Estrogen receptor 2b is the major determinant of sex-typical mating behavior and sexual preference in medaka.

Male and female animals typically display innate sex-specific mating behaviors, which, in vertebrates, are highly dependent on sex steroid signaling. While estradiol-17ß (E2) signaling through estrogen receptor 2 (ESR2) serves to defeminize male mating behavior in rodents, the available evidence suggests that E2 signaling is not required in teleosts for either male or female mating behavior. Here, we report that female medaka deficient for Esr2b, a teleost ortholog of ESR2, are not receptive to males but rather court females, despite retaining normal ovarian function with an unaltered sex steroid milieu. Thus, contrary to both prevailing views in rodents and teleosts, E2/Esr2b signaling in the brain plays a decisive role in feminization and demasculinization of female mating behavior and sexual preference in medaka. Further behavioral testing showed that mutual antagonism between E2/Esr2b signaling and androgen receptor-mediated androgen signaling in adulthood induces and actively maintains sex-typical mating behaviors and preference. Our results also revealed that the female-biased sexual dimorphism in esr2b expression in the telencephalic and preoptic nuclei implicated in mating behavior can be reversed between males and females by altering the sex steroid milieu in adulthood, likely via mechanisms involving direct E2-induced transcriptional activation. In addition, Npba, a neuropeptide mediating female sexual receptivity, was found to act downstream of E2/Esr2b signaling in these brain nuclei. Collectively, these functional and regulatory mechanisms of E2/Esr2b signaling presumably underpin the neural mechanism for induction, maintenance, and reversal of sex-typical mating behaviors and sexual preference in teleosts, at least in medaka.

Predictors of early postoperative pneumonia after oncologic surgery with the patients receiving professional oral health care: A prospective, multicentre, cohort study.

This study was a prospective, multicentre, cohort study on 685 patients who had undergone oncologic surgery. The patients were divided into two groups according to the presence or absence of postoperative pneumonia. The two groups were compared with respect to their background, index operation, food eaten, oral condition, contents of oral care and dental treatment, laboratory data, and bacterial flora. All postoperative pneumonias occurred in six cases within four days postoperatively. The multivariable logistic regression analysis showed that preoperative serum C-reactive protein was the strongest predictor of postoperative pneumonia. In addition, decreased postoperative Candida albicans colonies was an effective predictor of postoperative pneumonia. For patients with predictors of postoperative pneumonia, perioperative strategies for its prevention should be considered in addition to professional oral health care. This study was approved by the National Hospital Organization's Central Ethics Review Board and was also approved by the directors of the participating institutions.

Ovarian aromatase loss-of-function mutant medaka undergo ovary degeneration and partial female-to-male sex reversal after puberty.

Although estrogens have been generally considered to play a critical role in ovarian differentiation in non-mammalian vertebrates, the specific functions of estrogens during ovarian differentiation remain unclear. We isolated two mutants with premature stops in the ovarian aromatase (cyp19a1) gene from an N-ethyl-N-nitrosourea-based gene-driven mutagenesis library of the medaka, Oryzias latipes. In XX mutants, gonads first differentiated into normal ovaries containing many ovarian follicles that failed to accumulate yolk. Subsequently, ovarian tissues underwent extensive degeneration, followed by the appearance of testicular tissues on the dorsal side of ovaries. In the newly formed testicular tissue, strong expression of gsdf was detected in sox9a2-positive somatic cells surrounding germline stem cells suggesting that gsdf plays an important role in testicular differentiation during estrogen-depleted female-to-male sex reversal. We conclude that endogenous estrogens synthesized after fertilization are not essential for early ovarian differentiation but are critical for the maintenance of adult ovaries.

Sexually dimorphic expression of the sex chromosome-linked genes cntfa and pdlim3a in the medaka brain.

In vertebrates, sex differences in the brain have been attributed to differences in gonadal hormone secretion; however, recent evidence in mammals and birds shows that sex chromosome-linked genes, independent of gonadal hormones, also mediate sex differences in the brain. In this study, we searched for genes that were differentially expressed between the sexes in the brain of a teleost fish, medaka (Oryzias latipes), and identified two sex chromosome genes with male-biased expression, cntfa (encoding ciliary neurotrophic factor a) and pdlim3a (encoding PDZ and LIM domain 3 a). These genes were found to be located 3-4 Mb from and on opposite sides of the Y chromosome-specific region containing the sex-determining gene (the medaka X and Y chromosomes are genetically identical, differing only in this region). The male-biased expression of both genes was evident prior to the onset of sexual maturity. Sex-reversed XY females, as well as wild-type XY males, had more pronounced expression of these genes than XX males and XX females, indicating that the Y allele confers higher expression than the X allele for both genes. In addition, their expression was affected to some extent by sex steroid hormones, thereby possibly serving as focal points of the crosstalk between the genetic and hormonal pathways underlying brain sex differences. Given that sex chromosomes of lower vertebrates, including teleost fish, have evolved independently in different genera or species, sex chromosome genes with sexually dimorphic expression in the brain may contribute to genus- or species-specific sex differences in a variety of traits.

Draft assembly of the Symbiodinium minutum nuclear genome reveals dinoflagellate gene structure.

BACKGROUND: Dinoflagellates are known for their capacity to form harmful blooms (e.g., "red tides") and as symbiotic, photosynthetic partners for corals. These unicellular eukaryotes have permanently condensed, liquid-crystalline chromosomes and immense nuclear genome sizes, often several times the size of the human genome. Here we describe the first draft assembly of a dinoflagellate nuclear genome, providing insights into its genome organization and gene inventory. RESULTS: Sequencing reads from Symbiodinium minutum were assembled into 616 Mbp gene-rich DNA regions that represented roughly half of the estimated 1,500 Mbp genome of this species. The assembly encoded ∼42,000 protein-coding genes, consistent with previous dinoflagellate gene number estimates using transcriptomic data. The Symbiodinium genome contains duplicated genes for regulator of chromosome condensation proteins, nearly one-third of which have eukaryotic orthologs, whereas the remainder have most likely been acquired through bacterial horizontal gene transfers. Symbiodinium genes are enriched in spliceosomal introns (mean = 18.6 introns/gene). Donor and acceptor splice sites are unique, with 5' sites utilizing not only GT but also GC and GA, whereas at 3' sites, a conserved G is present after AG. All spliceosomal snRNA genes (U1-U6) are clustered in the genome. Surprisingly, the Symbiodinium genome displays unidirectionally aligned genes throughout the genome, forming a cluster-like gene arrangement. CONCLUSIONS: We show here that a dinoflagellate genome exhibits unique and divergent characteristics when compared to those of other eukaryotes. Our data elucidate the organization and gene inventory of dinoflagellates and lay the foundation for future studies of this remarkable group of eukaryotes.

ANGUSTIFOLIA3 signaling coordinates proliferation between clonally distinct cells in leaves.

Coordinated proliferation between clonally distinct cells via inter-cell-layer signaling largely determines the size and shape of plant organs. Nonetheless, the signaling mechanism underlying this coordination in leaves remains elusive because of a lack of understanding of the signaling molecule (or molecules) involved. ANGUSTIFOLIA3 (AN3, also called GRF-INTERACTING FACTOR1) encodes a putative transcriptional coactivator with homology to human synovial sarcoma translocation protein. AN3 transcripts accumulate in mesophyll cells but are not detectable in leaf epidermal cells. However, we found here that in addition to mesophyll cells, epidermal cells of an3 leaves show defective proliferation. This spatial difference between the accumulation pattern of AN3 transcripts and an3 leaf phenotype is explained by AN3 protein movement across cell layers. AN3 moves into epidermal cells after being synthesized within mesophyll cells and helps control epidermal cell proliferation. Interference with AN3 movement results in abnormal leaf size and shape, indicating that AN3 signaling is indispensable for normal leaf development. AN3 movement does not require type II chaperonin activity, which is needed for movement of some mobile proteins. Taking these findings together, we present a novel model emphasizing the role of mesophyll cells as a signaling source coordinating proliferation between clonally independent leaf cells.

[A survey examining the countermeasures taken by restaurants to prevent passive smoking and an analysis of the economic impact of smoking prohibition in restaurants].

OBJECTIVES: This study examines the countermeasures taken by restaurants to prevent passive smoking and the impact of smoking prohibition on both the number of customers and sales volume in restaurants. METHODS: An interview-based survey was administered to 8,558 restaurant managers in Aichi prefecture. The survey questions concerned the countermeasures taken against passive smoking within each restaurant and the effect of the prohibition of smoking on both the number of customers and sales volume between November 1, 2009, and February 26, 2010. RESULTS: Seven thousand and eighty managers responded to the survey (response rate 83%). The proportion of managers of restaurants with a complete smoking ban was 16.4%, of restaurants with a smoking and non-smoking room or section was 20.2%, and of restaurants where no countermeasures were taken was 63.4%. The results showed that among the restaurants with a complete smoking ban, the number of customers and sales volume increased in 1.5%, decreased in 3.9%, and did not change in 95%. Differences in countermeasures were seen according to the type of restaurant. A high proportion of restaurants with a complete ban were curry shops and fast food restaurants, while few such restaurants were bars or Izakaya (Japanese style bars) and Yakiniku (Korean style BBQ) restaurants. CONCLUSION: The results of this large-scale survey in Aichi prefecture suggest that the economic impact of smoking prohibition in restaurants, in terms of the number of customers and sales volume, is small.

Histological observation of the urogenital papillae in the bi-directional sex-changing gobiid fish, Trimma okinawae.

The gobiid fish Trimma okinawae changes its sex bi-directionally according to its social status. Morphological changes in the urinogenital papillae (UGP) of this fish have been reported during sex change. However, there have been no detailed observations of such changes. Here, we histologically examined the UGP structure of male- and female-phase fish. UGPs of fish in female and male phase contained both oviducts and sperm ducts. Both ducts were coalesced into one duct within the posterior region of the UGP. Female-phase fish had many longitudinal folds in the hypertrophied tunica mucosa of the oviduct, which was found to be responsible for the transport of eggs and the removal of follicular cells from the oocyte. In contrast, male-phase fish had an immature oviduct and a mature sperm duct in the UGP. In the male-phase fish, the co-existence of spermatozoa and fibrillar secretions was observed in the sperm duct during spermiation.

Draft genome of the pearl oyster Pinctada fucata: a platform for understanding bivalve biology.

The study of the pearl oyster Pinctada fucata is key to increasing our understanding of the molecular mechanisms involved in pearl biosynthesis and biology of bivalve molluscs. We sequenced ~1150-Mb genome at ~40-fold coverage using the Roche 454 GS-FLX and Illumina GAIIx sequencers. The sequences were assembled into contigs with N50 = 1.6 kb (total contig assembly reached to 1024 Mb) and scaffolds with N50 = 14.5 kb. The pearl oyster genome is AT-rich, with a GC content of 34%. DNA transposons, retrotransposons, and tandem repeat elements occupied 0.4, 1.5, and 7.9% of the genome, respectively (a total of 9.8%). Version 1.0 of the P. fucata draft genome contains 23 257 complete gene models, 70% of which are supported by the corresponding expressed sequence tags. The genes include those reported to have an association with bio-mineralization. Genes encoding transcription factors and signal transduction molecules are present in numbers comparable with genomes of other metazoans. Genome-wide molecular phylogeny suggests that the lophotrochozoan represents a distinct clade from ecdysozoans. Our draft genome of the pearl oyster thus provides a platform for the identification of selection markers and genes for calcification, knowledge of which will be important in the pearl industry.

Key proliferative activity in the junction between the leaf blade and leaf petiole of Arabidopsis.

Leaves are the most important, fundamental units of organogenesis in plants. Although the basic form of a leaf is clearly divided into the leaf blade and leaf petiole, no study has yet revealed how these are differentiated from a leaf primordium. We analyzed the spatiotemporal pattern of mitotic activity in leaf primordia of Arabidopsis (Arabidopsis thaliana) in detail using molecular markers in combination with clonal analysis. We found that the proliferative zone is established after a short interval following the occurrence of a rod-shaped early leaf primordium; it is separated spatially from the shoot apical meristem and seen at the junction region between the leaf blade and leaf petiole and produces both leaf-blade and leaf-petiole cells. This proliferative region in leaf primordia is marked by activity of the ANGUSTIFOLIA3 (AN3) promoter as a whole and seems to be differentiated into several spatial compartments: activities of the CYCLIN D4;2 promoter and SPATULA enhancer mark parts of it specifically. Detailed analyses of the an3 and blade-on-petiole mutations further support the idea that organogenesis of the leaf blade and leaf petiole is critically dependent on the correct spatial regulation of the proliferative region of leaf primordia. Thus, the proliferative zone of leaf primordia is spatially differentiated and supplies both the leaf-blade and leaf-petiole cells.

Expression of gonadal soma derived factor (GSDF) is spatially and temporally correlated with early testicular differentiation in medaka.

In the teleost fish, medaka (Oryzias latipes), the sex is genetically determined at the time of fertilization. The males are heterogametic with XY chromosome composition, while females are of XX chromosome composition. The male sexual differentiation is initiated in XY embryos of medaka by the sex-determining gene Dmy. In this study, we have cloned the gonadal soma derived factor (Gsdf) from medaka and characterized its expression pattern during the initiation of morphological testicular differentiation. By real-time PCR, an XY-specific up-regulation was detected in the expression levels of Gsdf in the whole embryos of medaka at 6days post fertilization (dpf), coincident with the initiation of testicular differentiation in the XY gonads. Whole mount and section in situ hybridizations reaffirmed that Gsdf was expressed exclusively in primordial gonads of only the genetic males at 6dpf. Conversely, the expression of Gsdf was found to be very weak in the XX gonads during embryogenesis. Importantly, Gsdf and Dmy were found to be co-localized in the same somatic cells in the XY gonads. When the XY embryos were treated with estradiol-17beta, in order to reverse their phenotypic sex, a decline was observed in the expression of Gsdf in these embryos by real-time PCR.

The more and smaller cells mutants of Arabidopsis thaliana identify novel roles for SQUAMOSA PROMOTER BINDING PROTEIN-LIKE genes in the control of heteroblasty.

Regulation of cell number and cell size is essential for controlling the shape and size of leaves. Here, we report a novel class of Arabidopsis thaliana mutants, more and smaller cells 1 (msc1)-msc3, which have increased cell number and decreased cell size in leaves. msc1 has a miR156-resistant mutation in the SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 15 (SPL15) gene. msc2 and msc3 are new alleles of paused and squint mutants, respectively. All msc mutants showed accelerated heteroblasty, a phenomenon in which several morphological traits of leaves change along with phase change. Consistent with this finding, in the wild type, leaves at higher nodes (adult leaves) also have increased cell number and reduced cell size compared with those at lower nodes (juvenile leaves). These facts indicate that precocious acquisition of adult leaf characteristics in the msc mutants may cause alterations in the number and size of cells, and that heteroblasty plays an important role in the regulation of cell number and size. In agreement with this suggestion, such heteroblasty-associated changes in cell number and size are severely inhibited by the constitutive overexpression of miR156 and are promoted by the elevated expression of miR156-insensitive forms of SPL genes. By contrast, rdr6, sgs3, zip, arf3 and arf4 mutations, which affect progression of heteroblasty, had little or no effect on number or size of cells. These results suggest that cell number and size are mainly regulated by an SPL-dependent pathway rather than by a tasiR-ARF-dependent pathway.

Sex change in the Gobiid fish is mediated through rapid switching of gonadotropin receptors from ovarian to testicular portion or vice versa.

Sex-changing fish Trimma okinawae can change its sex back and forth from male to female and then to male serially, depending on the social status in the harem. T. okinawae is well equipped to respond to its social status by possessing both ovarian and testicular tissues even though only one gonad remains active at one time. Here we investigated the involvement of gonadotropins in sex change by determining the changes in gonadotropin receptor (GtHR) gene expression during the onset of sex change from female to male and male to female. The expression of the GtHR was found to be confined to the active gonad of the corresponding sexual phase. During the sex-change from female to male, initially the ovary had high levels of FSHR and LHR, which eventually went up in the testicular tissue if the fish was bigger. Changing of the gonads started with switching of GtHR expression discernible within 8-12 h of the visual cue. Further in vitro culture of the transitional gonads with a supply of exogenous gonadotropin (human chorionic gonadotropin) revealed that the to-be-active gonad acquired the ability to produce the corresponding sex hormone within 1 d of the activation of GtHR. Conversely, the to-be-regressed gonad did not respond to the exogenous gonadotropin. Our findings show that the gonads of successive sex-changing fish possess the intrinsic mechanism to respond to the social cue differentially. Additionally, this location switching of GtHR expression also could substantiate the importance of the hypothalamo-pituitary-gonadotropic axis.

Identification of a quantitative trait locus regulating B cell-dominant infiltration into autoimmune sialitis lesions of the IQI mouse model of primary Sjögren's syndrome.

Sjögren's syndrome (SS) is caused by an autoimmune sialodacryoadenitis, and up to 5% of patients with SS develop malignant B cell growth. The IQI mouse is a spontaneous model of primary SS in which B cells are the dominant cellular subpopulation among mononuclear infiltrates in sialitis lesions. Understanding the genetic control of aberrant B cell growth in IQI mice may help elucidate the genetic mechanisms involved in B-lineage hyperplasia leading to malignant transformation in human SS. B cell-dominant infiltration in the submandibular glands of 6-month-old IQI and C57BL/6 (B6) mice and their F1 and F2 progenies was quantified as B-lymphocytic sialitis score, and a genome-wide scan of 179 (IQI x B6) F2 females was performed to identify a quantitative trait locus (QTL) controlling this phenotype. A QTL significantly associated with variance in B-lymphocytic sialitis score was mapped to the D6Mit138 marker (position of 0.68cM) on proximal chromosome 6, with a logarithm of odds score of 4.3 (p = 0.00005). This QTL, named autoimmune sialitis in IQI mice, associated locus 1 (Asq1), colocalized with Islet cell autoantigen 1 (Ica1), which encodes a target protein of the immune processes that define the pathogenesis of primary SS in humans and in the nonobese diabetic mouse model.

Gene expression profile during the life cycle of the urochordate Ciona intestinalis.

Recent whole-genome studies and in-depth expressed sequence tag (EST) analyses have identified most of the developmentally relevant genes in the urochordate, Ciona intestinalis. In this study, we made use of a large-scale oligo-DNA microarray to further investigate and identify genes with specific or correlated expression profiles, and we report global gene expression profiles for about 66% of all the C. intestinalis genes that are expressed during its life cycle. We succeeded in categorizing the data set into 5 large clusters and 49 sub-clusters based on the expression profile of each gene. This revealed the higher order of gene expression profiles during the developmental and aging stages. Furthermore, a combined analysis of microarray data with the EST database revealed the gene groups that were expressed at a specific stage or in a specific organ of the adult. This study provides insights into the complex structure of ascidian gene expression, identifies co-expressed gene groups and marker genes and makes predictions for the biological roles of many uncharacterized genes. This large-scale oligo-DNA microarray for C. intestinalis should facilitate the understanding of global gene expression and gene networks during the development and aging of a basal chordate.

Regional differences in end-stage renal disease and amount of protein intake in Japan.

OBJECTIVE: We recently showed regional differences in the incidence of end-stage renal disease (ESRD) within Japan, which is generally ethnically homogenous, suggesting that factors other than genetic may contribute to the difference. We examined regional differences in the amounts of dietary nutrient intake, especially protein in our search for an explanation. DESIGN AND SETTING: Annually, the Japanese Society for Dialysis Therapy reports the numbers of patients entering maintenance dialysis in each prefecture of Japan. We used these numbers from 1984 to 2002 to calculate the annual ESRD incidence in each of 12 regions of Japan. The regional differences were analyzed in relation to the amounts of nutrient intake reported annually by National Nutrition Survey in corresponding regions for these 19 years. Each year, approximately 15,000 subjects from 5000 households in randomly selected 300 districts were included to obtain a representative sample of the entire population of Japanese in a manner of age, sex, and body mass matched. RESULTS: There were marked regional differences in the annual ESRD incidence and small regional differences in dietary intake of each nutrient. Multiple regression analysis showed that the annual ESRD incidence was negatively correlated with energy intake (r = -0.65, F = 240, n = 228) and positively correlated with animal protein intake (r = 0.25, F = 30). Across 12 regions in the values averaged for 19 years in each region, however, the incidence of ESRD was negatively correlated only with the amounts of energy intake (r = -0.74, F = 12, n = 12), but not with animal protein (r = 0.07, F = 0.04). CONCLUSION: The present study, relating regional differences between ESRD dynamics and the amounts of nutrient intake in a nationwide population of Japan, revealed that the renal protective effects of dietary restriction of protein, suggested by animal models of progressive nephropathies but yet unproved by large-scale clinical trials, remained unestablished even on a macro level of whole Japan through mapping approaches.

Roles for the N- and C-terminal domains of phytochrome B in interactions between phytochrome B and cryptochrome signaling cascades.

Plants fine-tune light responses through interactions between photoreceptors. We have previously reported that the greening of Arabidopsis thaliana roots is regulated synergistically by phytochromes and cryptochromes. In the present study, we investigated the functions of the N- and C-terminal domains of phytochrome B (phyB) in the interactions between phyB and cryptochrome signaling cascades. Transgenic Arabidopsis expressing the phyB N-terminal domain fused to green fluorescent protein (GFP), beta-glucuronidase (GUS) and the nuclear localization signal (NLS) showed intense root greening under blue light, indicating that the C-terminal domain was dispensable for the synergistic interaction in the induction of root greening. However, root greening under red light was substantially reduced in the absence of the C-terminal domain. This effect was opposite to the previous observation that removal of the C-terminal domain enhanced the signaling activity of phyB in the inhibition of hypocotyl elongation. In addition, we found that overexpression of the isolated C-terminal domain of phyB enhanced the blue light response not only for root greening but also for the inhibition of hypocotyl elongation. Analysis of this activity on various photoreceptor mutant backgrounds demonstrated that the isolated C-terminal domain enhanced cryptochrome signaling. In summary, these results demonstrate that different domains of phyB can play various roles which are dependent on light conditions as well as on the specific physiological response.

cDNA microarray analyses reveal candidate marker genes for the detection of ascidian disease in Korea.

A serious disease of the ascidian Halocynthia roretzi has been spread extensively among Korean aquaculture sites. To reveal the cause of the disease and establish a monitoring system for it, we constructed a cDNA microarray spotted with 2,688 cDNAs derived from H. roretzi hemocyte cDNA libraries to detect genes differentially expressed in hemocytes between diseased and non-diseased ascidians. We detected 21 genes showing increased expression and 16 genes showing decreased expression in hemocytes from diseased ascidians compared with those from non-diseased ascidians. RT-PCR analyses confirmed that the expression levels of genes encoding astacin, lysozyme, ribosomal protein PO, and ubiquitin-ribosomal protein L40e fusion protein were increased in hemocytes from diseased ascidians, while those of genes encoding HSP40, HSP70, fibronectin, carboxypeptidase and lactate dehydrogenase were decreased. These genes were expressed not only in hemocytes but also in various other tissues in ascidians. Furthermore, the expression of glutathione-S transferase omega, which is known to be up-regulated in H. roretzi hemocytes during inflammatory responses, was strongly increased in hemocytes from diseased ascidians. These gene expression profiles suggest that immune and inflammatory reactions occur in the hemocytes of diseased ascidians. These genes will be good markers for detecting and monitoring this disease of ascidians in Korean aquaculture sites.

Altered gene activity correlated with long-term memory formation of conditioned taste aversion in Lymnaea.

The pond snail Lymnaea stagnalis is capable of learning conditioned taste aversion (CTA) and then consolidating that learning into long-term memory (LTM) that persists for at least 1 month. LTM requires de novo protein synthesis and altered gene activity. Changes in gene activity in Lymnaea that are correlated with, much less causative, memory formation have not yet been identified. As a first step toward rectifying this situation, we constructed a cDNA microarray with mRNAs extracted from the central nervous system (CNS) of Lymnaea. We then, using this microarray assay, identified genes whose activity either increased or decreased following CTA memory consolidation. We also identified genes whose expression levels were altered after inhibition of the cyclic AMP response element-binding protein (CREB) that is hypothesized to be a key transcription factor for CTA memory. We found that the molluscan insulin-related peptide II (MIP II) was up-regulated during CTA-LTM, whereas the gene encoding pedal peptide preprohormone (Pep) was down-regulated by CREB2 RNA interference. We next examined mRNAs of MIP II and Pep using real-time RT-PCR with SYBR Green. The MIP II mRNA level in the CNS of snails exhibiting "good" memory for CTA was confirmed to be significantly higher than that from the CNS of snails exhibiting "poor" memory. In contrast, there was no significant difference in expression levels of the Pep mRNA between "good" and "poor" performers. These data suggest that in Lymnaea MIP II may play a role in the consolidation process that forms LTM following CTA training.

Polynocturia in chronic kidney disease is related to natriuresis rather than to water diuresis.

BACKGROUND: Nocturnal polyuria has been well known in renal insufficiency. Recently, we found that as renal function deteriorated in chronic kidney disease (CKD), natriuresis was enhanced during the night with nocturnal blood pressure elevation. In the present study, we investigated whether nocturnal polyuria in CKD was due to the inability to concentrate urine, as previously proposed, or based on osmotic diuresis mainly by natriuresis. METHODS: In 27 CKD patients, circadian rhythms of urinary sodium, potassium, urea and osmolar excretion rates (U(Na)V, U(K)V, U(urea)V, U(osm)V) as well as of urinary volume (V) and free-water clearance (C(H(2)O)) were estimated during both daytime (6:00 to 21:00) and nighttime (21:00 to 6:00). Then, the night/day ratios of these parameters were analysed in relation to creatinine clearance (C(cr)) as a marker of glomerular filtration rate. RESULTS: C(cr) had significantly negative relationships with night/day ratios of V (R = -0.69; P < 0.0001), U(osm)V (R = -0.54; P = 0.004) and U(Na)V (R = -0.63; P = 0.0005), but no correlation with night/day ratios of C(H(2)O) (R = -0.33; P = 0.1), U(K)V (R = -0.29; P = 0.1) or U(urea)V (R = -0.31; P = 0.1). Linear and multiple regression analysis identified nocturnal natriuresis rather than urea excretion as an independent determinant of nocturia. CONCLUSION: As renal function deteriorated, nocturnal polyuria was seen, being consistent with classical recognition. Furthermore, this increase in nocturnal urine volume seemed related to osmotic diuresis mainly by natriuresis rather than to water diuresis or urea excretion.