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1.
Arch. argent. pediatr ; 119(5): e480-e486, oct. 2021. ilus
Article in English, Spanish | LILACS, BINACIS | ID: biblio-1292126

ABSTRACT

El bajo peso al nacer (BP, < 2500 g), la restricción del crecimiento intrauterino (RCIU) y el parto prematuro (PP, < 37 semanas de gestación) son los factores clínicos más habituales para la programación alterada del número de nefronas y se asocian con un mayor riesgo de hipertensión, proteinuria y enfermedad renal futura en la vida. En la actualidad la evaluación indirecta del número total de nefronas mediante el uso de marcadores en el período posnatal representa el enfoque principal para evaluar el riesgo de evolución futura de los trastornos renales en los recién nacidos con BP, RCIU o PP.Se presentan los avances en la investigación en animales y sobre marcadores bioquímicos en humanos, y recomendaciones para la prevención del daño renal preconcepcional, incluidos los factores sociales y las enfermedades crónicas. La evidencia demuestra que la restricción de crecimiento y la prematuridad solas son capaces de modular la nefrogénesis y la función renal y, cuando son concurrentes, sus efectos tienden a ser acumulativos.


A low birth weight (LBW, < 2500 g), intrauterine growth restriction (IUGR), and preterm birth (PB, < 37 weeks of gestational age) are the most common clinical factors for an altered programming of nephron number and are associated with a greater risk for hypertension, proteinuria, and kidney disease later in life. At present, an indirect assessment of total nephron number based on postnatal markers is the most important approach to evaluate the risk for future kidney disorders in newborn infants with a LBW, IUGR or PB.Here we describe advances made in animal experiments and biochemical markers in humans, and the recommendations for the prevention of preconception kidney injury, including social factors and chronic diseases. According to the evidence, IUGR and prematurity alone can modulate nephrogenesis and kidney function, and, if occurring simultaneously, their effects tend to be cumulative.


Subject(s)
Humans , Animals , Female , Pregnancy , Infant, Newborn , Adult , Premature Birth , Kidney Diseases/etiology , Kidney Diseases/epidemiology , Infant, Low Birth Weight , Gestational Age , Kidney , Nephrons
2.
Int. braz. j. urol ; 46(2): 234-241, Mar.-Apr. 2020. tab, graf
Article in English | LILACS | ID: biblio-1090590

ABSTRACT

ABSTRACT Purpose Preoperative computed tomography or magnetic resonance (MR) imaging are commonly used for radiological evaluation of renal cell carcinoma (RCC) before radical nephrectomy or nephron sparing surgery(NSS). This study aimed to assess the role of MRI for predicting postoperative renal function by preoperative estimation of renal parenchymal volume and correlation with glomerular filtration rate (GFR). Materials and Methods A prospective observational study was conducted from February 2015 to October 2016 at a tertiary care hospital in northern India. MR imaging was done on 3 Tesla MR scanner (Signa Hdxt General Electrics, Milwaukee, USA). MR volumetry was used to estimate the renal parenchymal volume. GFR was measured in all patients using Tc99m Diethyl-triamine-penta-acetic acid using Russell's algorithm. Such measurement was done preoperatively, and postoperatively 3 months after surgery. Results 30 patients with suspected RCC underwent NSS (n=10) and radical nephrectomy (n=20). Median tumour volume was 175.7cc (range: 4.8 to 631.8cc). The median volume of the residual parenchyma on the affected side was 84.25±41.97cc while that on the unaffected side was 112.25±26.35cc. There was good correlation among the unaffected kidney volume and postoperative GFR for the radical nephrectomy group (r=0.83) as well as unaffected kidney volume, total residual kidney volume and residual volume of affected kidney with postoperative GFR for the NSS group (r=0.71, r=0.73, r=0.79 respectively; P <0.05). Conclusion Preoperative residual parenchymal volume on MR renal volumetry correlates well with postoperative GFR in patients with RCC undergoing radical nephrectomy or NSS.


Subject(s)
Humans , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/diagnostic imaging , Kidney Neoplasms/surgery , Kidney Neoplasms/diagnostic imaging , Nephrectomy/methods , Nephrons/surgery , Postoperative Period , Prognosis , Magnetic Resonance Imaging , Prospective Studies , Glomerular Filtration Rate , Middle Aged
4.
Article in English | WPRIM | ID: wpr-761922

ABSTRACT

BACKGROUND: Chronic kidney disease is a severe threat to human health with no ideal treatment strategy. Mature mammalian kidneys have a fixed number of nephrons, and regeneration is difficult once they are damaged. For this reason, developing an efficient approach to achieve kidney regeneration is necessary. The technology of the combination of decellularized kidney scaffolds with stem cells has emerged as a new strategy; however, in previous studies, the differentiation of stem cells in decellularized scaffolds was insufficient for functional kidney regeneration, and many problems remain. METHODS: We used 0.5% sodium dodecyl sulfate (SDS) to produce rat kidney decellularized scaffolds, and induce adipose-derived stem cells (ADSCs) into intermediate mesoderm by adding Wnt agonist CHIR99021 and FGF9 in vitro. The characteristics of decellularized scaffolds and intermediate mesoderm induced from adipose–derived stem cells were identified. The scaffolds were recellularized with ADSCs and intermediate mesoderm cells through the renal artery and ureter. After cocultured for 10 days, cells adhesion and differentiation was evaluated. RESULTS: Intermediate mesoderm cells were successfully induced from ADSCs and identified by immunofluorescence and Western blotting assays (OSR1 + , PAX2 +). Immunofluorescence showed that intermediate mesoderm cells differentiated into tubular-like (E-CAD + , GATA3 +) and podocyte-like (WT1 +) cells with higher differentiation efficiency than ADSCs in the decellularized scaffolds. Comparatively, this phenomenon was not observed in induced intermediate mesoderm cells cultured in vitro. CONCLUSION: In this study, we demonstrated that intermediate mesoderm cells could be induced from ADSCs and that they could differentiate well after cocultured with decellularized scaffolds.


Subject(s)
Animals , Blotting, Western , Fluorescent Antibody Technique , Humans , In Vitro Techniques , Kidney , Mesoderm , Nephrons , Rats , Regeneration , Renal Artery , Renal Insufficiency, Chronic , Sodium Dodecyl Sulfate , Stem Cells , Ureter
5.
Article in English | WPRIM | ID: wpr-759013

ABSTRACT

Proximal renal tubular acidosis (RTA) is caused by a defect in bicarbonate (HCO₃⁻) reabsorption in the kidney proximal convoluted tubule. It usually manifests as normal anion-gap metabolic acidosis due to HCO₃⁻ wastage. In a normal kidney, the thick ascending limb of Henle’s loop and more distal nephron segments reclaim all of the HCO₃⁻ not absorbed by the proximal tubule. Bicarbonate wastage seen in type II RTA indicates that the proximal tubular defect is severe enough to overwhelm the capacity for HCO₃⁻ reabsorption beyond the proximal tubule. Proximal RTA can occur as an isolated syndrome or with other impairments in proximal tubular functions under the spectrum of Fanconi syndrome. Fanconi syndrome, which is characterized by a defect in proximal tubular reabsorption of glucose, amino acids, uric acid, phosphate, and HCO₃⁻, can occur due to inherited or acquired causes. Primary inherited Fanconi syndrome is caused by a mutation in the sodium-phosphate cotransporter (NaPₐ-II) in the proximal tubule. Recent studies have identified new causes of Fanconi syndrome due to mutations in the EHHADH and the HNF4A genes. Fanconi syndrome can also be one of many manifestations of various inherited systemic diseases, such as cystinosis. Many of the acquired causes of Fanconi syndrome with or without proximal RTA are drug-induced, with the list of causative agents increasing as newer drugs are introduced for clinical use, mainly in the oncology field.


Subject(s)
Acidosis , Acidosis, Renal Tubular , Amino Acids , Cystinosis , Extremities , Fanconi Syndrome , Glucose , Kidney , Nephrons , Sodium-Phosphate Cotransporter Proteins , Uric Acid
6.
Article in English | WPRIM | ID: wpr-765011

ABSTRACT

BACKGROUND: Hypertension is one of the major causes of chronic diseases. The effect on high blood pressure (BP) with fetal growth restriction is now well-established. Recent studies suggest that a reduced number of nephrons programmed during the intrauterine period contribute to a subsequently elevated BP, due to a permanent nephron deficit. However, few studies have examined this in children. We investigated the effects of low birth weight (LBW) and preterm birth on the renal function markers related to a high BP in childhood. METHODS: We used data from 304 children aged 7–12 years who participated in the 2014 Ewha Birth and Growth Cohort survey in Korea. We assessed the serum uric acid, cystatin C, blood urea nitrogen (BUN), creatinine levels, and the estimated glomerular filtration rate (eGFR) in childhood. Anthropometric characteristics, BP in childhood, birth weight and gestational age were collected. RESULTS: The serum uric acid was significantly higher in LBW children (4.0 mg/dL) than in normal birth weight children (3.7 mg/dL). The cystatin C levels were highest among children who were very preterm (0.89 mg/dL) compared with those who were not (preterm, 0.84 mg/dL; normal, 0.81 mg/dL), although the result was only borderline significant (P for trend = 0.06). Decreased birth weight was found to be significantly associated with an increased serum BUN level in childhood. In the analysis of the effects of renal function on BP, subjects with an eGFR lower than the median value had a significantly higher diastolic BP in childhood (difference = 2.4 mmHg; P < 0.05). CONCLUSION: These findings suggest that LBW and preterm birth are risk factors for increased serum levels of renal function markers in childhood. Reduced eGFR levels were significantly associated with elevated diastolic BP in childhood. It is necessary to identify vulnerable individuals during their life and intervene appropriately to reduce the risk of an increased BP in the future.


Subject(s)
Birth Weight , Blood Pressure , Blood Urea Nitrogen , Child , Chronic Disease , Cohort Studies , Creatinine , Cystatin C , Fetal Development , Gestational Age , Glomerular Filtration Rate , Humans , Hypertension , Infant, Low Birth Weight , Infant, Newborn , Korea , Nephrons , Parturition , Premature Birth , Renal Insufficiency , Risk Factors , Uric Acid
7.
Braz. j. med. biol. res ; 51(10): e7417, 2018. graf
Article in English | LILACS | ID: biblio-951710

ABSTRACT

It is well known that the aminoglycoside antibiotic gentamicin is capable of causing damage to kidney cells. Given the known involvement of Ca2+ in the nephrotoxic action of gentamicin, the purpose of this study was to establish a relationship between the concentration of intracellular Ca2+ ([Ca2+]i) and cellular cytotoxicity using MDCK-C11 cells, a clone that has several properties that resemble those of intercalated cells of the distal nephron. Changes in [Ca2+]i was determined using fluorescence microscopy. Cell viability was evaluated by the neutral red method, and cell cytotoxicity by the MTT method. The [Ca2+]i gradually increased when cells were exposed to 0.1 mM gentamicin for 10, 20, and 30 min. The presence of extracellular Ca2+ was found to be necessary to stimulate the increase in [Ca2+]i induced by gentamicin, since this stimulus disappeared by using 1.8 mM EGTA (a Ca2+ chelator). Morphological changes were observed with scanning electron microscopy in epithelial cells exposed to the antibiotic. Furthermore, with the MTT method, a decrease in metabolic activity induced by gentamicin was observed, which indicates a cytotoxic effect. In conclusion, gentamicin was able to alter [Ca2+]i, change the morphology of MDCK-C11 cells, and promote cytotoxicity.


Subject(s)
Animals , Dogs , Gentamicins/toxicity , Calcium/metabolism , Toxicity Tests/methods , Madin Darby Canine Kidney Cells/drug effects , Anti-Bacterial Agents/toxicity , Microscopy, Electron, Scanning , Cell Membrane/metabolism , Cell Survival/drug effects , Clone Cells , Models, Animal , Madin Darby Canine Kidney Cells/metabolism , Madin Darby Canine Kidney Cells/ultrastructure , Nephrons/cytology , Nephrons/drug effects
8.
Article in English | WPRIM | ID: wpr-717220

ABSTRACT

Acute kidney injury is a clinical syndrome that can be caused by numerous diseases including acute tubular necrosis (ATN). ATN evolves in several phases, all of which are accompanied by different immune mechanisms as an integral component of the disease process. In the early injury phase, regulated necrosis, damage-associated molecular patterns, danger sensing, and neutrophil-driven sterile inflammation enhance each other and contribute to the crescendo of necroinflammation and tissue injury. In the late injury phase, renal dysfunction becomes clinically apparent, and M1 macrophage-driven sterile inflammation contributes to ongoing necroinflammation and renal dysfunction. In the recovery phase, M2-macrophages and anti-inflammatory mediators counteract the inflammatory process, and compensatory remnant nephron and cell hypertrophy promote an early functional recovery of renal function, while some tubules are still badly injured and necrotic material is removed by phagocytes. The resolution of inflammation is required to promote the intrinsic regenerative capacity of tubules to replace at least some of the necrotic cells. Several immune mechanisms support this wound-healing-like re-epithelialization process. Similar to wound healing, this response is associated with mesenchymal healing, with a profound immune cell contribution in terms of collagen production and secretion of profibrotic mediators. These and numerous other factors determine whether, in the chronic phase, persistent loss of nephrons and hyperfunction of remnant nephrons will result in stable renal function or progress to decline of renal function such as progressive chronic kidney disease.


Subject(s)
Acute Kidney Injury , Collagen , Extracellular Traps , Hypertrophy , Inflammation , Necrosis , Nephrons , Phagocytes , Re-Epithelialization , Renal Insufficiency, Chronic , Wound Healing
9.
Article in English | WPRIM | ID: wpr-197942

ABSTRACT

Mitogen-activated protein kinases (MAPKs) play important roles in various cellular functions including proliferation, differentiation, and apoptosis. We showed that MAPKs are developmentally regulated in the rat kidney. p38 MAPK (p38) and extracellular signal-regulated kinase (ERK) were strongly expressed in the fetal kidney, whereas c-Jun N-terminal kinase (JNK) was detected predominantly in the adult kidney. The inhibition of p38 or ERK in organ culture resulted in reduced nephron formation with or without reduced kidney size. On the other hand, persistent fetal expression pattern of MAPKs, i.e., upregulation of p38 and ERK and downregulation of JNK, was observed in the cyst epithelium of human renal dysplasia, ovine fetal obstructive uropathy, and pcy mice, a model of polycystic kidney disease. Furthermore, activated p38 and ERK induced by cyclic stretch mediated proliferation and TGF-β1 expression in ureteric bud cells, probably leading to cyst formation and dysplastic changes. Inhibition of ERK slowed the disease progression in pcy mice. Finally, ERK and p38 were inactivated in the early embryonic kidney subjected to maternal nutrient restriction, characterized by reduced ureteric branching and nephron number. Thus, MAPKs mediate the development of normal and diseased kidney. Their modulation may result in novel therapeutic strategies against developmental abnormalities of the kidney.


Subject(s)
Adult , Animals , Apoptosis , Disease Progression , Down-Regulation , Epithelium , Hand , Humans , JNK Mitogen-Activated Protein Kinases , Kidney , Mice , Mitogen-Activated Protein Kinases , Nephrons , Organ Culture Techniques , p38 Mitogen-Activated Protein Kinases , Phosphotransferases , Polycystic Kidney Diseases , Rats , Up-Regulation , Ureter
10.
Article in English | WPRIM | ID: wpr-143322

ABSTRACT

Type B and non-A, non-B intercalated cells are found within the connecting tubule and the cortical collecting duct. Of these cell types, type B intercalated cells are known to mediate Cl⁻ absorption and HCO₃⁻ secretion largely through pendrin-dependent Cl⁻/HCO₃⁻ exchange. This exchange is stimulated by angiotensin II administration and is also stimulated in models of metabolic alkalosis, for instance after aldosterone or NaHCO₃ administration. In some rodent models, pendrin-mediated HCO₃⁻ secretion modulates acid-base balance. However, the role of pendrin in blood pressure regulation is likely of more physiological or clinical significance. Pendrin regulates blood pressure not only by mediating aldosterone-sensitive Cl⁻ absorption, but also by modulating the aldosterone response for epithelial Na⁺ channel (ENaC)-mediated Na⁺ absorption. Pendrin regulates ENaC through changes in open channel of probability, channel surface density, and channels subunit total protein abundance. Thus, aldosterone stimulates ENaC activity through both direct and indirect effects, the latter occurring through its stimulation of pendrin expression and function. Therefore, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contributory role of pendrin in distal nephron function and blood pressure.


Subject(s)
Absorption , Acid-Base Equilibrium , Adrenal Medulla , Aldosterone , Alkalosis , Angiotensin II , Angiotensins , Blood Pressure , Catecholamines , Epithelial Sodium Channels , Negotiating , Nephrons , Rodentia
11.
Article in English | WPRIM | ID: wpr-143315

ABSTRACT

Type B and non-A, non-B intercalated cells are found within the connecting tubule and the cortical collecting duct. Of these cell types, type B intercalated cells are known to mediate Cl⁻ absorption and HCO₃⁻ secretion largely through pendrin-dependent Cl⁻/HCO₃⁻ exchange. This exchange is stimulated by angiotensin II administration and is also stimulated in models of metabolic alkalosis, for instance after aldosterone or NaHCO₃ administration. In some rodent models, pendrin-mediated HCO₃⁻ secretion modulates acid-base balance. However, the role of pendrin in blood pressure regulation is likely of more physiological or clinical significance. Pendrin regulates blood pressure not only by mediating aldosterone-sensitive Cl⁻ absorption, but also by modulating the aldosterone response for epithelial Na⁺ channel (ENaC)-mediated Na⁺ absorption. Pendrin regulates ENaC through changes in open channel of probability, channel surface density, and channels subunit total protein abundance. Thus, aldosterone stimulates ENaC activity through both direct and indirect effects, the latter occurring through its stimulation of pendrin expression and function. Therefore, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contributory role of pendrin in distal nephron function and blood pressure.


Subject(s)
Absorption , Acid-Base Equilibrium , Adrenal Medulla , Aldosterone , Alkalosis , Angiotensin II , Angiotensins , Blood Pressure , Catecholamines , Epithelial Sodium Channels , Negotiating , Nephrons , Rodentia
13.
Article in English | WPRIM | ID: wpr-285301

ABSTRACT

From January 2008 to January 2013, 11 patients with central renal tumors underwent ultrasound-guided open nephron sparing surgery (ONSS) without renal artery occlusion. We removed the lesions, and the cut edges of the tumors were negative. Thus, we deduced that ultrasound-guided ONSS is suitable for the cases with obscure tumor boundary or multiple lesions. It could achieve the purpose of thoroughly removing lesions, as well as to expand the application range of nephron sparing surgery.


Subject(s)
Arterial Occlusive Diseases , Carcinoma, Renal Cell , General Surgery , Female , Humans , Kidney Neoplasms , General Surgery , Male , Nephrons , General Surgery , Postoperative Complications , Renal Artery , Pathology , General Surgery , Surgery, Computer-Assisted , Methods , Ultrasonography
14.
Article in English | WPRIM | ID: wpr-97088

ABSTRACT

Appropriate control of diet and water intake is important for maintaining normal blood pressure, fluid and electrolyte homeostasis in the body. It is relatively understood that the amount of sodium and potassium intake directly affects blood pressure and regulates ion transporters; Na and K channel functions in the kidney. However, little is known about whether diet and water intake regulates Aquaporin (AQP) function. AQPs, a family of aquaporin proteins with different types being expressed in different tissues, are important for water absorption by the cell. Water reabsorption is a passive process driven by osmotic gradient and water permeability is critical for this process. In most of the nephron, however, water reabsorption is unregulated and coupled to solute reabsorption, such as AQP1 mediated water absorption in the proximal tubule. AQP2 is the only water channel founded so far that can be regulated by hormones in the kidney. AQP2 expressed in the apical membrane of the principal cells in the collecting tubule can be regulated by vasopressin (antidiuretic hormone) controlling the final volume of urine excretion. When vasopressin binds to its receptor on the collecting duct cells, it stimulates the translocation of AQP2 to the membrane, leading to increased water absorption via this AQP2 water channel. However, some studies also indicated that the AQP2 is also been regulated by vasopressin independent mechanism. This review is focused on the regulation of AQP2 by diet and the amount of water intake on salt and water homeostasis.


Subject(s)
Absorption , Aquaporin 2 , Arginine Vasopressin , Blood Pressure , Diet , Drinking , Homeostasis , Humans , Ion Transport , Kidney , Membranes , Nephrons , Osmolar Concentration , Permeability , Potassium , Sodium , Vasopressins , Water
15.
Article in English | WPRIM | ID: wpr-218762

ABSTRACT

Congenital chloride diarrhea (CLD) is a rare autosomal recessive disease that is difficult to diagnose. CLD requires early treatment to correct electrolyte imbalance and alkalosis and to prevent severe dehydration. Renal injury is clearly associated with defective electrolyte balance induced by CLD, particularly during the first months or years of life. A 7-year-old boy was diagnosed with CLD following detection of a homozygous mutation (c.2063-1G>T) in SLC26A3 at 6 months of age. During treatment with electrolyte supplements, mild proteinuria was detected at 8 months of age, and is still present. Renal biopsy showed the presence of focal renal dysplasia, with metaplastic cartilage and mononuclear cell infiltration, calcification, and fibrosis in the interstitium. Up to two-thirds of the glomeruli exhibited global obsolescence, mostly aggregated in the dysplastic area. In nondysplastic areas, the glomeruli were markedly increased in size and severely hypercellular, with increased mesangial matrix, and displayed segmental sclerosis. The marked glomerular hypertrophy with focal segmental glomerulosclerosis suggested a compensatory reaction to the severe nephron loss or glomerular obsolescence associated with renal dysplasia, with superimposed by CLD aggravating the tubulointerstitial damage.


Subject(s)
Alkalosis , Biopsy , Cartilage , Child , Dehydration , Diarrhea , Fibrosis , Glomerulosclerosis, Focal Segmental , Humans , Hypertrophy , Male , Nephrons , Proteinuria , Sclerosis , Water-Electrolyte Balance
16.
Acta cir. bras ; 30(2): 127-133, 02/2015. tab, graf
Article in English | LILACS | ID: lil-741031

ABSTRACT

PURPOSE: To evaluate renal histological changes and renal function in single kidney rats submitted to renal ischemia-reperfusion and to immunosuppression with tacrolimus and mycophenolate-mofetil. METHODS: Experimental study with 80 Wistar rats distributed into control, Sham and six other groups treated with immunosuppressive drugs. Animals undergoing surgery, right nephrectomy and left renal clamping, killed on the 14th day and analyzed for renal histology, urea and creatinine. RESULTS: The group receiving tacrolimus at higher doses (T3) showed renal histological lesions indicative of early nephrotoxicity, and significant increase in urea and creatinine. The group M (mycophenolate-mofetil alone) and the group M2 (mycophenolate-mofetil combined with half the usual dose of tacrolimus) presented a slight rise in serum urea. The groups using mycophenolate-mofetil alone or combined with tacrolimus showed creatinine levels similar to that of the group T3. CONCLUSIONS: Histologically, the association of injury by ischemia-reperfusion with the use of tacrolimus or mycophenolate-mofetil alone demonstrated a higher rate of renal changes typical of early nephrotoxicity. In laboratory, the combination of injury by ischemia-reperfusion with tacrolimus at higher doses proved to be nephrotoxic. .


Subject(s)
Animals , Male , Immunosuppressive Agents/adverse effects , Ischemia/complications , Kidney Diseases/etiology , Kidney/blood supply , Mycophenolic Acid/analogs & derivatives , Reperfusion Injury/complications , Tacrolimus/adverse effects , Calcineurin Inhibitors/adverse effects , Creatinine/blood , Immunosuppression/adverse effects , Immunosuppressive Agents/blood , Kidney Diseases/pathology , Kidney Diseases/physiopathology , Kidney/pathology , Mycophenolic Acid/adverse effects , Nephrons/drug effects , Random Allocation , Rats, Wistar , Time Factors , Tacrolimus/blood , Urea/blood
17.
Article in Chinese | WPRIM | ID: wpr-246137

ABSTRACT

On the basis of web databases, 111 compounds with nephrotoxicity and 90 compounds without nephrotoxicity were collected as data set of nephrotoxicity discrimination model, 39 compounds with tubular necrosis and 39 compounds without tubular necrosis were collected as data set of tubular necrosis discrimination model. The 6 122 molecular descriptors, including physicochemical, charge distribution and geometrical descriptors were calculated to characterize the molecular structure of the above-mentioned compounds. CfsSubsetEval valuation method and BestFirst-D1-N5 searching method were used to select molecular descriptors. Two models with high accuracy were built based on the support vector machine (SVM) approach, respectively. Accuracy, sensitivity, specificity and matthew's correlation coefficient of the two models were all above 70%. By using 22 nephrotoxicity compounds of Chinese medicine, the nephrotoxicity discrimination model was further verified with an accuracy of 72.73%. Using the tubular necrosis discrimination model, 10 potential compounds which can cause tubular necrosis were screened from the positive results of nephrotoxicity discrimination model, 6 of them have been verified by literatures. The results demonstrated that the discrimination models can be applied to screen nephrotoxic compounds from Chinese medicinal materials, and they also offer a new research idea for the further studies on the mechanism of nephrotoxicity.


Subject(s)
Drugs, Chinese Herbal , Toxicity , Nephrons , Support Vector Machine , Toxicity Tests , Methods
18.
Article in English | WPRIM | ID: wpr-29477

ABSTRACT

Reciprocal exchange of morphogenetic proteins between epithelial and mesenchymal cells in a stem/progenitor cell niche results in formation of a nephron. To maintain diffusion of morphogenetic proteins, it is assumed that a close contact exists between involved cells. However, recent publications underline that both types of stem/progenitor cells are separated by a striking interface. To explore this microarchitecture in detail, neonatal rabbit kidneys were fixed in traditional glutaraldehyde (GA) solution for transmission electron microscopy. For contrast enhancing specimens were fixed in GA solution including cupromeronic blue, ruthenium red or tannic acid. To record same perspectives, embedded blocks of parenchyma were cut in exactly orientated vertical and transverse planes to lining collecting ducts. Electron microscopy of specimens fixed by traditional GA solution illustrates a spatial separation of stem/progenitor cells and an unobstrusively looking interface. In contrast, advanced fixation of specimens in GA solution including cupromeronic blue, ruthenium red and tannic acid unmasks earlier not visible extracellular matrix. In addition, projections of mesenchymal cells covered by matrix cross the interface to contact epithelial cells. Surprisingly, the end of a mesenchymal cell projection does not dangle but is enclosed in a fitting sleeve and connected via tunneling nanotubes with the plasma membrane of an epithelial cell. Regarding this complex ensemble the question is to what extent illustrated cell-cell connections and extracellular matrix are involved in communication and transmission of morphogenetic proteins during induction of a nephron.


Subject(s)
Cell Membrane , Diffusion , Epithelial Cells , Extracellular Matrix , Glutaral , Kidney , Microscopy, Electron , Microscopy, Electron, Transmission , Nanotubes , Nephrons , Ruthenium Red , Strikes, Employee , Tannins
19.
Article in English | WPRIM | ID: wpr-79189

ABSTRACT

To understand the functions of the kidney, the transcriptome of each part of the nephron needs to be profiled using a highly sensitive and unbiased tool. RNA sequencing (RNA-seq) has revolutionized transcriptomic research, enabling researchers to define transcription activity and functions of genomic elements with unprecedented sensitivity and precision. Recently, RNA-seq for polyadenylated messenger RNAs [poly(A)'-mRNAs] and classical microdissection were successfully combined to investigate the transcriptome of glomeruli and 14 different renal tubule segments. A rat kidney is perfused with and incubated in collagenase solution, and the digested kidney was manually dissected under a stereomicroscope. Individual glomeruli and renal tubule segments are identified by their anatomical and morphological characteristics and collected in phosphate-buffered saline. Poly(A)'-tailed mRNAs are released from cell lysate, captured by oligo-dT primers, and made into complementary DNAs (cDNAs) using a highly sensitive reverse transcription method. These cDNAs are sheared by sonication and prepared into adapter-ligated cDNA libraries for Illumina sequencing. Nucleotide sequences reported from the sequencing reaction are mapped to the rat reference genome for gene expression analysis. These RNA-seq transcriptomic data were highly consistent with prior knowledge of gene expression along the nephron. The gene expression data obtained in this work are available as a public Web page (https://helixweb.nih.gov/ESBL/Database/NephronRNAseq/) and can be used to explore the transcriptomic landscape of the nephron.


Subject(s)
Animals , Base Sequence , Collagenases , DNA, Complementary , Gene Expression , Gene Library , Genome , Kidney , Microdissection , Nephrons , Rats , Reverse Transcription , RNA , RNA, Messenger , Sequence Analysis, RNA , Sonication , Transcriptome
20.
Intestinal Research ; : 227-232, 2015.
Article in English | WPRIM | ID: wpr-96061

ABSTRACT

Proton pump inhibitors (PPIs) are widely used though an association with hypomagnesaemia and hypocalcaemia has only been described since 2006. Patients typically present after years of stable dosing with musculoskeletal, neurological or cardiac arrhythmic symptoms, but it is likely that many cases are under-recognised. Magnesium levels resolve rapidly on discontinuation of PPI therapy and hypomagnesaemia recurs rapidly on rechallenge with any agent in the class. The cellular mechanisms of magnesium homeostasis are increasingly being understood, including both passive paracellular absorption through claudins and active transcellular transporters, including the transient receptor potential channels (TRPM6) identified in the intestine and nephron. PPIs may alter luminal pH by modulating pancreatic secretions, affecting non-gastric H+K+ATPase secretion, altering transporter transcription or channel function. A small reduction in intestinal absorption appears pivotal in causing cumulative deficiency. Risk factors have been associated to help identify patients at risk of this effect but clinical vigilance remains necessary for diagnosis.


Subject(s)
Absorption , Claudins , Diagnosis , Fatigue , Homeostasis , Humans , Hydrogen-Ion Concentration , Intestinal Absorption , Intestines , Magnesium , Nephrons , Phenobarbital , Proton Pump Inhibitors , Risk Factors , Transcytosis , Transient Receptor Potential Channels
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