[Hip fracture in the elderly: epidemiology and costs of care]. / Fractura de cadera en el adulto mayor: epidemiología y costos de la atención.

INTRODUCTION: The aim of this study was to describe the epidemiology and to estimate the direct medical costs of hip fracture among elderly patients in Mexico. MATERIAL AND METHODS: An observational, cross sectional and retrospective study was undertaken. Hospital discharge and surgical procedures for the period 2013-2018 were the databases used for the analysis, and obtained from General Directorate of Health Information. Variables included were sex, federal entity, age, year of discharge, and fracture type according to the CIE-10; and also, the supplies needed for the surgical procedures. RESULTS: A total of 16,829 patients with hip fracture were discharge, 69% were women, and the mean for age was 79 years old and for the hospital stay length was nine days. The most frequent fracture type was the femur neck with 77% and the average medical costs was USD$45,122,228.00. CONCLUSION: Falling risks increase with age, especially in patients among 80-89 years of age, hence, is expected that this type of pathology increases in the following years. The medical costs for treatment of hip fracture represents an economic impact on health services. For that reason, the implementation of prevention strategies, risk of falling for example, is the one of most efficient approach.

INTRODUCCIÓN: El objetivo general de la investigación fue describir la epidemiología y estimar los costos médicos directos de la fractura de cadera en el adulto mayor en México. MATERIAL Y MÉTODOS: Se realizó un estudio observacional y transversal retrospectivo. Se utilizaron dos bases de datos obtenidas de la Dirección General de Información en Salud del período 2013-2018: egresos hospitalarios y procedimientos quirúrgicos. Las variables incluidas fueron: sexo, entidad federativa, edad, año de registro y tipo de fractura de acorde a la CIE-10; de igual forma, todos los insumos necesarios para la realización del procedimiento quirúrgico. RESULTADOS: Se registraron 16,829 ingresos de pacientes con fractura de cadera. Las mujeres representaron 69% del total de pacientes, la edad en promedio fue de 79 años y la estancia hospitalaria fue de nueve días, 77% de las fracturas fueron de cuello de fémur y el promedio de los costos médicos directos de los procedimientos ascendieron a USD $45,122,228.00 para el período estudiado. CONCLUSIÓN: El riesgo de caídas aumenta con la edad, especialmente en el grupo etario de 80-89 años, por lo que se espera que este tipo de patologías se incremente en los próximos años. De igual forma, los costos para la atención de estas fracturas representan un impacto económico para los sistemas de salud. De manera que la implementación de estrategias de prevención, por ejemplo, en caídas es el método más eficiente para contribuir al envejecimiento saludable.

Macrophage secretion of miR-106b-5p causes renin-dependent hypertension.

Myeloid cells are known mediators of hypertension, but their role in initiating renin-induced hypertension has not been studied. Vitamin D deficiency causes pro-inflammatory macrophage infiltration in metabolic tissues and is linked to renin-mediated hypertension. We tested the hypothesis that impaired vitamin D signaling in macrophages causes hypertension using conditional knockout of the myeloid vitamin D receptor in mice (KODMAC). These mice develop renin-dependent hypertension due to macrophage infiltration of the vasculature and direct activation of renal juxtaglomerular (JG) cell renin production. Induction of endoplasmic reticulum stress in knockout macrophages increases miR-106b-5p secretion, which stimulates JG cell renin production via repression of transcription factors E2f1 and Pde3b. Moreover, in wild-type recipient mice of KODMAC/miR106b-/- bone marrow, knockout of miR-106b-5p prevents the hypertension and JG cell renin production induced by KODMAC macrophages, suggesting myeloid-specific, miR-106b-5p-dependent effects. These findings confirm macrophage miR-106b-5p secretion from impaired vitamin D receptor signaling causes inflammation-induced hypertension.

RBP-J in FOXD1+ renal stromal progenitors is crucial for the proper development and assembly of the kidney vasculature and glomerular mesangial cells.

The mechanisms underlying the establishment, development, and maintenance of the renal vasculature are poorly understood. Here, we propose that the transcription factor "recombination signal binding protein for immunoglobulin kappa J region" (RBP-J) plays a key role in the differentiation of the mural cells of the kidney arteries and arterioles, as well as the mesangial cells of the glomerulus. Deletion of RBP-J in renal stromal cells of the forkhead box D1 (FOXD1) lineage, which differentiate into all the mural cells of the kidney arterioles along with mesangial cells and pericytes, resulted in significant kidney abnormalities and mortality by day 30 postpartum (P30). In newborn mutant animals, we observed a decrease in the total number of arteries and arterioles, along with thinner vessel walls, and depletion of renin cells. Glomeruli displayed striking abnormalities, including a failure of FOXD1-descendent cells to populate the glomerulus, an absence of mesangial cells, and in some cases complete loss of glomerular interior structure and the development of aneurysms. By P30, the kidney malformations were accentuated by extensive secondary fibrosis and glomerulosclerosis. We conclude that RBP-J is essential for proper formation and maintenance of the kidney vasculature and glomeruli.

Comparative effects of ractopamine hydrochloride and zilpaterol hydrochloride on growth performance, carcass traits, and longissimus tenderness of finishing steers.

Ractopamine hydrochloride (RAC) and zilpaterol hydrochloride (ZH) are beta-adrenergic agonists that improve growth performance and affect carcass characteristics. The objective of this study was to evaluate the comparative effects of RAC and ZH when fed to beef steers during the last 33 d of the finishing period. Three hundred crossbred beef steers (516 +/- 8 kg) were grouped by BW, BCS, and breed type and randomly assigned to 1 of 3 treatments (10 steers per pen; 10 pens per treatment). Treatments were control (no beta-agonists added), RAC (200 mg of ractopaminexhdx(-1)d(-1), for 33 d), or ZH (75 mg of zilpaterolxanimalx(-1)d(-1), for 30 d, removed 3 d for required withdrawal period). Steers were slaughtered, carcass characteristics were evaluated, and cut-out yields were determined. Both RAC and ZH increased final BW, ADG, feed efficiency (G:F), and HCW compared with controls (P < 0.05). Compared with RAC, ZH decreased ADG, ADFI, and final BW, but increased HCW and dressing percentage (P < 0.05). Carcass yield was not affected by RAC in this experiment, whereas ZH decreased adjusted fat thickness and KPH, increased ribeye area, improved yield grade, and increased cut-out yields, when compared with controls (P < 0.05). Marbling, lean maturity, and skeletal maturity were not different between treatments (P > 0.05). Steaks from RAC steers had greater (P < 0.05) Warner-Bratzler shear force (WBSF) values than steaks from control steers at 3 and 7 d of aging, but did not differ from controls after 14 d of aging. Steaks from ZH steers had greater WBSF values (P < 0.05) than steaks from controls and RAC steaks throughout the 21-d postmortem aging period. Although both beta-adrenergic agonists were effective at improving feedlot performance, RAC showed no negative effect on WBSF after 14 d, whereas WBSF values for ZH steaks were significantly greater than controls after 21 d.

Renin uptake by the endothelium mediates vascular angiotensin formation.

We investigated the role of the vascular endothelium in the local production of angiotensin. Angiotensin release from isolated rat hindquarters perfused with an artificial medium was measured by high-performance liquid chromatography and radioimmunoassay. Perfused hindquarters with endothelium released angiotensin I spontaneously, indicating ongoing renin-angiotensinogen reaction. Endothelium denudation (by a detergent, validated by electron microscopy and by the absence of a vasodilator response to acetylcholine) reduced angiotensin I release by >90%, whereas bilateral nephrectomy 24 hours before perfusion abolished the release completely. Infusion of renin into perfused hindquarters induced sustained local angiotensin I release in the presence of an intact endothelium but not after endothelium denudation. The conversion of angiotensin I to angiotensin II was abrogated by endothelium denudation, whereas the disappearance of angiotensin II was unchanged. Endothelium denudation diminished the pressor response to angiotensin II but abolished the response to renin and angiotensin I. Expression of renin messenger RNA, investigated by reverse-transcription polymerase chain reaction using 4 different primer combinations, was not detected in up to 5 microg vascular RNA, whereas a renin signal was readily detected with 5 ng kidney RNA. The effects of endothelium destruction on Ang I formation support the notion that the endothelium mediates vascular angiotensin formation by taking up renin.

Embryonic origin and lineage of juxtaglomerular cells.

To define the embryonic origin and lineage of the juxtaglomerular (JG) cell, transplantation of embryonic kidneys between genetically marked and wild-type mice; labeling studies for renin, smooth muscle, and endothelial cells at different developmental stages; and single cell RT-PCR for renin and other cell identity markers in prevascular kidneys were performed. From embryonic kidney day 12 to day 15 (E12 to E15), renin cells did not yet express smooth muscle or endothelial markers. At E16 renin cells acquired smooth muscle but not endothelial markers, indicating that these cells are not related to the endothelial lineage, and that the smooth muscle phenotype is a later event in the differentiation of the JG cell. Prevascular genetically labeled E12 mouse kidneys transplanted into the anterior chamber of the eye or under the kidney capsule of adult mice demonstrated that renin cell progenitors originating within the metanephric blastema differentiated in situ to JG cells. We conclude that JG cells originate from the metanephric mesenchyme rather than from an extrarenal source. We propose that renin cells are less differentiated than (and have the capability to give rise to) smooth muscle cells of the renal arterioles.

Ren1d and Ren2 cooperate to preserve homeostasis: evidence from mice expressing GFP in place of Ren1d.

To distinguish the contributions of Ren1(d) and Ren2 to kidney development and blood pressure homeostasis, we placed green fluorescent protein (GFP) under control of the Ren1(d) renin locus by homologous recombination in mice. Homozygous Ren1(d)-GFP animals make GFP mRNA in place of Ren1(d) mRNA in the kidney and maintain Ren2 synthesis in the juxtaglomerular (JG) cells. GFP expression provides an accurate marker of Ren1(d) expression during development. Kidneys from homozygous animals are histologically normal, although with fewer secretory granules in the JG cells. Blood pressure and circulating renin are reduced in Ren1(d)-GFP homozygotes. Acute administration of losartan decreases blood pressure further, suggesting a role for Ren2 protein in blood pressure homeostasis. These studies demonstrate that, in the absence of Ren1(d), Ren2 preserves normal kidney development and prevents severe hypotension. Chronic losartan treatment results in compensation via recruitment of both Ren1(d)- and Ren2-expressing cells along the preglomerular vessels. This response is achieved by metaplastic transformation of arteriolar smooth muscle cells, a major mechanism to control renin bioavailability and blood pressure homeostasis.

Novel expression and regulation of the renin-angiotensin system in metanephric organ culture.

To evaluate the presence and regulation of the renin-angiotensin system (RAS) in metanephric organ culture, embryonic day 14 (E14) rat metanephroi were cultured for 6 days. mRNAs for renin and both ANG II receptors (AT(1) and AT(2)) are expressed at E14, and all three genes continue to be expressed in culture. Renin mRNA is localized to developing tubules and ureteral branches in the cultured explants. At E14, renin immunostaining is found in isolated cells scattered within the mesenchyme. As differentiation progresses, renin localizes to the ureteric epithelium, developing tubules and glomeruli. E14 metanephroi contain ANG II, and peptide production persists in culture. Renin activity is present at E14 (6.13 +/- 0.61 pg ANG I. kidney(-1). h(-1)) and in cultured explants (28.84 +/- 1. 13 pg ANG I. kidney(-1). h(-1)). Renin activity in explants is increased by ANG II treatment (70.1 +/- 6.36 vs. 40.97 +/- 1.94 pg ANG I. kidney(-1). h(-1) in control). This increase is prevented by AT(1) blockade, whereas AT(2) antagonism has no effect. These studies document an operational local RAS and a previously undescribed positive-feedback mechanism for renin generation in avascular, cultured developing metanephroi. This novel expression pattern and regulatory mechanism highlight the unique ability of developing renal cells to express an active RAS.

Tmp21-I, a vesicular trafficking protein, is differentially expressed during induction of the ureter and metanephros.

PURPOSE: To identify genes participating in the reciprocal induction of the metanephros and ureter. MATERIALS AND METHODS: Embryonic day 14 Sprague-Dawley rat kidneys and ureters were microdissected into differentiating mesenchyme, ureteric buds, and extrarenal ureter and prepared for RT/PCR differential display. Differentially displayed cDNAs were reamplified, cloned, and sequenced. Expression was verified in the embryonic, newborn or adult kidneys by Northern blot hybridization or RT/PCR using sequence specific primers. A newborn rat kidney cDNA library was prepared and screened with probes of interest. Positive clones were screened, sequenced and compared to the GenBank/EMBL databases. A rabbit polyclonal antibody was raised to a synthetic peptide of the Tmp21-I protein and was used for immunohistochemistry. RESULTS: From the cDNAs differentially displayed by the ureteric buds cDNA B11, is 254 bp in length. The gene for B11 is expressed in adult and newborn kidneys as two transcripts (3.4 kb and 1.3 kb). More importantly, RT/PCR on E14 kidneys using B11 sequence specific primers identified expression in the embryonic kidney at the beginning of induction. B11 cDNA library screening yielded clones with inserts of 1.3 kb. This sequence encodes Tmp21-I, a vesicular trafficking protein. Immunohistochemistry demonstrates that Tmp21-I is abundant in the nephrogenic cortex of the newborn kidney and as a nephron matures, the protein levels decline. The protein is essentially absent in the adult rat kidney. CONCLUSIONS: Tmp21-I is a developmentally regulated gene expressed during kidney induction. Localized within the nephrogenic zone, it may direct the intracellular trafficking or secretion of proteins responsible for nephrogenesis.

Uncompensated polyuria in a mouse model of Bartter's syndrome.

We have used homologous recombination to disrupt the mouse gene coding for the NaK2Cl cotransporter (NKCC2) expressed in kidney epithelial cells of the thick ascending limb and macula densa. This gene is one of several that when mutated causes Bartter's syndrome in humans, a syndrome characterized by severe polyuria and electrolyte imbalance. Homozygous NKCC2-/- pups were born in expected numbers and appeared normal. However, by day 1 they showed signs of extracellular volume depletion (hematocrit 51%; wild type 37%). They subsequently failed to thrive. By day 7, they were small and markedly dehydrated and exhibited renal insufficiency, high plasma potassium, metabolic acidosis, hydronephrosis of varying severity, and high plasma renin concentrations. None survived to weaning. Treatment of -/- pups with indomethacin from day 1 prevented growth retardation and 10% treated for 3 weeks survived, although as adults they exhibited severe polyuria (10 ml/day), extreme hydronephrosis, low plasma potassium, high blood pH, hypercalciuria, and proteinuria. Wild-type mice treated with furosemide, an inhibitor of NaK2Cl cotransporters, have a phenotype similar to the indomethacin-rescued -/- adults except that hydronephrosis was mild. The polyuria, hypercalciuria, and proteinuria of the -/- adults and furosemide-treated wild-type mice were unresponsive to inhibitors of the renin angiotensin system, vasopressin, and further indomethacin. Thus absence of NKCC2 in the mouse causes polyuria that is not compensated elsewhere in the nephron. The NKCC2 mutant animals should be valuable for uncovering new pathophysiologic and therapeutic aspects of genetic disturbances in water and electrolyte recovery by the kidney.

Vascular endothelial growth factor induces nephrogenesis and vasculogenesis.

The expression of vascular endothelial growth factor (VEGF) and its receptors Flt-1 and Flk-1 in the rat kidney was examined during ontogeny using Northern blot analysis and immunocytochemistry. In prevascular embryonic kidneys (embryonic day 14 [E14]), immunoreactive Flt-1 and Flk-1 were observed in isolated angioblasts, whereas VEGF was not detected. Angioblasts aligned forming cords before morphologically differentiating into endothelial cells. In late fetal kidneys (E19), immunoreactive VEGF was detected in glomerular epithelial and tubular cells, whereas Flt-1 and Flk-1 were expressed in contiguous endothelial cells. To determine whether VEGF induces endothelial cell differentiation and vascular development in the kidney, the effect of recombinant human VEGF (5 ng/ml) was examined on rat metanephric organ culture, a model known to recapitulate nephrogenesis in the absence of vessels. After 6 d in culture in serum-free, defined media, metanephric kidney growth and morphology were assessed. DNA content was higher in VEGF-treated explants (1.9 +/- 0.17 microg/kidney, n = 9) than in paired control explants (1.4 +/- 0.10 microg/kidney, n = 9) (P < 0.05). VEGF induced proliferation of tubular epithelial cells, as indicated by an increased number of tubules and tubular proliferating cell nuclear antigen-containing cells. VEGF induced upregulation of Flk-1 and Flt-1 expression, as assessed by Western blot analysis. Developing endothelial cells were identified and localized using immunocytochemistry and electron microscopy. Flt-1, Flk-1, and angiotensin-converting enzyme-containing cells were detected in VEGF-treated explants, whereas control explants were negative. These studies confirmed previous reports indicating that the expression of VEGF and its receptors is temporally and spatially associated with kidney vascularization and identified angioblasts expressing Flt-1 and Flk-1 in prevascular embryonic kidneys. The data indicate that VEGF expression is downregulated in standard culture conditions and that VEGF stimulates growth of embryonic kidney explants by expanding both endothelium and epithelium, resulting in vasculogenesis and enhanced tubulogenesis. These data suggest that VEGF plays a critical role in renal development by promoting endothelial cell differentiation, capillary formation, and proliferation of tubular epithelia.

The maturing kidney: development and susceptibility.

Kidney morphogenesis is accomplished by the coordinated interaction of molecular signals that culminate in the production of an organ that is architecturally and functionally ready for extrauterine, free life. In humans, nephrogenesis is completed before birth. However the kidney continues to mature both from a functional and anatomical point of view. Throughout its development, the kidney is susceptible to a variety of injurious agents. This brief review considers the basic mechanisms of kidney organogenesis and functional maturation. To illustrate some concepts, the renal alterations caused by interference with a normal regulatory system, the renin-angiotensin system is discussed.

Homeostasis in mice with genetically decreased angiotensinogen is primarily by an increased number of renin-producing cells.

Here we investigate the biochemical, molecular, and cellular changes directed toward blood pressure homeostasis that occur in the endocrine branch of the renin-angiotensin system of mice having one angiotensinogen gene inactivated. No compensatory up-regulation of the remaining normal allele occurs in the liver, the main tissue of angiotensinogen synthesis. No significant changes occur in expression of the genes coding for the angiotensin converting enzyme or the major pressor-mediating receptor for angiotensin, but plasma renin concentration in the mice having only one copy of the angiotensinogen gene is greater than twice wild-type. This increase is mediated primarily by a modest increase in the proportion of renal glomeruli producing renin in their juxtaglomerular apparatus and by four times wild-type numbers of renin-producing cells along afferent arterioles of the glomeruli rather than by up-regulating renin production in cells already committed to its synthesis.

Recent advances in renal development.

Anatomical development of the kidney is achieved by the reciprocal induction of the ureteric bud and the metanephric mesenchyma. This interaction triggers the process of nephrogenesis and culminates in the formation of the mature kidney. In vivo, nephrogenesis is coordinated with renal vascularization. In fact, vascular precursors, epithelial progenitors, and mesenchymal cells communicate with one another in a highly organized fashion. As a result of this complex interaction, a mature kidney, architecturally and functionally ready for extrauterine life, is produced. This review deals with the relevant molecules and mechanisms governing nephrovascular development.

Molecular cloning of KS, a novel rat gene expressed exclusively in the kidney.

BACKGROUND: We aimed to identify genes with kidney specific, developmentally regulated expression. Here we report the cDNA sequence and expression pattern of KS, a novel kidney-specific rat gene. METHODS: A partial cDNA was identified by differential display polymerase chain reaction (PCR) of a renal cell fraction enriched for proximal tubular and renin-expressing cells. Using the partial cDNA as a probe, a rat kidney cDNA library was screened. The full-length KS sequence was obtained by PCR amplification of cDNA ends. The expression pattern of KS was investigated by Northern blot. RNA was extracted from several organs of newborn and adult rats, as well as from the kidneys of rats with altered tubular function, that is, rats that had undergone unilateral nephrectomy, unilateral ureteral obstruction, neonatal losartan treatment, and the appropriate control animals. The expression of KS was also investigated in the kidneys of rats with spontaneous or renovascular hypertension. RESULTS: The KS cDNA (2426 bp) contained one open reading frame encoding a predicted 572 amino acid protein. The derived peptide sequence displayed approximately 70% similarity to the hypertension-related SA gene product and approximately 50% similarity to prokaryotic and eukaryotic acetyl-CoA synthases (EC 6. 2.1.1). KS was expressed in the kidney and not in any other organ assayed. KS RNA was not detected in fetal and newborn rat kidney but became apparent after one week of postnatal life. Gene expression was downregulated in rat models of altered tubular function. KS expression was decreased in spontaneously hypertensive rats but not in renovascular hypertension. CONCLUSION: KS, a novel rat gene, exhibits a unique tissue-specific expression exclusively in mature kidneys. The data suggest KS may encode an adenosine monophosphate binding enzyme.

Embryonic development of the ureter.

During human embryonic development, the ureteric bud, a simple epithelial tube that arises from the Wolffian duct, initiates a cascade of events which results in the formation of the metanephros and its collecting system. In this review, the anatomic and molecular basis of ureteric development are discussed. Although it is difficult to separate metanephrogenesis from ureterogenesis of the proximal segment, the data presented are biased toward the latter. Some of the factors involved in the budding and branching of the embryonic ureter and the maturation of the fetal ureter into a peristaltic conduit are discussed as presently understood. Finally, a brief description of congenital abnormalities in ureteral development is presented with some putative mechanisms.