RESUMO
The pathophysiology behind sodium retention in heart failure with preserved ejection fraction (HFpEF) remains poorly understood. We hypothesized that patients with HFpEF have impaired natriuresis and diuresis in response to volume expansion and diuretic challenge, which is associated with renal hypo-responsiveness to endogenous natriuretic peptides. Nine HFpEF patients and five controls received saline infusion (0.25 mL/kg/min for 60 min) followed by intravenous furosemide (20 mg or home dose) 2 h after the infusion. Blood and urine samples were collected at baseline, 2 h after saline infusion, and 2 h after furosemide administration; urinary volumes were recorded. The urinary cyclic guanosine monophosphate (ucGMP)/plasma B-type NP (BNP) ratio was calculated as a measure of renal response to endogenous BNP. Wilcoxon rank-sum test was used to compare the groups. Compared to controls, HFpEF patients had reduced urine output (2480 vs.3541 mL; p = 0.028), lower urinary sodium excretion over 2 h after saline infusion (the percentage of infused sodium excreted 12% vs. 47%; p = 0.003), and a lower baseline ucGMP/plasma BNP ratio (0.7 vs. 7.3 (pmol/mL)/(mg/dL)/(pg/mL); p = 0.014). Patients with HFpEF had impaired natriuretic response to intravenous saline and furosemide administration and lower baseline ucGMP/plasma BNP ratios indicating renal hypo-responsiveness to NPs.
Assuntos
Furosemida , Insuficiência Cardíaca , Rim , Peptídeo Natriurético Encefálico , Sódio , Volume Sistólico , Humanos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/metabolismo , Masculino , Feminino , Idoso , Projetos Piloto , Furosemida/farmacologia , Furosemida/administração & dosagem , Sódio/metabolismo , Sódio/urina , Peptídeo Natriurético Encefálico/sangue , Peptídeo Natriurético Encefálico/metabolismo , Rim/metabolismo , Rim/fisiopatologia , Rim/efeitos dos fármacos , Pessoa de Meia-Idade , Natriurese/efeitos dos fármacos , Diuréticos/farmacologia , Diuréticos/administração & dosagem , GMP Cíclico/metabolismo , GMP Cíclico/urina , Idoso de 80 Anos ou maisRESUMO
In response to decreasing numbers of individuals entering into nephrology fellowships, the American Society of Nephrology launched Kidney Tutored Research and Education for Kidney Scholars (TREKS) to stimulate interest in nephrology among medical students, graduate students, and postdoctoral fellows. The program combines a 1-week intensive exposure to kidney physiology with a longitudinal mentorship program at the participants' home institutions. Ten years in, an analysis was conducted to assess its effectiveness. We surveyed participants to assess their opinions regarding nephrology before and after the course and followed them longitudinally to determine their career choices. TREKS applicants who were not selected to participate were used as a comparison group. Three hundred eighty-one people participated in the program, and 242 completed the survey. After TREKS, both medical students and graduate students showed increased interest in nephrology, with rank scores of 5.6±0.2 before to 7.5±0.1 after the course for medical students (mean±SD, n =189, P = 0.001) and 7.3±0.3 to 8.7±0.3 ( n =53, P = 0.001) for graduate students. In long-term follow-up, TREKS medical students chose a nephrology pipeline residency at a higher rate than medical students overall (57% versus 31%, P = 0.01) and TREKS applicants who did not participate (47% versus 31%, P = 0.04). Nephrology fellowship rates for these groups exceeded the general population but did not significantly differ between TREKS participants and applicants. Doctor of Philosophy students and postdoctoral TREKS participants had a higher rate of participation in nephrology research compared with TREKS applicants (66% versus 30%, P = 0.01). In summary, the American Society of Nephrology Kidney TREKS program has demonstrated that it can increase interest in nephrology in the short term and increase the number of individuals going into nephrology careers. This long-term effect is most evident in Doctor of Philosophy students and postdoctoral participants. Further study is needed to assess the impact of TREKS on enrollment in nephrology fellowship programs.
RESUMO
The kidneys play a critical role in maintaining total body sodium (Na+) balance across a wide range of dietary intake, accomplished by a concerted effort involving multiple Na+ transporters along the nephron. Furthermore, nephron Na+ reabsorption and urinary Na+ excretion are closely linked to renal blood flow and glomerular filtration such that perturbations in either of them can modify Na+ transport along the nephron, ultimately resulting in hypertension and other Na+-retentive states. In this article, we provide a brief physiological overview of nephron Na+ transport and illustrate clinical syndromes and therapeutic agents that affect Na+ transporter function. We highlight recent advances in kidney Na+ transport, particularly the role of immune cells, lymphatics, and interstitial Na+ in regulating Na+ reabsorption, the emergence of potassium (K+) as a regulator of Na+ transport, and the evolution of the nephron to modulate Na+ transport.
Assuntos
Hipertensão , Néfrons , Humanos , Rim , Circulação Renal , Proteínas de Membrana Transportadoras , SódioAssuntos
Injúria Renal Aguda , Hipercalcemia , Hiperparatireoidismo Primário , Cálculos Renais , Nefrocalcinose , Pancreatite Necrosante Aguda , Humanos , Nefrocalcinose/diagnóstico por imagem , Nefrocalcinose/etiologia , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/diagnóstico , Pancreatite Necrosante Aguda/diagnóstico , Pancreatite Necrosante Aguda/diagnóstico por imagem , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Hipercalcemia/complicações , Hipercalcemia/diagnósticoRESUMO
AIM: The kaliuretic action of the renin-angiotensin-aldosterone system (RAAS) is well established as highlighted by hyperkalemia side effect of RAAS inhibitors but such action is usually ascribed to systemic RAAS. The present study addresses the involvement of intrarenal RAAS in K+ homeostasis with emphasis on locally generated renin within the collecting duct (CD). METHODS: Wild-type (Floxed) and CD-specific deletion of renin (CD renin KO) mice were treated for 7 days with a high K+ (HK) diet to investigate the role of CD renin in kaliuresis regulation and further define the underlying mechanism with emphasis on analysis of intrarenal aldosterone biosynthesis. RESULTS: In floxed mice, renin levels were elevated in the renal medulla and urine following a 1-week HK diet, indicating activation of the intrarenal renin. CD renin KO mice had blunted HK-induced intrarenal renin response and developed impaired kaliuresis and elevated plasma K+ level (4.45 ± 0.14 vs. 3.89 ± 0.04 mM, p < 0.01). In parallel, HK-induced intrarenal aldosterone and CYP11B2 expression along with expression of renal outer medullary K+ channel (ROMK), calcium-activated potassium channel subunit alpha-1 (α-BK), α-Na+ -K+ -ATPase, and epithelial sodium channel (ß-ENaC and cleaved-γ-ENaC) expression were all significantly blunted in CD renin KO mice in contrast to the unaltered responses of plasma aldosterone and adrenal CYP11B2. CONCLUSION: Taken together, these results support a kaliuretic action of CD renin during HK intake.
Assuntos
Renina , Desequilíbrio Hidroeletrolítico , Camundongos , Animais , Renina/metabolismo , Aldosterona/metabolismo , Citocromo P-450 CYP11B2/metabolismo , Potássio/metabolismo , Homeostase , Canais Epiteliais de Sódio/metabolismo , Camundongos KnockoutRESUMO
The concept of local formation of angiotensin II in the kidney has changed over the last 10-15 years. Local synthesis of angiotensinogen in the proximal tubule has been proposed, combined with prorenin synthesis in the collecting duct. Binding of prorenin via the so-called (pro)renin receptor has been introduced, as well as megalin-mediated uptake of filtered plasma-derived renin-angiotensin system (RAS) components. Moreover, angiotensin metabolites other than angiotensin II [notably angiotensin-(1-7)] exist, and angiotensins exert their effects via three different receptors, of which angiotensin II type 2 and Mas receptors are considered renoprotective, possibly in a sex-specific manner, whereas angiotensin II type 1 (AT1) receptors are believed to be deleterious. Additionally, internalized angiotensin II may stimulate intracellular receptors. Angiotensin-converting enzyme 2 (ACE2) not only generates angiotensin-(1-7) but also acts as coronavirus receptor. Multiple, if not all, cardiovascular diseases involve the kidney RAS, with renal AT1 receptors often being claimed to exert a crucial role. Urinary RAS component levels, depending on filtration, reabsorption, and local release, are believed to reflect renal RAS activity. Finally, both existing drugs (RAS inhibitors, cyclooxygenase inhibitors) and novel drugs (angiotensin receptor/neprilysin inhibitors, sodium-glucose cotransporter-2 inhibitors, soluble ACE2) affect renal angiotensin formation, thereby displaying cardiovascular efficacy. Particular in the case of the latter three, an important question is to what degree they induce renoprotection (e.g., in a renal RAS-dependent manner). This review provides a unifying view, explaining not only how kidney angiotensin formation occurs and how it is affected by drugs but also why drugs are renoprotective when altering the renal RAS. SIGNIFICANCE STATEMENT: Angiotensin formation in the kidney is widely accepted but little understood, and multiple, often contrasting concepts have been put forward over the last two decades. This paper offers a unifying view, simultaneously explaining how existing and novel drugs exert renoprotection by interfering with kidney angiotensin formation.
Assuntos
Angiotensinogênio , Doenças Cardiovasculares , Feminino , Humanos , Masculino , Angiotensina II/metabolismo , Enzima de Conversão de Angiotensina 2 , Angiotensinogênio/metabolismo , Doenças Cardiovasculares/metabolismo , Sistemas de Liberação de Medicamentos , Rim/irrigação sanguínea , Rim/metabolismo , Renina/metabolismo , Sistema Renina-Angiotensina , Inibidores do Transportador 2 de Sódio-Glicose/metabolismoRESUMO
Two recent clinical trials, using sodium glucose cotransporter (SGLT2) or endothelin-A receptor (ET-A) blocker, reported the first efficacious treatments in 18 years to slow progression of diabetic kidney disease (DKD). We hypothesized that combined inhibition of SGLT2 and ET-A receptor may confer greater protection against renal injury than either agent alone. Uninephrectomized male db/db mice were randomized to four groups: vehicle, SGLT2 inhibitor (dapagliflozin (dapa), 1 mg/kg/day), ET-A blocker (atrasentan (atra), 5 mg/kg/day), or dual treatment from 10 weeks until 22 weeks of age. At 10 weeks of age, no differences were observed in body weight, blood glucose or urinary albumin excretion among the four groups. At 16 and 22 weeks of age, body weight was lower and blood glucose levels higher in the vehicle and atra groups compared with dapa- and dual-treated groups. No notable differences were observed among the four groups in urinary albumin excretion at weeks 16 and 22. Histological analysis showed mild glomerulosclerosis and tubular injury (<5%) in all four groups with reduced glomerulosclerosis in the dual treatment group compared with vehicle. Individual or combined treatment with an SGLT2 inhibitor and (or) an ET-A antagonist did not confer renoprotective effects in this model.
Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Inibidores do Transportador 2 de Sódio-Glicose , Animais , Masculino , Camundongos , Albuminas/análise , Albuminas/farmacologia , Albuminas/uso terapêutico , Compostos Benzidrílicos/farmacologia , Glicemia/análise , Peso Corporal , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/patologia , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/prevenção & controle , Modelos Animais de Doenças , Glucose/farmacologia , Rim , Receptor de Endotelina A , Transportador 2 de Glucose-Sódio , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêuticoRESUMO
The collecting duct is a highly adaptive terminal part of the nephron, which is essential for maintaining systemic homeostasis. Principal and intercalated cells perform different physiological tasks and exhibit distinctive morphology. However, acid-secreting A- and base secreting B-type of intercalated cells cannot be easily separated in functional studies. We used BCECF-sensitive intracellular pH (pHi ) measurements in split-opened collecting ducts followed by immunofluorescent microscopy in WT and intercalated cell-specific ClC-K2-/- mice to demonstrate that ClC-K2 inhibition enables to distinguish signals from A- and B-intercalated cells. We show that ClC-K2 Cl- channel is expressed on the basolateral side of intercalated cells, where it governs Cl- -dependent H+ /HCO3- transport. ClC-K2 blocker, NPPB, caused acidification or alkalization in different subpopulations of intercalated cells in WT but not ClC-K2-/- mice. Immunofluorescent assessment of the same collecting ducts revealed that NPPB increased pHi in AE1-positive A-type and decreased pHi in pendrin-positive B-type of intercalated cells. Induction of metabolic acidosis led to a significantly augmented abundance and H+ secretion in A-type and decreased proton transport in B-type of intercalated cells, whereas metabolic alkalosis caused the opposite changes in intercalated cell function, but did not substantially change their relative abundance. Overall, we show that inhibition of ClC-K2 can be employed to discriminate between A- and B-type of intercalated cells in split-opened collecting duct preparations. We further demonstrate that this method can be used to independently monitor changes in the functional status and abundance of A- and B-type in response to systemic acid/base stimuli.
Assuntos
Acidose , Túbulos Renais Coletores , Acidose/metabolismo , Animais , Proteínas de Transporte de Ânions/genética , Proteínas de Transporte de Ânions/metabolismo , Túbulos Renais Coletores/metabolismo , Camundongos , Néfrons/metabolismo , Transportadores de Sulfato/metabolismoRESUMO
BACKGROUND: Identification of target antigens PLA2R, THSD7A, NELL1, or Semaphorin-3B can explain the majority of cases of primary membranous nephropathy (MN). However, target antigens remain unidentified in 15%-20% of patients. METHODS: A multipronged approach, using traditional and modern technologies, converged on a novel target antigen, and capitalized on the temporal variation in autoantibody titer for biomarker discovery. Immunoblotting of human glomerular proteins followed by differential immunoprecipitation and mass spectrometric analysis was complemented by laser-capture microdissection followed by mass spectrometry, elution of immune complexes from renal biopsy specimen tissue, and autoimmune profiling on a protein fragment microarray. RESULTS: These approaches identified serine protease HTRA1 as a novel podocyte antigen in a subset of patients with primary MN. Sera from two patients reacted by immunoblotting with a 51-kD protein within glomerular extract and with recombinant human HTRA1, under reducing and nonreducing conditions. Longitudinal serum samples from these patients seemed to correlate with clinical disease activity. As in PLA2R- and THSD7A- associated MN, anti-HTRA1 antibodies were predominantly IgG4, suggesting a primary etiology. Analysis of sera collected during active disease versus remission on protein fragment microarrays detected significantly higher titers of anti-HTRA1 antibody in active disease. HTRA1 was specifically detected within immune deposits of HTRA1-associated MN in 14 patients identified among three cohorts. Screening of 118 "quadruple-negative" (PLA2R-, THSD7A-, NELL1-, EXT2-negative) patients in a large repository of MN biopsy specimens revealed a prevalence of 4.2%. CONCLUSIONS: Conventional and more modern techniques converged to identify serine protease HTRA1 as a target antigen in MN.
RESUMO
[Figure: see text].
Assuntos
Angiotensina II , Pressão Sanguínea , Hipertensão/prevenção & controle , Nefropatias/prevenção & controle , Rim/metabolismo , Artérias Mesentéricas/metabolismo , ATPases Translocadoras de Prótons/deficiência , Receptores de Superfície Celular/deficiência , Animais , Modelos Animais de Doenças , Hipertensão/induzido quimicamente , Hipertensão/genética , Hipertensão/metabolismo , Rim/patologia , Rim/fisiopatologia , Nefropatias/induzido quimicamente , Nefropatias/genética , Nefropatias/metabolismo , Masculino , Artérias Mesentéricas/fisiopatologia , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Mutação , ATPases Translocadoras de Prótons/genética , Receptores de Superfície Celular/genética , Sistema Renina-Angiotensina , Transdução de Sinais , Vasoconstrição , Vasodilatação , Equilíbrio Hidroeletrolítico , Receptor de Pró-ReninaRESUMO
INTRODUCTION: Diabetes is the most common cause of chronic kidney disease (CKD). For patients with diabetes and CKD, the underlying cause of their kidney disease is often assumed to be a consequence of their diabetes. Without histopathological confirmation, however, the underlying cause of their disease is unclear. Recent studies have shown that next-generation sequencing (NGS) provides a promising avenue toward uncovering and establishing precise genetic diagnoses in various forms of kidney disease. METHODS: Here, we set out to investigate the genetic basis of disease in nondiabetic kidney disease (NDKD) and diabetic kidney disease (DKD) patients by performing targeted NGS using a custom panel comprising 345 kidney disease-related genes. RESULTS: Our analysis identified rare diagnostic variants based on ACMG-AMP guidelines that were consistent with the clinical diagnosis of 19% of the NDKD patients included in this study. Similarly, 22% of DKD patients were found to carry rare pathogenic/likely pathogenic variants in kidney disease-related genes included on our panel. Genetic variants suggestive of NDKD were detected in 3% of the diabetic patients included in this study. DISCUSSION/CONCLUSION: Our findings suggest that rare variants in kidney disease-related genes in a diabetic background may play a role in the pathogenesis of DKD and NDKD in patients with diabetes.
Assuntos
Nefropatias Diabéticas/genética , Sequenciamento de Nucleotídeos em Larga Escala , Análise de Sequência de DNA , Nefropatias Diabéticas/classificação , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Prorenin, a precursor of renin, and renin play an important role in regulation of the renin-angiotensin system. More recently, receptor-bound prorenin has been shown to activate intracellular signaling pathways that mediate fibrosis, independent of angiotensin II. Prorenin and renin may thus be of physiologic significance in CKD, but their plasma concentrations have not been well characterized in CKD. METHODS: We evaluated distribution and longitudinal changes of prorenin and renin concentrations in the plasma samples collected at follow-up years 1, 2, 3, and 5 of the Chronic Renal Insufficiency Cohort (CRIC) study, an ongoing longitudinal observational study of 3,939 adults with CKD. Descriptive statistics and multivariable regression of log-transformed values were used to describe cross-sectional and longitudinal variation and associations with participant characteristics. RESULTS: A total of 3,361 CRIC participants had plasma available for analysis at year 1. The mean age (±standard deviation, SD) was 59 ± 11 years, and the mean estimated glomerular filtration rate (eGFR, ± SD) was 43 ± 17 mL/min per 1.73 m2. Median (interquartile range) values of plasma prorenin and renin at study entry were 4.4 (2.1, 8.8) ng/mL and 2.0 (0.8, 5.9) ng/dL, respectively. Prorenin and renin were positively correlated (Spearman correlation 0.51, p < 0.001) with each other. Women and non-Hispanic blacks had lower prorenin and renin values at year 1. Diabetes, lower eGFR, and use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statins, and diuretics were associated with higher levels. Prorenin and renin decreased by a mean of 2 and 5% per year, respectively. Non-Hispanic black race and eGFR <30 mL/min/1.73 m2 at year 1 predicted a steeper decrease in prorenin and renin over time. In addition, each increase in urinary sodium excretion by 2 SDs at year 1 increased prorenin and renin levels by 4 and 5% per year, respectively. DISCUSSION/CONCLUSIONS: The cross-sectional clinical factors associated with prorenin and renin values were similar. Overall, both plasma prorenin and renin concentrations decreased over the years, particularly in those with severe CKD at study entry.
Assuntos
Insuficiência Renal Crônica/sangue , Renina/sangue , Adulto , Negro ou Afro-Americano , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Estudos Transversais , Diabetes Mellitus/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores Raciais , Insuficiência Renal Crônica/fisiopatologia , Fatores Sexuais , Sódio/urina , Fatores de TempoRESUMO
Recent research by Miguel et al. and Dhillon et al. reveals associations between impaired lipid metabolism and kidney fibrosis. Kidney tubule fatty acid oxidation (FAO) gain-of-function in mouse models of kidney disease stimulated cellular respiration, mitochondrial dynamics, and tubular epithelial cell (TEC) differentiation, while upregulation of FAO in kidney tubules provided protection from kidney fibrosis and functional decline.
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Modelos Animais de Doenças , Nefropatias , Metabolismo dos Lipídeos , Animais , Fibrose , Mutação com Ganho de Função , CamundongosRESUMO
BACKGROUND: Hypertension often occurs before renal function deteriorates in autosomal dominant polycystic kidney disease (ADPKD). It is unknown whether the Pkd1 gene product polycystin-1-the predominant causal factor in ADPKD-itself contributes to ADPKD hypertension independent of cystogenesis. METHODS: We induced nephron-specific disruption of the Pkd1 gene in 3-month-old mice and examined them at 4-5 months of age. RESULTS: Kidneys from the Pkd1 knockout mice showed no apparent renal cysts, tubule dilation, or increased cell proliferation. Compared with control mice, Pkd1 knockout mice exhibited reduced arterial pressure during high salt intake; this associated with an increased natriuretic, diuretic, and kaliuretic response during the first 2-3 days of salt loading. The lower arterial pressure and enhanced natriuresis during high salt loading in Pkd1 knockout mice were associated with lower urinary nitrite/nitrate excretion and markedly increased urinary PGE2 excretion, whereas GFR, plasma renin concentration, and urinary endothelin-1 excretion were similar between knockout and control mice. Kidney cyclooxygenase-2 protein levels were increased in Pkd1 knockout mice during high salt intake; administration of NS-398, a selective cyclooxygenase-2 inhibitor, abolished the arterial pressure difference between the knockout and control mice during high salt intake. Total kidney Na+/K+/2Cl- cotransporter isoform 2 (NKCC2) levels were greatly reduced in Pkd1 knockout mice fed a high salt diet compared with controls. CONCLUSIONS: These studies suggest that nephron polycystin-1 deficiency does not itself contribute to ADPKD hypertension and that it may, in fact, exert a relative salt-wasting effect. The work seems to comprise the first in vivo studies to describe a potential physiologic role for nephron polycystin-1 in the absence of cysts, tubule dilation, or enhanced cell proliferation.
Assuntos
Pressão Sanguínea/fisiologia , Ciclo-Oxigenase 2/fisiologia , Néfrons/fisiologia , Rim Policístico Autossômico Dominante/etiologia , Canais de Cátion TRPP/fisiologia , Animais , Dinoprostona/urina , Taxa de Filtração Glomerular , Camundongos , Camundongos Knockout , Membro 1 da Família 12 de Carreador de Soluto/fisiologiaRESUMO
The antidiuretic hormone vasopressin (AVP), acting through its type 2 receptor (V2R) in the collecting duct (CD), critically controls urine concentrating capability. Here, we report that site-1 protease-derived (S1P-derived) soluble (pro)renin receptor (sPRR) participates in regulation of fluid homeostasis via targeting V2R. In cultured inner medullary collecting duct (IMCD) cells, AVP-induced V2R expression was blunted by a PRR antagonist, PRO20; a PRR-neutralizing antibody; or a S1P inhibitor, PF-429242. In parallel, sPRR release was increased by AVP and reduced by PF-429242. Administration of histidine-tagged sPRR, sPRR-His, stimulated V2R expression and also reversed the inhibitory effect of PF-429242 on the expression induced by AVP. PF-429242 treatment in C57/BL6 mice impaired urine concentrating capability, which was rescued by sPRR-His. This observation was recapitulated in mice with renal tubule-specific deletion of S1P. During the pharmacological or genetic manipulation of S1P alone or in combination with sPRR-His, the changes in urine concentration were paralleled with renal expression of V2R and aquaporin-2 (AQP2). Together, these results support that S1P-derived sPRR exerts a key role in determining renal V2R expression and, thus, urine concentrating capability.
Assuntos
Capacidade de Concentração Renal/fisiologia , Túbulos Renais Coletores/metabolismo , ATPases Translocadoras de Prótons/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores de Vasopressinas/metabolismo , Animais , Antagonistas dos Receptores de Hormônios Antidiuréticos/farmacologia , Aquaporina 2/genética , Células Cultivadas , Células Epiteliais , Capacidade de Concentração Renal/efeitos dos fármacos , Túbulos Renais Coletores/citologia , Túbulos Renais Coletores/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout , Modelos Animais , Fragmentos de Peptídeos/farmacologia , Cultura Primária de Células , Pró-Proteína Convertases/antagonistas & inibidores , Pró-Proteína Convertases/genética , Pró-Proteína Convertases/metabolismo , Pirrolidinas/farmacologia , Ratos , Receptores de Vasopressinas/genética , Renina/metabolismo , Renina/farmacologia , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Urotélio/citologia , ATPases Vacuolares Próton-TranslocadorasRESUMO
The (pro)renin receptor (PRR) is a multifunctional protein that is expressed in multiple organs. Binding of prorenin/renin to the PRR activates angiotensin II-dependent and angiotensin II-independent pathways. The PRR is also involved in autophagy and Wnt/ß catenin signaling, functions that are not contingent on prorenin binding. Emerging evidence suggests that the PRR plays an important role in blood pressure regulation and glucose and lipid metabolism. Herein, we review PRR function in health and disease, with particular emphasis on hypertension and the metabolic syndrome.