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Acta Physiologica (Oxford, England) Nov 2023This review outlines the features of tandem regulation of glomerular microcirculation by autoregulatory mechanisms and intraglomerular redistribution of blood flow.... (Review)
Review
This review outlines the features of tandem regulation of glomerular microcirculation by autoregulatory mechanisms and intraglomerular redistribution of blood flow. Multiple points of cooperation exist between autoregulatory and distributional mechanisms. Mutual interactions between myogenic and tubuloglomerular feedback (TGF) mechanisms regulating the inflow are briefly discussed. In addition to this, TGF operation involving purinergic, autocoid, and NO signaling affects, however, not only afferent arteriolar tone, but mesangial cell tone as well. The latter reversibly reconfigures the distribution of blood flow between the shorter and longer pathways in the glomerular tuft. I advance a hypothesis that blood flow in these pathways spontaneously alternates, and mesangial cell tonicity serves as a rheostatic shift between them. Furthermore, humoral messengers from macula densa cells, themselves dependent on myogenic mechanisms, fine-tune the secretion of renin and, subsequently, the local, intrarenal generation of angiotensin II, which, in turn, provides additional vasomotor signaling to glomerular capillaries through changing the tone of mesangial cells. This complex regulatory network may partially explain the phenomenon of renal functional reserve, as well as suggest implications for changes in renal function during pregnancy, early diabetes mellitus, and acute kidney injury.
Topics: Female; Humans; Pre-Eclampsia; Microcirculation; Kidney; Kidney Glomerulus; Diabetes Mellitus; Kidney Diseases
PubMed: 37688412
DOI: 10.1111/apha.14048 -
Nephron 2023A 39-year-old woman with end-stage renal failure of unknown origin was on peritoneal dialysis for 10 years. One year ago, she underwent ABO-incompatible living-donor...
A 39-year-old woman with end-stage renal failure of unknown origin was on peritoneal dialysis for 10 years. One year ago, she underwent ABO-incompatible living-donor kidney transplantation from her husband. After the kidney transplantation, her serum creatinine level remained around 0.7 mg/dL, but her serum potassium level remained low at around 3.5 mEq/L despite potassium supplementation and spironolactone. The patient's plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were markedly elevated (20 ng/mL/h and 868 pg/mL, respectively). A CT angiogram of the abdomen performed 1 year previously suggested stenosis of the left native renal artery, which was considered responsible for the hypokalemia. Renal venous sampling was done on both the native kidneys and the transplanted kidney. Since renin secretion from the left native kidney was significantly elevated, a laparoscopic left nephrectomy was performed. Postoperatively, the renin-angiotensin-aldosterone system was markedly improved (PRA: 6.4 ng/mL/h, PAC: 147.3 pg/mL), and the serum potassium levels also improved. Pathological examination of the removed kidney showed many atubular glomeruli and hyperplasia of the juxtaglomerular apparatus (JGA) in residual glomeruli. In addition, renin staining showed strong positivity in the JGA of these glomeruli. Here, we report a case of hypokalemia caused by left native renal artery stenosis in a kidney transplant recipient. This valuable case study provides histological confirmation of maintained renin secretion in an abandoned native kidney after kidney transplantation.
Topics: Humans; Female; Adult; Renin; Renal Artery; Hypokalemia; Renal Artery Obstruction; Kidney Transplantation; Constriction, Pathologic; Aldosterone; Potassium
PubMed: 36940677
DOI: 10.1159/000530229 -
Archives of Virology Feb 2023There is an urgent need to understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-host interactions involved in virus spread and pathogenesis, which...
There is an urgent need to understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-host interactions involved in virus spread and pathogenesis, which might contribute to the identification of new therapeutic targets. In this study, we investigated the presence of SARS-CoV-2 in postmortem lung, kidney, and liver samples of patients who died with coronavirus disease (COVID-19) and its relationship with host factors involved in virus spread and pathogenesis, using microscopy-based methods. The cases analyzed showed advanced stages of diffuse acute alveolar damage and fibrosis. We identified the SARS-CoV-2 nucleocapsid (NC) in a variety of cells, colocalizing with mitochondrial proteins, lipid droplets (LDs), and key host proteins that have been implicated in inflammation, tissue repair, and the SARS-CoV-2 life cycle (vimentin, NLRP3, fibronectin, LC3B, DDX3X, and PPARγ), pointing to vimentin and LDs as platforms involved not only in the viral life cycle but also in inflammation and pathogenesis. SARS-CoV-2 isolated from a patient´s nasal swab was grown in cell culture and used to infect hamsters. Target cells identified in human tissue samples included lung epithelial and endothelial cells; lipogenic fibroblast-like cells (FLCs) showing features of lipofibroblasts such as activated PPARγ signaling and LDs; lung FLCs expressing fibronectin and vimentin and macrophages, both with evidence of NLRP3- and IL1β-induced responses; regulatory cells expressing immune-checkpoint proteins involved in lung repair responses and contributing to inflammatory responses in the lung; CD34 liver endothelial cells and hepatocytes expressing vimentin; renal interstitial cells; and the juxtaglomerular apparatus. This suggests that SARS-CoV-2 may directly interfere with critical lung, renal, and liver functions involved in COVID-19-pathogenesis.
Topics: Humans; COVID-19; Fibronectins; Vimentin; SARS-CoV-2; Endothelial Cells; NLR Family, Pyrin Domain-Containing 3 Protein; PPAR gamma; Lung; Inflammation; Kidney; Liver
PubMed: 36842152
DOI: 10.1007/s00705-023-05711-y -
Nephron 2023Gitelman syndrome (GS) is a rare renal tubular salt-wasting disorder. Besides kidney electrolyte loss, proteinuria and renal dysfunction were also observed. However,...
INTRODUCTION
Gitelman syndrome (GS) is a rare renal tubular salt-wasting disorder. Besides kidney electrolyte loss, proteinuria and renal dysfunction were also observed. However, their incidence, risk factors, pathological features, and prognosis were unclear.
METHODS
We retrospectively reviewed 116 GS patients and analyzed their clinical, genetic, and pathological characteristics. We also systematically reviewed articles on GS with proteinuria and renal dysfunction.
RESULTS
Twenty-three GS patients had proteinuria (69.6%) and renal dysfunction (43.5%) with a mean age of 35.3 ± 13.2 years, and 65.2% were male. Compared to patients without proteinuria or renal dysfunction, these patients had elevated plasma angiotensin II level (440.2 ± 351.7 vs. 253.2 ± 187.4 pg/mL, p = 0.031) and three times higher incidence of diabetes. The renal pathology of nine biopsied patients indicated hypertrophy of the juxtaglomerular apparatus (100%), chronic tubulointerstitial changes (66.7%), intrarenal vascular changes (66.7%), and glomerulopathy (55.6%). More extensive renin staining was observed in patients with GS than in the control group with glomerular minor lesion (p < 0.001). During a median of 85 months (range, 11-205 months) of follow-up for 19 out of the 23 GS-renal patients, the renal function was generally stable, except one died of cancer and one developed end-stage renal disease because of concomitant membranous nephropathy and IgA nephropathy.
CONCLUSION
Proteinuria and renal dysfunction were more common than expected and might indicate glomerulopathy and vascular lesions besides a tubulointerstitial injury in GS. Renal function may maintain stable with effective therapy in most cases.
Topics: Humans; Male; Young Adult; Adult; Middle Aged; Female; Gitelman Syndrome; Retrospective Studies; Kidney; Proteinuria; Glomerulonephritis, IGA
PubMed: 36806220
DOI: 10.1159/000529775 -
Journal of Biomedical Science Feb 2023Genome-wide association studies (GWASs) have linked RRBP1 (ribosomal-binding protein 1) genetic variants to atherosclerotic cardiovascular diseases and serum lipoprotein...
BACKGROUND
Genome-wide association studies (GWASs) have linked RRBP1 (ribosomal-binding protein 1) genetic variants to atherosclerotic cardiovascular diseases and serum lipoprotein levels. However, how RRBP1 regulates blood pressure is unknown.
METHODS
To identify genetic variants associated with blood pressure, we performed a genome-wide linkage analysis with regional fine mapping in the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) cohort. We further investigated the role of the RRBP1 gene using a transgenic mouse model and a human cell model.
RESULTS
In the SAPPHIRe cohort, we discovered that genetic variants of the RRBP1 gene were associated with blood pressure variation, which was confirmed by other GWASs for blood pressure. Rrbp1- knockout (KO) mice had lower blood pressure and were more likely to die suddenly from severe hyperkalemia caused by phenotypically hyporeninemic hypoaldosteronism than wild-type controls. The survival of Rrbp1-KO mice significantly decreased under high potassium intake due to lethal hyperkalemia-induced arrhythmia and persistent hypoaldosteronism, which could be rescued by fludrocortisone. An immunohistochemical study revealed renin accumulation in the juxtaglomerular cells of Rrbp1-KO mice. In the RRBP1-knockdown Calu-6 cells, a human renin-producing cell line, transmission electron and confocal microscopy revealed that renin was primarily retained in the endoplasmic reticulum and was unable to efficiently target the Golgi apparatus for secretion.
CONCLUSIONS
RRBP1 deficiency in mice caused hyporeninemic hypoaldosteronism, resulting in lower blood pressure, severe hyperkalemia, and sudden cardiac death. In juxtaglomerular cells, deficiency of RRBP1 reduced renin intracellular trafficking from ER to Golgi apparatus. RRBP1 is a brand-new regulator of blood pressure and potassium homeostasis discovered in this study.
Topics: Animals; Humans; Mice; Aldosterone; Aluminum Oxide; Blood Pressure; Genome-Wide Association Study; Homeostasis; Hyperkalemia; Hypertension; Hypoaldosteronism; Potassium; Renin; Carrier Proteins
PubMed: 36803854
DOI: 10.1186/s12929-023-00905-7 -
Archivos Argentinos de Pediatria Aug 2023Severe arterial hypertension (HTN) in pediatrics is mainly due to secondary causes. Here we describe the case of a 14-year-old female adolescent with severe HTN,...
Severe arterial hypertension (HTN) in pediatrics is mainly due to secondary causes. Here we describe the case of a 14-year-old female adolescent with severe HTN, metabolic alkalosis, and hypokalemia, secondary to a renin-secreting juxtaglomerular cell tumor diagnosed after 2 years of HTN progression.
Topics: Female; Humans; Adolescent; Child; Juxtaglomerular Apparatus; Hypertension; Renin; Hypokalemia; Kidney Neoplasms
PubMed: 36729016
DOI: 10.5546/aap.2022-02835.eng -
Journal of Anatomy Jun 2023The macula densa (MD) is an anatomical structure having a plaque shape, placed in the distal end of thick ascending limb of each nephron and belonging to juxtaglomerular...
The macula densa (MD) is an anatomical structure having a plaque shape, placed in the distal end of thick ascending limb of each nephron and belonging to juxtaglomerular apparatus (JGA). The aim of the present investigation is to investigate the presence of ZO-1, a specific marker of tight juncions (TJs), in MD cells. Six samples of normal human renal tissue were embedded in paraffin for ZO-1 expression analysis by immunohistochemical and immunofluorescence techniques. We detected ZO-1 expression in the apical part of cell membrane in MD cells by immunohistochemistry. In addition, ZO-1 and nNOS expressions (a specific marker of MD) were colocalized in MD cells providing clear evidence of TJs presence in normal human MD. Since ZO-1 is responsible for diffusion barrier formation, its presence in the MD supports the existence of a tubulomesangial barrier that ensures a regulated exchange between MD and JGA effectors in renal and glomerular haemodynamic homeostasis.
Topics: Humans; Kidney Tubules; Juxtaglomerular Apparatus; Kidney Glomerulus; Nephrons; Fluorescent Antibody Technique
PubMed: 36719664
DOI: 10.1111/joa.13832 -
Acta Histochemica Jan 2023Although the regeneration of renal glomeruli and nephrons after injuries especially in adult mammals is not possible, understanding normal glomerular histogenesis is...
Age-related glomerular histogenesis in inbred indigenous rabbit (Oryctolagus cuniculus): A morphological, morphometrical, and immunohistochemical study with emphasis on Lgr5-positive cells.
Although the regeneration of renal glomeruli and nephrons after injuries especially in adult mammals is not possible, understanding normal glomerular histogenesis is important. Here, we sought to study the morphometrical and histological development of the normal renal glomeruli of rabbits from birth until postnatal day 40. Moreover, we immunohistochemically evaluated the extent and rate of the Lgr5 expression in the immature renal stem/progenitor cells. The untreated, clinically healthy inbred indigenous rabbits (from Duhok city of Iraqi Kurdistan) were sacrificed at postnatal days 1, 10, 15, 30, and 40. After being processed and embedded in paraffin, rabbit anti-human Lgr5 as a primary antibody and rabbit ImmunoCruz LSAB as a staining kit were used for the immunohistochemical detection of Lgr5 cells. For normal histology, hematoxylin and eosin were used. The peak generation and regression of renal corpuscles were at postnatal days 10, and 40, respectively, with 50% decrease. The glomeruli diameter significantly increased (1.3-fold, p = 0.001), whereas the Bowman's space diameter decreased (50%, p < 0.0001) from postnatal day 1-40. The immature nephrons were seen only in one-day postnatal rabbits. While the superficial glomeruli were compact and small, the juxtamedullary glomeruli were larger and segmented. The formation and development of the juxtaglomerular apparatus were documented at postnatal days 30 and 40 only. Our data revealed highly expressed Lgr5 protein at postnatal day one, and the expression level decreased gradually with advancing age. It was moderately expressed on day 10 and mildly expressed on day 15, whereas no expression was recorded on days 30 and 40 postnatally. Our study provides evidence that the Lgr5 gene, within multipotent stem cells and their lineage progeny, was activated within newly formed glomeruli throughout the early postnatal stages of nephrogenesis.
Topics: Animals; Rabbits; Kidney Glomerulus; Kidney; Kidney Diseases; Mammals
PubMed: 36610219
DOI: 10.1016/j.acthis.2022.151994