a small initial eGFR fall had a significantly steeper long-term eGFR slope than those with a large initial fall (tertile 1 versus 2, P=0.025; tertile 1 versus 3, P=0.017). These associations were not identified in the adrenalectomy group. Thus, the smaller the acute fall in eGFR by initiation of MR antagonists, the greater was the rate of long-term eGFR decline. While the acute fall in eGFR induced by primary aldosteronism-specific treatment is occasionally a clinical concern, our findings highlight the favorable implications of the acute fall with respect to long-term renal outcomes.

Lateralizing Asymmetry of Adrenal Imaging and Adrenal Vein Sampling in Patients With Primary Aldosteronism.

CONTEXT: In patients with primary aldosteronism (PA), it remains unclear whether aldosterone-producing adenomas are likely to develop in the left or right adrenal gland. OBJECTIVE: To investigate left-right differences of PA laterality diagnoses via CT imaging and adrenal vein sampling (AVS). DESIGN: Retrospective, observational study. PATIENTS: From the Japan Primary Aldosteronism Study, 1493 patients with PA were enrolled who underwent CT and ACTH-stimulated AVS. MEASUREMENTS: Left or right adrenal nodular lesion distribution and laterality observed on CT scans and from AVS were noted. RESULTS: Both on CT scans and AVS, unilateral results were observed more frequently on the left side than on the right side (25.1% vs 15.4% and 17.3% vs 13.5%, respectively; P < 0.01for both diagnostic techniques). There was no significant difference in the concordance rate for CT and AVS between patients with left and right unilateral nodular lesions observed on CT scans (44.1% and 50.9%, respectively; P = 0.15). In patients with nodules <20 mm, the concordance rate was significantly greater on the right side than the left side (45.8% vs 56.4%; P = 0.03). In patients with bilateral results of AVS, unilateral nodular lesions were detected more frequently on the left side than the right side (17.8% vs 9.4%; P < 0.01). CONCLUSION: These results suggest aldosterone-producing adenomas and nonfunctioning tumors are more likely to develop on the left side in patients with PA and that misdiagnosis of CT-based lateralization may occur more frequently on the left side.

Renal impairment is closely associated with plasma aldosterone concentration in patients with primary aldosteronism.

OBJECTIVE: Several clinical studies have reported that renal impairments are sometimes observed in patients with primary aldosteronism (PA). We analyzed the prevalence of renal impairments in PA patients and identified parameters that increase the risk for them. DESIGN: This is a retrospective cross-sectional study. We assessed the PA database established by the multicenter Japan PA study (JPAS). Data were also collected from patients with essential hypertension (EHT). METHODS: We compared the prevalences of proteinuria and lowered estimated glomerular filtration rate (eGFR) between patients with PA and age, sex, blood pressure and duration of hypertension-matched patients with EHT. We also performed logistic regression analysis to identify parameters that increase the risk for these renal impairments. RESULTS: Among 2366 PA patients, the prevalences of proteinuria and lowered eGFR were 10.3 and 11.6%, respectively. The prevalence of proteinuria was significantly higher in PA patients than matched-EHT patients (16.8 vs 4.4%), whereas there was no significant difference in the prevalence of lowered eGFR (17.2 vs 15.0%). The logistic regression analysis also showed that the plasma aldosterone concentration (PAC) significantly increases the risk of proteinuria and lowered eGFR, independent of other known risk factors. CONCLUSION: Plasma aldosterone levels are closely associated with renal impairment in patients with PA. This is contrast to our earlier finding that the PAC was not itself linearly associated with cardiovascular events such as stroke or ischemic heart disease. The mechanism underlying the kidney damage in patients with PA may differ from that affecting the cardiovascular system.