scholarly journals EFFECTS OF PROTEINURIA ON THE KIDNEY

1949 ◽  
Vol 89 (6) ◽  
pp. 643-668 ◽  
Author(s):  
James H. Baxter ◽  
George C. Cotzias
Keyword(s):  
Casein Hydrolysate ◽  
Blood Stream ◽  
Renal Tissue ◽  
Human Albumin ◽  
Tubular Damage ◽  
Renal Tubules ◽  
Rat Serum ◽  
Tubular Cells ◽  
Functional Studies ◽  
Renal Enlargement

Repeated intraperitoneal injections twice daily of various proteins into young rats were regularly accompanied by an increase in the protein content of the urine, significant renal enlargement, and often some degree of renal pallor. The most marked changes were induced by gelatin, followed in order by human albumin and bovine globulin. Rat serum produced similar but less conclusive changes. Similar changes were not produced by equivalent amounts of urea or casein hydrolysate. In sections from the kidneys of animals receiving gelatin, the cells of the convoluted tubules appeared enlarged, and they contained clear "spaces" throughout the cytoplasm. The tubular cells of the animals receiving the other solutions were not obviously altered in size or shape, and the cytoplasmic changes were slight or absent. There was little evidence of increased multiplication of cells or of tubular dilatation in the kidneys of any of the groups. Changes in concentrations of plasma proteins and hemoglobin, and the results of preliminary studies of the injected proteins in urine and renal tissue following the injections, are described and their possible significance discussed. It appears that the renal enlargement, as well as the increase in proteinuria and the tubular alterations which followed the protein injections, might have been caused in part by effects on the kidney of protein molecules per se, perhaps most likely by the effects on the tubular cells of an increased amount of protein filtered through the glomerular membranes, rather than entirely by effects of products of protein digestion and metabolism reaching the kidney through the blood stream. In the majority of animals there was no evidence from the morphological or functional studies, that the prolonged and continuous proteinuria induced by the protein injections resulted in renal damage, unless the renal enlargement, and the cytoplasmic changes which occurred regularly with gelatin, are considered evidence of damage. Renal enlargement and proteinuria promptly regressed after injections were discontinued. Lesions characterized by severe degrees of tubular damage, possibly as a result of tubular plugging, were observed in some of the animals of one group receiving gelatin solution of the usual concentration, and dilatation of renal tubules and glomerular capsules was present in some other gelatin-treated animals autopsied after relatively brief injection periods. A description is also presented of lesions of remarkable character which developed in the kidneys of all the animals of one small group receiving homologous serum obtained from severely anoxic donors. The possible relationship between the renal changes in the protein-injected animals and certain alterations of the kidneys observed in diseases characterized by large amounts of protein in the urine, is considered.

scholarly journals Inhibition of HDAC6 protects against rhabdomyolysis-induced acute kidney injury

2017 ◽  
Vol 312 (3) ◽  
pp. F502-F515 ◽  
Author(s):  
Yingfeng Shi ◽  
Liuqing Xu ◽  
Jinhua Tang ◽  
Lu Fang ◽  
Shuchen Ma ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Therapeutic Potential ◽  
Apoptotic Cell ◽  
Kidney Injury ◽  
Acute Injury ◽  
Tubular Damage ◽  
Renal Tubules ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Renal Tubular

Histone deacetylase 6 (HDAC6) inhibition has been reported to protect against ischemic stroke and prolong survival after sepsis in animal models. However, it remains unknown whether HDAC6 inhibition offers a renoprotective effect after acute kidney injury (AKI). In this study, we examined the effect of tubastatin A (TA), a highly selective inhibitor of HDAC6, on AKI in a murine model of glycerol (GL) injection-induced rhabdomyolysis. Following GL injection, the mice developed severe acute tubular injury as indicated by renal dysfunction; expression of neutrophil gelatinase-associated lipocalin (NGAL), an injury marker of renal tubules; and an increase of TdT-mediated dUTP nick-end labeling (TUNEL)-positive tubular cells. These changes were companied by increased HDAC6 expression in the cytoplasm of renal tubular cells. Administration of TA significantly reduced serum creatinine and blood urea nitrogen levels as well as attenuated renal tubular damage in injured kidneys. HDAC6 inhibition also resulted in decreased expression of NGAL, reduced apoptotic cell, and inactivated caspase-3 in the kidney after acute injury. Moreover, injury to the kidney increased phosphorylation of nuclear factor (NF)-κB and expression of multiple cytokines/chemokines including tumor necrotic factor-α and interleukin-6 and monocyte chemoattractant protein-1, as well as macrophage infiltration. Treatment with TA attenuated all those responses. Finally, HDAC6 inhibition reduced the level of oxidative stress by suppressing malondialdehyde (MDA) and preserving expression of superoxide dismutase (SOD) in the injured kidney. Collectively, these data indicate that HDAC6 contributes to the pathogenesis of rhabdomyolysis-induced AKI and suggest that HDAC6 inhibitors have therapeutic potential for AKI treatment.

scholarly journals Renal Involvement in Congenital Cytomegalovirus Infection: A Systematic Review

2021 ◽  
Vol 9 (6) ◽  
pp. 1304
Author(s):  
María Ríos-Barnés ◽  
Clàudia Fortuny ◽  
Ana Alarcón ◽  
Antoni Noguera-Julian
Keyword(s):  
Renal Involvement ◽  
Congenital Nephrotic Syndrome ◽  
Renal Tissue ◽  
Renal Tubules ◽  
Level Of Evidence ◽  
Transmitted Infection ◽  
Congenital Cytomegalovirus ◽  
Functional Studies ◽  
Increased Risk

Background: Congenital cytomegalovirus (cCMV) infection is the most frequent mother-to-child transmitted infection worldwide and a prevalent cause of neonatal disease and long-term morbidity. The kidney is a target organ for CMV, which replicates in renal tubules and is excreted in large quantities in urine for years in children with cCMV infection. Nonetheless, kidney disease has rarely been reported in cCMV-infected patients. Objective: We aimed to describe the available data on renal involvement in patients with cCMV infection at the pathologic, functional, anatomical, and/or clinical levels. Methods: A systematic search was performed in the MEDLINE/PubMed, SCOPUS, and Cochrane databases. Studies describing any renal involvement in fetuses or neonates aged ≤3 weeks at diagnosis of microbiologically confirmed cCMV infection were eligible. Results: Twenty-four articles were included, with a very low level of evidence. Pathologic findings in autopsy studies universally described CMV typical inclusion bodies in tubular cells. No functional studies were identified. cCMV infection was not associated with an increased risk of kidney malformations. Congenital nephrotic syndrome was the most common clinical condition associated with cCMV, but a causal relationship cannot be established. Conclusions: Typical pathological features of cCMV infection are very common in renal tissue, but they do not seem to entail significant consequences at the anatomical or clinical levels.

Histopathological and Hematological Changes in Mummichogs, Fundulus heteroclitus, Infected by a Pseudomonad

1978 ◽  
Vol 35 (10) ◽  
pp. 1376-1381 ◽  
Author(s):  
M. F. Li ◽  
G. S. Traxler ◽  
S. Clyburne
Keyword(s):  
Fundulus Heteroclitus ◽  
Renal Tissue ◽  
Infected Fish ◽  
Splenic Tissue ◽  
Hepatic Veins ◽  
Renal Tubules ◽  
Fish Disease ◽  
Histopathological Changes ◽  
Key Words Fish ◽  
Hematological Changes

The hematological and histopathological changes in mummichogs infected by Pseudomonas reptilivora included a dramatic reduction in hematocrit values; massive structural lymphoid necrosis with formation of edematous spaces in the splenic tissue; empty and degenerate hepatic veins and sinusoids; and necrosis of the renal tubules in naturally and experimentally infected fish. Electron microscopy of the renal tissue revealed clumps of chromatin in the nuclei, disintegration or degeneration of organelles, and an increase of digestive vesicles or autophagic vacuoles in the cells. This is the first description of the pathology of this bacteria in a marine fish. Key words: fish disease, Pseudomonas, bacteria, hemorrhagic septicemia

Inhibition of tubular cell proliferation by neutralizing endogenous HGF leads to renal hypoxia and bone marrow-derived cell engraftment in acute renal failure

2008 ◽  
Vol 294 (2) ◽  
pp. F326-F335 ◽  
Author(s):  
Hiroyuki Ohnishi ◽  
Shinya Mizuno ◽  
Toshikazu Nakamura
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
Renal Failure ◽  
Acute Renal Failure ◽  
Repair Process ◽  
Tubular Cell ◽  
Tubular Damage ◽  
Renal Tubules ◽  
Stromal Cell Derived Factor ◽  
Renal Tubular

During the progression of acute renal failure (ARF), the renal tubular S3 segment is sensitive to ischemic stresses. For reversing tubular damage, resident tubular cells proliferate, and bone marrow-derived cells (BMDC) can be engrafted into injured tubules. However, how resident epithelium or BMDC are involved in tubular repair remains unknown. Using a mouse model of ARF, we examined whether hepatocyte growth factor (HGF) regulates a balance of resident cell proliferation and BMDC recruitment. Within 48 h post-renal ischemia, tubular destruction became evident, followed by two-waved regenerative events: 1) tubular cell proliferation between 2 and 4 days, along with an increase in blood HGF; and 2) appearance of BMDC in the tubules from 6 days postischemia. When anti-HGF IgG was injected in the earlier stage, tubular cell proliferation was inhibited, leading to an increase in BMDC in renal tubules. Under the HGF-neutralized state, stromal cell-derived factor-1 (SDF1) levels increased in renal tubules, associated with the enhanced hypoxia. Administrations of anti-SDF1 receptor IgG into ARF mice reduced the number of BMDC in interstitium and tubules. Thus possible cascades include 1) inhibition of tubular cell proliferation by neutralizing HGF leads to renal hypoxia and SDF1 upregulation; and 2) BMDC are eventually engrafted in tubules through SDF1-mediated chemotaxis. Inversely, administration of recombinant HGF suppressed the renal hypoxia, SDF1 upregulation, and BMDC engraftment in ARF mice by enhancing resident tubular cell proliferation. Thus we conclude that HGF is a positive regulator for eliciting resident tubular cell proliferation, and SDF1 for BMDC engraftment during the repair process of ARF.

Abstract 061: Cell Fate Changes During Tubular Damage and Regeneration in the Mouse Kidney

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Vidya K Nagalakshmi ◽  
Minghong Li ◽  
R. A Gomez ◽  
Maria Luisa S Sequeira-Lopez
Keyword(s):  
Cell Fate ◽  
Ureteral Obstruction ◽  
Molecular Mechanisms ◽  
Interstitial Fibrosis ◽  
Kidney Diseases ◽  
Collecting Duct ◽  
Lineage Tracing ◽  
Tubular Damage ◽  
Renal Tubules ◽  
Atubular Glomeruli

Tubular degeneration, loss of renal tubules and interstitial fibrosis due to kidney injury lead to chronic renal disease and hypertension. Using a partial unilateral ureteral obstruction (pUUO) model in neonatal mice, we analyzed the fate cell changes that occur during obstruction and during recovery following the release of UUO. We traced the fate of cells derived from the renal stroma, cap mesenchyme and ureteric bud epithelium using Foxd1-Cre, Six2-Cre and HoxB7-Cre mice respectively, crossed with double fluorescent reporter (mT/mG) mice. pUUO was performed 24-36h after birth (n=84). In a group of pups (n=37), the obstruction was released after seven days. Sham operated animals (n=35) were used as controls. Lineage tracing revealed that Foxd1-derived interstitial pericytes acquired α-smooth muscle actin expression and underwent significant expansion due to pUUO (fibrotic area 91.06+/-6.77 %). Release of obstruction resulted in complete resolution of fibrotic areas (0.00%; p<0.005). Further, loss of Six2-derived cells at the glomerular-tubular junction in pUUO kidneys resulted in the formation of atubular glomeruli (39%). Atubular glomeruli were not observed after release. In addition, a significant loss of HoxB7-derived collecting duct tubules was observed during pUUO. Most collecting ducts recovered following release. Our study indicates that obstruction leads to significant tubular damage, expansion of interstitial pericytes, fibrosis, tubular loss and formation of atubular glomeruli. The striking recovery observed after release of ureteral obstruction suggests a reversal of cell fate changes and tubular regeneration. Elucidation of the cellular and molecular mechanisms mediating these events may be of use in the design of strategies for the prevention and/or treatment of kidney diseases and secondary hypertension.

scholarly journals Roles of Nrf2 in Protecting the Kidney from Oxidative Damage

2020 ◽  
Vol 21 (8) ◽  
pp. 2951 ◽  
Author(s):  
Masahiro Nezu ◽  
Norio Suzuki
Keyword(s):  
Oxidative Stress ◽  
Kidney Disease ◽  
Ischemia Reperfusion Injury ◽  
Interstitial Fibrosis ◽  
Ischemia Reperfusion ◽  
Organ Damage ◽  
Tubular Damage ◽  
Renal Tubules ◽  
Renal Vasculature ◽  
Nrf2 Activation

Over 10% of the global population suffers from kidney disease. However, only kidney replacement therapies, which burden medical expenses, are currently effective in treating kidney disease. Therefore, elucidating the complicated molecular pathology of kidney disease is an urgent priority for developing innovative therapeutics for kidney disease. Recent studies demonstrated that intertwined renal vasculature often causes ischemia-reperfusion injury (IRI), which generates oxidative stress, and that the accumulation of oxidative stress is a common pathway underlying various types of kidney disease. We reported that activating the antioxidative transcription factor Nrf2 in renal tubules in mice with renal IRI effectively mitigates tubular damage and interstitial fibrosis by inducing the expression of genes related to cytoprotection against oxidative stress. Additionally, since the kidney performs multiple functions beyond blood purification, renoprotection by Nrf2 activation is anticipated to lead to various benefits. Indeed, our experiments indicated the possibility that Nrf2 activation mitigates anemia, which is caused by impaired production of the erythroid growth factor erythropoietin from injured kidneys, and moderates organ damage worsened by anemic hypoxia. Clinical trials investigating Nrf2-activating compounds in kidney disease patients are ongoing, and beneficial effects are being obtained. Thus, Nrf2 activators are expected to emerge as first-in-class innovative medicine for kidney disease treatment.

scholarly journals Sodium Glucose Co-Transporter 2 Inhibitor Ameliorates Autophagic Flux Impairment on Renal Proximal Tubular Cells in Obesity Mice

2020 ◽  
Vol 21 (11) ◽  
pp. 4054
Author(s):  
Kazuhiko Fukushima ◽  
Shinji Kitamura ◽  
Kenji Tsuji ◽  
Yizhen Sang ◽  
Jun Wada
Keyword(s):  
Renal Injury ◽  
Tubular Damage ◽  
Autophagic Flux ◽  
Protective Effects ◽  
Renal Protection ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Renal Proximal Tubular Cells ◽  
Renal Proximal Tubular

Obesity is supposed to cause renal injury via autophagy deficiency. Recently, sodium glucose co-transporter 2 inhibitors (SGLT2i) were reported to protect renal injury. However, the mechanisms of SGLT2i for renal protection are unclear. Here, we investigated the effect of SGLT2i for autophagy in renal proximal tubular cells (PTCs) on obesity mice. We fed C57BL/6J mice with a normal diet (ND) or high-fat and -sugar diet (HFSD) for nine weeks, then administered SGLT2i, empagliflozin, or control compound for one week. Each group contained N = 5. The urinary N-acetyl-beta-d-glucosaminidase level in the HFSD group significantly increased compared to ND group. The tubular damage was suppressed in the SGLT2i–HFSD group. In electron microscopic analysis, multi lamellar bodies that increased in autophagy deficiency were increased in PTCs in the HFSD group but significantly suppressed in the SGLT2i group. The autophagosomes of damaged mitochondria in PTCs in the HFSD group frequently appeared in the SGLT2i group. p62 accumulations in PTCs were significantly increased in HFSD group but significantly suppressed by SGLT2i. In addition, the mammalian target of rapamycin was activated in the HFSD group but significantly suppressed in SGLT2i group. These data suggest that SGLT2i has renal protective effects against obesity via improving autophagy flux impairment in PTCs on a HFSD.

Difference in H2O2 toxicity between intact renal tubules and cultured proximal tubular cells

1998 ◽  
Vol 56 (4) ◽  
pp. 489-495 ◽  
Author(s):  
Yong Keun Kim ◽  
Sun Hee Ko ◽  
Jae Suk Woo ◽  
Sang Ho Lee ◽  
Jin Sup Jung
Keyword(s):  
Renal Tubules ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular

Urolithiasis, Kidney Transplantation, and Pregnancy and Kidney Disease

2012 ◽  
Author(s):  
Stephen B. Erickson ◽  
Hatem Amer ◽  
Timothy S. Larson
Keyword(s):  
Kidney Stones ◽  
End Stage Renal Disease ◽  
Stone Formation ◽  
Renal Tubules ◽  
Anatomical Changes ◽  
Renal Enlargement ◽  
Ureteral Peristalsis ◽  
Total Body ◽  
Stage Renal Disease ◽  
End Stage

It was previously assumed that all kidney stones crystallized as urine passed through the renal tubules and were retained by means of crystal-tubular cell interactions. Recently uroscopy with papillary biopsies has shown 2 different pathways for stone formation, both mediated by calcium phosphate crystals. Kidney transplant has become the preferred treatment for patients with end-stage renal disease. Those benefiting from transplant included patients who would be deemed "high risk," such as those with diabetes mellitus and those older than 70 years. Anatomical changes associated with pregnancy are renal enlargement and dilatation of the calyces, renal pelvis, and ureters. Physiologic changes include a 30% to 50% increase in glomerular filtration rate and renal blood flow; a mean decrease of 0.5 mg/dL in the creatinine level and a mean decrease of 18 mg/dL in the serum urea nitrogen level; intermittent glycosuria independent of plasma glucose; proteinuria; aminoaciduria; increased uric acid excretion; increased total body water, with osmostat resetting; 50% increase in plasma volume and cardiac output; and increased ureteral peristalsis.

scholarly journals Therapeutic plasma exchange (TPE) for semi-critical neurology presentations in a non-acute neurology set-up: clinical practice and challenges

2020 ◽  
Vol 2 (1) ◽  
pp. e000020
Author(s):  
Keng Seng Fu ◽  
Pei Yin Wong ◽  
Fu Liong Hiew
Keyword(s):  
Critical Care ◽  
Plasma Exchange ◽  
Blood Stream Infection ◽  
Blood Stream ◽  
Human Albumin ◽  
Therapeutic Plasma Exchange ◽  
Manufacturing Defects ◽  
Technical Errors ◽  
Set Up ◽  
Acute Set

IntroductionTherapeutic plasma exchange (TPE) for semi-critical neurological manifestations can be managed in non-acute setting instead of critical care unit. In 2014, we established a non-acute neurology TPE unit for semi-critical haemodynamically stable patients. In this study, we aimed to evaluate the technical and safety parameters from the first 3 years of service.Materials and methodsWe analysed prospectively collected TPE data for patients treated with centrifugation TPE at our non-acute neurology TPE unit in Kuala Lumpur Hospital between May 2015 and June 2018.ResultsA total of 245 TPE procedures were performed in 55 patients for nine neurological indications, predominantly the central nervous system (79%). Twenty four per cent (n=13) had category I and 73% (n=40) had category II indication (American Society for Apheresis (ASFA) 2019). Others (4%) were not in ASFA indications. Neuromyelitis optica spectrum disorders accounted for half (51%) of the total patients. Twenty-three (41.8%) patients experienced adverse events, with hypotensive episodes being the the most common (n=12/55, 21.8%). Five (9.1%) patients had catheter-related blood stream infection, correlating with higher exchange plasma volume (p=0.023). Symptomatic hypocalcaemia was less common (n=5/55, 9.1%) and allergic reaction to human albumin was rare (n=1/55, 1.8%). Four technical errors detected. Three involved centrifugation sets manufacturing defects and one involved error in centrifugation set installation. Seven (2.9%) procedures were terminated: 5 for adverse effects and 2 for technical errors.ConclusionPerforming TPE among semi-critical patients with neurology manifestations in basic non-acute set-up proved safe, with predictable complications. This set-up reduced the reliance on critical care services for TPE procedures.

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