Significance of Technetium-99m Human Serum Albumin Diethylenetriamine Pentaacetic Acid Scintigraphy in Patients with Nephrotic Syndrome

PubMed Central

Takashima, Tsuyoshi; Kishi, Tomoya; Onozawa, Koji; Rikitake, Shuichi; Miyazono, Motoaki; Otsuka, Takateru; Irie, Hiroyuki; Iwakiri, Ryuichi; Fujimoto, Kazuma; Ikeda, Yuji

2015-01-01

It is thought that a large amount of albumin leaking from the glomerulus in nephrotic syndrome (NS) is reabsorbed at the proximal tubule and catabolized. Therefore, it is possible the final quantity of urinary protein does not always reflect the amount of leakage of protein from the glomerulus. We experienced two cases without nephrotic range proteinuria thought to involve hypoproteinemia due to the same pathophysiology as NS. On these patients, we performed protein leakage scintigraphy with technetium-99m human serum albumin diethylenetriamine pentaacetic acid (99mTc-HSAD) to exclude a diagnosis of protein-losing gastroenteropathy and observed diffuse positive accumulation in the kidneys with more intense uptake in the kidney than the liver on the anterior view 24 hours after 99mTc-HSAD administration. In healthy adults intravenously given 99mTc-HSAD, the same dynamics are observed as in albumin metabolism, and the organ radioactivity of the liver and kidneys after 24 hours is equal. Therefore, we thought it was possible that the renal uptake 24 hours after 99mTc-HSAD administration was a characteristic finding of NS. In order to confirm it, the subjects were divided into two groups: the NS group (n = 10) and the non-NS group (n = 7). We defined more intense uptake in the kidney than the liver on the anterior view 24 hours after 99mTc-HSAD administration as Dense Kidney (+). Furthermore, we designed regions of interest in the right and left kidneys and liver on anterior and posterior images, then calculated the kidney-liver ratio. Nine of the ten patients had Dense Kidney (+) in the NS group, compared to none in the non-NS group. And the kidney-liver ratio was significantly higher in the NS group than in the non-NS group on each view in the bilateral kidneys. In conclusion, our results suggest that the renal uptake 24 hours after 99mTc-HSAD administration is a characteristic finding of NS. PMID:25859658

CXC Chemokine Receptor 7 (CXCR7) Regulates CXCR4 Protein Expression and Capillary Tuft Development in Mouse Kidney

PubMed Central

Haege, Sammy; Mueller, Wiebke; Nietzsche, Sandor; Lupp, Amelie; Mackay, Fabienne; Schulz, Stefan; Stumm, Ralf

2012-01-01

Background The CXCL12/CXCR4 axis is involved in kidney development by regulating formation of the glomerular tuft. Recently, a second CXCL12 receptor was identified and designated CXCR7. Although it is established that CXCR7 regulates heart and brain development in conjunction with CXCL12 and CXCR4, little is known about the influence of CXCR7 on CXCL12 dependent kidney development. Methodology/Principal Findings We provided analysis of CXCR7 expression and function in the developing mouse kidney. Using in situ hybridization, we identified CXCR7 mRNA in epithelial cells including podocytes at all nephron stages up to the mature glomerulus. CXCL12 mRNA showed a striking overlap with CXCR7 mRNA in epithelial structures. In addition, CXCL12 was detected in stromal cells and the glomerular tuft. Expression of CXCR4 was complementary to that of CXCR7 as it occurred in mesenchymal cells, outgrowing ureteric buds and glomerular endothelial cells but not in podocytes. Kidney examination in CXCR7 null mice revealed ballooning of glomerular capillaries as described earlier for CXCR4 null mice. Moreover, we detected a severe reduction of CXCR4 protein but not CXCR4 mRNA within the glomerular tuft and in the condensed mesenchyme. Malformation of the glomerular tuft in CXCR7 null mice was associated with mesangial cell clumping. Conclusions/Significance We established that there is a similar glomerular pathology in CXCR7 and CXCR4 null embryos. Based on the phenotype and the anatomical organization of the CXCL12/CXCR4/CXCR7 system in the forming glomerulus, we propose that CXCR7 fine-tunes CXCL12/CXCR4 mediated signalling between podocytes and glomerular capillaries. PMID:22880115

CXC chemokine receptor 7 (CXCR7) regulates CXCR4 protein expression and capillary tuft development in mouse kidney.

PubMed

Haege, Sammy; Einer, Claudia; Thiele, Stefanie; Mueller, Wiebke; Nietzsche, Sandor; Lupp, Amelie; Mackay, Fabienne; Schulz, Stefan; Stumm, Ralf

2012-01-01

The CXCL12/CXCR4 axis is involved in kidney development by regulating formation of the glomerular tuft. Recently, a second CXCL12 receptor was identified and designated CXCR7. Although it is established that CXCR7 regulates heart and brain development in conjunction with CXCL12 and CXCR4, little is known about the influence of CXCR7 on CXCL12 dependent kidney development. We provided analysis of CXCR7 expression and function in the developing mouse kidney. Using in situ hybridization, we identified CXCR7 mRNA in epithelial cells including podocytes at all nephron stages up to the mature glomerulus. CXCL12 mRNA showed a striking overlap with CXCR7 mRNA in epithelial structures. In addition, CXCL12 was detected in stromal cells and the glomerular tuft. Expression of CXCR4 was complementary to that of CXCR7 as it occurred in mesenchymal cells, outgrowing ureteric buds and glomerular endothelial cells but not in podocytes. Kidney examination in CXCR7 null mice revealed ballooning of glomerular capillaries as described earlier for CXCR4 null mice. Moreover, we detected a severe reduction of CXCR4 protein but not CXCR4 mRNA within the glomerular tuft and in the condensed mesenchyme. Malformation of the glomerular tuft in CXCR7 null mice was associated with mesangial cell clumping. We established that there is a similar glomerular pathology in CXCR7 and CXCR4 null embryos. Based on the phenotype and the anatomical organization of the CXCL12/CXCR4/CXCR7 system in the forming glomerulus, we propose that CXCR7 fine-tunes CXCL12/CXCR4 mediated signalling between podocytes and glomerular capillaries.

Ameliorative Effect of Arctium lappa Against Cadmium Genotoxicity and Histopathology in Kidney of Wistar Rat.

PubMed

Suliman Al-Gebaly, Asma

2017-01-01

Cadmium (Cd) is a non-essential metal whose dispersion in the environment has increased recently, Cd may enhance cell oxidative stress that leads to DNA damage and apoptotic cell death. The study aimed to evaluate the antioxidative capability of Burdock root 'Arctium lappa' on cadmium-induced oxidative stress and histopathology of the kidney of Wistar rats. Cadmium was applied in a form of cadmium chloride to three groups (15 mg Cd kg-1) for five weeks with two groups pre-treated with 'Arctium lappa' administration, 100 and 200 mg kg-1 b.wt. Data were analyzed using one way analysis of variance (ANOVA) followed by Least Significant Difference (LSD) test to determine the difference among means using the JMP version 12. Results revealed that cadmium induced a significant disorganization (p<0.05) of renal structure with collapsed tubular lamina and 76 μm tail length of the cells was observed, while histological sections of kidney pre-treated with 100 mg Arctium lappa kg-1 b.wt., showed a slightly less hypercellularity of glomerulus and reduction in the cell tail (59 μm). Furthermore, histological sections of kidney of rats pre-treated with 200 mg Arctium lappa kg-1 b.wt., showed high improvement of renal tubules and glomerulus with a prominent urinary space beside tail length of cells was recorded as 39 μm which was lower in comparison to other groups. Moreover, cadmium induced cellular destruction of the kidney was resumed with the pre-treatment of the secondary metabolites as an antioxidant compounds that produced from plant extracts. Arctium lappa leaf extract was efficient at both applied doses while 200 mg Arctium lappa kg-1 b.wt., had the most ameliorative effect.

Myxobolus sp. and Henneguya sp. (Cnidaria: Myxobolidae) natural co-infection in the kidney of Piaractus mesopotamicus (Characiformes: Serrasalmidae).

PubMed

Manrique, Wilson Gómez; Figueiredo, Mayra Araguaia Pereira; de Andrade Belo, Marco Antonio; Martins, Maurício Laterça; Molnár, Kálmán

2017-10-01

This study evaluated the myxozoan infection and histopathology of the kidney of freshwater fish Piaractus mesopotamicus from intensive fish farming in Brazil. A total of 55 fish were examined for myxozoan infection. Infected organs were processed by usual histology and stained with hematoxylin-eosin (H&E) and Ziehl-Neelsen (ZN). From the total of 55 fish analyzed, 47 (85.45%) presented myxospores, being 9.09% (5/55) only with Myxobolus sp., 5.45% (3/55) only with Henneguya sp., and 70.91% (39/55) presenting both parasites. The presence of myxospores was associated with histological alterations in both stromal and renal parenchyma. Myxospores were found mostly in the peritubular interstitial tissue and in low intensity in the glomerulus which caused nuclear hypertrophy and loss of Bowman space. An increase in the glomerular tuft and a reduction in the lumen of the collector tubules were also observed, besides the high number of melanomacrophage cells in the glomerulus. This study reports for the first time detection of myxozoan mixed infection in one organ of pacu and discuss the possible transportation of myxospores in the circulating blood.

Early development of the zebrafish pronephros and analysis of mutations affecting pronephric function.

PubMed

Drummond, I A; Majumdar, A; Hentschel, H; Elger, M; Solnica-Krezel, L; Schier, A F; Neuhauss, S C; Stemple, D L; Zwartkruis, F; Rangini, Z; Driever, W; Fishman, M C

1998-12-01

The zebrafish pronephric kidney provides a simplified model of nephron development and epithelial cell differentiation which is amenable to genetic analysis. The pronephros consists of two nephrons with fused glomeruli and paired pronephric tubules and ducts. Nephron formation occurs after the differentiation of the pronephric duct with both the glomeruli and tubules being derived from a nephron primordium. Fluorescent dextran injection experiments demonstrate that vascularization of the zebrafish pronephros and the onset of glomerular filtration occurs between 40 and 48 hpf. We isolated fifteen recessive mutations that affect development of the pronephros. All have visible cysts in place of the pronephric tubule at 2-2.5 days of development. Mutants were grouped in three classes: (1) a group of twelve mutants with defects in body axis curvature and manifesting the most rapid and severe cyst formation involving the glomerulus, tubule and duct, (2) the fleer mutation with distended glomerular capillary loops and cystic tubules, and (3) the mutation pao pao tang with a normal glomerulus and cysts limited to the pronephric tubules. double bubble was analyzed as a representative of mutations that perturb the entire length of the pronephros and body axis curvature. Cyst formation begins in the glomerulus at 40 hpf at the time when glomerular filtration is established suggesting a defect associated with the onset of pronephric function. Basolateral membrane protein targeting in the pronephric duct epithelial cells is also severely affected, suggesting a failure in terminal epithelial cell differentiation and alterations in electrolyte transport. These studies reveal the similarity of normal pronephric development to kidney organogenesis in all vertebrates and allow for a genetic dissection of genes needed to establish the earliest renal function.

Nephrin is necessary for podocyte recovery following injury in an adult mature glomerulus.

PubMed

Verma, Rakesh; Venkatareddy, Madhusudan; Kalinowski, Anne; Li, Theodore; Kukla, Joanna; Mollin, Ashomathi; Cara-Fuentes, Gabriel; Patel, Sanjeevkumar R; Garg, Puneet

2018-01-01

Nephrin (Nphs1) is an adhesion protein that is expressed at the podocyte intercellular junction in the glomerulus. Nphs1 mutations in humans or deletion in animal genetic models results in a developmental failure of foot process formation. A number of studies have shown decrease in expression of nephrin in various proteinuric kidney diseases as well as in animal models of glomerular disease. Decrease in nephrin expression has been suggested to precede podocyte loss and linked to the progression of kidney disease. Whether the decrease in expression of nephrin is related to loss of podocytes or lead to podocyte detachment is unclear. To answer this central question we generated an inducible model of nephrin deletion (Nphs1Tam-Cre) in order to lower nephrin expression in healthy adult mice. Following tamoxifen-induction there was a 75% decrease in nephrin expression by 14 days. The Nphs1Tam-Cre mice had normal foot process ultrastructure and intact filtration barriers up to 4-6 weeks post-induction. Despite the loss of nephrin expression, the podocyte number and density remained unchanged during the initial period. Unexpectedly, nephrin expression, albeit at low levels persisted at the slit diaphragm up to 16-20 weeks post-tamoxifen induction. The mice became progressively proteinuric with glomerular hypertrophy and scarring reminiscent of focal and segmental glomerulosclerosis at 20 weeks. Four week-old Nphs1 knockout mice subjected to protamine sulfate model of podocyte injury demonstrated failure to recover from foot process effacement following heparin sulfate. Similarly, Nphs1 knockout mice failed to recover following nephrotoxic serum (NTS) with persistence of proteinuria and foot process effacement. Our results suggest that as in development, nephrin is necessary for maintenance of a healthy glomerular filter. In contrast to the developmental phenotype, lowering nephrin expression in a mature glomerulus resulted in a slowly progressive disease that histologically resembles FSGS a disease linked closely with podocyte depletion. Podocytes with low levels of nephrin expression are both susceptible and unable to recover following perturbation. Our results suggest that decreased nephrin expression independent of podocyte loss occurring as an early event in proteinuric kidney diseases might play a role in disease progression.

Combination therapy of exendin-4 and allogenic adipose-derived mesenchymal stem cell preserved renal function in a chronic kidney disease and sepsis syndrome setting in rats

PubMed Central

Chen, Chih-Hung; Cheng, Ben-Chung; Chen, Kuan-Hung; Shao, Pei-Lin; Sung, Pei-Hsun; Chiang, Hsin-Ju; Yang, Chih-Chao; Lin, Kun-Chen; Sun, Cheuk-Kwan; Sheu, Jiunn-Jye; Chang, Hsueh-Wen; Lee, Mel S.; Yip, Hon-Kan

2017-01-01

Combined therapy with exendin-4 (Ex4) and allogenic adipose-derived mesenchymal stem cells (ADMSC) was tested against either therapy alone for protecting kidney function against chronic kidney disease (CKD) complicated by sepsis syndrome (SS) [i.e., by intraperitoneal injection of cecal-derived bacteria (1.0 × 104) cells/milliliter/total 5.0 cc].Adult-male-Sprague Dawley rats (n=36) were equally divided into group 1 (sham-control), group 2 (CKD), group 3 (CKD-SS), group 4 (CKD-SS-Ex4), group 5 (CKD-SS-ADMSC) and group 6 (CKD-SS-Ex4-ADMSC). At day 42 after CKD induction SS was induced. Thirty-minutes after SS induction, ADMSCs (2.0 ×106 cells) were intravenously administered to groups 5 and 6. Ex4 (10 μg/kg) was intraperitoneally administered groups 4 and 6 at 30 min and days 1 to 5 after SS induction. Animals were euthanized at day 47 after CKD induction. Kidney-injury score, collagen-deposition area, and creatinine/BUN levels were lowest in group 1, highest in group 3 and significantly higher in group 2 than in groups 4 to 6 in a progressively increasing manner (all P<0.0001). Protein expressions of inflammatory (MMP-9/TNF-α/NF-κB/IL-1ß/ICAM-1), oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptotic (mitochondrial-Bax/cleaved-caspase-3/cleaved-PARP) and fibrotic/DNA-damaged (Smad3/TGF-ß/γ-H2AX) biomarkers showed an identical pattern, whereas anti-fibrotic (BMP-2/Smad1/5), anti-apoptotic/endothelial-integrity (Bcl-2/eNOS) and podocyte-integrity (ZO-1/p-cadherin) biomarkers exhibited an opposite pattern of kidney-injury score among the six groups (all P>0.0001). Cellular expressions of inflammatory (CD14/CD68) and glomerulus/tubular-injury (WT-1/KIM-1) biomarkers displayed an identical pattern, whereas glomerulus/podocyte-component (dystroglycan/nephrin/ZO-1/fibronectin/p-cadherin) biomarkers showed an opposite kidney-injury score among the six groups (all P<0.0001). In conclusion, Ex4-ADMSC therapy effectively preserved renal function in the CKD-SS setting. PMID:29245956

The lineage-specific gene ponzr1 is essential for zebrafish pronephric and pharyngeal arch development.

PubMed

Bedell, Victoria M; Person, Anthony D; Larson, Jon D; McLoon, Anna; Balciunas, Darius; Clark, Karl J; Neff, Kevin I; Nelson, Katie E; Bill, Brent R; Schimmenti, Lisa A; Beiraghi, Soraya; Ekker, Stephen C

2012-02-01

The Homeobox (Hox) and Paired box (Pax) gene families are key determinants of animal body plans and organ structure. In particular, they function within regulatory networks that control organogenesis. How these conserved genes elicit differences in organ form and function in response to evolutionary pressures is incompletely understood. We molecularly and functionally characterized one member of an evolutionarily dynamic gene family, plac8 onzin related protein 1 (ponzr1), in the zebrafish. ponzr1 mRNA is expressed early in the developing kidney and pharyngeal arches. Using ponzr1-targeting morpholinos, we show that ponzr1 is required for formation of the glomerulus. Loss of ponzr1 results in a nonfunctional glomerulus but retention of a functional pronephros, an arrangement similar to the aglomerular kidneys found in a subset of marine fish. ponzr1 is integrated into the pax2a pathway, with ponzr1 expression requiring pax2a gene function, and proper pax2a expression requiring normal ponzr1 expression. In addition to pronephric function, ponzr1 is required for pharyngeal arch formation. We functionally demonstrate that ponzr1 can act as a transcription factor or co-factor, providing the first molecular mode of action for this newly described gene family. Together, this work provides experimental evidence of an additional mechanism that incorporates evolutionarily dynamic, lineage-specific gene families into conserved regulatory gene networks to create functional organ diversity.

In vivo imaging of leukocyte recruitment to glomeruli in mice using intravital microscopy.

PubMed

Kitching, A Richard; Kuligowski, Michael P; Hickey, Michael J

2009-01-01

Leukocytes mediate some forms of glomerulonephritis, particularly severe proliferative and crescentic forms. The renal glomerulus is one of the few sites within the microvasculature in which leukocyte recruitment occurs in capillaries. However, due to the difficulty of directly visualising the glomerulus, the mechanisms of leukocyte recruitment to glomerular capillaries are poorly understood. To overcome this, a murine kidney can be rendered hydronephrotic, by ligating one ureter, and allowing the mouse to rest for 12 weeks. This allows the visualisation of the glomerular microvasculature during inflammatory responses. In inflammation, in this example induced by anti-glomerular basement membrane (GBM) antibody, leukocytes can be observed undergoing adhesion in glomerular capillaries using intravital microscopy. Leukocyte adhesion can be quantitated using this approach. An observation protocol involving few, limited periods of epifluorescence avoids phototoxicity-induced leukocyte recruitment. The process of hydronephrosis does not alter the ability of anti-GBM-antibody to induce a glomerular inflammatory response. This approach allows detailed investigation of the mechanisms of leukocyte recruitment within glomeruli.

In vivo imaging of kidney glomeruli transplanted into the anterior chamber of the mouse eye

PubMed Central

Kistler, Andreas D.; Caicedo, Alejandro; Abdulreda, Midhat H.; Faul, Christian; Kerjaschki, Dontscho; Berggren, Per-Olof; Reiser, Jochen; Fornoni, Alessia

2014-01-01

Multiphoton microscopy enables live imaging of the renal glomerulus. However, repeated in vivo imaging of the same glomerulus over extended periods of time and the study of glomerular function independent of parietal epithelial and proximal tubular cell effects has not been possible so far. Here, we report a novel approach for non-invasive imaging of acapsular glomeruli transplanted into the anterior chamber of the mouse eye. After microinjection, glomeruli were capable of engrafting on the highly vascularized iris. Glomerular structure was preserved, as demonstrated by podocyte specific expression of cyan fluorescent protein and by electron microscopy. Injection of fluorescence-labeled dextrans of various molecular weights allowed visualization of glomerular filtration and revealed leakage of 70 kDa dextran in an inducible model of proteinuria. Our findings demonstrate functionality and long-term survival of glomeruli devoid of Bowman's capsule and provide a novel approach for non-invasive longitudinal in vivo study of glomerular physiology and pathophysiology. PMID:24464028

Lin28 sustains early renal progenitors and induces Wilms tumor

PubMed Central

Urbach, Achia; Yermalovich, Alena; Zhang, Jin; Spina, Catherine S.; Zhu, Hao; Perez-Atayde, Antonio R.; Shukrun, Rachel; Charlton, Jocelyn; Sebire, Neil; Mifsud, William; Dekel, Benjamin; Pritchard-Jones, Kathy; Daley, George Q.

2014-01-01

Wilms Tumor, the most common pediatric kidney cancer, evolves from the failure of terminal differentiation of the embryonic kidney. Here we show that overexpression of the heterochronic regulator Lin28 during kidney development in mice markedly expands nephrogenic progenitors by blocking their final wave of differentiation, ultimately resulting in a pathology highly reminiscent of Wilms tumor. Using lineage-specific promoters to target Lin28 to specific cell types, we observed Wilms tumor only when Lin28 is aberrantly expressed in multiple derivatives of the intermediate mesoderm, implicating the cell of origin as a multipotential renal progenitor. We show that withdrawal of Lin28 expression reverts tumorigenesis and markedly expands the numbers of glomerulus-like structures and that tumor formation is suppressed by enforced expression of Let-7 microRNA. Finally, we demonstrate overexpression of the LIN28B paralog in a significant percentage of human Wilms tumor. Our data thus implicate the Lin28/Let-7 pathway in kidney development and tumorigenesis. PMID:24732380

The lineage-specific gene ponzr1 is essential for zebrafish pronephric and pharyngeal arch development

PubMed Central

Bedell, Victoria M.; Person, Anthony D.; Larson, Jon D.; McLoon, Anna; Balciunas, Darius; Clark, Karl J.; Neff, Kevin I.; Nelson, Katie E.; Bill, Brent R.; Schimmenti, Lisa A.; Beiraghi, Soraya; Ekker, Stephen C.

2012-01-01

The Homeobox (Hox) and Paired box (Pax) gene families are key determinants of animal body plans and organ structure. In particular, they function within regulatory networks that control organogenesis. How these conserved genes elicit differences in organ form and function in response to evolutionary pressures is incompletely understood. We molecularly and functionally characterized one member of an evolutionarily dynamic gene family, plac8 onzin related protein 1 (ponzr1), in the zebrafish. ponzr1 mRNA is expressed early in the developing kidney and pharyngeal arches. Using ponzr1-targeting morpholinos, we show that ponzr1 is required for formation of the glomerulus. Loss of ponzr1 results in a nonfunctional glomerulus but retention of a functional pronephros, an arrangement similar to the aglomerular kidneys found in a subset of marine fish. ponzr1 is integrated into the pax2a pathway, with ponzr1 expression requiring pax2a gene function, and proper pax2a expression requiring normal ponzr1 expression. In addition to pronephric function, ponzr1 is required for pharyngeal arch formation. We functionally demonstrate that ponzr1 can act as a transcription factor or co-factor, providing the first molecular mode of action for this newly described gene family. Together, this work provides experimental evidence of an additional mechanism that incorporates evolutionarily dynamic, lineage-specific gene families into conserved regulatory gene networks to create functional organ diversity. PMID:22274699

The effect of cholesterol overload on mouse kidney and kidney-derived cells.

PubMed

Honzumi, Shoko; Takeuchi, Miho; Kurihara, Mizuki; Fujiyoshi, Masachika; Uchida, Masashi; Watanabe, Kenta; Suzuki, Takaaki; Ishii, Itsuko

2018-11-01

Dyslipidemia is one of the onset and risk factors of chronic kidney disease and renal function drop is seen in lipoprotein abnormal animal models. However, the detailed molecular mechanism of renal lipotoxicity has not been clarified. Therefore, the present study aimed to investigate the influence of cholesterol overload using mouse kidney tissue and kidney-derived cultured cells. C57BL/6 mice were fed normal diet (ND) or 1.25% cholesterol-containing high-cholesterol diet (HCD) for 11 weeks, and we used megalin as a proximal tubule marker for immunohistology. We added beta-very low density lipoprotein (βVLDL) to kidney-derived cells and examined the effect of cholesterol overload on megalin protein and mRNA expression level, cell proliferation and cholesterol content in cells. In the kidney of HCD mice, the gap between glomerulus and the surrounding Bowman's capsule decreased and the expression level of megalin decreased. After βVLDL treatment to the cells, the protein expression and mRNA expression level of megalin decreased and cell proliferation was restrained. We also observed an increase in cholesterol accumulation in the cell and free cholesterol/phospholipid ratios increased. These findings suggest that the increased cholesterol load on kidney contribute to the decrease of megalin and the overloaded cholesterol is taken into the renal tubule epithelial cells, causing suppression on cell proliferation, which may be the cause of kidney damage.

Suramin-restricted blood volume in the placenta of normal and diabetic rats is normalized by vitamin E treatment.

PubMed

Nash, P; Eriksson, U J

2007-01-01

Previously maternal and fetal alterations resembling human pre-eclampsia were induced in pregnant rats by injections of the angiogenesis inhibitor Suramin. These alterations were aggravated by maternal diabetes and partly rectified by vitamin E supplementation. In the present study we evaluated the morphology of placentae and kidneys in this model. Non-diabetic and streptozotocin-induced diabetic pregnant rats of two rat strains (U and H) were treated with Suramin or saline, and given standard or vitamin E-enriched food. On gestational day 20 one placenta and the left kidney of the mother were collected for morphological and stereological analysis. In the placental trophospongium Suramin treatment caused cysts, which were further enhanced by maternal diabetes. Vitamin E treatment had no effect on the vacuolization. In the placental labyrinth of the non-diabetic rats Suramin treatment restricted maternal placental blood volume and increased the interface between maternal and fetal circulation. These changes were reversed by vitamin E treatment. Diabetes increased slightly the interface between the circulations in both rat strains. Suramin treatment decreased the interface, and vitamin E further decreased the interface in the diabetic U rats, whereas neither treatment affected the maternal-fetal interface in the diabetic H rats. The kidneys of Suramin-treated and diabetic rats were heavier compared to controls. Suramin treatment and maternal diabetes damaged renal glomeruli to a similar extent. Vitamin E treatment diminished the Suramin- and diabetes-induced glomerular damage in U rats, but not in H rats. The average cell count per glomerulus was decreased by Suramin in the U rats. Vitamin E treatment did not affect cell number per glomerulus in any group. We conclude that Suramin-injected pregnant rats constitute a valid animal model for placental dysfunction and pre-eclampsia, also from the histological perspective. The present work supports the notion that one important effect of untreated maternal diabetes may be impaired placentation, leading to oxidative stress, morphological damage, and compromised placental function.

[Plasma cell dyscrasias and renal damage].

PubMed

Pasquali, Sonia; Iannuzzella, Francesco; Somenzi, Danio; Mattei, Silvia; Bovino, Achiropita; Corradini, Mattia

2012-01-01

Kidney damage caused by immunoglobulin free light chains in the setting of plasma cell dyscrasias is common and may involve all renal compartments, from the glomerulus to the tubulointerstitium, in a wide variety of histomorphological and clinical patterns. The knowledge of how free light chains can promote kidney injury is growing: they can cause functional changes, be processed and deposited, mediate inflammation, apoptosis and fibrosis, and obstruct nephrons. Each clone of the free light chain is unique and its primary structure and post-translation modification can determine the type of renal disease. Measurement of serum free light chain concentrations and calculation of the serum kappa/lambda ratio, together with renal biopsy, represent essential diagnostic tools. An early and correct diagnosis of renal lesions due to plasma cell dyscrasias will allow early initiation of disease-specific treatment strategies. The treatment of free light chain nephropathies is evolving and knowledge of the pathways that promote renal damage should lead to further therapeutic developments.

Accelerated podocyte detachment and progressive podocyte loss from glomeruli with age in Alport Syndrome.

PubMed

Ding, Fangrui; Wickman, Larysa; Wang, Su Q; Zhang, Yanqin; Wang, Fang; Afshinnia, Farsad; Hodgin, Jeffrey; Ding, Jie; Wiggins, Roger C

2017-12-01

Podocyte depletion is a common mechanism driving progression in glomerular diseases. Alport Syndrome glomerulopathy, caused by defective α3α4α5 (IV) collagen heterotrimer production by podocytes, is associated with an increased rate of podocyte detachment detectable in urine and reduced glomerular podocyte number suggesting that defective podocyte adherence to the glomerular basement membrane might play a role in driving progression. Here a genetically phenotyped Alport Syndrome cohort of 95 individuals [urine study] and 41 archived biopsies [biopsy study] were used to test this hypothesis. Podocyte detachment rate (measured by podocin mRNA in urine pellets expressed either per creatinine or 24-hour excretion) was significantly increased 11-fold above control, and prior to a detectably increased proteinuria or microalbuminuria. In parallel, Alport Syndrome glomeruli lose an average 26 podocytes per year versus control glomeruli that lose 2.3 podocytes per year, an 11-fold difference corresponding to the increased urine podocyte detachment rate. Podocyte number per glomerulus in Alport Syndrome biopsies is projected to be normal at birth (558/glomerulus) but accelerated podocyte loss was projected to cause end-stage kidney disease by about 22 years. Biopsy data from two independent cohorts showed a similar estimated glomerular podocyte loss rate comparable to the measured 11-fold increase in podocyte detachment rate. Reduction in podocyte number and density in biopsies correlated with proteinuria, glomerulosclerosis, and reduced renal function. Thus, the podocyte detachment rate appears to be increased from birth in Alport Syndrome, drives the progression process, and could potentially help predict time to end-stage kidney disease and response to treatment. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Laser capture microdissection-microarray analysis of focal segmental glomerulosclerosis glomeruli.

PubMed

Bennett, Michael R; Czech, Kimberly A; Arend, Lois J; Witte, David P; Devarajan, Prasad; Potter, S Steven

2007-01-01

Focal segmental glomerulosclerosis (FSGS) is a major cause of end-stage renal disease. In this report we used laser capture microdissection to purify diseased glomeruli, and microarrays to provide universal gene expression profiles. The results provide a deeper understanding of the molecular mechanisms of the disease process and suggest novel therapeutic strategies. Consistent with earlier studies, molecular markers of the differentiated podocyte, including WT1, nephrin, and VEGF, were dramatically downregulated in the diseased glomerulus. We also observed multiple changes consistent with increased TGF-beta signaling, including elevated expression of TGF-beta(2), TGF-beta(3), SMAD2, TGF-beta(1) receptor, and thrombospondin. In addition, there was relatively low level expression of Csf1r, a marker of macrophages, but elevated expression of the chemokines CXCL1, CXCL2, CCL3, and CXCL14. We also observed strongly upregulated expression of Sox9, a transcription factor that can drive a genetic program of chondrogenesis and fibrosis. Further, the gene with the greatest fold increase in expression in the diseased glomerulus was osteopontin, which has been previously strongly implicated in kidney fibrosis in the unilateral ureteral obstruction mouse model. These results confirm old findings, and indicate the involvement of new genetic pathways in the cause and progression of FSGS. Copyright 2007 S. Karger AG, Basel.

A case of Serratia granuloma in the soft tissue around the left kidney: a role of PTHrP in the formation of Serratia granuloma.

PubMed

Yoshihiro, Yuko; Soejima, Yoshifumi; Taniguchi, Keisuke; Makino, Kenji; Naito, Shinji

2010-04-01

Serratia marcescens is an ubiquitous, saprophytic gram-negative bacillus that is associated with infections such as bacteremia, pneumonia and osteomyelitis. However, it has not been known to form granulomas. A 72-year-old man with a history of tricuspidal insufficiency, mitral insufficiency and ureterolithiasis presented with lumbago on the left side. He was admitted to our hospital, where abscess formation in the subcapsular space and perirenal fat space of the left kidney, and left renal calculi were identified by computed tomography of the abdomen. As infection and/or a tumor were suspected, nephrectomy was performed. The histopathological findings in the resected kidney indicated severe infiltration by inflammatory cells with lymphoid follicles in the interstitium, and the proliferation of mesangial cells and matrix in glomerulus. Furthermore, giant cell granulomas were observed in the soft tissue around the kidney. As an aerobic culture of the abscess from the granulomas only produced Serratia marcescens, these granulomas were diagnosed as Serratia marcescens granulomas. In addition, expressions of PTHrP and PTH/PTHrP-receptor were observed in the giant cells in Serratia granuloma, which suggested that PTHrP might be involved in giant cell formation in Serratia granuloma by autocrine and/or paracrine mechanisms.

Liver fatty-acid-binding protein in heart and kidney allograft recipients in relation to kidney function.

PubMed

Przybylowski, P; Koc-Zorawska, E; Malyszko, J S; Kozlowska, S; Mysliwiec, M; Malyszko, J

2011-10-01

Mammalian intracellular fatty-acid-binding proteins (FABPs), a large multigene family, encode 14-kD proteins that are members of a superfamily of lipid-binding proteins. FABPs are tissue specific. Liver-type FABP (L-FABP) can be filtered through the glomerulus owing to its small molecular size, similar to cystatin C, but it is reabsorbed by proximal tubule epithelial cells like other small proteins. In the human kidney, L-FABP is expressed predominantly in proximal tubules. It had been suggested that the presence of L-FABP in urine reflects hypoxic conditions resulting from decreased peritubular capillary flow, serving as a marker of acute kidney injury. The aim of this study was to assess urinary L-FABP in 111 heart and 76 kidney transplant recipients in relation to kidney function. Complete blood count, urea, fasting glucose, creatinine, and the N-terminal fragment of brain natriuretic protein were studied by standard laboratory methods; L-FABP and cystatin C, by ELISA using commercially available kits. Kidney transplant recipients displayed significantly higher L-FABP than heart recipients. Upon univariate analysis, urinary L-FABP correlated, with serum creatinine, cystatin C and estimated glomerular filtration ratio (eGFR) in kidney allograft recipients. However, in heart transplant recipients it was not related to kidney function, as reflected by creatinine or eGFR; was strongly related to cystatin C (r=0.34; P<.001) and urinary creatinine (r=-0.29; P<.01), and NGAL (r=0.29; P<.01). Upon multiple regression analysis, the best predictor of urinary L-FABP in kidney allograft recipients, was eGFR whereas in heart recipients, no parameter independently predicted L-FABP. Successful heart transplantation is associated with kidney injury as reflected by a reduced eGFR; however, in this population, L-FABP did not serve as a marker of kidney function. In contrast, in kidney allograft recipients, L-FABP may be a potential early marker for impaired kidney function/injury. Copyright © 2011 Elsevier Inc. All rights reserved.

Atrazine affects kidney and adrenal hormones (AHs) related genes expressions of rare minnow (Gobiocypris rarus).

PubMed

Yang, Lihua; Zha, Jinmiao; Li, Wei; Li, Zhaoli; Wang, Zijian

2010-05-05

Atrazine, one of the most widely used herbicides, has been proved to interfere with sexual hormones. However few studies have considered the effects of atrazine on adrenal hormones (AH). In this study, rare minnow (Gobiocypris rarus) was exposed to 0, 3, 10, 33, 100 and 333microg/l atrazine for 28 days. The histopathology of kidney and gill was examined and the expressions of AHs-related genes including Na(+),K(+)-ATPase, glucocorticoid receptor (gr), heat shock protein 70 (hsp70), and heat shock protein 90 (hsp90) in kidney and gill were quantitatively determined. Histopathological observation revealed obvious lesions in gill including hyperplasia, necrosis in epithelium region, aneurysm and lamellar fusion at concentrations as low as 10microg/l. The observed lesions in kidney included extensive expansion in the lumen, degenerative and necrotic changes of the tubular epithelia, shrinkage of the glomerulus as well as increase of the Bowman's space at concentrations as low as 10microg/l. The expressions of Na(+),K(+)-ATPase, gr, hsp70 and hsp90 in the kidney of females were significantly decreased at all concentrations. For males, the expressions of hsp90 in the kidney of all treated groups were significantly down-regulated, while gr at all concentrations and hsp70 at 10, 33, 100microg/l were significantly up-regulated. However in the gill, the expressions of these genes were not significantly different from the control. These results indicated that exposure to atrazine caused impairments of kidney and gill of fish at environmental related concentrations. Histopathological lesions could partly attribute to the changes of the expressions of AHs-related genes in kidney. We concluded also that atrazine is a potential AHs-disruptor and AHs-related genes in kidney of fish could be used as sensitive molecular biomarkers.

Detection and Clinical Patterns of Nephron Hypertrophy and Nephrosclerosis Among Apparently Healthy Adults.

PubMed

Denic, Aleksandar; Alexander, Mariam P; Kaushik, Vidhu; Lerman, Lilach O; Lieske, John C; Stegall, Mark D; Larson, Joseph J; Kremers, Walter K; Vrtiska, Terri J; Chakkera, Harini A; Poggio, Emilio D; Rule, Andrew D

2016-07-01

Even among ostensibly healthy adults, there is often mild pathology in the kidney. The detection of kidney microstructural variation and pathology by imaging and the clinical pattern associated with these structural findings is unclear. Cross-sectional (clinical-pathologic correlation). Living kidney donors at Mayo Clinic (Minnesota and Arizona sites) and Cleveland Clinic 2000 to 2011. Predonation kidney function, risk factors, and contrast computed tomographic scan of the kidneys. These scans were segmented for cortical volume and medullary volume, reviewed for parenchymal cysts, and scored for kidney surface roughness. Nephrosclerosis (glomerulosclerosis, interstitial fibrosis/tubular atrophy, and arteriosclerosis) and nephron size (glomerular volume, mean profile tubular area, and cortical volume per glomerulus) determined from an implantation biopsy of the kidney cortex at donation. Among 1,520 living kidney donors, nephrosclerosis associated with increased kidney surface roughness, cysts, and smaller cortical to medullary volume ratio. Larger nephron size (nephron hypertrophy) associated with larger cortical volume. Nephron hypertrophy and larger cortical volume associated with higher systolic blood pressure, glomerular filtration rate, and urine albumin excretion; larger body mass index; higher serum uric acid level; and family history of end-stage renal disease. Both nephron hypertrophy and nephrosclerosis associated with older age and mild hypertension. The net effect of both nephron hypertrophy and nephrosclerosis associating with cortical volume was that nephron hypertrophy diminished volume loss with age-related nephrosclerosis and fully negated volume loss with mild hypertension-related nephrosclerosis. Kidney donors are selected on health, restricting the spectrum of pathologic findings. Kidney biopsies in living donors are a small tissue sample leading to imprecise estimates of structural findings. Among apparently healthy adults, the microstructural findings of nephron hypertrophy and nephrosclerosis differ in their associations with kidney function, macrostructure, and risk factors. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

The Prediction of Key Cytoskeleton Components Involved in Glomerular Diseases Based on a Protein-Protein Interaction Network.

PubMed

Ding, Fangrui; Tan, Aidi; Ju, Wenjun; Li, Xuejuan; Li, Shao; Ding, Jie

2016-01-01

Maintenance of the physiological morphologies of different types of cells and tissues is essential for the normal functioning of each system in the human body. Dynamic variations in cell and tissue morphologies depend on accurate adjustments of the cytoskeletal system. The cytoskeletal system in the glomerulus plays a key role in the normal process of kidney filtration. To enhance the understanding of the possible roles of the cytoskeleton in glomerular diseases, we constructed the Glomerular Cytoskeleton Network (GCNet), which shows the protein-protein interaction network in the glomerulus, and identified several possible key cytoskeletal components involved in glomerular diseases. In this study, genes/proteins annotated to the cytoskeleton were detected by Gene Ontology analysis, and glomerulus-enriched genes were selected from nine available glomerular expression datasets. Then, the GCNet was generated by combining these two sets of information. To predict the possible key cytoskeleton components in glomerular diseases, we then examined the common regulation of the genes in GCNet in the context of five glomerular diseases based on their transcriptomic data. As a result, twenty-one cytoskeleton components as potential candidate were highlighted for consistently down- or up-regulating in all five glomerular diseases. And then, these candidates were examined in relation to existing known glomerular diseases and genes to determine their possible functions and interactions. In addition, the mRNA levels of these candidates were also validated in a puromycin aminonucleoside(PAN) induced rat nephropathy model and were also matched with existing Diabetic Nephropathy (DN) transcriptomic data. As a result, there are 15 of 21 candidates in PAN induced nephropathy model were consistent with our predication and also 12 of 21 candidates were matched with differentially expressed genes in the DN transcriptomic data. By providing a novel interaction network and prediction, GCNet contributes to improving the understanding of normal glomerular function and will be useful for detecting target cytoskeleton molecules of interest that may be involved in glomerular diseases in future studies.

The Prediction of Key Cytoskeleton Components Involved in Glomerular Diseases Based on a Protein-Protein Interaction Network

PubMed Central

Ju, Wenjun; Li, Xuejuan; Li, Shao; Ding, Jie

2016-01-01

Maintenance of the physiological morphologies of different types of cells and tissues is essential for the normal functioning of each system in the human body. Dynamic variations in cell and tissue morphologies depend on accurate adjustments of the cytoskeletal system. The cytoskeletal system in the glomerulus plays a key role in the normal process of kidney filtration. To enhance the understanding of the possible roles of the cytoskeleton in glomerular diseases, we constructed the Glomerular Cytoskeleton Network (GCNet), which shows the protein-protein interaction network in the glomerulus, and identified several possible key cytoskeletal components involved in glomerular diseases. In this study, genes/proteins annotated to the cytoskeleton were detected by Gene Ontology analysis, and glomerulus-enriched genes were selected from nine available glomerular expression datasets. Then, the GCNet was generated by combining these two sets of information. To predict the possible key cytoskeleton components in glomerular diseases, we then examined the common regulation of the genes in GCNet in the context of five glomerular diseases based on their transcriptomic data. As a result, twenty-one cytoskeleton components as potential candidate were highlighted for consistently down- or up-regulating in all five glomerular diseases. And then, these candidates were examined in relation to existing known glomerular diseases and genes to determine their possible functions and interactions. In addition, the mRNA levels of these candidates were also validated in a puromycin aminonucleoside(PAN) induced rat nephropathy model and were also matched with existing Diabetic Nephropathy (DN) transcriptomic data. As a result, there are 15 of 21 candidates in PAN induced nephropathy model were consistent with our predication and also 12 of 21 candidates were matched with differentially expressed genes in the DN transcriptomic data. By providing a novel interaction network and prediction, GCNet contributes to improving the understanding of normal glomerular function and will be useful for detecting target cytoskeleton molecules of interest that may be involved in glomerular diseases in future studies. PMID:27227331

Intraglomerular thrombotic tendency and glomerular ADPase. Unilateral impairment of ADPase elicits a proaggregatory microenvironment in experimental glomerulonephritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poelstra, K.; Baller, J.F.; Hardonk, M.J.

1991-04-01

It has been proposed, predominantly from ex vivo studies, that glomerular ADPase may function as an antithrombotic principle within the rat kidney. Therefore, intraglomerular platelet aggregation was studied in vivo in rats after impairment of glomerular ADPase activity using local X-irradiation (20 Gy). Biochemical assays in suspensions of glomeruli obtained from rats 24 hours after local X-irradiation (group I) demonstrated a significant reduction in ADPase activity as compared to sham treated rats (group II; p less than 0.01). Cytochemical observations at the ultrastructural level showed that this reduction in glomerular enzyme activity represents in particular ADPase activity detectable in themore » basement membrane. Following X-irradiation, intraglomerular platelet aggregation was quantitatively studied in two groups of rats. Both groups received X-irradiation of the left kidney (20 Gy). Twenty-four hours after X-irradiation, animals received an intravenous injection of either 0.5 ml of saline (group III; N = 6) or 0.5 ml of heterologous nephrotoxic serum (NTS; group IV; N = 6). Subsequently, 24 hours after this injection, platelet aggregation in left kidneys was compared with aggregation in contralateral non-X-irradiated kidneys. The results showed that while X-irradiation per se did not induce intraglomerular platelet aggregation as compared with the contralateral kidney (0.20 +/- 0.08% versus 0.17 +/- 0.06% platelet aggregation/glomerulus), a significant increase in platelet aggregation could be demonstrated in X-irradiated kidneys in the early phase of nephrotoxic serum nephritis as compared with the contralateral nephritic kidney. A potential effect of altered influx of inflammatory cells after X-irradiation could be excluded since no difference in H2O2 producing cells was observed between left and right kidneys.« less

Differential expression of the intermediate filament protein nestin during renal development and its localization in adult podocytes.

PubMed

Chen, Jing; Boyle, Scott; Zhao, Min; Su, Wei; Takahashi, Keiko; Davis, Linda; Decaestecker, Mark; Takahashi, Takamune; Breyer, Matthew D; Hao, Chuan-Ming

2006-05-01

Nestin, an intermediate filament protein, is widely used as stem cell marker. Nestin has been shown to interact with other cytoskeleton proteins, suggesting a role in regulating cellular cytoskeletal structure. These studies examined renal nestin localization and developmental expression in mice. In developing kidney, anti-nestin antibody revealed strong immunoreactivity in vascular cleft of the S-shaped body and vascular tuft of capillary loop-stage glomerulus. The nestin-positive structures also were labeled by endothelial cell markers FLK1 and CD31 in immature glomeruli. Nestin was not detected in epithelial cells of immature glomeruli. In contrast, in mature glomerular, nestin immunoreactivity was observed only outside laminin-positive glomerular basement membrane, and co-localized with nephrin, consistent with podocyte nestin expression. In adult kidney, podocytes were the only cells that exhibited persistent nestin expression. Nestin was not detected in ureteric bud and its derivatives throughout renal development. Cell lineage studies, using a nestin promoter-driven Cre mouse and a ROSA26 reporter mouse, showed a strong beta-galactosidase activity in intermediate mesoderm in an embryonic day 10 embryo and all of the structures except those that were derived from ureteric bud in embryonic kidney through adult kidney. These studies show that nestin is expressed in progenitors of glomerular endothelial cells and renal progenitors that are derived from metanephric mesenchyme. In the adult kidney, nestin expression is restricted to differentiated podocytes, suggesting that nestin could play an important role in maintaining the structural integrity of the podocytes.

Selenium deficiency induced damages and altered expressions of metalloproteinases and their inhibitors (MMP1/3, TIMP1/3) in the kidneys of growing rats.

PubMed

Han, Jing; Liang, Hua; Yi, Jianhua; Tan, Wuhong; He, Shulan; Wu, Xiaofang; Shi, Xiaowei; Ma, Jing; Guo, Xiong

2016-03-01

Selenium is an essential trace element for the maintenance of structures and functions of kidney. To evaluate the effects of low selenium on the kidneys of growing rats, newborn rats were fed with selenium deficient and normal diets respectively for 109 days. As a result, rats fed with low selenium diets resulted in a decline in the body weight and the concentration of selenium in the kidney, especially the male rats from the low selenium groups. Moreover, the ultrastructure of glomerulus and tubules were damaged in low selenium group: the glomeruli were observed with hyperplasia of mesangial cells, fusion of podocyte foot processes and thickening of basement membrane; and the tubules were observed with vacuolar degenerated epithelial cells, increased edema fluid or protein solution between cells, microvilli edema, increased cell gaps and decreased cell links. Furthermore, the pathological changes in selenium deficient group included the increase of fibers around renal hilum aorta and in the renal collecting duct, and shed of cells in the proximal convoluted tubules. In addition, up-regulated expressions of matrix metalloproteinases (MMP1/3) and down-regulated expressions of their inhibitors (TIMP1/3) at the mRNA and protein levels were also appeared to be relevant to low selenium. The results suggested that low selenium in diet may cause low selenium concentration in the kidney of growing rat and lead to damages of the ultrastructure and extracellular matrix (ECM) of kidney. Copyright © 2015 Elsevier GmbH. All rights reserved.

siRNA Delivery to the Glomerular Mesangium Using Polycationic Cyclodextrin Nanoparticles Containing siRNA

PubMed Central

Gale, Aaron; Wu, Peiwen; Ma, Rong; Davis, Mark E.

2015-01-01

There is an urgent need for new therapies that can halt or reverse the course of chronic kidney disease with minimal side-effect burden on the patient. Small interfering RNA (siRNA) nanoparticles are new therapeutic entities in clinical development that could be useful for chronic kidney disease treatment because they combine the tissue-specific targeting properties of nanoparticles with the gene-specific silencing effects of siRNA. Recent reports have emerged demonstrating that the kidney, specifically the glomerulus, is a readily accessible site for nanoparticle targeting. Here, we explore the hypothesis that intravenously administered polycationic cyclodextrin nanoparticles containing siRNA (siRNA/CDP-NPs) can be used for delivery of siRNA to the glomerular mesangium. We demonstrate that siRNA/CDP-NPs localize to the glomerular mesangium with limited deposition in other areas of the kidney after intravenous injection. Additionally, we report that both mouse and human mesangial cells rapidly internalize siRNA/CDP-NPs in vitro and that nanoparticle uptake can be enhanced by attaching the targeting ligands mannose or transferrin to the nanoparticle surface. Lastly, we show knockdown of mesangial enhanced green fluorescent protein expression in a reporter mouse strain following iv treatment with siRNA/CDP-NPs. Altogether, these data demonstrate the feasibility of mesangial targeting using intravenously administered siRNA/CDP-NPs. PMID:25734248

Glomerular Podocytes Express Type 1 Adenylate Cyclase: Inactivation Results in Susceptibility to Proteinuria

PubMed Central

Xiao, Zhijie; He, Liqun; Takemoto, Minoru; Jalanko, Hannu; Chan, Guy C.; Storm, Daniel R.; Betsholtz, Christer; Tryggvason, Karl; Patrakka, Jaakko

2011-01-01

Background/Aims The organization of actin cytoskeleton in podocyte foot processes plays a critical role in the maintenance of the glomerular filtration barrier. The cAMP pathway is an important regulator of the actin network assembly in cells. However, the role of the cAMP pathway in podocytes is not well understood. Type 1 adenylate cyclase (Adcy1), previously thought to be specific for neuronal tissue, is a member of the family of enzymes that catalyses the formation of cAMP. In this study, we characterized the expression and role of Adcy1 in the kidney. Methods Expression of Adcy1 was studied by RT-PCR, Northern blotting and in situ hybridization. The role of Adcy1 in podocytes was investigated by analyzing Adcy1 knockout mice (Adcy1–/–). Results and Conclusion: Adcy1 is expressed in the kidney specifically by podocytes. In the kidney, Adcy1 does not have a critical role in normal physiological functioning as kidney histology and function are normal in Adcy1–/– mice. However, albumin overload resulted in severe albuminuria in Adcy1–/– mice, whereas wild-type control mice showed only mild albumin leakage to urine. In conclusion, we have identified Adcy1 as a novel podocyte signaling protein that seems to have a role in compensatory physiological processes in the glomerulus. PMID:21196775

The early modern kidney--nephrology in and about the nineteenth century. Part 1.

PubMed

Eknoyan, Garabed

2013-01-01

The 19th century was a period of momentous scientific discoveries, technological achievements, and societal changes. A beneficiary of these revolutionary upheavals was medical empiricism that supplanted the rationalism of the past giving rise to early modern scientific medicine. Continued reliance on sensory data now magnified by technical advances generated new medical information that could be quantified with increasing precision, verified by repeated experimentation, and validated by statistical analysis. The institutionalization and integration of these methodologies into medical education were a defining step that assured their progress and perpetuation. Major advances were made in the nosography of diseases of the kidney, notably that of the diagnosis of progressive kidney disease from the presence of albuminuria by Richard Bright (1789-1858); and of renal structure and function, notably the demonstration of the continuity of the glomerular capsule with the tubular basement membrane by William Bowman (1816-1892), and the arguments for hemodynamic physical forces mediated glomerular filtration by Carl Ludwig (1816-1895) and for active tubular transport by Rudolf Heidenhain (1834-1897). Improvements in microscopy and tissue processing were instrumental in describing the cellular ultrastructure of the glomerulus and tubular segments, but their integrated function remained to be elucidated. The kidney continued to be considered a tubular secretory organ and its pathology attributed to injury of the interstitium (interstitial nephritis) or tubules (parenchymatous nephritis). © 2012 Wiley Periodicals, Inc.

Platelet-activating factor dilates efferent arterioles through glomerulus-derived nitric oxide.

PubMed

Arima, S; Ren, Y; Juncos, L A; Ito, S

1996-01-01

Despite evidence that platelet-activating factor (PAF) is produced by the glomerulus, its direct action on the glomerular microcirculation is poorly understood. It was recently reported that at picomolar concentrations, PAF dilates isolated microperfused afferent arterioles (Af-Art) via nitric oxide (NO). The present study tested the hypothesis that PAF acts on the glomerulus to release NO, which in turn controls the resistance of the efferent arteriole (Ef-Art). Rabbit Ef-Art were perfused from the distal end (retrograde perfusion [RP]) to eliminate the influence of the glomerulus, or through the glomerulus from the end of the Af-Art (orthograde perfusion [OP]) to maintain the influence of the glomerulus. Ef-Art were preconstricted by approximately 40% with norepinephrine and increasing doses of PAF were added to both the arteriolar perfusate and bath. Only with OP did PAF at picomolar concentrations cause significant dilation: at 400 pmol, the diameter increased by 64 +/- 11% from the preconstricted level (N = 6, P < 0.01). This dilation was completely abolished by pretreatment with an NO-synthesis inhibitor. To study its possible constrictor action, PAF was added to nonpreconstricted Ef-Art. At nanomolar concentrations, PAF constricted Ef-Art similarly in both RP and OP: at 40 nM, the diameter decreased by 24 +/- 4% (N = 6, P < 0.01) and 20 +/- 2% (N = 6, P < 0.01), respectively. This constriction was attenuated by pretreatment with indomethacin (Indo) in both RP (14 +/- 2%, N = 7; P < 0.02 versus without Indo) and OP (10 +/- 2%, N = 6; P < 0.02 versus without Indo). (1) at picomolar concentrations, PAF stimulates the glomerulus to release NO, which in turn dilates the Ef-Art; and (2) at nanomolar concentrations, PAF constricts the Ef-Art partly through release of cyclooxygenase metabolites. Thus, PAF may play a role in glomerular hemodynamics under various physiological and pathological conditions.

Selective Insulin Resistance in the Kidney

PubMed Central

Horita, Shoko; Nakamura, Motonobu; Suzuki, Masashi; Satoh, Nobuhiko; Suzuki, Atsushi; Seki, George

2016-01-01

Insulin resistance has been characterized as attenuation of insulin sensitivity at target organs and tissues, such as muscle and fat tissues and the liver. The insulin signaling cascade is divided into major pathways such as the PI3K/Akt pathway and the MAPK/MEK pathway. In insulin resistance, however, these pathways are not equally impaired. For example, in the liver, inhibition of gluconeogenesis by the insulin receptor substrate (IRS) 2 pathway is impaired, while lipogenesis by the IRS1 pathway is preserved, thus causing hyperglycemia and hyperlipidemia. It has been recently suggested that selective impairment of insulin signaling cascades in insulin resistance also occurs in the kidney. In the renal proximal tubule, insulin signaling via IRS1 is inhibited, while insulin signaling via IRS2 is preserved. Insulin signaling via IRS2 continues to stimulate sodium reabsorption in the proximal tubule and causes sodium retention, edema, and hypertension. IRS1 signaling deficiency in the proximal tubule may impair IRS1-mediated inhibition of gluconeogenesis, which could induce hyperglycemia by preserving glucose production. In the glomerulus, the impairment of IRS1 signaling deteriorates the structure and function of podocyte and endothelial cells, possibly causing diabetic nephropathy. This paper mainly describes selective insulin resistance in the kidney, focusing on the proximal tubule. PMID:27247938

Ultrasensitive sensor for detection of early stage chronic kidney disease in human.

PubMed

Desai, Dignya; Kumar, Ashok; Bose, Debajyoti; Datta, Manali

2018-05-15

A facile label free, ultrasensitive platform for a rapid detection of chronic kidney disease has been fabricated. Early intervention in patients with chronic kidney disease has the potential to delay, or even prevent, the development of end stage renal disease and complications, leading to a marked impact on life expectancy and quality of life. Thus, a potable electrochemical diagnostic biosensor has become an attractive option as electrochemical analysis is feasible to use for on-site detection of samples. In human, Cystatin C present in human body fluids is freely filtered by the glomerulus, but reabsorbed and catabolised by the renal tubules. Trace detectable amount is eliminated in urine, giving this molecular marker an edge over serum creatinine's disadvantages. A carboxyl functionalized multiwalled carbon nanotubes screen printed electrode was immobilized with papain (cysteine protease) where amino group of papain covalently bound carboxyl group on electrode surface by EDC (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide) and NHS (N-hydroxysuccinimide) chemistry. The modifications on sensor surface were characterized by field emission scanning electron microscopy. Interaction between papain and chronic kidney disease specific biomarker, Cystatin C was detected by cyclic voltammetry and differential pulse voltammetry within 10min. The sensor is highly specific to Cystatin C and showed negligible response to non-specific macromolecules present in urine. The sensitivity of the sensor was 1583.49µAcm -2 µg -1 and lower limit of detection of Cystatin C was found 0.58ngL -1 which presents as a promising platform for designing potable kidney disease detector. Copyright © 2018 Elsevier B.V. All rights reserved.

Liver and kidney toxicity induced by Afzal smokeless tobacco product in Oman.

PubMed

Al-Mukhaini, Nawal; Ba-Omar, Taher; Eltayeb, Elsadig; Al-Shihi, Aisha; Al-Riyami, Nafila; Al-Belushi, Jamila; Al-Adawi, Kawthar

2017-04-01

Afzal, the common smokeless tobacco product (STP) in Oman, is believed to contain toxins that may impair the function of some organs such as liver and kidney. An aqueous extract from Afzal was added to drinking water to be administrated orally to Wistar albino rats (n=72) young and adult from both genders weighing between 60-80g and 150-240g respectively for 8 weeks. Animals were divided into three groups: control (distilled water instead of Afzal extract), low-dose (3mgnicotine/kgbodyweight/day) and high-dose (6mgnicotine/kgbodyweight/day). The animals were euthanized and their blood, liver and kidney were collected for biochemical and histopathological investigations. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assayed for the liver function, while blood urea nitrogen (BUN) and creatinine (CRT) were assayed for the kidney function. The results showed a significant increase in the ALT, AST, BUN and CRT levels (P<0.05) in both Afzal-treated groups (low and high doses) compared with the control. Histopathological findings revealed the initial but seem to be serious degenerative alterations of periportal fibrosis in liver and edematous and calcified changes in renal glomerulus among Afzal-treated groups. Additionally, the weight gain of the Afzal-treated groups was lower than the control group. Our findings show that the exposure of Wistar rats to the Afzal extract has the potentials of causing decreased weight gain and dose-dependent functional and structural damage to the biochemical and histological profiles of liver and kidney as well as serious biochemical effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Matrix Gelatinases in Atherosclerosis and Diabetic Nephropathy: Progress and Challenges.

PubMed

Dimas, Grigorios G; Didangelos, Triantafyllos P; Grekas, Dimitrios M

2017-01-01

Matrix metalloproteinases (MMPs) are zinc-dependent proteases that degrade components of the extracellular matrix (ECM). In glomerular disease, MMPs are major regulators of ECM degradation as well as structural and functional integrity in the glomerulus. In altered matrix composition diseases, glomerular damage is due to increased degradation of kidney and vessel basement membranes (BMs) by MMPs. MMP -2 and -9 are both considered as the main enzymes that degrade collagen type-IV (coll-IV), which represents the key collagenous component of ECM and constitutes the architectural structure of vessels and glomerular BM. There is growing evidence implicating MMPs in atherosclerosis as well as in cardiovascular disease (CVD) and chronic kidney disease (CKD). Specific endogenous tissue inhibitors of MMPs (TIMPs) are also implicated in CKD, CVD and diabetic nephropathy (DN). The present review discusses the role of MMPs -2 and -9 in DN, as a leading cause of endstage renal disease and as a model of the link between progressive glomerulosclerosis and MMP expression. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Diabetic rats present higher urinary loss of proteins and lower renal expression of megalin, cubilin, ClC-5, and CFTR.

PubMed

Figueira, Miriam F; Castiglione, Raquel C; de Lemos Barbosa, Carolina M; Ornellas, Felipe M; da Silva Feltran, Geórgia; Morales, Marcelo M; da Fonseca, Rodrigo N; de Souza-Menezes, Jackson

2017-07-01

Diabetic nephropathy (DN) occurs in around 40% of those with diabetes. Proteinuria is the main characteristic of DN and develops as a result of increased permeability of the glomerulus capillary wall and/or decreased proximal tubule endocytosis. The goal of this work was to evaluate renal function and the expression of megalin, cubilin, CFTR (cystic fibrosis transmembrane conductance regulator), and ClC-5 in the proximal tubule and renal cortex of rats with type 1 diabetes. Male Wistar rats were randomly assigned to control (CTRL) and diabetic (DM) groups for 4 weeks. Renal function was assessed in 24-h urine sample by calculating clearance and fractional excretion of solutes. The RNA and protein contents of ClC-5, CFTR, megalin, and cubilin were determined in the renal proximal tubule and cortex using real-time polymerase chain reaction and western blotting techniques, respectively. The results showed higher creatinine clearance and higher urinary excretion of proteins, albumin, and transferrin in the DM group than in the CTRL group. Furthermore, the renal cortex and proximal tubule of diabetic animals showed downregulation of megalin, cubilin, ClC-5, and CFTR, critical components of the endocytic apparatus. These data suggest dysfunction in proximal tubule low-molecular-weight endocytosis and protein glomerulus filtration in the kidney of diabetic rats. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

A Review of Podocyte Biology.

PubMed

Garg, Puneet

2018-05-31

Podocyte biology is a developing science that promises to help improve understanding of the mechanistic nature of multiple diseases associated with proteinuria. Proteinuria in nephrotic syndrome has been linked to mechanistic dysfunctions in the renal glomerulus involving the function of podocyte epithelial cells, including podocyte foot process effacement. Developments in imaging technology are improving knowledge of the detailed structure of the human renal glomerulus and cortex. Podocyte foot processes attach themselves to the glomerular capillaries at the glomerular basement membrane (GBM) forming intercellular junctions that form slit diaphragm filtration barriers that help maintain normal renal function. Damage in this area has been implicated in glomerular disease. Injured podocytes undergo effacement whereby they lose their structure and spread out, leading to a reduction in filtration barrier function. Effacement is typically associated with the presence of proteinuria in focal segmental glomerulosclerosis, minimal change disease, and diabetes. It is thought to be due to a breakdown in the actin cytoskeleton of the foot processes, complex contractile apparatuses that allow podocytes to dynamically reorganize according to changes in filtration requirements. The process of podocyte depletion correlates with the development of glomerular sclerosis and chronic kidney disease. Focal adhesion complexes that interact with the underlying GBM bind the podocytes within the glomerular structure and prevent their detachment. Key Messages: Knowledge of glomerular podocyte biology is helping to advance our understanding of the science and mechanics of the glomerular filtering process, opening the way to a variety of new potential applications for clinical targeting. © 2018 S. Karger AG, Basel.

Multiphoton imaging for assessing renal disposition in acute kidney injury

NASA Astrophysics Data System (ADS)

Liu, Xin; Liang, Xiaowen; Wang, Haolu; Roberts, Darren M.; Roberts, Michael S.

2016-11-01

Estimation of renal function and drug renal disposition in acute kidney injury (AKI), is important for appropriate dosing of drugs and adjustment of therapeutic strategies, but is challenging due to fluctuations in kidney function. Multiphoton microscopy has been shown to be a useful tool in studying drug disposition in liver and can reflect dynamic changes of liver function. We extend this imaging technique to investigate glomerular filtration rate (GFR) and tubular transporter functional change in various animal models of AKI, which mimic a broad range of causes of AKI such as hypoxia (renal ischemia- reperfusion), therapeutic drugs (e.g. cisplatin), rhabdomyolysis (e.g. glycerol-induced) and sepsis (e.g. LPSinduced). The MPM images revealed acute injury of tubular cells as indicated by reduced autofluorescence and cellular vacuolation in AKI groups compared to control group. In control animal, systemically injected FITC-labelled inulin was rapidly cleared from glomerulus, while the clearance of FITC-inulin was significantly delayed in most of animals in AKI group, which may reflect the reduced GFR in AKI. Following intravenous injection, rhodamine 123, a fluorescent substrate of p-glycoprotein (one of tubular transporter), was excreted into urine in proximal tubule via p-glycoprotein; in response to AKI, rhodamine 123 was retained in tubular cells as revealed by slower decay of fluorescence intensity, indicating P-gp transporter dysfunction in AKI. Thus, real-time changes in GFR and transporter function can be imaged in rodent kidney with AKI using multiphoton excitation of exogenously injected fluorescent markers.

Loss of the BMP antagonist USAG-1 ameliorates disease in a mouse model of the progressive hereditary kidney disease Alport syndrome.

PubMed

Tanaka, Mari; Asada, Misako; Higashi, Atsuko Y; Nakamura, Jin; Oguchi, Akiko; Tomita, Mayumi; Yamada, Sachiko; Asada, Nariaki; Takase, Masayuki; Okuda, Tomohiko; Kawachi, Hiroshi; Economides, Aris N; Robertson, Elizabeth; Takahashi, Satoru; Sakurai, Takeshi; Goldschmeding, Roel; Muso, Eri; Fukatsu, Atsushi; Kita, Toru; Yanagita, Motoko

2010-03-01

The glomerular basement membrane (GBM) is a key component of the filtering unit in the kidney. Mutations involving any of the collagen IV genes (COL4A3, COL4A4, and COL4A5) affect GBM assembly and cause Alport syndrome, a progressive hereditary kidney disease with no definitive therapy. Previously, we have demonstrated that the bone morphogenetic protein (BMP) antagonist uterine sensitization-associated gene-1 (USAG-1) negatively regulates the renoprotective action of BMP-7 in a mouse model of tubular injury during acute renal failure. Here, we investigated the role of USAG-1 in renal function in Col4a3-/- mice, which model Alport syndrome. Ablation of Usag1 in Col4a3-/- mice led to substantial attenuation of disease progression, normalization of GBM ultrastructure, preservation of renal function, and extension of life span. Immunohistochemical analysis revealed that USAG-1 and BMP-7 colocalized in the macula densa in the distal tubules, lying in direct contact with glomerular mesangial cells. Furthermore, in cultured mesangial cells, BMP-7 attenuated and USAG-1 enhanced the expression of MMP-12, a protease that may contribute to GBM degradation. These data suggest that the pathogenetic role of USAG-1 in Col4a3-/- mice might involve crosstalk between kidney tubules and the glomerulus and that inhibition of USAG-1 may be a promising therapeutic approach for the treatment of Alport syndrome.

Effect of methanol leaf extract of Dalbergia saxatilis Hook.f (fabaceae) on renal function.

PubMed

Hassan, Fatima Ismail; Abdulkadir Umar, Zezi; Umar Habib, Danmalam; Abdullahi Hamza, Yaro

2016-01-01

Dalbegia saxatilis ( D.saxatilis ) is used as a decoction in traditional medicine for ailments such as cough, small pox, skin lesions, bronchial ailments and toothache. This study is aimed at evaluating the toxic effect of methanol leaf extract of D.saxatilis on renal function. Wistar rats of both sexes were divided into four groups of five: control animals (group 1) received distilled water 1 ml/kg while groups 2, 3 and 4 were given graded doses of the extract (250, 500 and 1000 mg/kg body weight, respectively) daily for 28 days. Body weight changes were estimated by weighing the rats twice weekly using digital weighing balance. After 28 days, blood samples were obtained for evaluation of renal indices and the kidney was used for histopathology. Data were analysed using one-way and repeated measures ANOVA using SPSS version 20. Significant weight increase in all groups were observed (p<0.05). Significant reduction in electrolytes concentration was observed following treatment with extract (250 and 500 mg/kg) (p<0.05). Histopathological findings of the kidney revealed massive necrosis of the glomerulus with tubular distortion and lymphocyte hyperplasia at 250 and 500 mg/kg while intense glomerular and tubular necrosis was observed at 1000 mg/kg of the extract. Since different doses of the extract caused reduction in electrolyte concentration and damage to the kidney it is suggested that prolonged administration of the extract is associated with increased risk of kidney toxicity .

Consumption of a high-salt diet by ewes during pregnancy alters nephrogenesis in 5-month-old offspring.

PubMed

Tay, S H; Blache, D; Gregg, K; Revell, D K

2012-11-01

Maternal nutrition during pregnancy can affect kidney development in the foetus, which may lead to adverse consequences in the mature kidney. It was expected that high-salt intake by pregnant ewes would lead to a reduction in foetal glomerular number but that the ovine kidney would adapt to maintain homoeostasis, in part by increasing the size of each glomerulus. Merino ewes that were fed either a control (1.5% NaCl) or high-salt (10.5% NaCl) diet during pregnancy, as well as their 5-month-old offspring, were subjected to a dietary salt challenge, and glomerular number and size and sodium excretion were measured. The high-salt offspring had 20% fewer glomeruli compared with the control offspring (P < 0.001), but they also had larger glomerular radii compared with the control offspring (P < 0.001). Consequently, the cross-sectional area of glomeruli was 18% larger in the high-salt offspring than in the control offspring (P < 0.05). There was no difference in the daily urinary sodium excretion between the two offspring groups (P > 0.05), although the high-salt offspring produced urine with a higher concentration of sodium. Our results demonstrated that maternal high-salt intake during pregnancy affected foetal nephrogenesis, altering glomerular number at birth. However, the ability to concentrate and excrete salt was not compromised, which indicates that the kidney was able to adapt to the reduction in the number of glomeruli.

High-Fat Diet Increased Renal and Hepatic Oxidative Stress Induced by Vanadium of Wistar Rat.

PubMed

Wang, J P; Cui, R Y; Zhang, K Y; Ding, X M; Luo, Y H; Bai, S P; Zeng, Q F; Xuan, Y; Su, Z W

2016-04-01

The study was conducted to assess the effect of vanadium (V) in high-fat diet on the liver and kidney of rats in a 5-week trial. Seventy-two female Wistar rats (BW = 95 ± 5 g) were randomly allotted into eight groups. Groups I, II, III, and IV obtained low-fat diet containing 0, 3, 15, and 30 mg/kg V, and V, VI, VII, and VIII groups received the respective vanadium doses with high-fat diet, respectively. There were lesions in the liver and kidney of V, VI, VII, and VIII groups, granular degeneration and vacuolar degeneration were observed in the renal tubular and glomerulus epithelial cells, and hepatocytes showed granular degeneration and vacuolar degeneration. Supplemented high-fat diet with vanadium was shown to decrease (P < 0.05) activities of superoxide dismutase, total antioxidant capacity, glutathione-S transferase, and NAD(P)H/quinone oxidoreductase 1 (NQO1) and increase malondialdehyde content in the liver and kidney. The relative expression of hepatic nuclear factor erythroid 2-related factor 2 (Nrf-2) and NQO1 mRNA was downregulated by V addition and high-fat diet, and the effect of V was more pronounced in high-fat diet (interaction, P < 0.05), with VIII group having the lowest mRNA expression of Nrf-2 and NQO1 in the liver and kidney. In conclusion, it suggested that dietary vanadium ranging from 15 to 30 mg/kg could lead to oxidative damage and vanadium accumulation in the liver and kidney, which caused renal and hepatic toxicity. The high-fat diet enhanced vanadium-induced hepatic and renal damage, and the mechanism was related to the modulation of the hepatic and renal mRNA expression of Nrf-2 and NQO1.

Podocyte-specific RAP1GAP expression contributes to focal segmental glomerulosclerosis–associated glomerular injury

PubMed Central

Potla, Uma; Ni, Jie; Vadaparampil, Justin; Yang, Guozhe; Leventhal, Jeremy S.; Campbell, Kirk N.; Chuang, Peter Y.; Morozov, Alexei; He, John C.; D’Agati, Vivette D.; Klotman, Paul E.; Kaufman, Lewis

2014-01-01

Injury to the specialized epithelial cells of the glomerulus (podocytes) underlies the pathogenesis of all forms of proteinuric kidney disease; however, the specific genetic changes that mediate podocyte dysfunction after injury are not fully understood. Here, we performed a large-scale insertional mutagenic screen of injury-resistant podocytes isolated from mice and found that increased expression of the gene Rap1gap, encoding a RAP1 activation inhibitor, ameliorated podocyte injury resistance. Furthermore, injured podocytes in murine models of disease and kidney biopsies from glomerulosclerosis patients exhibited increased RAP1GAP, resulting in diminished glomerular RAP1 activation. In mouse models, podocyte-specific inactivation of Rap1a and Rap1b induced massive glomerulosclerosis and premature death. Podocyte-specific Rap1a and Rap1b haploinsufficiency also resulted in severe podocyte damage, including features of podocyte detachment. Over-expression of RAP1GAP in cultured podocytes induced loss of activated β1 integrin, which was similarly observed in kidney biopsies from patients. Furthermore, preventing elevation of RAP1GAP levels in injured podocytes maintained β1 integrin–mediated adhesion and prevented cellular detachment. Taken together, our findings suggest that increased podocyte expression of RAP1GAP contributes directly to podocyte dysfunction by a mechanism that involves loss of RAP1-mediated activation of β1 integrin. PMID:24642466

Integrin beta1-mediated matrix assembly and signaling are critical for the normal development and function of the kidney glomerulus.

PubMed

Kanasaki, Keizo; Kanda, Yoshiko; Palmsten, Kristin; Tanjore, Harikrishna; Lee, Soo Bong; Lebleu, Valerie S; Gattone, Vincent H; Kalluri, Raghu

2008-01-15

The human kidneys filter 180 l of blood every day via about 2.5 million glomeruli. The three layers of the glomerular filtration apparatus consist of fenestrated endothelium, specialized extracellular matrix known as the glomerular basement membrane (GBM) and the podocyte foot processes with their modified adherens junctions known as the slit diaphragm (SD). In this study we explored the contribution of podocyte beta1 integrin signaling for normal glomerular function. Mice with podocyte specific deletion of integrin beta1 (podocin-Cre beta1-fl/fl mice) are born normal but cannot complete postnatal renal development. They exhibit detectable proteinuria on day 1 and die within a week. The kidneys of podocin-Cre beta1-fl/fl mice exhibit normal glomerular endothelium but show severe GBM defects with multilaminations and splitting including podocyte foot process effacement. The integrin linked kinase (ILK) is a downstream mediator of integrin beta1 activity in epithelial cells. To further explore whether integrin beta1-mediated signaling facilitates proper glomerular filtration, we generated mice deficient of ILK in the podocytes (podocin-Cre ILK-fl/fl mice). These mice develop normally but exhibit postnatal proteinuria at birth and die within 15 weeks of age due to renal failure. Collectively, our studies demonstrate that podocyte beta1 integrin and ILK signaling is critical for postnatal development and function of the glomerular filtration apparatus.

Zika Virus Infection of the Human Glomerular Cells: Implications for Viral Reservoirs and Renal Pathogenesis.

PubMed

Alcendor, Donald J

2017-07-15

Zika virus (ZIKV) infection in the human renal compartment has not been reported. Several clinical reports have describe high-level persistent viral shedding in the urine of infected patients, but the associated mechanisms have not been explored until now. The current study examined cellular components of the glomerulus of the human kidney for ZIKV infectivity. I infected primary human podocytes, renal glomerular endothelial cells (GECs), and mesangial cells with ZIKV. Viral infectivity was analyzed by means of microscopy, immunofluorescence, real-time reverse-transcription polymerase chain reaction (RT-PCR), and quantitative RT-PCR (qRT-PCR), and the proinflammatory cytokines interleukin 1β, interferon β, and RANTES (regulated on activation of normal T cells expressed and secreted) were assessed using qRT-PCR. I show that glomerular podocytes, renal GECs, and mesangial cells are permissive for ZIKV infection. ZIKV infectivity was confirmed in all 3 cell types by means of immunofluorescence staining, RT-PCR, and qRT-PCR, and qRT-PCR analysis revealed increased transcriptional induction of interleukin 1β, interferon β, and RANTES in ZIKV-infected podocytes at 72 hours, compared with renal GECs and mesangial cells. The findings of this study support the notion that the glomerulus may serve as an amplification reservoir for ZIKV in the renal compartment. The impact of ZIKV infection in the human renal compartment is unknown and will require further study. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Defining the Molecular Character of the Developing and Adult Kidney Podocyte

PubMed Central

Brunskill, Eric W.; Georgas, Kylie; Rumballe, Bree; Little, Melissa H.; Potter, S. Steven

2011-01-01

Background The podocyte is a remarkable cell type, which encases the capillaries of the kidney glomerulus. Although mesodermal in origin it sends out axonal like projections that wrap around the capillaries. These extend yet finer projections, the foot processes, which interdigitate, leaving between them the slit diaphragms, through which the glomerular filtrate must pass. The podocytes are a subject of keen interest because of their key roles in kidney development and disease. Methodology/Principal Findings In this report we identified and characterized a novel transgenic mouse line, MafB-GFP, which specifically marked the kidney podocytes from a very early stage of development. These mice were then used to facilitate the fluorescent activated cell sorting based purification of podocytes from embryos at E13.5 and E15.5, as well as adults. Microarrays were then used to globally define the gene expression states of podocytes at these different developmental stages. A remarkable picture emerged, identifying the multiple sets of genes that establish the neuronal, muscle, and phagocytic properties of podocytes. The complete combinatorial code of transcription factors that create the podocyte was characterized, and the global lists of growth factors and receptors they express were defined. Conclusions/Significance The complete molecular character of the in vivo podocyte is established for the first time. The active molecular functions and biological processes further define their unique combination of features. The results provide a resource atlas of gene expression patterns of developing and adult podocytes that will help to guide further research of these incredible cells. PMID:21931791

Roles of mitogen-activated protein kinases and angiotensin II in renal development.

PubMed

Balbi, A P C; Francescato, H D C; Marin, E C S; Costa, R S; Coimbra, T M

2009-01-01

Experimental and clinical evidence suggests that angiotensin II (AII) participates in renal development. Renal AII content is several-fold higher in newborn rats and mice than in adult animals. AII receptors are also expressed in higher amounts in the kidneys of newborn rats. The kidneys of fetuses whose mother received a type 1 AII receptor (AT1) antagonist during gestation present several morphological alterations. Mutations in genes that encode components of the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Morphological changes were detected in the kidneys of 3-week-old angiotensin-deficient mice. Mitogen-activated protein kinases (MAPKs) are important mediators that transduce extracellular stimuli to intracellular responses. The MAPK family comprises three major subgroups, namely extracellular signal-regulated protein kinase (ERK), c-jun N-terminal kinases (JNK), and p38 MAPK (p38). Important events in renal growth during nephrogenesis such as cellular proliferation and differentiation accompanied by apoptosis on a large scale can be mediated by MAPK pathways. A decrease in glomerulus number was observed in embryos cultured for 48 and 120 h with ERK or p38 inhibitors. Many effects of AII are mediated by MAPK pathways. Treatment with losartan during lactation provoked changes in renal function and structure associated with alterations in AT1 and type 2 AII (AT2) receptors and p-JNK and p-p38 expression in the kidney. Several studies have shown that AII and MAPKs play an important role in renal development. However, the relationship between the effects of AII and MAPK activation on renal development is still unclear.

Albumin-associated free fatty acids induce macropinocytosis in podocytes

PubMed Central

Chung, Jun-Jae; Huber, Tobias B.; Gödel, Markus; Jarad, George; Hartleben, Björn; Kwoh, Christopher; Keil, Alexander; Karpitskiy, Aleksey; Hu, Jiancheng; Huh, Christine J.; Cella, Marina; Gross, Richard W.; Miner, Jeffrey H.; Shaw, Andrey S.

2015-01-01

Podocytes are specialized epithelial cells in the kidney glomerulus that play important structural and functional roles in maintaining the filtration barrier. Nephrotic syndrome results from a breakdown of the kidney filtration barrier and is associated with proteinuria, hyperlipidemia, and edema. Additionally, podocytes undergo changes in morphology and internalize plasma proteins in response to this disorder. Here, we used fluid-phase tracers in murine models and determined that podocytes actively internalize fluid from the plasma and that the rate of internalization is increased when the filtration barrier is disrupted. In cultured podocytes, the presence of free fatty acids (FFAs) associated with serum albumin stimulated macropinocytosis through a pathway that involves FFA receptors, the Gβ/Gγ complex, and RAC1. Moreover, mice with elevated levels of plasma FFAs as the result of a high-fat diet were more susceptible to Adriamycin-induced proteinuria than were animals on standard chow. Together, these results support a model in which podocytes sense the disruption of the filtration barrier via FFAs bound to albumin and respond by enhancing fluid-phase uptake. The response to FFAs may function in the development of nephrotic syndrome by amplifying the effects of proteinuria. PMID:25915582

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dekan, G.; Farquhar, M.G.; Gabel, C.

Podocalyxin is the major sialoprotein of the rat glomerulus. Its function is to maintain the filtration slits of the glomerular epithelium open by virtue of its high net negative charge. The authors have used biosynthetic labeling and oligosaccharide analysis to characterize the anionic-charge-carrying moieties on this protein. Kidney slices from 2-day-old rats were biosynthetically labeled with ({sup 35}S)Cys, ({sup 3}H)Man, ({sup 3}H)GlcN, and {sup 35}SO{sub 4}, after which podocalyxin was immunoprecipitated and purified by SDS/PAGE. All these labels were incorporated into podocalyxin. Immunoprecipitates were subjected to digestion with specific glycosidases or digested with Pronase followed by chromatographic analysis of themore » released glycopeptides. Analysis of the {sup 35}SO{sub 4}-labeled glycopeptides indicated that both the N- and O-linked structures were sulfated. They conclude that in newborn rat kidney (i) podocalyxin contains both O- and N-linked oligosaccharides (ii) podocalyxin is sulfated, and (iii) sulfate is located on both O-linked oligosaccharides and on glycopeptides carrying tri- or tetrantennary N-linked structures. These results indicate that the net negative charge of podocalyxin is most likely derived from sulfate as well as from sialic acid residues.« less

Integrating temperature with odor processing in the olfactory bulb.

PubMed

Kludt, Eugen; Okom, Camille; Brinkmann, Alexander; Schild, Detlev

2015-05-20

Temperature perception has long been classified as a somesthetic function solely. However, in recent years several studies brought evidence that temperature perception also takes place in the olfactory system of rodents. Temperature has been described as an effective stimulus for sensory neurons of the Grueneberg ganglion located at the entrance of the nose. Here, we investigate whether a neuronal trace of temperature stimulation can be observed in the glomeruli and mitral cells of the olfactory bulb, using calcium imaging and fast line-scanning microscopy. We show in the Xenopus tadpole system that the γ-glomerulus, which receives input from olfactory neurons, is highly sensitive to temperature drops at the olfactory epithelium. We observed that thermo-induced activity in the γ-glomerulus is conveyed to the mitral cells innervating this specific neuropil. Surprisingly, a substantial number of thermosensitive mitral cells were also chemosensitive. Moreover, we report another unique feature of the γ-glomerulus: it receives ipsilateral and contralateral afferents. The latter fibers pass through the contralateral bulb, cross the anterior commissure, and then run to the ipsilateral olfactory bulb, where they target the γ-glomerulus. Temperature drops at the contralateral olfactory epithelium also induced responses in the γ-glomerulus and in mitral cells. Temperature thus appears to be a relevant physiological input to the Xenopus olfactory system. Each olfactory bulb integrates and codes temperature signals originating from receptor neurons of the ipsilateral and contralateral nasal cavities. Finally, temperature and chemical information is processed in shared cellular networks. Copyright © 2015 the authors 0270-6474/15/357892-11$15.00/0.

Expression of adropin in rat brain, cerebellum, kidneys, heart, liver, and pancreas in streptozotocin-induced diabetes.

PubMed

Aydin, Suleyman; Kuloglu, Tuncay; Aydin, Suna; Eren, Mehmet Nesimi; Yilmaz, Musa; Kalayci, Mehmet; Sahin, Ibrahim; Kocaman, Nevin; Citil, Cihan; Kendir, Yalcin

2013-08-01

We have investigated how diabetes affects the expression of adropin (ADR) in rat brain, cerebellum, kidneys, heart, liver, and pancreas tissues. The rats in the diabetic group were administered an intraperitoneal (i.p.) injection of a single dose of 60 mg/kg streptozotocin (STZ) dissolved in a 0.1 M phosphate-citrate buffer (pH 4.5). The rats were maintained in standard laboratory conditions in a temperature between 21 and 23 °C and a relative humidity of 70 %, under a 12-h light/dark cycle. The animals were fed a standard commercial pellet diet. After 10 weeks, the animals were sacrified. ADR concentrations in the serum and tissue supernatants were measured by ELISA, and immunohistochemical staining was used to follow the expression of the hormones in the brain, cerebellum, kidneys, heart, liver, and pancreas tissues. The quantities were then compared. Increased ADR immunoreaction was seen in the brain, cerebellum, kidneys, heart, liver, and pancreas in the diabetes-induced rats compared to control subjects. ADR was detected in the brain (vascular area, pia mater, neuroglial cell, and neurons), cerebellum (neuroglial cells, Purkinje cells, vascular areas, and granular layer), kidneys (glomerulus, peritubular interstitial cells, and peritubular capillary endothelial cells), heart (endocardium, myocardium, and epicardium), liver (sinusoidal cells), and pancreas (serous acini). Its concentrations (based on mg/wet weight tissues) in these tissues were measured by using ELISA showed that the levels of ADR were higher in the diabetic rats compared to the control rats. Tissue ADR levels based on mg/wet weight tissues were as follows: Pancreas > liver > kidney > heart > brain > cerebellar tissues. Evidence is presented that shows ADR is expressed in various tissues in the rats and its levels increased in STZ-induced diabetes; however, this effect on the pathophysiology of the disorder remains to be understood.

Resolving an 80-Yr-Old Controversy: The Beginning of the Modern Era of Renal Physiology

ERIC Educational Resources Information Center

Jamison, Rex L.

2014-01-01

Marcello Malpighi discovered the glomerulus that bears his name in the 17th century, but it was not until the middle of the 19th century, in 1842, that William Bowman in London published his studies of the histological structure of the glomerulus and proposed that urine formation begins with glomerular secretion. At nearly the same time in…

The nonuniformity of antibody distribution in the kidney and its influence on dosimetry.

PubMed

Flynn, Aiden A; Pedley, R Barbara; Green, Alan J; Dearling, Jason L; El-Emir, Ethaar; Boxer, Geoffrey M; Boden, Robert; Begent, Richard H J

2003-02-01

The therapeutic efficacy of radiolabeled antibody fragments can be limited by nephrotoxicity, particularly when the kidney is the major route of extraction from the circulation. Conventional dose estimates in kidney assume uniform dose deposition, but we have shown increased antibody localization in the cortex after glomerular filtration. The purpose of this study was to measure the radioactivity in cortex relative to medulla for a range of antibodies and to assess the validity of the assumption of uniformity of dose deposition in the whole kidney and in the cortex for these antibodies with a range of radionuclides. Storage phosphor plate technology (radioluminography) was used to acquire images of the distributions of a range of antibodies of various sizes, labeled with 125I, in kidney sections. This allowed the calculation of the antibody concentration in the cortex relative to the medulla. Beta-particle point dose kernels were then used to generate the dose-rate distributions from 14C, 131I, 186Re, 32P and 90Y. The correlation between the actual dose-rate distribution and the corresponding distribution calculated assuming uniform antibody distribution throughout the kidney was used to test the validity of estimating dose by assuming uniformity in the kidney and in the cortex. There was a strong inverse relationship between the ratio of the radioactivity in the cortex relative to that in the medulla and the antibody size. The nonuniformity of dose deposition was greatest with the smallest antibody fragments but became more uniform as the range of the emissions from the radionuclide increased. Furthermore, there was a strong correlation between the actual dose-rate distribution and the distribution when assuming a uniform source in the kidney for intact antibodies along with medium- to long-range radionuclides, but there was no correlation for small antibody fragments with any radioisotope or for short-range radionuclides with any antibody. However, when the cortex was separated from the whole kidney, the correlation between the actual dose-rate distribution and the assumed dose-rate distribution, if the source was uniform, increased significantly. During radioimmunotherapy, the extent of nonuniformity of dose deposition in the kidney depends on the properties of the antibody and radionuclide. For dosimetry estimates, the cortex should be taken as a separate source region when the radiopharmaceutical is small enough to be filtered by the glomerulus.

Apoptosis of rat renal cells by organophosphate pesticide, quinalphos: Ultrastructural study.

PubMed

Eid, Refaat A

2017-01-01

Quinalphos or Ekalux, an organophosphate pesticide, is used in controlling the pests of a variety of crops. Quinalphos was studied on male Sprague-Dawley albino rats. The acute po LD50 of technical Ekalux was 19.95 mg/kg in males. Ekalux, produced several pathological changes in the kidney. A glomerulus demonstrated capillary lumina occluded by degenerated cellular debris. Basement membrane showed irregular wrinkling and branching. The proximal tubular cells showed damage such as dilation of endoplasmic reticulum, accumulation of glycogen granules, and pyknotic nucleus. The changes also included swelling of the mitochondria and reduction of the cristae up to total destruction. The distal tubular changes included electron lucency and vacuolation of cytoplasm. The distal convoluted tubule wall showed edematous epithelial cells, formation of blebs, and microvilli loss. These results suggest that subchronic exposure of rats to Ekalux causes ultrastructural changes in renal corpuscle and marked ultrastructural changes in proximal and distal tubules.

Neural control of renal function: cardiovascular implications.

PubMed

DiBona, G F

1989-06-01

The innervation of the kidney serves to function of its component parts, for example, the blood vessels, the nephron (glomerulus, tubule), and the juxtaglomerular apparatus. Alterations in efferent renal sympathetic nerve activity produce significant changes in renal blood flow, glomerular filtration rate, the reabsorption of water, sodium, and other ions, and the release of renin, prostaglandins, and other vasoactive substances. These functional effects contribute significantly to the renal regulation of total body sodium and fluid volumes with important implications for the control of arterial pressure. The renal nerves, both efferent and afferent, are known to be important contributors to the pathogenesis of hypertension. In addition, the efferent renal nerves participate in the mediation of the excessive renal sodium retention, which characterizes edema-forming states such as congestive heart failure. Thus, the renal nerves play an important role in overall cardiovascular homeostasis in both normal and pathological conditions.

Measurement of glomerulus diameter and Bowman's space width of renal albino rats.

PubMed

Kotyk, Taras; Dey, Nilanjan; Ashour, Amira S; Balas-Timar, Dana; Chakraborty, Sayan; Ashour, Ahmed S; Tavares, João Manuel R S

2016-04-01

Glomerulus diameter and Bowman's space width in renal microscopic images indicate various diseases. Therefore, the detection of the renal corpuscle and related objects is a key step in histopathological evaluation of renal microscopic images. However, the task of automatic glomeruli detection is challenging due to their wide intensity variation, besides the inconsistency in terms of shape and size of the glomeruli in the renal corpuscle. Here, a novel solution is proposed which includes the Particles Analyzer technique based on median filter for morphological image processing to detect the renal corpuscle objects. Afterwards, the glomerulus diameter and Bowman's space width are measured. The solution was tested with a dataset of 21 rats' renal corpuscle images acquired using light microscope. The experimental results proved that the proposed solution can detect the renal corpuscle and its objects efficiently. As well as, the proposed solution has the ability to manage any input images assuring its robustness to the deformations of the glomeruli even with the glomerular hypertrophy cases. Also, the results reported significant difference between the control and affected (due to ingested additional daily dose (14.6mg) of fructose) groups in terms of glomerulus diameter (97.40±19.02μm and 177.03±54.48μm, respectively). Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Expression of cytochrome P-450 4 enzymes in the kidney and liver: regulation by PPAR and species-difference between rat and human.

PubMed

Ito, Osamu; Nakamura, Yasuhiro; Tan, Liping; Ishizuka, Tsuneo; Sasaki, Yuko; Minami, Naoyoshi; Kanazawa, Masayuki; Ito, Sadayoshi; Sasano, Hironobu; Kohzuki, Masahiro

2006-03-01

Members of the cytochrome P-450 4 (CYP4) family catalyze the omega-hydroxylation of fatty acids, and some of them have the PPAR response element in the promoter area of the genes. The localization of CYP4A and PPAR isoforms and the effect of PPAR agonists on CYP4A protein level and activity were determined in rat kidney and liver. Immunoblot analysis showed that CYP4A was expressed in the liver and proximal tubule, with lower expression in the preglomerular microvessel, glomerulus and thick ascending limb (TAL), but the expression was not detected in the collecting duct. PPARalpha was expressed in the liver, proximal tubule and TAL. PPARgamma was expressed in the collecting duct, with lower expression in the TAL, but no expression in the proximal tubule and liver. The PPARalpha agonist clofibrate induced CYP4A protein levels and activity in the renal cortex and liver. The PPARgamma agonist pioglitazone did not modulate them in these tissues. The localization of CYP4A and CYP4F were further determined in human kidney and liver by immunohistochemical technique. Immunostainings for CYP4A and CYP4F were observed in the hepatocytes of the liver lobule and the proximal tubules, with lower stainings in the TALs and collecting ducts, but no staining in the glomeruli or renal vasculatures. These results indicate that the inducibility of CYP4A by PPAR agonists in the rat tissues correlates with the expression of the respective PPAR isoforms, and that the localization of CYP4 in the kidney has a species-difference between rat and human.

Actin dynamics at focal adhesions: a common endpoint and putative therapeutic target for proteinuric kidney diseases.

PubMed

Sever, Sanja; Schiffer, Mario

2018-06-01

Proteinuria encompasses diverse causes including both genetic diseases and acquired forms such as diabetic and hypertensive nephropathy. The basis of proteinuria is a disturbance in size selectivity of the glomerular filtration barrier, which largely depends on the podocyte: a terminally differentiated epithelial cell type covering the outer surface of the glomerulus. Compromised podocyte structure is one of the earliest signs of glomerular injury. The phenotype of diverse animal models and podocyte cell culture firmly established the essential role of the actin cytoskeleton in maintaining functional podocyte structure. Podocyte foot processes, actin-based membrane extensions, contain 2 molecularly distinct "hubs" that control actin dynamics: a slit diaphragm and focal adhesions. Although loss of foot processes encompasses disassembly of slit diaphragm multiprotein complexes, as long as cells are attached to the glomerular basement membrane, focal adhesions will be the sites in which stress due to filtration flow is counteracted by forces generated by the actin network in foot processes. Numerous studies within last 20 years have identified actin binding and regulatory proteins as well as integrins as essential components of signaling and actin dynamics at focal adhesions in podocytes, suggesting that some of them may become novel, druggable targets for proteinuric kidney diseases. Here we review evidence supporting the idea that current treatments for chronic kidney diseases beneficially and directly target the podocyte actin cytoskeleton associated with focal adhesions and suggest that therapeutic reagents that target the focal adhesion-regulated actin cytoskeleton in foot processes have potential to modernize treatments for chronic kidney diseases. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

High Glucose Impairs Insulin Signaling in the Glomerulus: An In Vitro and Ex Vivo Approach

PubMed Central

Katsoulieris, Elias N.; Drossopoulou, Garyfalia I.; Kotsopoulou, Eleni S.; Vlahakos, Dimitrios V.; Lianos, Elias A.; Tsilibary, Effie C.

2016-01-01

Objective Chronic hyperglycaemia, as seen in type II diabetes, results in both morphological and functional impairments of podocytes in the kidney. We investigated the effects of high glucose (HG) on the insulin signaling pathway, focusing on cell survival and apoptotic markers, in immortalized human glomerular cells (HGEC; podocytes) and isolated glomeruli from healthy rats. Methods and Findings HGEC and isolated glomeruli were cultured for various time intervals under HG concentrations in the presence or absence of insulin. Our findings indicated that exposure of HGEC to HG led to downregulation of all insulin signaling markers tested (IR, p-IR, IRS-1, p-Akt, p-Fox01,03), as well as to increased sensitivity to apoptosis (as seen by increased PARP cleavage, Casp3 activation and DNA fragmentation). Short insulin pulse caused upregulation of insulin signaling markers (IR, p-IR, p-Akt, p-Fox01,03) in a greater extent in normoglycaemic cells compared to hyperglycaemic cells and for the case of p-Akt, in a PI3K-dependent manner. IRS-1 phosphorylation of HG-treated podocytes was negatively regulated, favoring serine versus tyrosine residues. Prolonged insulin treatment caused a significant decrease of IR levels, while alterations in glucose concentrations for various time intervals demonstrated changes of IR, p-IR and p-Akt levels, suggesting that the IR signaling pathway is regulated by glucose levels. Finally, HG exerted similar effects in isolated glomeruli. Conclusions These results suggest that HG compromises the insulin signaling pathway in the glomerulus, promoting a proapoptotic environment, with a possible critical step for this malfunction lying at the level of IRS-1 phosphorylation; thus we herein demonstrate glomerular insulin signaling as another target for investigation for the prevention and/ or treatment of diabetic nephropathy. PMID:27434075

Regulation of cytochrome P-450 4A activity by peroxisome proliferator-activated receptors in the rat kidney.

PubMed

Ishizuka, Tsuneo; Ito, Osamu; Tan, Liping; Ogawa, Susumu; Kohzuki, Masahiro; Omata, Ken; Takeuchi, Kazuhisa; Ito, Sadayoshi

2003-11-01

The localization of cytochrome P-450 4A, peroxisome proliferator-activated receptor (PPAR) alpha, and PPARgamma proteins, and the inducibility of P-450 4A expression and activity by PPAR agonists were determined in the rat kidney. The expressions of these proteins in isolated nephron segments were evaluated by immunoblot analysis, and the production of 20-hydroxyeicosatetraenoic acid (20-HETE) was measured as P-450 4A activity. P-450 4A proteins were expressed predominantly in the proximal tubule (PT), with lower expression in the preglomerular arteriole (Art), glomerulus (Glm), and medullary thick ascending limb (mTAL), but their expression was not detected in the inner medullary collecting duct (IMCD). PPARalpha protein was expressed in the PT and mTAL, and PPARgamma protein was expressed in the IMCD and mTAL. Treatment with clofibrate, the PPARalpha agonist, increased P-450 4A protein levels and the production of 20-HETE in microsomes prepared from the renal cortex, whereas treatment with pioglitazone, the PPARgamma agonist, affected neither of them. These results indicate that PPARalpha and PPARgamma proteins are localized in different nephron segments and the inducibility of P-450 4A expression and activity by the PPAR agonists correlates with the nephron-specific localization of the respective PPAR isoforms.

A proteolytic modification of AIM promotes its renal excretion

PubMed Central

Yamazaki, Tomoko; Sugisawa, Ryoichi; Hiramoto, Emiri; Takai, Ryosuke; Matsumoto, Ayaka; Senda, Yoshie; Nakashima, Katsuhiko; Nelson, Peter S.; Lucas, Jared M.; Morgan, Andrew; Li, Zhenghua; Yamamura, Ken-ichi; Arai, Satoko; Miyazaki, Toru

2016-01-01

Apoptosis inhibitor of macrophage (AIM, encoded by cd5l) is a multi-functional circulating protein that has a beneficial role in the regulation of a broad range of diseases, some of which are ameliorated by AIM administration in mice. In blood, AIM is stabilized by association with IgM pentamers and maintains its high circulating levels. The mechanism regulating the excessive accumulation of blood AIM remains unknown, although it is important, since a constitutive increase in AIM levels promotes chronic inflammation. Here we found a physiological AIM-cleavage process that induces destabilization of AIM and its excretion in urine. In blood, IgM-free AIM appeared to be cleaved and reduced in size approximately 10 kDa. Cleaved AIM was unable to bind to IgM and was selectively filtered by the glomerulus, thereby excreted in urine. Amino acid substitution at the cleavage site resulted in no renal excretion of AIM. Interestingly, cleaved AIM retained a comparable potency with full-length AIM in facilitating the clearance of dead cell debris in injured kidney, which is a key response in the recovery of acute kidney injury. Identification of AIM-cleavage and resulting functional modification could be the basis for designing safe and efficient AIM therapy for various diseases. PMID:27929116

Changes in glomerular parietal epithelial cells in mouse kidneys with advanced age

PubMed Central

Roeder, Sebastian S.; Stefanska, Ania; Eng, Diana G.; Kaverina, Natalya; Sunseri, Maria W.; McNicholas, Bairbre A.; Rabinovitch, Peter; Engel, Felix B.; Daniel, Christoph; Amann, Kerstin; Lichtnekert, Julia; Pippin, Jeffrey W.

2015-01-01

Kidney aging is accompanied by characteristic changes in the glomerulus, but little is known about the effect of aging on glomerular parietal epithelial cells (PECs), nor if the characteristic glomerular changes in humans and rats also occur in very old mice. Accordingly, a descriptive analysis was undertaken in 27-mo-old C57B6 mice, considered advanced age. PEC density was significantly lower in older mice compared with young mice (aged 3 mo), and the decrease was more pronounced in juxtamedullary glomeruli compared with outer cortical glomeruli. In addition to segmental and global glomerulosclerosis in older mice, staining for matrix proteins collagen type IV and heparan sulfate proteoglycan were markedly increased in Bowman's capsules of older mouse glomeruli, consistent with increased extracellular matrix production by PECs. De novo staining for CD44, a marker of activated and profibrotic PECs, was significantly increased in aged glomeruli. CD44 staining was more pronounced in the juxtamedullary region and colocalized with phosphorylated ERK. Additionally, a subset of aged PECs de novo expressed the epithelial-to-mesenchymal transition markers α-smooth muscle and vimentin, with no changes in epithelial-to-mesenchymal transition markers E-cadherin and β-catenin. The mural cell markers neural/glial antigen 2, PDGF receptor-β, and CD146 as well as Notch 3 were also substantially increased in aged PECs. These data show that mice can be used to better understand the aging kidney and that PECs undergo substantial changes, especially in juxtamedullary glomeruli, that may participate in the overall decline in glomerular structure and function with advancing age. PMID:26017974

Protective Effects of Hydrocortisone, Vitamin C and E Alone or in Combination against Renal Ischemia-Reperfusion Injury in Rat.

PubMed

Azari, Omid; Kheirandish, Reza; Azizi, Shahrzad; Farajli Abbasi, Mohammad; Ghahramani Gareh Chaman, Shahin; Bidi, Masoud

2015-01-01

Renal ischemia reperfusion injury may occur in a variety of clinical situations, following a transient drop in total or regional blood flow to the kidney. This study was performed to investigate the protective effects of different antioxidants such as vitamin C, vitamin E, hydrocortisone and combination of these agents against experimental renal ischemia-reperfusion injury. Thirty male rats were divided into six groups. Group Sham, Group I/R: (45 min of ischemia followed by 1h of reperfusion), Group I/R+Vit C: (50 mg/kg Vit C, IV, immediately after reperfusion), Group I/R+Vit E: (20 mg/kg Vit E, IM, 15 min before reperfusion), Group I/R+Hydrocortisone: (50 mg/kg, IV, immediately after reperfusion), and Group Combination: Ischemia-reperfusion plus combination of Vit C, E and hydrocortisone. After the experiments, the left kidney was removed and the tissues were processed for histopathological examination. Severe injuries such as necrosis of tubules, atrophy of glomerulus, and hemorrhage were observed in group I/R. Histological scores indicating tissue injury significantly decreased in all treatment groups compared to the group I/R. The renal tissue in group treatment was preserved in comparison with the group I/R. Comparison between the treatment groups showed that group combination was more effective and group vit E was less effective in protecting of renal tissue against I/R injuries. The results demonstrated simultaneous administration of combination of Vit C, E and hydrocortisone before reperfusion of blood flow to the ischemic tissue could show a synergy against deleterious effects of I/R injuries in kidney.

Human podocyte depletion in association with older age and hypertension.

PubMed

Puelles, Victor G; Cullen-McEwen, Luise A; Taylor, Georgina E; Li, Jinhua; Hughson, Michael D; Kerr, Peter G; Hoy, Wendy E; Bertram, John F

2016-04-01

Podocyte depletion plays a major role in the development and progression of glomerulosclerosis. Many kidney diseases are more common in older age and often coexist with hypertension. We hypothesized that podocyte depletion develops in association with older age and is exacerbated by hypertension. Kidneys from 19 adult Caucasian American males without overt renal disease were collected at autopsy in Mississippi. Demographic data were obtained from medical and autopsy records. Subjects were categorized by age and hypertension as potential independent and additive contributors to podocyte depletion. Design-based stereology was used to estimate individual glomerular volume and total podocyte number per glomerulus, which allowed the calculation of podocyte density (number per volume). Podocyte depletion was defined as a reduction in podocyte number (absolute depletion) or podocyte density (relative depletion). The cortical location of glomeruli (outer or inner cortex) and presence of parietal podocytes were also recorded. Older age was an independent contributor to both absolute and relative podocyte depletion, featuring glomerular hypertrophy, podocyte loss, and thus reduced podocyte density. Hypertension was an independent contributor to relative podocyte depletion by exacerbating glomerular hypertrophy, mostly in glomeruli from the inner cortex. However, hypertension was not associated with podocyte loss. Absolute and relative podocyte depletion were exacerbated by the combination of older age and hypertension. The proportion of glomeruli with parietal podocytes increased with age but not with hypertension alone. These findings demonstrate that older age and hypertension are independent and additive contributors to podocyte depletion in white American men without kidney disease. Copyright © 2016 the American Physiological Society.

Advanced Glycation End Products Predict Loss of Renal Function and Correlate With Lesions of Diabetic Kidney Disease in American Indians With Type 2 Diabetes.

PubMed

Saulnier, Pierre-Jean; Wheelock, Kevin M; Howell, Scott; Weil, E Jennifer; Tanamas, Stephanie K; Knowler, William C; Lemley, Kevin V; Mauer, Michael; Yee, Berne; Nelson, Robert G; Beisswenger, Paul J

2016-12-01

We examined associations of advanced glycation end products (AGEs) with renal function loss (RFL) and its structural determinants in American Indians with type 2 diabetes. Data were from a 6-year clinical trial that assessed renoprotective efficacy of losartan. Participants remained under observation after the trial concluded. Glomerular filtration rate (GFR) was measured annually. Kidney biopsies were performed at the end of the trial. Five AGEs were measured in serum collected at enrollment and at kidney biopsy. RFL was defined as ≥40% decline of measured GFR from baseline. Of 168 participants (mean baseline age 41 years, HbA 1c 9.2%, GFR 164 mL/min, and albumin-to-creatinine ratio 31 mg/g), 104 reached the RFL end point during median follow-up of 8.0 years. After multivariable adjustment, each doubling of carboxyethyl lysine (hazard ratio [HR] 1.60 [95% CI 1.08-2.37]) or methylglyoxal hydroimidazolone (HR 1.30 [95% CI 1.02-1.65]) concentration was associated with RFL. Carboxyethyl lysine, carboxymethyl lysine, and methylglyoxal hydroimidazolone correlated positively with cortical interstitial fractional volume (partial r = 0.23, P = 0.03; partial r = 0.25, P = 0.02; and partial r = 0.31, P = 0.003, respectively). Glyoxyl hydroimidazolone and methylglyoxal hydroimidazolone correlated negatively with total filtration surface per glomerulus (partial r = -0.26, P = 0.01; and partial r = -0.21, P = 0.046, respectively). AGEs improve prediction of RFL and its major structural correlates. © 2016 by the American Diabetes Association.

Advanced Glycation End Products Predict Loss of Renal Function and Correlate With Lesions of Diabetic Kidney Disease in American Indians With Type 2 Diabetes

PubMed Central

Saulnier, Pierre-Jean; Wheelock, Kevin M.; Howell, Scott; Weil, E. Jennifer; Tanamas, Stephanie K.; Knowler, William C.; Lemley, Kevin V.; Mauer, Michael; Yee, Berne; Beisswenger, Paul J.

2016-01-01

We examined associations of advanced glycation end products (AGEs) with renal function loss (RFL) and its structural determinants in American Indians with type 2 diabetes. Data were from a 6-year clinical trial that assessed renoprotective efficacy of losartan. Participants remained under observation after the trial concluded. Glomerular filtration rate (GFR) was measured annually. Kidney biopsies were performed at the end of the trial. Five AGEs were measured in serum collected at enrollment and at kidney biopsy. RFL was defined as ≥40% decline of measured GFR from baseline. Of 168 participants (mean baseline age 41 years, HbA1c 9.2%, GFR 164 mL/min, and albumin-to-creatinine ratio 31 mg/g), 104 reached the RFL end point during median follow-up of 8.0 years. After multivariable adjustment, each doubling of carboxyethyl lysine (hazard ratio [HR] 1.60 [95% CI 1.08–2.37]) or methylglyoxal hydroimidazolone (HR 1.30 [95% CI 1.02–1.65]) concentration was associated with RFL. Carboxyethyl lysine, carboxymethyl lysine, and methylglyoxal hydroimidazolone correlated positively with cortical interstitial fractional volume (partial r = 0.23, P = 0.03; partial r = 0.25, P = 0.02; and partial r = 0.31, P = 0.003, respectively). Glyoxyl hydroimidazolone and methylglyoxal hydroimidazolone correlated negatively with total filtration surface per glomerulus (partial r = −0.26, P = 0.01; and partial r = −0.21, P = 0.046, respectively). AGEs improve prediction of RFL and its major structural correlates. PMID:27609106

Integrated β-catenin, BMP, PTEN, and Notch signalling patterns the nephron.

PubMed

Lindström, Nils O; Lawrence, Melanie L; Burn, Sally F; Johansson, Jeanette A; Bakker, Elvira R M; Ridgway, Rachel A; Chang, C-Hong; Karolak, Michele J; Oxburgh, Leif; Headon, Denis J; Sansom, Owen J; Smits, Ron; Davies, Jamie A; Hohenstein, Peter

2015-02-03

The different segments of the nephron and glomerulus in the kidney balance the processes of water homeostasis, solute recovery, blood filtration, and metabolite excretion. When segment function is disrupted, a range of pathological features are presented. Little is known about nephron patterning during embryogenesis. In this study, we demonstrate that the early nephron is patterned by a gradient in β-catenin activity along the axis of the nephron tubule. By modifying β-catenin activity, we force cells within nephrons to differentiate according to the imposed β-catenin activity level, thereby causing spatial shifts in nephron segments. The β-catenin signalling gradient interacts with the BMP pathway which, through PTEN/PI3K/AKT signalling, antagonises β-catenin activity and promotes segment identities associated with low β-catenin activity. β-catenin activity and PI3K signalling also integrate with Notch signalling to control segmentation: modulating β-catenin activity or PI3K rescues segment identities normally lost by inhibition of Notch. Our data therefore identifies a molecular network for nephron patterning.

High sensitive volumetric imaging of renal microcirculation in vivo using ultrahigh sensitive optical microangiography

NASA Astrophysics Data System (ADS)

Zhi, Zhongwei; Jung, Yeongri; Jia, Yali; An, Lin; Wang, Ruikang K.

2011-03-01

We present a non-invasive, label-free imaging technique called Ultrahigh Sensitive Optical Microangiography (UHSOMAG) for high sensitive volumetric imaging of renal microcirculation. The UHS-OMAG imaging system is based on spectral domain optical coherence tomography (SD-OCT), which uses a 47000 A-line scan rate CCD camera to perform an imaging speed of 150 frames per second that takes only ~7 seconds to acquire a 3D image. The technique, capable of measuring slow blood flow down to 4 um/s, is sensitive enough to image capillary networks, such as peritubular capillaries and glomerulus within renal cortex. We show superior performance of UHS-OMAG in providing depthresolved volumetric images of rich renal microcirculation. We monitored the dynamics of renal microvasculature during renal ischemia and reperfusion. Obvious reduction of renal microvascular density due to renal ischemia was visualized and quantitatively analyzed. This technique can be helpful for the assessment of chronic kidney disease (CKD) which relates to abnormal microvasculature.

The C3aR promotes macrophage infiltration and regulates ANCA production but does not affect glomerular injury in experimental anti-myeloperoxidase glomerulonephritis

PubMed Central

Gan, Poh-Yi; Kitching, A. Richard; Holdsworth, Stephen R.

2018-01-01

The anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides are autoimmune diseases associated with significant morbidity and mortality. They often affect the kidney causing rapidly progressive glomerulonephritis. While signalling by complement anaphylatoxin C5a though the C5a receptor is important in this disease, the role of the anaphylatoxin C3a signalling via the C3a receptor (C3aR) is not known. Using two different murine models of anti-myeloperoxidase (MPO) glomerulonephritis, one mediated by passive transfer of anti-MPO antibodies, the other by cell-mediated immunity, we found that the C3aR did not alter histological disease severity. However, it promoted macrophage recruitment to the inflamed glomerulus and inhibited the generation of MPO-ANCA whilst not influencing T cell autoimmunity. Thus, whilst the C3aR modulates some elements of disease pathogenesis, overall it is not critical in effector responses and glomerular injury caused by autoimmunity to MPO. PMID:29315316

Nephron segment specific microRNA biomarkers of pre-clinical drug-induced renal toxicity: Opportunities and challenges

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nassirpour, Rounak, E-mail: Rounak.nassirpour@pfiz

Drug-induced nephrotoxicity is a common drug development complication for pharmaceutical companies. Sensitive, specific, translatable and non-invasive biomarkers of renal toxicity are urgently needed to diagnose nephron segment specific injury. The currently available gold standard biomarkers for nephrotoxicity are not kidney-specific, lack sensitivity for early detection, and are not suitable for renal damage localization (glomerular vs tubulointerstitial injury). MicroRNAs (miRNAs) are increasingly gaining momentum as promising biomarkers of various organ toxicities, including drug induced renal injury. This is mostly due to their stability in easily accessible biofluids, ease of developing nucleic acids detection compared to protein detection assays, as well asmore » their interspecies translatability. Increasing concordance of miRNA findings by standardizing methodology most suitable for their detection and quantitation, as well as characterization of their expression pattern in a cell type specific manner, will accelerate progress toward validation of these miRNAs as biomarkers in pre-clinical, and clinical settings. This review aims to highlight the current pre-clinical findings surrounding miRNAs as biomarkers in two important segments of the nephron, the glomerulus and tubules. - Highlights: • miRNAs are promising biomarkers of drug-induced kidney injury. • Summarized pre-clinical miRNA biomarkers of drug-induced nephrotoxicity. • Described the strengths and challenges associated with miRNAs as biomarkers.« less

Green synthesis of silver nanoparticles using Piper nigrum: tissue-specific bioaccumulation, histopathology, and oxidative stress responses in Indian major carp Labeo rohita.

PubMed

Shobana, Chellappan; Rangasamy, Basuvannan; Poopal, Rama Krishnan; Renuka, Sivashankar; Ramesh, Mathan

2018-04-01

The aim of the present investigation is to assess the sublethal toxicity of biologically synthesized silver nanoparticles (Ag NPs) in Indian major carp Labeo rohita. Ag NPs used in the study were synthesized by using AgNO 3 with aqueous leaf extract of Piper nigrum. Median lethal concentration (LC 50 ) of synthesized Ag NPs was determined for 96 h (25 μg/L); 2.5 μg/L (1/10th LC 50 ) and 5 μg/L (1/5th LC 50 ) were taken as sublethal concentrations to evaluate the toxicity for 35 days. The results of the TEM, SEM, and EDX analyses revealed that Ag NPs were considerably accumulated in the gill, liver, and kidney of fish at both concentrations (2.5 and 5 μg/L). Consequently, the activity of the antioxidant enzymes, SOD and CAT, was significantly (P < 0.05) decreased in the gill, liver, and kidney when compared to the control group during the study period. However, lipid peroxidase (LPO) activity in the gill, liver, and kidney was significantly (P < 0.05) increased, and the result concluded a possible sign of free radical-induced oxidative stress in Ag NP-exposed fish than the sham-exposed individuals. The histopathological study also confirmed the alterations such as degeneration of lamella, lifting of lamellar epithelium, hepatic necrosis, pyknotic nuclei, increased intracellular space, and shrinkage of glomerulus elicited by Ag NPs in the gill, liver, and kidney of Labeo rohita with two different concentrations. The findings of the present study revealed that green synthesis of Ag NPs from Piper nigrum at sublethal concentrations leads to accumulation of Ag, oxidative stress, and histopathological alterations in the target organs of the fish, Labeo rohita.

Intravital Imaging Reveals Angiotensin II–Induced Transcytosis of Albumin by Podocytes

PubMed Central

Schießl, Ina Maria; Hammer, Anna; Kattler, Veronika; Gess, Bernhard; Theilig, Franziska; Witzgall, Ralph

2016-01-01

Albuminuria is a hallmark of kidney disease of various etiologies and usually caused by deterioration of glomerular filtration barrier integrity. We recently showed that angiotensin II (Ang II) acutely increases albumin filtration in the healthy kidney. Here, we used intravital microscopy to assess the effects of Ang II on podocyte function in rats. Acute infusion of 30, 60, or 80 ng/kg per minute Ang II enhanced the endocytosis of albumin by activation of the type 1 Ang II receptor and resulted in an average (±SEM) of 3.7±2.2, 72.3±18.6 (P<0.001), and 239.4±34.6 µm3 (P<0.001) albumin-containing vesicles per glomerulus, respectively, compared with none at baseline or 10 ng/kg per minute Ang II. Immunostaining of Ang II–infused kidneys confirmed the presence of albumin-containing vesicles, which colocalized with megalin, in podocin-positive cells. Furthermore, podocyte endocytosis of albumin was markedly reduced in the presence of gentamicin, a competitive inhibitor of megalin-dependent endocytosis. Ang II infusion increased the concentration of albumin in the subpodocyte space, a potential source for endocytic protein uptake, and gentamicin further increased this concentration. Some endocytic vesicles were acidified and colocalized with LysoTracker. Most vesicles migrated from the capillary to the apical aspect of the podocyte and were eventually released into the urinary space. This transcytosis accounted for approximately 10% of total albumin filtration. In summary, the transcellular transport of proteins across the podocyte constitutes a new pathway of glomerular protein filtration. Ang II enhances the endocytosis and transcytosis of plasma albumin by podocytes, which may eventually impair podocyte function. PMID:26116357

The insect nephrocyte is a podocyte-like cell with a filtration slit diaphragm

PubMed Central

Weavers, Helen; Prieto-Sánchez, Silvia; Grawe, Ferdinand; Garcia-López, Amparo; Artero, Ruben; Wilsch-Braeuninger, Michaela; Ruiz-Gómez, Mar; Skaer, Helen; Denholm, Barry

2009-01-01

The nephron is the basic structural and functional unit of the vertebrate kidney. It is composed of a glomerulus, the site of ultrafiltration, and a renal tubule, along which the filtrate is modified. Although widely regarded as a vertebrate adaptation1 ‘nephron-like’ features can be found in the excretory systems of many invertebrates, raising the possibility that components of the vertebrate excretory system were inherited from their invertebrate ancestors2. Here we show that the insect nephrocyte has remarkable anatomical, molecular and functional similarity with the glomerular podocyte, a cell in the vertebrate kidney that forms the main size-selective barrier as blood is ultrafiltered to make urine. In particular, both cell types possess a specialised filtration diaphragm, known as the slit diaphragm in podocytes or the nephrocyte diaphragm in nephrocytes. We find that fly orthologues of the major constituents of the slit diaphragm, including nephrin, neph1, CD2AP, ZO-1 and podocin are expressed in the nephrocyte and form a complex of interacting proteins that closely mirrors the vertebrate slit diaphragm complex. Furthermore, we find the nephrocyte diaphragm is completely lost in flies mutant for nephrin or neph1 orthologues, a phenotype resembling loss of the slit diaphragm in the absence of either nephrin (as in the human kidney disease NPHS1) or neph1. These changes drastically impair filtration function in the nephrocyte. The similarities we describe between invertebrate nephrocytes and vertebrate podocytes provide evidence suggesting the two cell types are evolutionarily related and establish the nephrocyte as a simple model in which to study podocyte biology and podocyte-associated diseases. PMID:18971929

Hydrogen Rich Water Attenuates Renal Injury and Fibrosis by Regulation Transforming Growth Factor-β Induced Sirt1.

PubMed

Xing, Zhaoyu; Pan, Wanma; Zhang, Jing; Xu, Xianlin; Zhang, Xuemei; He, Xiaozhou; Fan, Min

2017-01-01

The current research was designed to study the role of hydrogen in renal fibrosis and the renal epithelial to mesenchymal transition (EMT) induced by transforming growth factor-β1 (TGF-β1). Hydrogen rich water (HW) was used to treat animal and cell models. Unilateral ureteral obstruction (UUO) was performed on Balb/c mice to create a model of renal fibrosis. Human kidney proximal tubular epithelial cells (HK-2 cells) were treated with TGF-β1 for 36 h to induce EMT. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured to test renal function, in addition, kidney histology and immunohistochemical staining of alpha-smooth muscle actin (α-SMA) positive cells was performed to examine the morphological changes. The treatment with UUO induced a robust fibrosis of renal interstitium, shrink of glomerulus and partial fracture of basement membrane. Renal function was also impaired in the experimental group with UUO, with an increase of Scr and BUN in serum. After that, Western-blot was performed to examine the expression of α-SMA, fibronectin, E-cadherin, Smad2 and Sirtuin-1 (Sirt1). The treatment with HW attenuated the development of fibrosis and deterioration of renal function in UUO model. In HK-2 cells, the pretreatment of HW abolished EMT induced by TGF-β1. The down-regulation the expression of Sirt1 induced by TGF-β1 which was dampened by the treatment with HW. Sirtinol, a Sirt1 inhibitor, reversed the effect of HW on EMT induced by TGF-β1. HW can inhibit the development of fibrosis in kidney and prevents HK-2 cells from undergoing EMT which is mediated through Sirt1, a downstream molecule of TGF-β1.

Close relations between podocyte injuries and membranous proliferative glomerulonephritis in autoimmune murine models.

PubMed

Kimura, Junpei; Ichii, Osamu; Otsuka, Saori; Sasaki, Hayato; Hashimoto, Yoshiharu; Kon, Yasuhiro

2013-01-01

Membranous proliferative glomerulonephritis (MPGN) is a major primary cause of chronic kidney disease (CKD). Podocyte injury is crucial in the pathogenesis of glomerular disease with proteinuria, leading to CKD. To assess podocyte injuries in MPGN, the pathological features of spontaneous murine models were analyzed. The autoimmune-prone mice strains BXSB/MpJ-Yaa and B6.MRL-(D1Mit202-D1Mit403) were used as the MPGN models, and BXSB/MpJ-Yaa(+) and C57BL/6 were used as the respective controls. In addition to clinical parameters and glomerular histopathology, the protein and mRNA levels of podocyte functional markers were evaluated as indices for podocyte injuries. The relation between MPGN pathology and podocyte injuries was analyzed by statistical correlation. Both models developed MPGN with albuminuria and elevated serum anti-double-strand DNA (dsDNA) antibody levels. BXSB/MpJ-Yaa and B6.MRL showed severe proliferative lesions with T and B cell infiltrations and membranous lesions with T cell infiltrations, respectively. Foot process effacement and microvillus-like structure formation were observed ultrastructurally in the podocytes of both MPGN models. Furthermore, both MPGN models showed a decrease in immune-positive areas of nephrin, podocin and synaptopodin in the glomerulus, and in the mRNA expression of Nphs1, Nphs2, Synpo, Actn4, Cd2ap, and Podxl in the isolated glomerulus. Significant negative correlations were detected between serum anti-dsDNA antibody levels and glomerular Nphs1 expression, and between urinary albumin-to-creatinine ratio and glomerular expression of Nphs1, Synpo, Actn4, Cd2ap, or Podxl. MPGN models clearly developed podocyte injuries characterized by the decreased expression of podocyte functional markers with altered morphology. These data emphasized the importance of regulation of podocyte injuries in MPGN. Copyright © 2013 S. Karger AG, Basel.

Stage-Specific Action of Matrix Metalloproteinases Influences Progressive Hereditary Kidney Disease

PubMed Central

Zeisberg, Michael; Khurana, Mona; Rao, Velidi H; Cosgrove, Dominic; Rougier, Jean-Philippe; Werner, Michelle C; Shield, Charles F; Werb, Zena; Kalluri, Raghu

2006-01-01

Background Glomerular basement membrane (GBM), a key component of the blood-filtration apparatus in the in the kidney, is formed through assembly of type IV collagen with laminins, nidogen, and sulfated proteoglycans. Mutations or deletions involving α3(IV), α4(IV), or α5(IV) chains of type IV collagen in the GBM have been identified as the cause for Alport syndrome in humans, a progressive hereditary kidney disease associated with deafness. The pathological mechanisms by which such mutations lead to eventual kidney failure are not completely understood. Methods and Findings We showed that increased susceptibility of defective human Alport GBM to proteolytic degradation is mediated by three different matrix metalloproteinases (MMPs)—MMP-2, MMP-3, and MMP-9—which influence the progression of renal dysfunction in α3(IV) −/− mice, a model for human Alport syndrome. Genetic ablation of either MMP-2 or MMP-9, or both MMP-2 and MMP-9, led to compensatory up-regulation of other MMPs in the kidney glomerulus. Pharmacological ablation of enzymatic activity associated with multiple GBM-degrading MMPs, before the onset of proteinuria or GBM structural defects in the α3(IV) −/− mice, led to significant attenuation in disease progression associated with delayed proteinuria and marked extension in survival. In contrast, inhibition of MMPs after induction of proteinuria led to acceleration of disease associated with extensive interstitial fibrosis and early death of α3(IV) −/− mice. Conclusions These results suggest that preserving GBM/extracellular matrix integrity before the onset of proteinuria leads to significant disease protection, but if this window of opportunity is lost, MMP-inhibition at the later stages of Alport disease leads to accelerated glomerular and interstitial fibrosis. Our findings identify a crucial dual role for MMPs in the progression of Alport disease in α3(IV) −/− mice, with an early pathogenic function and a later protective action. Hence, we propose possible use of MMP-inhibitors as disease-preventive drugs for patients with Alport syndrome with identified genetic defects, before the onset of proteinuria. PMID:16509766

Sub-chronic 90-day toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Yanli

Neamine, an inhibitor of angiogenin (ANG), is a new investigative anticancer drug currently in preclinical stage. Here we report the 90-day sub-chronic toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo. Neamine has a No Observed Adverse Effect Level (NOAEL) of 12 and 16 mg·kg{sup −1}·d{sup −1} for female and male rats, respectively. No mortality was found. The adverse effects included increased organ coefficients of spleen and kidney, increased BUN in both female and male rats at high dose, increased CR and decreased organ coefficients of heart and liver in male rats atmore » high dose. All of which, except the kidney coefficient and BUN in males, returned to normal levels after 28-day recovery. Histopathological examination revealed vacuolar degeneration of glomerulus, degeneration of renal tubules and cast in the kidneys, which were also recovered except in males of high-dosing group. These results indicate that kidney is the most susceptible organ for neamine toxicity. Tissue microarray analysis validated that ANG is up-regulated in hepatocellular carcinoma accompanied by increased nuclear translocation, suggesting that ANG is a possible target for drug development in liver cancer treatment. Neamine blocked nuclear translocation of ANG in HUVEC and HepG2 cells, and inhibited ANG-stimulated cell proliferation without affecting basal level cell proliferation. Neamine also inhibited progression of HepG2 xenografts in athymic mice accompanied by decreased angiogenesis and cancer cell proliferation. These results suggest that neamine is a specific ANG inhibitor with low toxicity and high anti-liver cancer efficacy. - Highlights: • The NOAEL of neamine is 12 mg·kg{sup −1}·d{sup −1} for females and 16 mg·kg{sup −}1·d{sup −1} for males. • The most susceptible organ for neamine toxicity is kidney. • Neamine inhibits the progression of xenograft HepG2 liver cancer in athymic mice.« less

A nephron-based model of the kidneys for macro-to-micro α-particle dosimetry

NASA Astrophysics Data System (ADS)

Hobbs, Robert F.; Song, Hong; Huso, David L.; Sundel, Margaret H.; Sgouros, George

2012-07-01

Targeted α-particle therapy is a promising treatment modality for cancer. Due to the short path-length of α-particles, the potential efficacy and toxicity of these agents is best evaluated by microscale dosimetry calculations instead of whole-organ, absorbed fraction-based dosimetry. Yet time-integrated activity (TIA), the necessary input for dosimetry, can still only be quantified reliably at the organ or macroscopic level. We describe a nephron- and cellular-based kidney dosimetry model for α-particle radiopharmaceutical therapy, more suited to the short range and high linear energy transfer of α-particle emitters, which takes as input kidney or cortex TIA and through a macro to micro model-based methodology assigns TIA to micro-level kidney substructures. We apply a geometrical model to provide nephron-level S-values for a range of isotopes allowing for pre-clinical and clinical applications according to the medical internal radiation dosimetry (MIRD) schema. We assume that the relationship between whole-organ TIA and TIA apportioned to microscale substructures as measured in an appropriate pre-clinical mammalian model also applies to the human. In both, the pre-clinical and the human model, microscale substructures are described as a collection of simple geometrical shapes akin to those used in the Cristy-Eckerman phantoms for normal organs. Anatomical parameters are taken from the literature for a human model, while murine parameters are measured ex vivo. The murine histological slides also provide the data for volume of occupancy of the different compartments of the nephron in the kidney: glomerulus versus proximal tubule versus distal tubule. Monte Carlo simulations are run with activity placed in the different nephron compartments for several α-particle emitters currently under investigation in radiopharmaceutical therapy. The S-values were calculated for the α-emitters and their descendants between the different nephron compartments for both the human and murine models. The renal cortex and medulla S-values were also calculated and the results compared to traditional absorbed fraction calculations. The nephron model enables a more optimal implementation of treatment and is a critical step in understanding toxicity for human translation of targeted α-particle therapy. The S-values established here will enable a MIRD-type application of α-particle dosimetry for α-emitters, i.e. measuring the TIA in the kidney (or renal cortex) will provide meaningful and accurate nephron-level dosimetry.

Developmental Localization of Nephrin in Zebrafish and Medaka Pronephric Glomerulus

PubMed Central

Ichimura, Koichiro; Fukuyo, Yayoi; Nakamura, Tomomi; Powell, Rebecca; Sakai, Tatsuo; Janknecht, Ralf

2013-01-01

Slit diaphragm (SD) is a highly specialized intercellular junction between podocyte foot processes and plays a crucial role in the formation of the filtration barrier. In this study, we examined the developmental localization of Nephrin, an essential component of SD, in the pronephric glomerulus of zebrafish and medaka. In the mature glomerulus of both fish, Nephrin is localized along the glomerular basement membrane as seen in mammals, indicating that Nephrin is localized at the SD. Interestingly, Nephrin was detected already in immature podocytes before the SD and foot processes started to form in both fish. Nephrin was localized along the cell surface of immature podocytes but as different localization patterns. In zebrafish, Nephrin signal bordered the lateral membrane of podocytes, which were columnar in shape, as in rat immature podocytes. However, in medaka immature podocytes, Nephrin was localized in a punctate pattern among podocyte cell bodies. These findings suggest that Nephrin needs to be integrated to the membrane before the formation of the SD and then moves to the proper site to form the SD. Furthermore, a podocyte-specific marker, such as Nephrin, should be a useful tool for the future analysis of pronephric glomerular development in fish mutants and morphants. PMID:23324868

Integrated β-catenin, BMP, PTEN, and Notch signalling patterns the nephron

PubMed Central

Lindström, Nils O; Lawrence, Melanie L; Burn, Sally F; Johansson, Jeanette A; Bakker, Elvira RM; Ridgway, Rachel A; Chang, C-Hong; Karolak, Michele J; Oxburgh, Leif; Headon, Denis J; Sansom, Owen J; Smits, Ron; Davies, Jamie A; Hohenstein, Peter

2015-01-01

The different segments of the nephron and glomerulus in the kidney balance the processes of water homeostasis, solute recovery, blood filtration, and metabolite excretion. When segment function is disrupted, a range of pathological features are presented. Little is known about nephron patterning during embryogenesis. In this study, we demonstrate that the early nephron is patterned by a gradient in β-catenin activity along the axis of the nephron tubule. By modifying β-catenin activity, we force cells within nephrons to differentiate according to the imposed β-catenin activity level, thereby causing spatial shifts in nephron segments. The β-catenin signalling gradient interacts with the BMP pathway which, through PTEN/PI3K/AKT signalling, antagonises β-catenin activity and promotes segment identities associated with low β-catenin activity. β-catenin activity and PI3K signalling also integrate with Notch signalling to control segmentation: modulating β-catenin activity or PI3K rescues segment identities normally lost by inhibition of Notch. Our data therefore identifies a molecular network for nephron patterning. DOI: http://dx.doi.org/10.7554/eLife.04000.001 PMID:25647637

Epithelial-to-Mesenchymal Transition in Diabetic Nephropathy: Fact or Fiction?

PubMed

Loeffler, Ivonne; Wolf, Gunter

2015-10-09

The pathophysiology of diabetic nephropathy (DN), one of the most serious complications in diabetic patients and the leading cause of end-stage renal disease worldwide, is complex and not fully elucidated. A typical hallmark of DN is the excessive deposition of extracellular matrix (ECM) proteins in the glomerulus and in the renal tubulointerstitium, eventually leading to glomerulosclerosis and interstitial fibrosis. Although it is obvious that myofibroblasts play a major role in the synthesis and secretion of ECM, the origin of myofibroblasts in DN remains the subject of controversial debates. A number of studies have focused on epithelial-to-mesenchymal transition (EMT) as one source of matrix-generating fibroblasts in the diseased kidney. EMT is characterized by the acquisition of mesenchymal properties by epithelial cells, preferentially proximal tubular cells and podocytes. In this review we comprehensively review the literature and discuss arguments both for and against a function of EMT in renal fibrosis in DN. While the precise extent of the contribution to nephrotic fibrosis is certainly arduous to quantify, the picture that emerges from this extensive body of literature suggests EMT as a major source of myofibroblasts in DN.

The modulatory effect of Moringa oleifera leaf extract on endogenous antioxidant systems and inflammatory markers in an acetaminophen-induced nephrotoxic mice model

PubMed Central

Karthivashan, Govindarajan; Kura, Aminu Umar; Arulselvan, Palanisamy; Md. Isa, Norhaszalina

2016-01-01

N-Acetyl-p-Aminophenol (APAP), also known as acetaminophen, is the most commonly used over-the counter analgesic and antipyretic medication. However, its overdose leads to both liver and kidney damage. APAP-induced toxicity is considered as one of the primary causes of acute liver failure; numerous scientific reports have focused majorly on APAP hepatotoxicity. Alternatively, not many works approach APAP nephrotoxicity focusing on both its mechanisms of action and therapeutic exploration. Moringa oleifera (MO) is pervasive in nature, is reported to possess a surplus amount of nutrients, and is enriched with several bioactive candidates including trace elements that act as curatives for various clinical conditions. In this study, we evaluated the nephro-protective potential of MO leaf extract against APAP nephrotoxicity in male Balb/c mice. A single-dose acute oral toxicity design was implemented in this study. Group 2, 3, 4 and 5 received a toxic dose of APAP (400 mg/kg of bw, i.p) and after an hour, these groups were administered with saline (10 mL/kg), silymarin—positive control (100 mg/kg of bw, i.p), MO leaf extract (100 mg/kg of bw, i.p), and MO leaf extract (200 mg/kg bw, i.p) respectively. Group 1 was administered saline (10 mL/kg) during both the sessions. APAP-treated mice exhibited a significant elevation of serum creatinine, blood urea nitrogen, sodium, potassium and chloride levels. A remarkable depletion of antioxidant enzymes such as SOD, CAT and GSH-Px with elevated MDA levels has been observed in APAP treated kidney tissues. They also exhibited a significant rise in pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and decreased anti-inflammatory (IL-10) cytokine level in the kidney tissues. Disorganized glomerulus and dilated tubules with inflammatory cell infiltration were clearly observed in the histology of APAP treated mice kidneys. All these pathological changes were reversed in a dose-dependent manner after MO leaf extract treatment. Therefore, MO leaf extract has demonstrated some therapeutic effectiveness against APAP-induced nephrotoxicity through enhancement of the endogenous antioxidant system and a modulatory effect on specific inflammatory cytokines in kidney tissues. PMID:27441110

Effect of alterations in glomerular charge on deposition of cationic and anionic antibodies to fixed glomerular antigens in the rat.

PubMed

Adler, S; Baker, P; Pritzl, P; Couser, W G

1985-07-01

Reduction of the negative charge of the glomerular capillary wall alters its charge- and size-selective properties. To investigate the effect of alteration in glomerular charge properties on antibody localization, we prepared cationic and anionic fractions of antibodies to subepithelial and glomerular basement membrane (GBM) antigens, and compared their deposition in normal rats and rats treated with protamine sulfate or aminonucleoside of puromycin to reduce capillary wall charge. IgG antibodies were eluted from kidneys of rats with active Heymann's nephritis (AICN), passive Heymann's nephritis (PHN), or anti-GBM nephritis (NTN), separated into cationic and anionic fractions, and radiolabeled with iodine 125 or iodine 131. Relative antibody content of each fraction was determined by incubation with an excess of glomerular antigen. Varying amounts of cationic and anionic IgG eluted from kidneys of rats with AICN or PHN were injected into 24 normal or protamine sulfate-treated rats. Glomerular binding of all antibodies was highly correlated with IgG delivery to the kidney. The ratio of cationic to anionic antibody deposited in the glomeruli of normal rats after 4 hours was 1.08 +/- 0.07 for AICN eluate and 0.37 +/- 0.04 for PHN eluate. The ratios were not significantly different in animals pretreated with protamine sulfate (1.15 +/- 0.06 and 0.44 +/- 0.06, respectively; P greater than 0.05). Varying amounts of cationic and anionic IgG eluted from kidneys of rats with NTN were injected into 10 normal rats and four rats treated with aminonucleoside of puromycin. Glomerular binding of antibody was again highly correlated with IgG delivery to the kidney. The ratio of cationic to anionic antibody deposited in the glomeruli of normal rats after 1 hour was 1.03 +/- 0.06, and was not significantly altered in rats treated with aminonucleoside of puromycin (1.05 +/- 0.03, P greater than 0.5). Proteinuria in PHN rats was also unaffected by treatment with protamine sulfate for 5 days (controls: 68 +/- 21 mg/day; protamine sulfate-treated: 65 +/- 14 mg/day; n = 25, P greater than 0.08). These results demonstrate that treatment to reduce glomerular polyanion does not significantly alter the ratio of cationic to anionic antibodies to fixed glomerular antigens that deposit in the glomerulus, or reduce proteinuria caused by deposition of antibody to a fixed subepithelial antigen.

Morphology of the kidney of adult bowfin, Amia calva, with emphasis on "renal chloride cells" in the tubule.

PubMed

Youson, J H; Butler, D G

1988-05-01

The nephron of adult bowfin, Amia calva, was described using light and electron microscopic techniques. The kidney of the bowfin possesses an abundant supply of renal corpuscles with each consisting of a glomerulus and a Bowman's capsule of visceral (podocyte) and parietal layers. No juxtaglomerular apparatus is present. The epithelium of the tubule is continuous with the parietal epithelium and is divisible in descending order into neck, first proximal, second proximal, first distal, second distal, and collecting segments. The tubules drain into a complex system of collecting ducts that ultimately unite with the main excretory duct, the archinephric duct. Mucous cells are the dominant cell throughout the entire ductular system. Nephrostomes are dispersed along the kidney capsule. The neck segment has a ciliated epithelium, and while both proximal segments possess a prominent brush border, the fine structure of the first implies involvement in protein absorption and the second in the transport and reabsorption of solutes. The cells of the first distal segment are characterized by deep infolding of the plasma membrane and a rich supply of mitochondria suggesting the presence of a mechanism for ion transport. The second distal segment is composed of cells resembling the chloride cells of fishes and these cells are present in progressively decreasing numbers in the collecting segment and duct system so that only a few are present in the epithelium of the archinephric duct. The "renal chloride cells" possess an abundant network of smooth tubules and numerous mitochondria with a rich supply of cristae. Glycogen is also a conspicuous component of these cells. The presence of "renal chloride cells" in this freshwater holostean, in other relatively primitive freshwater teleosts, and in larval and adult lampreys is discussed with reference to both phylogeny and the need for a special mechanism for renal ion conservation through absorption.

Puerarin attenuates cisplatin-induced rat nephrotoxicity: The involvement of TLR4/NF-κB signaling pathway

PubMed Central

Ma, Xu; Yan, Lei; Zhu, Qing; Shao, Fengmin

2017-01-01

Puerarin was a major isoflavonoid derived from the Chinese medical herb radix puerariae (Gegen). In present study effect of puerarin on cisplatin nephrotoxicity was evaluated. Rat model of nephrotoxicity was established by a single intraperitoneal injection of cisplatin (7mg/kg). Puerarin was administrated through caudal vein injection once per day at the dose of 10mg/kg, 30mg/kg and 50mg/kg. Biochemical assays showed that after cisplatin treatment the serum urea and creatinine increased significantly compared with control (P<0.05). Cisplatin treatment significantly increased xanthine oxidase (XO) activity and malondialdehyde (MDA) formation, and significantly decreased the levels and /or activities of enzymatic and non-enzymatic antioxidants (GSH, GPx, GST, GR, SOD, CAT), in the kidney tissues. Renal levels of TNF-α and IL-6, two important inflammatory cytokines, were also upregulated by cisplatin. Histopathological examination indicated that cisplatin treatment resulted in severe necrosis and degeneration, hyaline casts in the tubules, intertubular hemorrhage, congestion and swelling in glomerulus and leukocytes infiltration in the kidney tissues. Western blot results demonstrated that cisplatin increased TLR4 and NF-κB protein expression in the kidney tissues. However, all these changes induced by cisplatin were significantly attenuated by puerarin treatment in dose-dependent manner, which indicated the renal protective effect of puerarin. Cell culture experiments illustrated that puerarin alone treatment concentration-dependently inhibited COLO205 and HeLa tumor cell growth and dose-dependently promoted the antitumor activity of cisplatin in COLO205 and HeLa tumor cells. The promotion effects might be attributed to suppression of cisplatin-increased NF-κB p65 expression by puerarin. Taken together, findings in this study suggested that puerarin exhibited renal protection against cisplatin nephrotoxicity via inhibiting TLR4/NF-κB signaling, with no inhibition but promotion effect on the antitumor activity of cisplatin. Puerarin might be a promising adjuvant agent for cisplatin chemotherapy. PMID:28182789

Attenuation of the activated mammalian target of rapamycin pathway might be associated with renal function reserve by a low-protein diet in the rat remnant kidney model.

PubMed

Ohkawa, Sakae; Yanagida, Momoko; Uchikawa, Tsuyoshi; Yoshida, Takuya; Ikegaya, Naoki; Kumagai, Hiromichi

2013-09-01

The mammalian target of rapamycin (mTOR), a regulator of cellular protein synthesis and cell growth, plays an important role in the progression of renal hypertrophy and renal dysfunction in experimental chronic kidney disease models. Because the mTOR activity is regulated by nutrients including amino acids, we tested the hypothesis that the renoprotective effect of a low-protein diet (LPD) might be associated with the attenuation of the renal mTOR pathway. In this study, 5/6 nephrectomized rats were fed an LPD or a normal protein diet (NPD), and a number of rats that were fed an NPD received rapamycin (1.0 mg kg⁻¹ d⁻¹), a specific inhibitor of mTOR. After 6 weeks, renal tissue was collected to evaluate the activity of the mTOR pathway and histologic changes. The phosphorylation of p70S6k, a kinase in the downstream of mTOR, was significantly higher in the NPD-fed rats that showed progressive renal dysfunction than in the sham-operated rats (NPD). The LPD attenuated the excessive phosphorylation of p70S6k concomitant with reduced proteinuria and improved renal histologic changes in the 5/6 nephrectomized rats. The effects of the LPD were similar to the effects of rapamycin. The expression of phosphorylated p70S6k was significantly correlated with proteinuria (r² = 0.63, P < .001), the glomerular area (r² = 0.60, P < .001), and the number of phosphorylated Smad2-positive cells in the glomerulus (r² = 0.26, P < .05) of these rats. These results suggest that the preventive effect of an LPD on the progression of renal failure is associated with attenuation of the activated mTOR/p70S6k pathway in the rat remnant kidney model. © 2013.

A SAGE based approach to human glomerular endothelium: defining the transcriptome, finding a novel molecule and highlighting endothelial diversity.

PubMed

Sengoelge, Guerkan; Winnicki, Wolfgang; Kupczok, Anne; von Haeseler, Arndt; Schuster, Michael; Pfaller, Walter; Jennings, Paul; Weltermann, Ansgar; Blake, Sophia; Sunder-Plassmann, Gere

2014-08-27

Large scale transcript analysis of human glomerular microvascular endothelial cells (HGMEC) has never been accomplished. We designed this study to define the transcriptome of HGMEC and facilitate a better characterization of these endothelial cells with unique features. Serial analysis of gene expression (SAGE) was used for its unbiased approach to quantitative acquisition of transcripts. We generated a HGMEC SAGE library consisting of 68,987 transcript tags. Then taking advantage of large public databases and advanced bioinformatics we compared the HGMEC SAGE library with a SAGE library of non-cultured ex vivo human glomeruli (44,334 tags) which contained endothelial cells. The 823 tags common to both which would have the potential to be expressed in vivo were subsequently checked against 822,008 tags from 16 non-glomerular endothelial SAGE libraries. This resulted in 268 transcript tags differentially overexpressed in HGMEC compared to non-glomerular endothelia. These tags were filtered using a set of criteria: never before shown in kidney or any type of endothelial cell, absent in all nephron regions except the glomerulus, more highly expressed than statistically expected in HGMEC. Neurogranin, a direct target of thyroid hormone action which had been thought to be brain specific and never shown in endothelial cells before, fulfilled these criteria. Its expression in glomerular endothelium in vitro and in vivo was then verified by real-time-PCR, sequencing and immunohistochemistry. Our results represent an extensive molecular characterization of HGMEC beyond a mere database, underline the endothelial heterogeneity, and propose neurogranin as a potential link in the kidney-thyroid axis.

Mild zinc deficiency in male and female rats: early postnatal alterations in renal nitric oxide system and morphology.

PubMed

Tomat, Analia Lorena; Veiras, Luciana Cecilia; Aguirre, Sofía; Fasoli, Héctor; Elesgaray, Rosana; Caniffi, Carolina; Costa, María Ángeles; Arranz, Cristina Teresa

2013-03-01

Fetal and postnatal zinc deficiencies induce an increase in arterial blood pressure and impair renal function in male adult rats. We therefore hypothesized that these renal alterations are present in early stages of life and that there are sexual differences in the adaptations to this nutritional injury. The aim was to study the effects of moderate zinc deficiency during fetal life and lactation on renal morphology, oxidative stress, apoptosis, and the nitric oxide system in male and female rats at 21 d of life. Female Wistar rats received low (8 ppm) or control (30 ppm) zinc diets from the beginning of pregnancy to weaning. Glomerulus number, morphology, oxidative stress, apoptotic cells, nitric oxide synthase activity, and protein expression were evaluated in the kidneys of offspring at 21 d. Zinc deficiency decreased the nephron number, induced glomerular hypertrophy, increased oxidative damage, and decreased nitric oxide synthase activity in the male and female rat kidneys. Nitric oxide synthase activity was not affected by inhibitors of the neuronal or inducible isoforms, so nitric oxide was mainly generated by the endothelial isoenzyme. Gender differences were observed in glomerular areas and antioxidant enzyme activities. Zinc deficiency during fetal life and lactation induces an early decrease in renal functional units, associated with a decrease in nitric oxide activity and an increase in oxidative stress, which would contribute to increased arterial blood pressure and renal dysfunction in adulthood. The sexual differences observed in this model may explain the dissimilar development of hypertension and renal diseases in adult life. Copyright © 2013 Elsevier Inc. All rights reserved.

Prenatal and Early Postnatal Odorant Exposure Heightens Odor-Evoked Mitral Cell Responses in the Mouse Olfactory Bulb

PubMed Central

2017-01-01

Abstract Early sensory experience shapes the anatomy and function of sensory circuits. In the mouse olfactory bulb (OB), prenatal and early postnatal odorant exposure through odorized food (food/odorant pairing) not only increases the volume of activated glomeruli but also increases the number of mitral and tufted cells (M/TCs) connected to activated glomeruli. Given the importance of M/TCs in OB output and in mediating lateral inhibitory networks, increasing the number of M/TCs connected to a single glomerulus may significantly change odorant representation by increasing the total output of that glomerulus and/or by increasing the strength of lateral inhibition mediated by cells connected to the affected glomerulus. Here, we seek to understand the functional impact of this long-term odorant exposure paradigm on the population activity of mitral cells (MCs). We use viral expression of GCaMP6s to examine odor-evoked responses of MCs following prenatal and early postnatal odorant exposure to two dissimilar odorants, methyl salicylate (MS) and hexanal, which are both strong activators of glomeruli on the dorsal OB surface. Previous work suggests that odor familiarity may decrease odor-evoked MC response in rodents. However, we find that early food-based odorant exposure significantly changes MC responses in an unexpected way, resulting in broad increases in the amplitude, number, and reliability of excitatory MC responses across the dorsal OB. PMID:28955723

The mesangial matrix in the normal and sclerotic glomerulus.

PubMed

Rosenblum, N D

1994-02-01

Mesangial sclerosis is a final common pathway to glomerular destruction in a variety of glomerular diseases. The expression of several classes of extracellular matrix (ECM) molecules has been defined in the normal and diseased mesangial matrix (MM). However, the manner in which these ECM components determine the three dimensional structure and function of the MM remains to be defined. Structural studies of the MM suggest that its constituent molecules are regionally organized into subcompartments with different three dimensional structures. The diversity of matrix molecules expressed within the MM as well as the organization of these components in nonrenal ECM's, such as the cornea, provides further support for this organizational model. The study of the cornea has also revealed that novel short chain collagenous proteins partially determine the three dimensional structure of the matrix. Recently, a novel collagen, type VIII collagen, has been described in mesangial cells and in the intact glomerulus. It is hypothesized that type VIII collagen is expressed both as a polymer and as a monomer within the glomerulus, and depending on its conformation, may serve unique functions. In the chronically diseased MM, normal MM components are overexpressed and fibrillar collagens are expressed de novo in a delayed fashion. Enhanced proteoglycan expression, observed early in disease, may determine increased volume of the mesangium. This, in turn, may stimulate the production of fibrillar collagens by mesangial cells resulting in a fibrillar noncompliant mesangial matrix.

Neuronal proteins are novel components of podocyte major processes and their expression in glomerular crescents supports their role in crescent formation.

PubMed

Sistani, Laleh; Rodriguez, Patricia Q; Hultenby, Kjell; Uhlen, Mathias; Betsholtz, Christer; Jalanko, Hannu; Tryggvason, Karl; Wernerson, Annika; Patrakka, Jaakko

2013-01-01

The podocyte has a central role in the glomerular filtration barrier typified by a sophisticated morphology of highly organized primary (major) and secondary (foot) processes. The molecular makeup of foot processes is well characterized, but that of major processes is poorly known. Previously, we profiled the glomerular transcriptome through large-scale sequencing and microarray profiling. Unexpectedly, the survey found expression of three neuronal proteins (Huntingtin interacting protein 1 (Hip1), neurofascin (Nfasc), and olfactomedin-like 2a (Olfml2a)), all enriched in the glomerulus. These proteins were expressed exclusively by podocytes, wherein they localized to major processes as verified by RT-PCR, western blotting, immunofluorescence, and immunoelectron microscopy. During podocyte development, these proteins colocalized with vimentin, confirming their association with major processes. Using immunohistochemistry, we found coexpression of Hip1 and Olfml2a along with the recognized podocyte markers synaptopodin and Pdlim2 in glomerular crescents of human kidneys, indicating the presence of podocytes in these lesions. Thus, three neuronal proteins are highly expressed in podocyte major process. Using these new markers we found that podocytes contribute to the formation of glomerular crescents.

Two distinct clinical courses of renal involvement in rheumatoid patients with AA amyloidosis.

PubMed

Uda, Hiroshi; Yokota, Akira; Kobayashi, Kumiko; Miyake, Tadao; Fushimi, Hiroaki; Maeda, Akira; Saiki, Osamu

2006-08-01

We conducted a prospective study to investigate whether a correlation exists between the clinical course of renal involvement and the pathological findings of renal amyloidosis in patients with rheumatoid arthritis (RA). Patients with RA of more than 5 years' duration and who did not show renal manifestations were selected and received a duodenal biopsy for the diagnosis of amyloidosis. After the diagnosis of AA amyloidosis, patients received a renal biopsy, and patterns of amyloid deposition were examined. We followed the renal functions (serum levels of blood urea nitrogen and creatinine) of patients diagnosed with AA amyloidosis for 5 years. We diagnosed 53 patients with AA amyloidosis and monitored the renal function of 38 of them for > 5 years. The histological patterns were examined; in the 38 patients there were appreciable variations in the patterns of amyloid deposition. In 27 patients, amyloid deposits were found exclusively in the glomerulus (type 1). In the other 11 patients, however, amyloid deposits were found selectively around blood vessels and were totally absent in the glomerulus (type 2). In type 1 patients with glomerular involvement, renal function deteriorated rapidly regardless of disease state; most patients received hemodialysis. In type 2 patients with purely vascular involvement, however, renal function did not deteriorate significantly. In patients with RA and AA amyloidosis, 2 distinct clinical courses in terms of renal involvement were identified. It is suggested that renal function does not deteriorate when amyloid deposition is totally lacking in the glomerulus.

Histopathological changes of renal tissue following sodium fluoride administration in two consecutive generations of mice. Correlation with the urinary elimination of fluoride.

PubMed

Dimcevici Poesina, Nicoleta; Bălălău, Cristian; Nimigean, Vanda Roxana; Nimigean, Victor; Ion, Ion; Baconi, Daniela; Bârcă, Maria; Băran Poesina, Violeta

2014-01-01

The present study was designed to investigate the toxic effects (evaluated as histopathological changes) of sodium fluoride on the kidney in two consecutive generations of NMRI mice. An attempt to correlate the toxicity with the urinary elimination of fluoride has been made, as urinary fluoride excretion has been widely used as an indicator of fluoride intake and exposure. Six mixed (males and females) animal groups have been constituted by dividing the populations of mice derived from pregnant females (named "mothers" 0.5 mg sodium fluoride) treated with 0.5 mg sodium fluoride by daily gavage and pregnant females (named "mothers" 0.25 mg sodium fluoride) treated with 0.25 mg sodium fluoride by daily gavage; three types of sodium fluoride treatments were administrated: homeopathic, allopathic-homeopathic and allopathic. When the animals reached the adulthood, by randomization, they were selected in pairs for giving birth to the second generation of mice. No treatments were administrated to the second generation of mice; thus, the urinary elimination of fluoride in the second generation is attributed to exposure at sodium fluoride before birth. The administration of sodium fluoride to the first generation (F1) is realized until the mice reached the adulthood. For the first generation, the urine was collected at three times, every three weeks: at the age of four weeks, seven weeks and 11 weeks; single sampling urine, at the age of four weeks, has been conducted for the second generation. The urine samples have been analyzed using the ion selective electrode method for fluoride. For the histopathological examination, the animals were killed by cervical dislocation; the kidneys were collected in a 10% formalin solution. The preparation of samples for optical microscopy was realized with Hematoxylin-Eosin staining. The results indicate that the elimination of fluoride was similar (at the second evaluation, at 7-week-old of the first generation) for the both generations of mice. Histopathological observation of the kidney has revealed granular dystrophy of the renal tubules, necrosis of the endothelial cells and of the mesangial cells of renal glomerulus. The study indicates that different sodium fluoride treatments produce some pathological aspects of the kidneys and influence the urinary elimination of fluoride in two consecutive generations of mice. For the higher doses, the pathological changes of the kidney are more important, and the urinary elimination of fluoride is higher, especially for the allopathic doses.

Aortic stenosis concomitant with microscopic polyangiitis: a challenge in medical reasoning and thinking.

PubMed

Gutierrez, Paulo Sampaio; Aiello, Vera Demarchi

2014-01-01

Microscopic polyangiitis (MPA) is part of the anti-neutrophil cytoplasmic antibodies (ANCA)-related vasculitis, which usually presents as renal pulmonary syndrome. It is defined as a pauci-immune necrotizing small vessel vasculitis, which usually affects the kidneys, followed by the lungs. It also presents systemic symptoms. The etiology of MPA is still unclear, but evidence reinforces the autoimmune mechanisms as the main etiopathogenic factor. Aortic valve stenosis (AS) is not an uncommon disease whose etiology varies according to geographical differences and the patient's age. The natural history of AS begins with a prolonged asymptomatic period, but when symptomatic, respiratory failure is one of its main clinical presentations. The authors present the case of a 55-year-old woman who was admitted with the diagnosis of renal failure, anemia, and a cardiac murmur. The patient had been recently diagnosed with pneumonia. During hospitalization, diagnostic workup disclosed a normal kidney size as well as parenchymal thickness. A renal biopsy was undertaken but the specimen was exiguous, showing 4 sclerotic glomeruli and 1 glomerulus with crescentic glomerulonephritis. The search for ANCA was positive. The investigation of the cardiac murmur disclosed AS. The patient, on hemodialysis, presented episodes of respiratory failure, which was interpreted as acute pulmonary edema, but a suspicion of ANCA-related pulmonary renal syndrome was raised. However, the aortic valve replacement was prioritized. While awaiting cardiac surgery, the patient died because of respiratory insufficiency. Autopsy findings concluded that MPA with pulmonary hemorrhage due to vasculitis was the immediate cause of death. Although AS was present at autopsy and classified as moderate/severe, this lesion was a bystander in the process of this patient's end of life, demonstrating the value of autopsy for medical learning and reasoning purposes.

Aortic stenosis concomitant with microscopic polyangiitis: a challenge in medical reasoning and thinking

PubMed Central

Aiello, Vera Demarchi

2014-01-01

Microscopic polyangiitis (MPA) is part of the anti-neutrophil cytoplasmic antibodies (ANCA)-related vasculitis, which usually presents as renal pulmonary syndrome. It is defined as a pauci-immune necrotizing small vessel vasculitis, which usually affects the kidneys, followed by the lungs. It also presents systemic symptoms. The etiology of MPA is still unclear, but evidence reinforces the autoimmune mechanisms as the main etiopathogenic factor. Aortic valve stenosis (AS) is not an uncommon disease whose etiology varies according to geographical differences and the patient’s age. The natural history of AS begins with a prolonged asymptomatic period, but when symptomatic, respiratory failure is one of its main clinical presentations. The authors present the case of a 55-year-old woman who was admitted with the diagnosis of renal failure, anemia, and a cardiac murmur. The patient had been recently diagnosed with pneumonia. During hospitalization, diagnostic workup disclosed a normal kidney size as well as parenchymal thickness. A renal biopsy was undertaken but the specimen was exiguous, showing 4 sclerotic glomeruli and 1 glomerulus with crescentic glomerulonephritis. The search for ANCA was positive. The investigation of the cardiac murmur disclosed AS. The patient, on hemodialysis, presented episodes of respiratory failure, which was interpreted as acute pulmonary edema, but a suspicion of ANCA-related pulmonary renal syndrome was raised. However, the aortic valve replacement was prioritized. While awaiting cardiac surgery, the patient died because of respiratory insufficiency. Autopsy findings concluded that MPA with pulmonary hemorrhage due to vasculitis was the immediate cause of death. Although AS was present at autopsy and classified as moderate/severe, this lesion was a bystander in the process of this patient’s end of life, demonstrating the value of autopsy for medical learning and reasoning purposes. PMID:28652987

Transcriptional profiling reveals progeroid Ercc1-/Δ mice as a model system for glomerular aging

PubMed Central

2013-01-01

Background Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome maintenance in the Ercc1-/Δ progeroid mouse model result in premature aging and typical age-related pathologies. Here, we compared the glomerular transcriptome of young and aged Ercc1-deficient mice to young and aged WT mice in order to establish a novel model for research of aging-related kidney disease. Results In a principal component analysis, age and genotype emerged as first and second principal components. Hierarchical clustering of all 521 genes differentially regulated between young and old WT and young and old Ercc1-/Δ mice showed cluster formation between young WT and Ercc1-/Δ as well as old WT and Ercc1-/Δ samples. An unexpectedly high number of 77 genes were differentially regulated in both WT and Ercc1-/Δ mice (p < 0.0001). GO term enrichment analysis revealed these genes to be involved in immune and inflammatory response, cell death, and chemotaxis. In a network analysis, these genes were part of insulin signaling, chemokine and cytokine signaling and extracellular matrix pathways. Conclusion Beyond insulin signaling, we find chemokine and cytokine signaling as well as modifiers of extracellular matrix composition to be subject to major changes in the aging glomerulus. At the level of the transcriptome, the pattern of gene activities is similar in the progeroid Ercc1-/Δ mouse model constituting a valuable tool for future studies of aging-associated glomerular pathologies. PMID:23947592

Transcriptional profiling reveals progeroid Ercc1(-/Δ) mice as a model system for glomerular aging.

PubMed

Schermer, Bernhard; Bartels, Valerie; Frommolt, Peter; Habermann, Bianca; Braun, Fabian; Schultze, Joachim L; Roodbergen, Marianne; Hoeijmakers, Jan Hj; Schumacher, Björn; Nürnberg, Peter; Dollé, Martijn Et; Benzing, Thomas; Müller, Roman-Ulrich; Kurschat, Christine E

2013-08-16

Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome maintenance in the Ercc1(-/Δ) progeroid mouse model result in premature aging and typical age-related pathologies. Here, we compared the glomerular transcriptome of young and aged Ercc1-deficient mice to young and aged WT mice in order to establish a novel model for research of aging-related kidney disease. In a principal component analysis, age and genotype emerged as first and second principal components. Hierarchical clustering of all 521 genes differentially regulated between young and old WT and young and old Ercc1(-/Δ) mice showed cluster formation between young WT and Ercc1(-/Δ) as well as old WT and Ercc1(-/Δ) samples. An unexpectedly high number of 77 genes were differentially regulated in both WT and Ercc1(-/Δ) mice (p < 0.0001). GO term enrichment analysis revealed these genes to be involved in immune and inflammatory response, cell death, and chemotaxis. In a network analysis, these genes were part of insulin signaling, chemokine and cytokine signaling and extracellular matrix pathways. Beyond insulin signaling, we find chemokine and cytokine signaling as well as modifiers of extracellular matrix composition to be subject to major changes in the aging glomerulus. At the level of the transcriptome, the pattern of gene activities is similar in the progeroid Ercc1(-/Δ) mouse model constituting a valuable tool for future studies of aging-associated glomerular pathologies.

Coexistence of Anti-Glomerular Basement Membrane Glomerulonephritis and Membranous Nephropathy in a Female Patient with Preserved Renal Function.

PubMed

Ogawara, Aoi; Harada, Makoto; Ichikawa, Tohru; Fujii, Kazuaki; Ehara, Takashi; Kobayashi, Mamoru

2017-12-01

Renal prognosis for anti-glomerular basement membrane (GBM) glomerulonephritis is poor. The greater the amount of anti-GBM antibody binding the antigen (type IV collagen of the glomerular basement membrane), the greater the number of crescents that develop in glomeruli, resulting in progression of renal impairment. Immunofluorescence staining reveals linear IgG depositions on glomerular capillary walls. Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in middle-aged to elderly patients. Immune complex is deposited in the sub-epithelial space of the glomerulus resulting in the development of a membranous lesion. Immunofluorescence staining reveals granular IgG depositions on glomerular capillary walls. Coexisting anti-GBM glomerulonephritis and MN are rare and, here we report a case of coexisting anti-GBM glomerulonephritis and MN with preserved renal function. There are some cases of coexisting anti-GBM glomerulonephritis and MN do not show severely decreased renal function. A 76-year-old Japanese woman presented with nephrotic syndrome, microscopic hematuria, and was positive for anti-GBM antibody. Kidney biopsy revealed linear and granular IgG depositions in glomerular capillary walls, crescent formations, and electron-dense deposits in the sub-epithelial space. She was diagnosed with anti-GBM glomerulonephritis and MN. Steroid and cyclosporine therapy achieved complete remission, and kidney function was preserved. In conclusion, coexisting anti-GBM glomerulonephritis and MN can have preserved renal function. IgG subclass of deposited anti-GBM antibody may be associated with the severity of anti-GBM glomerulonephritis. In addition, in the case of nephrotic syndrome with hematuria, we should consider the possibility of coexisting anti-GBM glomerulonephritis and MN.

Connective tissue growth factor and its regulation: a new element in diabetic glomerulosclerosis.

PubMed

Riser, B L; Cortes, P

2001-01-01

Connective tissue growth factor (CTGF), a member of the closely related CCN family of cytokines appears to be fibrotic in skin. To determine whether CTGF is implicated in diabetic glomerulosclerosis we studied cultured rat mesangial cells (MC) as well as kidney cortex and microdissected glomeruli from obese, diabetic db/db mice and their normal counterparts. Exposure of MC to rhCTGF significantly increased fibronectin and collagen type I secretion. Further, unstimulated MC expressed low levels of CTGF message and secreted minimal amounts of CTGF protein (36-38 kDa). However, exposure to TGF-beta, increased glucose concentrations, or cyclic mechanical strain, all causal factors in glomerulosclerosis, markedly induced the expression of CTGF transcripts. With all but mechanical strain there was a concomitant stimulation of CTGF protein secretion. TGF-beta also induced abundant quantities of a small molecular weight form of CTGF (18 kDa). The induction of CTGF protein by a high glucose concentration was mediated by TGF-beta, since a TGF-beta neutralizing antibody blocked this stimulation. In vivo studies using quantitative RT-PCR demonstrated that while CTGF transcripts were low in the glomeruli of control mice, expression was increased 27-fold after approximately 3.5 months of diabetes. These changes occurred early in diabetic nephropathy when mesangial expansion was mild, and interstitial disease and proteinuria were absent. A substantially reduced elevation of CTGF mRNA (2-fold) observed in whole kidney cortices indicted that the primary alteration of CTGF expression was in the glomerulus. These results suggest that CTGF upregulation is an important factor in the pathogenesis of mesangial matrix accumulation in both diabetic and non-diabetic glomerulosclerosis, acting downstream of TGF-beta.

Origins of correlated activity in an olfactory circuit.

PubMed

Kazama, Hokto; Wilson, Rachel I

2009-09-01

Multineuronal recordings often reveal synchronized spikes in different neurons. The manner in which correlated spike timing affects neural codes depends on the statistics of correlations, which in turn reflects the connectivity that gives rise to correlations. However, determining the connectivity of neurons recorded in vivo can be difficult. We investigated the origins of correlated activity in genetically labeled neurons of the Drosophila antennal lobe. Dual recordings showed synchronized spontaneous spikes in projection neurons (PNs) postsynaptic to the same type of olfactory receptor neuron (ORN). Odors increased these correlations. The primary origin of correlations lies in the divergence of each ORN onto every PN in its glomerulus. Reciprocal PN-PN connections make a smaller contribution to correlations and PN spike trains in different glomeruli were only weakly correlated. PN axons from the same glomerulus reconverge in the lateral horn, where pooling redundant signals may allow lateral horn neurons to average out noise that arises independently in these PNs.

Characteristics of renin release from isolated superfused glomeruli in vitro.

PubMed Central

Blendstrup, K; Leyssac, P P; Poulsen, K; Skinner, S L

1975-01-01

1. A method is described for studying renin release from superfused rat glomeruli following their rapid isolation by a magnetic iron-oxide technique. 2. Microscopically selected glomeruli were free of tubular components. Some possessed vascular pole protrusions of up to 20 mum, unrelated to renin content. 3. Renin content of 102 batches, each of 400 glomeruli, was 1.34 plus or minus 0.08 times 10-4 Goldblatt hog units per 100 glomeruli (plus or minus S.E. of mean). Different osmolarities (305, 355 and 400 m-osmole/1.), sodium concentrations (110 and 135 mM) and buffer compositions of the preparation solution did not alter this value. Renin content per glomerulus in intact kidney was 100-fold higher. 4. At 30 degrees C the contained juxtaglomerular cells released renin at consistent but decreasing rates over 4-6 hr. Initial release rate in 110 mM sodium, 305 m-osmole/1. solutions were 0.86 plus or minus 0.068 times 10-6 units per 100 glomeruli per 30 min (plus or minus S.E. of mean, n = 42) or 0.546 plus or minus 0.046 percent of content per 30 min. In 135 mM sodium, 305 m-osmole/1. solutions, release was 2.4-fold higher (P less than 0.001) and remained elevated for at least 3 hr. When related to renin content per glomerulus resting release rate in vitro was higher by at most one order of magnitude than calculated in vivo values. 5. Release was augmented by gentle physical agitation of the glomeruli. 6. Release rate was inversely ralated to temperature. On reducing temperature from 30 degrees C, release increased 2.6-fold at 20 degrees C and 6.7-fold at 10 degrees C (P less than 0.001, n = 11). The response was reversible. 7. 3 mM sodium cyanide plus 3 mM sodium iodoacetate caused a variable release of renin associated with depletion of content within 4 hr. The response was progressive and reached a peak after 60 min. 8. Sensitivity of renin release to temperature and metabolic blockade indicates that energy is required for retention of renin by the cell. This, together with the release observed with increased sodium concentration at constant osmolarity, suggests a dependence of renin release upon the mechanism controlling the volume of the juxtaglomerular cell or its organelles. PMID:1133791

Digital Pathology Evaluation in the Multicenter Nephrotic Syndrome Study Network (NEPTUNE)

PubMed Central

Nast, Cynthia C.; Jennette, J. Charles; Hodgin, Jeffrey B.; Herzenberg, Andrew M.; Lemley, Kevin V.; Conway, Catherine M.; Kopp, Jeffrey B.; Kretzler, Matthias; Lienczewski, Christa; Avila-Casado, Carmen; Bagnasco, Serena; Sethi, Sanjeev; Tomaszewski, John; Gasim, Adil H.

2013-01-01

Summary Pathology consensus review for clinical trials and disease classification has historically been performed by manual light microscopy with sequential section review by study pathologists, or multi-headed microscope review. Limitations of this approach include high intra- and inter-reader variability, costs, and delays for slide mailing and consensus reviews. To improve this, the Nephrotic Syndrome Study Network (NEPTUNE) is systematically applying digital pathology review in a multicenter study using renal biopsy whole slide imaging (WSI) for observation-based data collection. Study pathology materials are acquired, scanned, uploaded, and stored in a web-based information system that is accessed through a web-browser interface. Quality control includes metadata and image quality review. Initially, digital slides are annotated, with each glomerulus identified, given a unique number, and maintained in all levels until the glomerulus disappears or sections end. The software allows viewing and annotation of multiple slide sections concurrently. Analysis utilizes “descriptors” for patterns of injury, rather than diagnoses, in renal parenchymal compartments. This multidimensional representation via WSI, allows more accurate glomerular counting and identification of all lesions in each glomerulus, with data available in a searchable database. The use of WSI brings about efficiency critical to pathology review in a clinical trial setting, including independent review by multiple pathologists, improved intraobserver and interobserver reproducibility, efficiencies and risk reduction in slide circulation and mailing, centralized management of data integrity and slide images for current or future studies, and web-based consensus meetings. The overall effect is improved incorporation of pathology review in a budget neutral approach. PMID:23393107

Effects of High Levels of Deoxynivalenol and Zearalenone on Growth Performance, and Hematological and Immunological Parameters in Pigs

PubMed Central

Reddy, Kondreddy Eswar; Song, Jaeyong; Lee, Hyun-Jeong; Kim, Minseok; Kim, Dong-Wook; Jung, Hyun Jung; Kim, Bumseok; Lee, Yookyung; Yu, Dongjo; Kim, Dong-Woon; Oh, Young Kyoon; Lee, Sung Dae

2018-01-01

Background: Deoxynivalenol (DON) and zearalenone (ZEN) are common food contaminants produced by Fusarium sp. Mycotoxins are a potential health hazard because of their toxicological effects on both humans and farmed animals. Methods: We analyzed three groups of pigs: a control group (fed a standard diet), and the DON and ZEN groups, fed a diet containing 8 mg/kg DON and 0.8 mg/kg ZEN respectively, for four weeks. Results: DON and ZEN exposure decreased body weight (BW), average daily feed intake (ADFI), food conversion rate (FCR), and the serum levels of immunoglobulin (Ig)G and IgM. The total antioxidant levels significantly decreased in serum and increased in urine samples of both treatment groups. Additionally, DON and ZEN exposure increased serotonin levels in urine. Hematological parameters were not affected by the investigated toxins. Microscopic lesions were evident in sections of kidneys from either treatment group: we found sporadic interstitial nephritis in the DON group and renal glomerulus atrophy in the ZEN group. The expression levels of inflammatory cytokines and chemokine marker genes were reduced in tissues from DON- and ZEN-exposed pigs. Conclusions: chronic ingestion of high doses of DON and ZEN alters the immune response and causes organs damage, and might be associated with various diseases in pigs. PMID:29518941

Erythropoietin withdrawal alters interactions between young red blood cells, splenic endothelial cells, and macrophages: an in vitro model of neocytolysis

NASA Technical Reports Server (NTRS)

Trial, J.; Rice, L.; Alfrey, C. P.

2001-01-01

BACKGROUND: We have described the rapid destruction of young red blood cells (neocytolysis) in astronauts adapting to microgravity, in polycythemic high altitude dwellers who descend to sea level, and in patients with kidney disorders. This destruction results from a decrease in erythropoietin (EPO) production. We hypothesized that such EPO withdrawal could trigger physiological changes in cells other than red cell precursors and possibly lead to the uptake and destruction of young red cells by altering endothelial cell-macrophage interactions, most likely occurring in the spleen. METHODS: We identified EPO receptors on human splenic endothelial cells (HSEC) and investigated the responses of these cells to EPO withdrawal. RESULTS: A monolayer of HSEC, unlike human endothelial cells from aorta, glomerulus, or umbilical vein, demonstrated an increase in permeability upon EPO withdrawal that was accompanied by unique morphological changes. When HSEC were cultured with monocyte-derived macrophages (but not when either cell type was cultured alone), EPO withdrawal induced an increased ingestion of young red cells by macrophages when compared with the constant presence or absence of EPO. CONCLUSIONS: HSEC may represent a unique cell type that is able to respond to EPO withdrawal by increasing permeability and interacting with phagocytic macrophages, which leads to neocytolysis.

Therapeutic Effects of Tangshen Formula on Diabetic Nephropathy in db/db Mice Using Cytokine Antibody Array

PubMed Central

Huang, Chun Lian; Wang, Yi Ming; Li, Ning; Liang, Qiong Lin

2018-01-01

Objective Cytokines are essential promoters in the pathogenesis of diabetic nephropathy (DN) in type 2 diabetes. The following study investigates the adjustment mechanism of Tangshen formula (TSF) on cytokine expressions in db/db mice (DN animal model). Materials and Methods Db/db mice were randomly divided into three groups. The treated groups were orally administered with TSF and losartan for 12 weeks. Biochemical and histological examinations were determined at 8 and 12 weeks posttreatment, while the cytokine antibody array analysis was applied to analyze the expression of 144 cytokines in kidney tissues at the end of the 12th week posttreatment. Results TSF significantly reduced urinary albumin excretion and the levels of blood glucose, cholesterol, triglyceride, creatinine, and urea nitrogen. Furthermore, a significant decrease in glomerulus and mesangial area, as well as the downregulation of 24 cytokines and upregulated expressions of 5 cytokines, was found in the TSF-treated mice. Conclusions The present study reveals that TSF could ameliorate the metabolic anomalies and renal injury in db/db mice. One of the important mechanisms for treatment of DN using the treatment of TSF is the control of the JAK/STAT signaling pathway via regulation of IL-2, IL-6, IL-13, Il-15, and IFN-γ expression. PMID:29682583

Permeability, ultrastructural changes, and distribution of novel proteins in the glomerular barrier in early puromycin aminonucleoside nephrosis.

PubMed

Dunér, Fredrik; Lindström, Karin; Hultenby, Kjell; Hulkko, Jenny; Patrakka, Jaakko; Tryggvason, Karl; Haraldsson, Börje; Wernerson, Annika; Pettersson, Erna

2010-01-01

It is still unclear what happens in the glomerulus when proteinuria starts. Using puromycin aminonucleoside nephrosis (PAN) rats, we studied early ultrastructural and permeability changes in relation to the expression of the podocyte-associated molecules nephrin, α-actinin, dendrin, and plekhh2, the last two of which were only recently discovered in podocytes. Using immune stainings, semiquantitative measurement was performed under the electron microscope. Permeability was assessed using isolated kidney perfusion with tracers. Possible effects of ACE inhibition were tested. By day 2, some patchy foot process effacement, but no proteinuria, appeared. The amount of nephrin was reduced in both diseased and normal areas. The other proteins showed few changes, which were limited to diseased areas. By day 4, foot process effacement was complete and proteinuria appeared in parallel with signs of size barrier damage. Nephrin decreased further, while dendrin and plekhh2 also decreased but α-actinin remained unchanged. ACE inhibition had no significant protective effect. PAN glomeruli already showed significant pathology by day 4, despite relatively mild proteinuria. This was preceded by altered nephrin expression, supporting its pivotal role in podocyte morphology. The novel proteins dendrin and plekhh2 were both reduced, suggesting roles in PAN, whereas α-actinin was unchanged. Copyright © 2010 S. Karger AG, Basel.

Expression of podocyte-associated molecules in acquired human kidney diseases.

PubMed

Koop, Klaas; Eikmans, Michael; Baelde, Hans J; Kawachi, Hiroshi; De Heer, Emile; Paul, Leendert C; Bruijn, Jan A

2003-08-01

Proteinuria is a poorly understood feature of many acquired renal diseases. Recent studies concerning congenital nephrotic syndromes and findings in genetically modified mice have demonstrated that podocyte molecules make a pivotal contribution to the maintenance of the selective filtration barrier of the normal glomerulus. However, it is unclear what role podocyte molecules play in proteinuria of acquired renal diseases. This study investigated the mRNA and protein expression of several podocyte-associated molecules in acquired renal diseases. Forty-eight patients with various renal diseases were studied, including minimal change nephropathy, focal segmental glomerulosclerosis, IgA nephropathy, lupus nephritis, and diabetic nephropathy, together with 13 kidneys with normal glomerular function. Protein levels of nephrin, podocin, CD2-associated protein, and podocalyxin were investigated using quantitative immunohistochemical assays. Real-time PCR was used to determine the mRNA levels of nephrin, podocin, and podoplanin in microdissected glomeruli. The obtained molecular data were related to electron microscopic ultrastructural changes, in particular foot process width, and to clinical parameters. In most acquired renal diseases, except in IgA nephropathy, a marked reduction was observed at the protein levels of nephrin, podocin, and podocalyxin, whereas an increase of the glomerular mRNA levels of nephrin, podocin, and podoplanin was found, compared with controls. The mean width of the podocyte foot processes was inversely correlated with the protein levels of nephrin (r = -0.443, P < 0.05), whereas it was positively correlated with podoplanin mRNA levels (r = 0.468, P < 0.05) and proteinuria (r = 0.585, P = 0.001). In the diseases studied, the decrease of slit diaphragm proteins was related to the effacement of foot processes and coincided with a rise of the levels of the corresponding mRNA transcripts. This suggests that the alterations in the expression of podocyte-associated molecules represent a compensatory reaction of the podocyte that results from damage associated with proteinuria.

The ionic charge of Copper-64 complexes conjugated to an engineered antibody effects biodistribution

DOE PAGES

Dearling, Jason L. J.; Smith, Suzanne V.; Paterson, Brett M.; ...

2015-04-15

The development of biomolecules as imaging probes requires radiolabeling methods that do not significantly influence their biodistribution. Sarcophagine (Sar) chelators form extremely stable complexes with copper, and are therefore a promising option for labeling proteins with ⁶⁴Cu. However, initial studies using the first-generation sarcophagine bifunctional chelator SarAr to label the engineered antibody fragment ch14.18-ΔC H2 (MW 120 kDa) with ⁶⁴Cu showed high tracer retention in the kidneys,(>38% injected dose per gram (ID/g) 48 h post-injection), presumably because the high local positive charge on the Cu II-SarAr moiety resulted in increased binding of the labeled protein to the negatively charged basalmore » cells of the glomerulus. To test this hypothesis, ch14.18-ΔC H2 was conjugated with a series of Sar derivatives of decreasing positive charge and three commonly used macrocyclic polyaza polycarboxylate (PAC) BFCs. The immunoconjugates were labeled with ⁶⁴Cu and injected into mice, and PET/CT images were obtained at 24 and 48 h post injection (p.i.). At 48 h p.i., ex vivo biodistribution was carried out. In addition, to demonstrate the potential of metastasis detection using ⁶⁴Cu-labeled ch14.18-ΔC H2, a preclinical imaging study of intrahepatic neuroblastoma tumors was performed carried out. Reducing the positive charge on the Sar chelators decreased kidney uptake of Cu-labeled ch14.18-ΔC H2 by more than 6-fold, from >45 ID/g to <6% ID/g, while the uptake in most other tissues, including liver, was relatively unchanged. However, despite this dramatic decrease, the renal uptake of the PAC BFCs was generally lower than that of the Sar derivatives, as was the liver uptake. Uptake of ⁶⁴Cu-labeled ch14.18-ΔC H2 in neuroblastoma hepatic metastases was detected using PET.« less

α Actinin 4 (ACTN4) Regulates Glucocorticoid Receptor-mediated Transactivation and Transrepression in Podocytes*

PubMed Central

Zhao, Xuan; Khurana, Simran; Charkraborty, Sharmistha; Tian, Yuqian; Sedor, John R.; Bruggman, Leslie A.; Kao, Hung-Ying

2017-01-01

Glucocorticoids are a general class of steroids that possess renoprotective activity in glomeruli through their interaction with the glucocorticoid receptor. However, the mechanisms by which glucocorticoids ameliorate proteinuria and glomerular disease are not well understood. In this study, we demonstrated that α actinin 4 (ACTN4), an actin-cross-linking protein known to coordinate cytoskeletal organization, interacts with the glucocorticoid receptor (GR) in the nucleus of human podocytes (HPCs), a key cell type in the glomerulus critical for kidney filtration function. The GR-ACTN4 complex enhances glucocorticoid response element (GRE)-driven reporter activity. Stable knockdown of ACTN4 by shRNA in HPCs significantly reduces dexamethasone-mediated induction of GR target genes and GRE-driven reporter activity without disrupting dexamethasone-induced nuclear translocation of GR. Synonymous mutations or protein expression losses in ACTN4 are associated with kidney diseases, including focal segmental glomerulosclerosis, characterized by proteinuria and podocyte injury. We found that focal segmental glomerulosclerosis-linked ACTN4 mutants lose their ability to bind liganded GR and support GRE-mediated transcriptional activity. Mechanistically, GR and ACTN4 interact in the nucleus of HPCs. Furthermore, disruption of the LXXLL nuclear receptor-interacting motif present in ACTN4 results in reduced GR interaction and dexamethasone-mediated transactivation of a GRE reporter while still maintaining its actin-binding activity. In contrast, an ACTN4 isoform, ACTN4 (Iso), that loses its actin-binding domain is still capable of potentiating a GRE reporter. Dexamethasone induces the recruitment of ACTN4 and GR to putative GREs in dexamethasone-transactivated promoters, SERPINE1, ANGPLT4, CCL20, and SAA1 as well as the NF-κB (p65) binding sites on GR-transrepressed promoters such as IL-1β, IL-6, and IL-8. Taken together, our data establish ACTN4 as a transcriptional co-regulator that modulates both dexamethasone-transactivated and -transrepressed genes in podocytes. PMID:27998979

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dearling, Jason L. J.; Smith, Suzanne V.; Paterson, Brett M.

The development of biomolecules as imaging probes requires radiolabeling methods that do not significantly influence their biodistribution. Sarcophagine (Sar) chelators form extremely stable complexes with copper, and are therefore a promising option for labeling proteins with ⁶⁴Cu. However, initial studies using the first-generation sarcophagine bifunctional chelator SarAr to label the engineered antibody fragment ch14.18-ΔC H2 (MW 120 kDa) with ⁶⁴Cu showed high tracer retention in the kidneys,(>38% injected dose per gram (ID/g) 48 h post-injection), presumably because the high local positive charge on the Cu II-SarAr moiety resulted in increased binding of the labeled protein to the negatively charged basalmore » cells of the glomerulus. To test this hypothesis, ch14.18-ΔC H2 was conjugated with a series of Sar derivatives of decreasing positive charge and three commonly used macrocyclic polyaza polycarboxylate (PAC) BFCs. The immunoconjugates were labeled with ⁶⁴Cu and injected into mice, and PET/CT images were obtained at 24 and 48 h post injection (p.i.). At 48 h p.i., ex vivo biodistribution was carried out. In addition, to demonstrate the potential of metastasis detection using ⁶⁴Cu-labeled ch14.18-ΔC H2, a preclinical imaging study of intrahepatic neuroblastoma tumors was performed carried out. Reducing the positive charge on the Sar chelators decreased kidney uptake of Cu-labeled ch14.18-ΔC H2 by more than 6-fold, from >45 ID/g to <6% ID/g, while the uptake in most other tissues, including liver, was relatively unchanged. However, despite this dramatic decrease, the renal uptake of the PAC BFCs was generally lower than that of the Sar derivatives, as was the liver uptake. Uptake of ⁶⁴Cu-labeled ch14.18-ΔC H2 in neuroblastoma hepatic metastases was detected using PET.« less

Histopathological alterations after a growth promoter boldenone injection in rabbits.

PubMed

Tousson, Ehab

2016-02-01

Boldenone (BOL) is a derivative of the testosterone that has dual effects on humans, both directly and indirectly; directly as injection to build muscles and indirectly as through consuming meat of animals that where treated with BOL. However, the action of these steroids on different body organs structures is still unclear; therefore, the aim of the present study was to investigate the effect of the intramuscular injection of BOL undecylenate on the different organ structures. A total of 10 adult New Zealand rabbits were divided into two main groups, the first group was the control group, which includes animals that were injected intramuscularly with olive oil and the second group included animals that received two intramuscular injections of 5 mg/kg body weight BOL dissected after 6 weeks. Our results showed that intramuscular injection of rabbits with BOL showed hypertrophy in both skeletal and cardiac muscles, disturbances of the hepatocytes radially arranged cords with multifocal hepatocellular vacuolations in the liver, glomerulus mass reduction with multifocal glomerular injury in the kidney, disturbances of the cycle of spermatogenesis in the testes. In conclusion, using BOL, while preparing for a young bodybuilding contest, may cause an alteration in the histological structure of most of the body organs; these findings suggested that especially young people who misuse anablic androgenic steroids should be careful if they want to use such steroids to enhance their strength and endurance. © The Author(s) 2013.

Revisiting renal amyloidosis with clinicopathological characteristics, grading, and scoring: A single-institutional experience.

PubMed

Kalle, Abhiram; Gudipati, Archana; Raju, Sree Bhushan; Kalidindi, Karthik; Guditi, Swarnalatha; Taduri, Gangadhar; Uppin, Megha S

2018-01-01

Kidney involvement is a major cause of mortality in systemic amyloidosis. Glomerulus is the most common site of deposition in renal amyloidosis, and nephrotic syndrome is the most common presentation. Distinction between AA and AL is done using immunofluorescence (IF) and immunohistochemistry (IHC). Renal biopsy helps in diagnosis and also predicting the clinical course by applying scoring and grading to the biopsy findings. The study includes all cases of biopsy-proven renal amyloidosis from January 2008 to May 2017. Light microscopic analysis; Congo red with polarization; IF; IHC for Amyloid A, kappa, and lambda; and bone marrow evaluation were done. Classification of glomerular amyloid deposition and scoring and grading are done as per the guidelines of Sen S et al . There are 40 cases of biopsy-proven renal amyloidosis with 12 primary and 23 secondary cases. Mean age at presentation was 42.5 years. Edema was the most common presenting feature. Secondary amyloidosis cases were predominant. Tuberculosis was the most common secondary cause. Multiple myeloma was detected in four primary cases. Grading of renal biopsy features showed a good correlation with the class of glomerular involvement. Clinical history, IF, and IHC are essential in amyloid typing. Grading helps provide a subtle guide regarding the severity of disease in the background of a wide range of morphological features and biochemical values. Typing of amyloid is also essential for choosing the appropriate treatment.

Involvement of Endoplasmic Reticulum Stress, Autophagy, and Apoptosis in Advanced Glycation End Products-Induced Glomerular Mesangial Cell Injury

PubMed Central

Chiang, Chih-Kang; Wang, Ching-Chia; Lu, Tien-Fong; Huang, Kuo-How; Sheu, Meei-Ling; Liu, Shing-Hwa; Hung, Kuan-Yu

2016-01-01

Advanced glycation end-products (AGEs)-induced mesangial cell death is one of major causes of glomerulus dysfunction in diabetic nephropathy. Both endoplasmic reticulum (ER) stress and autophagy are adaptive responses in cells under environmental stress and participate in the renal diseases. The role of ER stress and autophagy in AGEs-induced mesangial cell death is still unclear. Here, we investigated the effect and mechanism of AGEs on glomerular mesangial cells. AGEs dose-dependently decreased mesangial cell viability and induced cell apoptosis. AGEs also induced ER stress signals in a time- and dose-dependent manner. Inhibition of ER stress with 4-phenylbutyric acid effectively inhibited the activation of eIF2α and CHOP signals and reversed AGEs-induced cell apoptosis. AGEs also activated LC-3 cleavage, increased Atg5 expression, and decreased p62 expression, which indicated the autophagy induction in mesangial cells. Inhibition of autophagy by Atg5 siRNAs transfection aggravated AGEs-induced mesangial cell apoptosis. Moreover, ER stress inhibition by 4-phenylbutyric acid significantly reversed AGEs-induced autophagy, but autophagy inhibition did not influence the AGEs-induced ER stress-related signals activation. These results suggest that AGEs induce mesangial cell apoptosis via an ER stress-triggered signaling pathway. Atg5-dependent autophagy plays a protective role. These findings may offer a new strategy against AGEs toxicity in the kidney. PMID:27665710

Podocyte Purinergic P2X4 Channels Are Mechanotransducers That Mediate Cytoskeletal Disorganization.

PubMed

Forst, Anna-Lena; Olteanu, Vlad Sorin; Mollet, Géraldine; Wlodkowski, Tanja; Schaefer, Franz; Dietrich, Alexander; Reiser, Jochen; Gudermann, Thomas; Mederos y Schnitzler, Michael; Storch, Ursula

2016-03-01

Podocytes are specialized, highly differentiated epithelial cells in the kidney glomerulus that are exposed to glomerular capillary pressure and possible increases in mechanical load. The proteins sensing mechanical forces in podocytes are unconfirmed, but the classic transient receptor potential channel 6 (TRPC6) interacting with the MEC-2 homolog podocin may form a mechanosensitive ion channel complex in podocytes. Here, we observed that podocytes respond to mechanical stimulation with increased intracellular calcium concentrations and increased inward cation currents. However, TRPC6-deficient podocytes responded in a manner similar to that of control podocytes, and mechanically induced currents were unaffected by genetic inactivation of TRPC1/3/6 or administration of the broad-range TRPC blocker SKF-96365. Instead, mechanically induced currents were significantly decreased by the specific P2X purinoceptor 4 (P2X4) blocker 5-BDBD. Moreover, mechanical P2X4 channel activation depended on cholesterol and podocin and was inhibited by stabilization of the actin cytoskeleton. Because P2X4 channels are not intrinsically mechanosensitive, we investigated whether podocytes release ATP upon mechanical stimulation using a fluorometric approach. Indeed, mechanically induced ATP release from podocytes was observed. Furthermore, 5-BDBD attenuated mechanically induced reorganization of the actin cytoskeleton. Altogether, our findings reveal a TRPC channel-independent role of P2X4 channels as mechanotransducers in podocytes. Copyright © 2016 by the American Society of Nephrology.

Effects of Hyperbaric Oxygen Treatment on Renal System.

PubMed

Tezcan, Orhan; Caliskan, Ahmet; Demirtas, Sinan; Yavuz, Celal; Kuyumcu, Mahir; Nergiz, Yusuf; Guzel, Abdulmenap; Karahan, Oguz; Ari, Seyhmus; Soker, Sevda; Yalinkilic, Ibrahim; Turkdogan, Kenan Ahmet

2017-01-01

Hyperbaric oxygen (HBO) treatment is steadily increasing as a therapeutic modality for various types of diseases. Although good clinical outcomes were reported with HBO treatment for various diseases, the multisystemic effects of this modality are still unclear. This study aimed to investigate the renal effects of HBO experimentally. Fourteen New Zealand White rabbits were divided into 2 groups randomly as the control group and the study group. The study group received HBO treatment for 28 days (100% oxygen at 2.5 atmospheres for 90 minutes daily) and the control group was used to obtain normal renal tissue of the animal genus. After the intervention period, venous blood samples were obtained, and renal tissue samples were harvested for comparisons. Normal histological morphology was determined with Masson trichrome staining and periodic acid-Schiff staining in the control group. Atrophic glomerular structures, vacuolated tubule cells, and degeneration were detected in the renal samples of the study group with Masson trichrome staining. Additionally, flattening was observed on the brush borders of the proximal tubules, and tubular dilatation was visualized with periodic acid-Schiff staining. The histopathologic disruption of renal morphology was verified with detection of significantly elevated kidney function laboratory biomarkers in the study group. Our findings suggests that HBO has adverse effects on renal glomerulus and proximal tubules. However, the functional effects of this alteration should be investigated with further studies.

A histology-based fish health assessment of the tigerfish, Hydrocynus vittatus from a DDT-affected area

NASA Astrophysics Data System (ADS)

McHugh, K. J.; Smit, N. J.; Van Vuren, J. H. J.; Van Dyk, J. C.; Bervoets, L.; Covaci, A.; Wepener, V.

The Pongolapoort Dam (PPD) in the Phongola River, Kwa-Zulu Natal, South Africa and the surrounding area are classified as intermediate to low risk malaria areas and are continually being treated with DDT for malaria vector control. DDT is known as an endocrine disrupting chemical posing estrogenic and anti-androgenic properties and therefore might impact on the health of the 18 freshwater fish species found within this system. Of these species the tigerfish, Hydrocynus vittatus, is targeted by both recreational and local subsistence fishermen and was recently included in the South African threatened or protected species list. Their protected status and importance as a food source therefore emphasises the need for their health status elucidation. Previous research on H. vittatus in the Phongola floodplain highlighted DDT biomagnification in this species. Recent data show that the sum of the DDT levels in February 2009 (5403.9 ng/g lipid) and July 2009 (5537.4 ng/g lipid) is still comparable to the high levels found 30 years earlier. The aim of the current study was thus to determine the health status of H. vittatus in relation to DDT exposure by means of a histology-based fish health assessment protocol. Tigerfish were collected in February 2009 ( n = 30) and July 2009 ( n = 15) and gill, kidney and liver tissue were subjected to histological analyses. Mean Index values showed that the Kidney Index ( IK), Gill Index ( IG) and Fish Index ( IFISH) were higher in fish from the February survey while the Liver Index was higher in those collected during July. Liver alterations identified included intercellular oedema, granular degeneration, vacuolation, nuclear pleomorphism and lymphocyte infiltration. Kidney alterations included dilation of the glomerulus capillaries, vacuolation and hyaline droplet degeneration. Gill alterations identified included telangiectasia and hyperplasia of the secondary lamella, congestion, and rupture of pillar cells. Although histological alterations were observed, the histology based fish health assessment protocol indicated that the H. vittatus population in PPD were in a healthy state. The histological assessment did not reflect the DDT exposure induced effects that were anticipated. However, the biomagnification effects in other tertiary consumers in the PPD such as crocodiles and fish eagles cannot be ruled out.

Identification of copper/zinc superoxide dismutase as a novel nitric oxide-regulated gene in rat glomerular mesangial cells and kidneys of endotoxemic rats.

PubMed

Frank, S; Zacharowski, K; Wray, G M; Thiemermann, C; Pfeilschifter, J

1999-05-01

To define the mechanism of nitric oxide (NO) action in the glomerulus, we attempted to identify genes that are regulated by NO in rat glomerular mesangial cells. We identified a Cu/Zn superoxide dismutase (SOD) that was strongly induced in these cells by treatment with S-nitroso-glutathione as a NO-donating agent. Bacterial lipopolysaccharide (LPS) acutely decreased Cu/Zn SOD mRNA levels. The LPS-mediated decrease in Cu/Zn SOD is reversed by endogenously produced NO, as LPS also induced a delayed strong iNOS expression in these cells in vitro, which is accompanied by increased Cu/Zn SOD expression. NO dependency of Cu/Zn SOD mRNA recovery could be demonstrated by inhibition of this process by L-NG-monomethylarginine, an inhibitor of NOS enzymatic activity. To demonstrate the in vivo relevance of our observations, we have chosen LPS-treated rats as a model for induction of a systemic inflammatory response. In these animals, we demonstrate a direct coupling of Cu/Zn SOD expression levels to the presence of NO, as Cu/Zn SOD mRNA levels declined during acute inflammation in the presence of a selective inhibitor of iNOS. We propose that the up-regulation of Cu/Zn SOD by endogenous NO may serve as an adaptive, protective mechanism to prevent the formation of toxic quantities of peroxynitrite in conditions associated with iNOS induction during endotoxic shock.

Vinclozolin affects the interrenal system of the rare minnow (Gobiocypris rarus).

PubMed

Yang, Lihua; Zha, Jinmiao; Li, Wei; Li, Zhaoli; Wang, Zijian

2011-07-01

Vinclozolin, a widely used fungicide, has been characterized as a potent androgen antagonist. In this study, the effects of vinclozolin on the interrenal system of the rare minnow (Gobiocypris rarus) were evaluated. The results revealed a decline of the renal somatic index (RSI) and the presence of histopathological effects, including shrinkage of the glomerulus and expansion of the Bowman's space in the kidneys, in rare minnows exposed to vinclozolin. Elevated plasma cortisol concentrations in females exposed to ≥ 2 μg/L vinclozolin and males exposed to ≥ 10 μg/L vinclozolin (p<0.05) suggested that endocrine stress was evoked by vinclozolin exposure. Significant decreases in mRNA levels of interrenal crf, pomc, gr, and nka in females and gr and nka in males were observed after exposure to ≥ 0.5 μg/L and 2 μg/L vinclozolin (p<0.05), respectively; however, no changes in expression of these genes were observed in the brain of males (p ≥ 0.159) or females (p ≥ 0.053) compared with the control. The results indicated that female rare minnows were more sensitive than males to vinclozolin exposure. In conclusion, vinclozolin exposure evoked endocrine stress on the hypothalamic-pituitary-interrenal axis in the rare minnow, and the interrenal tissue was more sensitive than the brain tissue to stress caused by vinclozolin exposure. These results provide additional data about the modes of toxicological action of vinclozolin. Copyright © 2011 Elsevier B.V. All rights reserved.

Revisiting renal amyloidosis with clinicopathological characteristics, grading, and scoring: A single-institutional experience

PubMed Central

Kalle, Abhiram; Gudipati, Archana; Raju, Sree Bhushan; Kalidindi, Karthik; Guditi, Swarnalatha; Taduri, Gangadhar; Uppin, Megha S.

2018-01-01

INTRODUCTION: Kidney involvement is a major cause of mortality in systemic amyloidosis. Glomerulus is the most common site of deposition in renal amyloidosis, and nephrotic syndrome is the most common presentation. Distinction between AA and AL is done using immunofluorescence (IF) and immunohistochemistry (IHC). Renal biopsy helps in diagnosis and also predicting the clinical course by applying scoring and grading to the biopsy findings. MATERIALS AND METHODS: The study includes all cases of biopsy-proven renal amyloidosis from January 2008 to May 2017. Light microscopic analysis; Congo red with polarization; IF; IHC for Amyloid A, kappa, and lambda; and bone marrow evaluation were done. Classification of glomerular amyloid deposition and scoring and grading are done as per the guidelines of Sen S et al. RESULTS: There are 40 cases of biopsy-proven renal amyloidosis with 12 primary and 23 secondary cases. Mean age at presentation was 42.5 years. Edema was the most common presenting feature. Secondary amyloidosis cases were predominant. Tuberculosis was the most common secondary cause. Multiple myeloma was detected in four primary cases. Grading of renal biopsy features showed a good correlation with the class of glomerular involvement. CONCLUSION: Clinical history, IF, and IHC are essential in amyloid typing. Grading helps provide a subtle guide regarding the severity of disease in the background of a wide range of morphological features and biochemical values. Typing of amyloid is also essential for choosing the appropriate treatment. PMID:29692592

Superparamagnetic And Paramagnetic MRI Contrast Agents: Application Of Rapid Magnetic Resonance Imaging To Assess Renal Function

NASA Astrophysics Data System (ADS)

Carvlin, Mark J.; Renshaw, Perry F.; Arger, Peter; Kundel, Harold L.; Dougherty, Larry; Axel, Leon; Kassab, Eleanor; Moore, Bethanne

1988-06-01

The paramagnetic chelate complex, gadolinium-diethylene-triamine-pentaacetic acid, Gd-DTPA, and superparamagnetic particles, such as those composed of dextran coated magnetite, function as magnetic resonance contrast agents by changing the relaxation rates, 1/T1 and 1/T2. The effects that these agents have upon MR signal intensity are determined by: the inherent biophysical properties of the tissue being imaged, the concentration of the contrast agent and the data acquisition scheme (pulse sequence parameters) employed. Following the time course of MR signal change in the first minutes after the injection of contrast agent(s) allows a dynamic assessment of organ functions in a manner analogous to certain nuclear medicine studies. In order to study renal function, sequential MR fast scan images, gradient echo (TR=35/TE=7 msec, flip angle=25 degrees), were acquired, one every 12 seconds, after intravenous injection of Gd-DTPA and/or dextran-magnetite. Gd-DTPA, which is freely filtered at the glomerulus and is neither secreted nor reabsorbed, provides information concerning renal perfusion, glomerular filtration and tubular concentrating ability. Dextran-magnetite (200 A diameter), which is primarily contained within the intravascular space shortly after injection, provides information on blood flow to and distribution within the kidney. The MR signal change observed after administration of contrast agents varied dramatically depending upon the agents injected and the imaging parameters used. Hence a broad range of physiolgic processes may be described using these techniques, i.e. contrast agent enhanced functional MR examinations.

Dietary Fructose Enhances the Ability of Low Concentrations of Angiotensin II to Stimulate Proximal Tubule Na+ Reabsorption

PubMed Central

Gonzalez-Vicente, Agustin; Cabral, Pablo D.; Hong, Nancy J.; Asirwatham, Jessica; Yang, Nianxin; Berthiaume, Jessica M.; Dominici, Fernando P.; Garvin, Jeffrey L.

2017-01-01

Fructose-enriched diets cause salt-sensitive hypertension. Proximal tubules (PTs) reabsorb 70% of the water and salt filtered through the glomerulus. Angiotensin II (Ang II) regulates this process. Normally, dietary salt reduces Ang II allowing the kidney to excrete more salt, thereby preventing hypertension. We hypothesized that fructose-enriched diets enhance the ability of low concentrations of Ang II to stimulate PT transport. We measured the effects of a low concentration of Ang II (10−12 mol/L) on transport-related oxygen consumption (QO2), and Na/K-ATPase and Na/H-exchange (NHE) activities and expression in PTs from rats consuming tap water (Control) or 20% fructose (FRUC). In FRUC-treated PTs, Ang II increased QO2 by 14.9 ± 1.3 nmol/mg/min (p < 0.01) but had no effect in Controls. FRUC elevated NHE3 expression by 19 ± 3% (p < 0.004) but not Na/K-ATPase expression. Ang II stimulated NHE activity in FRUC PT (Δ + 0.7 ± 0.1 Arbitrary Fluorescent units (AFU)/s, p < 0.01) but not in Controls. Na/K-ATPase activity was not affected. The PKC inhibitor Gö6976 blocked the ability of FRUC to augment the actions of Ang II. FRUC did not alter the inhibitory effect of dopamine on NHE activity. We conclude that dietary fructose increases the ability of low concentrations of Ang II to stimulate PT Na reabsorption via effects on NHE. PMID:28813008

3D reconstruction of SEM images by use of optical photogrammetry software.

PubMed

Eulitz, Mona; Reiss, Gebhard

2015-08-01

Reconstruction of the three-dimensional (3D) surface of an object to be examined is widely used for structure analysis in science and many biological questions require information about their true 3D structure. For Scanning Electron Microscopy (SEM) there has been no efficient non-destructive solution for reconstruction of the surface morphology to date. The well-known method of recording stereo pair images generates a 3D stereoscope reconstruction of a section, but not of the complete sample surface. We present a simple and non-destructive method of 3D surface reconstruction from SEM samples based on the principles of optical close range photogrammetry. In optical close range photogrammetry a series of overlapping photos is used to generate a 3D model of the surface of an object. We adapted this method to the special SEM requirements. Instead of moving a detector around the object, the object itself was rotated. A series of overlapping photos was stitched and converted into a 3D model using the software commonly used for optical photogrammetry. A rabbit kidney glomerulus was used to demonstrate the workflow of this adaption. The reconstruction produced a realistic and high-resolution 3D mesh model of the glomerular surface. The study showed that SEM micrographs are suitable for 3D reconstruction by optical photogrammetry. This new approach is a simple and useful method of 3D surface reconstruction and suitable for various applications in research and teaching. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of the water disinfection by-product dichloroacetonitrile-induced biochemical, oxidative, histopathological, and mitochondrial functional alterations: Subacute oral toxicity in rats.

PubMed

Dong, Ying; Li, Fang; Shen, Haijun; Lu, Rongzhu; Yin, Siqi; Yang, Qi; Li, Zhuangfa; Wang, Suhua

2018-03-01

Dichloroacetonitrile (DCAN), an emerging nitrogenous disinfection by-product, is more genotoxic and cytotoxic than the currently regulated carbonaceous disinfection by-products such as haloacetic acids. Few mechanistic studies have been conducted on the hepatic and renal toxicities of DCAN. This study examined the clinical biochemical, hematological, histopathological, oxidative, and mitochondrial functional alterations to evaluate the systematic toxicity after subacute oral exposure of 11 or 44 mg/kg/day in rats for 28 days. Body and spleen weights were lower, and organ-to-body weight ratios of the liver and kidney were higher in rats administered 44-mg/kg DCAN than in controls. The activities of serum alanine aminotransferase and alkaline phosphatase, and concentrations of blood serum urea nitrogen and retinol-binding protein were increased in rats administered 44-mg/kg DCAN compared with those of controls, thereby indicating hepatic and renal damage in this group. This was confirmed by histopathological alterations, including hepatic sinus dilation, extensive hemorrhage, vacuolar degeneration in the liver and glomerulus hemorrhage, and renal tubular swelling, in DCAN-exposed rats. Exposure to 44-mg/kg DCAN induced hepatic oxidative damage shown by the significant increase in malonaldehyde levels, a poisonous product of lipid peroxidation. Exposure to 44-mg/kg DCAN significantly increased hepatic glutathione content and mitochondrial bioenergy as noted by the elevation of mitochondrial membrane potential and cytochrome c oxidase activity, which might be attributed to compensatory pathophysiologic responses to DCAN-induced hepatic mitochondrial damage.

Structural Predictors of Loss of Renal Function in American Indians with Type 2 Diabetes.

PubMed

Fufaa, Gudeta D; Weil, E Jennifer; Lemley, Kevin V; Knowler, William C; Brosius, Frank C; Yee, Berne; Mauer, Michael; Nelson, Robert G

2016-02-05

Diabetes is the leading cause of kidney failure in the United States, but early structural determinants of renal function loss in type 2 diabetes are poorly defined. We examined the association between morphometrically determined renal structural variables and loss of renal function in 111 American Indians with type 2 diabetes who volunteered for a research kidney biopsy at the end of a 6-year clinical trial designed to test the renoprotective efficacy of losartan versus placebo. Participants were subsequently followed in an observational study, in which annual measurements of GFR (iothalamate) initiated during the clinical trial were continued. Renal function loss was defined as ≥40% loss of GFR from the research examination performed at the time of kidney biopsy. Associations with renal function loss were evaluated by Cox proportional hazards regression. Hazard ratios (HRs) were reported per 1-SD increment for each morphometric variable. Of 111 participants (82% women; baseline mean [±SD] age, 46 years old [±10]; diabetes duration, 16 years [±6]; hemoglobin A1c =9.4% [±2.2]; GFR=147 ml/min [±56]; median albumin-to-creatinine ratio, 41 mg/g [interquartile range, 13-158]), 51 (46%) developed renal function loss during a median follow-up of 6.6 years (interquartile range, 3.1-9.0). Fourteen had baseline GFR <90 ml/min, and three had baseline GFR <60 ml/min. Higher mesangial fractional volume (HR, 2.27; 95% confidence interval [95% CI], 1.58 to 3.26), percentage of global glomerular sclerosis (HR, 1.63; 95% CI, 1.21 to 2.21), nonpodocyte cell number per glomerulus (HR, 1.50; 95% CI, 1.10 to 2.05), glomerular basement membrane width (HR, 1.48; 95% CI, 1.05 to 2.08), mean glomerular volume (HR, 1.42; 95% CI, 1.02 to 1.96), and podocyte foot process width (HR, 1.28; 95% CI, 1.03 to 1.60); lower glomerular filtration surface density (HR, 0.62; 95% CI, 0.41 to 0.94); and fewer endothelial fenestrations (HR, 0.68; 95% CI, 0.48 to 0.95) were each associated with GFR decline after adjustment for baseline age, sex, duration of diabetes, hemoglobin A1c, GFR, and treatment assignment during the clinical trial. Quantitative measures of glomerular structure predict loss of renal function in type 2 diabetes. Copyright © 2016 by the American Society of Nephrology.

Role of scanning electron microscopy in identifying drugs used in medical practice.

PubMed

Fazil Marickar, Y M; Sylaja, N; Koshy, Peter

2009-10-01

Several plant preparations are administered for treatment of stone disease without scientific basis. This paper presents the results of in vitro and animal experimental studies using scanning electron microscopy (SEM) in the identification of the therapeutic properties of trial drugs in medicine. In the first set of the study, urinary crystals namely calcium oxalate monohydrate and calcium oxalate dehydrate were grown in six sets of Hane's tubes in silica gel medium. Trial drugs namely scoparia dulcis Lynn, musa sapiens and dolicos biflorus were incorporated in the gel medium to identify the dopant effect of the trial drugs on the size and extent of crystal column growth. The changes in morphology of crystals were studied using SEM. In the second set, six male Wistar rats each were calculogenised by administering sodium oxalate and ethylene glycol and diabetised using streptozotocin. The SEM changes of calculogenisation were studied. The rats were administered trial drugs before calculogenisation or after. The kidneys of the rats studied under the scanning electron microscope showed changes in tissue morphology and crystal deposition produced by calculogenisation and alterations produced by addition of trial drugs. The trial drugs produced changes in the pattern of crystal growth and in the crystal morphology of both calcium oxalate monohydrate and calcium oxalate dihydrate grown in vitro. Elemental distribution analysis showed that the crystal purity was not altered by the trial drugs. Scoparia dulcis Lynn was found to be the most effective anticalculogenic agent. Musa sapiens and dolicos biflorus were found to have no significant effect in inhibiting crystal growth. The kidneys of rats on calculogenisation showed different grades of crystals in the glomerulus and interstitial tissues, extrusion of the crystals into the tubular lumen, collodisation and tissue inflammatory cell infiltration. Scoparia dulcis Lynn exhibited maximum protector effect against the changes of calculogenisation. Musa sapiens and dolicos biflorus had only minimal effect in preventing crystal deposition, inflammatory cell infiltration and other changes of calculogenisation. SEM was found to be effective in assessing the effect of drugs on crystal growth morphology and tissue histology.

Regulation of connective tissue growth factor activity in cultured rat mesangial cells and its expression in experimental diabetic glomerulosclerosis.

PubMed

Riser, B L; Denichilo, M; Cortes, P; Baker, C; Grondin, J M; Yee, J; Narins, R G

2000-01-01

Connective tissue growth factor (CTGF) is a peptide secreted by cultured endothelial cells and fibroblasts when stimulated by transforming growth factor-beta (TGF-beta), and is overexpressed during fibrotic processes in coronary arteries and in skin. To determine whether CTGF is implicated in the pathogenesis of diabetic glomerulosclerosis, cultured rat mesangial cells (MC) as well as kidney cortex and microdissected glomeruli were examined from obese, diabetic db/db mice and their normal counterparts. Exposure of MC to recombinant human CTGF significantly increased fibronectin and collagen type I production. Furthermore, unstimulated MC expressed low levels of CTGF message and secreted minimal amounts of CTGF protein (36 to 38 kD) into the media. However, sodium heparin treatment resulted in a greater than fourfold increase in media-associated CTGF, suggesting that the majority of CTGF produced was cell- or matrix-bound. Exposure of MC to TGF-beta, increased glucose concentrations, or cyclic mechanical strain, all causal factors in diabetic glomerulosclerosis, markedly induced the expression of CTGF transcripts, while recombinant human CTGF was able to autoinduce its own expression. TGF-, and high glucose, but not mechanical strain, stimulated the concomitant secretion of CTGF protein, the former also inducing abundant quantities of a small molecular weight form of CTGF (18 kD) containing the heparin-binding domain. The induction of CTGF protein by a high glucose concentration was mediated by TGF-beta, since a TGF-beta-neutralizing antibody blocked this stimulation. In vivo studies using quantitative reverse transcription-PCR demonstrated that although CTGF transcripts were low in the glomeruli of control mice, expression was increased 28-fold after approximately 3.5 mo of diabetes. This change occurred early in the course of diabetic nephropathy when mesangial expansion was mild, and interstitial disease and proteinuria were absent. A substantially reduced elevation of CTGF mRNA (twofold) observed in whole kidney cortices indicated that the primary alteration of CTGF expression was in the glomerulus. These results suggest that CTGF upregulation is an important factor in the pathogenesis of mesangial matrix accumulation and progressive glomerulosclerosis, acting downstream of TGF-beta.

The effect of charge on the renal distribution of ferritin.

PubMed

Cohen, S; Vernier, R L; Michael, A F

1983-02-01

The effect of charge on the tissue distribution of ferritin was evaluated in rats following intravenous administration of 3 monomeric species preparatively separated by molecular sieve chromatography from aggregated ferritin and having the same molecular weight but differing only in electrostatic charge: native ferritin, with a isoelectric point (pI) of 4.5 (NF); cationized ferritin, with a pI of 6.4-7.4 (CF 7.0); and cationized ferritin, with a pI of 8.25-8.75 (CF 8.5). At varying time intervals (30 minutes to 72 hours) after the administration of these ferritins in a dose of 10 mg/100 g, the levels in the blood were determined, the tissue (kidney, liver, spleen) distribution semiquantitatively evaluated by immunofluorescence (IF), and electron microscopic examination (EM) of the kidney carried out. The following results were obtained: 1) The plasma levels of CF (8.5) and CF (7.0) were significantly higher than NF after 6 hours. NF was not detected after 24 hours, whereas CF continued to circulate at 72 hours. 2) There was a striking decrease in the uptake of CF (7.0) and CF (8.5), when compared with NF, by Kupffer cells and splenic phagocytes in the red pulp at all time periods. 3) In the glomerulus, NF was found primarily in the mesangium and gradually disappeared over a period of 72 hours, whereas CF was present in greater amounts and persisted for longer periods of time in the mesangium and in the peripheral capillary wall. By electron microscopy, CF (8.5) could be seen in th lamina rara and within the mesangium in small aggregates aligned parallel to mesangial cell processes, whereas NF and CF (7.0) were distributed homogeneously throughout the mesangial matrix. 4) NF, but not CF, was also observed surrounding blood vessels and in interstitial phagocytes. These in vivo studies demonstrate that the electrostatic charge of ferritin affects its uptake in vivo by components of the mononuclear phagocytic system (MPS). The persistence and distribution of CF in glomeruli is a consequence of higher blood levels associated with impaired phagocytic uptake as well as charge-related binding to sites within the glomeruli.

Farnesol-Detecting Olfactory Neurons in Drosophila

PubMed Central

Ronderos, David S.; Lin, Chun-Chieh; Potter, Christopher J.

2014-01-01

We set out to deorphanize a subset of putative Drosophila odorant receptors expressed in trichoid sensilla using a transgenic in vivo misexpression approach. We identified farnesol as a potent and specific activator for the orphan odorant receptor Or83c. Farnesol is an intermediate in juvenile hormone biosynthesis, but is also produced by ripe citrus fruit peels. Here, we show that farnesol stimulates robust activation of Or83c-expressing olfactory neurons, even at high dilutions. The CD36 homolog Snmp1 is required for normal farnesol response kinetics. The neurons expressing Or83c are found in a subset of poorly characterized intermediate sensilla. We show that these neurons mediate attraction behavior to low concentrations of farnesol and that Or83c receptor mutants are defective for this behavior. Or83c neurons innervate the DC3 glomerulus in the antennal lobe and projection neurons relaying information from this glomerulus to higher brain centers target a region of the lateral horn previously implicated in pheromone perception. Our findings identify a sensitive, narrowly tuned receptor that mediates attraction behavior to farnesol and demonstrates an effective approach to deorphanizing odorant receptors expressed in neurons located in intermediate and trichoid sensilla that may not function in the classical “empty basiconic neuron” system. PMID:24623773

Synaptic Spinules in the Olfactory Circuit of Drosophila melanogaster

PubMed Central

Gruber, Lydia; Rybak, Jürgen; Hansson, Bill S.; Cantera, Rafael

2018-01-01

Here we report on ultrastructural features of brain synapses in the fly Drosophila melanogaster and outline a perspective for the study of their functional significance. Images taken with the aid of focused ion beam-scanning electron microscopy (EM) at 20 nm intervals across olfactory glomerulus DA2 revealed that some synaptic boutons are penetrated by protrusions emanating from other neurons. Similar structures in the brain of mammals are known as synaptic spinules. A survey with transmission EM (TEM) disclosed that these structures are frequent throughout the antennal lobe. Detailed neuronal tracings revealed that spinules are formed by all three major types of neurons innervating glomerulus DA2 but the olfactory sensory neurons (OSNs) receive significantly more spinules than other olfactory neurons. Double-membrane vesicles (DMVs) that appear to represent material that has pinched-off from spinules are also most abundant in presynaptic boutons of OSNs. Inside the host neuron, a close association was observed between spinules, the endoplasmic reticulum (ER) and mitochondria. We propose that by releasing material into the host neuron, through a process triggered by synaptic activity and analogous to axonal pruning, synaptic spinules could function as a mechanism for synapse tagging, synaptic remodeling and neural plasticity. Future directions of experimental work to investigate this theory are proposed. PMID:29636666

Ultrastructural Characterization of the Glomerulopathy in Alport Mice by Helium Ion Scanning Microscopy (HIM).

PubMed

Tsuji, Kenji; Suleiman, Hani; Miner, Jeffrey H; Daley, James M; Capen, Diane E; Păunescu, Teodor G; Lu, Hua A Jenny

2017-09-15

The glomerulus exercises its filtration barrier function by establishing a complex filtration apparatus consisting of podocyte foot processes, glomerular basement membrane and endothelial cells. Disruption of any component of the glomerular filtration barrier leads to glomerular dysfunction, frequently manifested as proteinuria. Ultrastructural studies of the glomerulus by transmission electron microscopy (TEM) and conventional scanning electron microscopy (SEM) have been routinely used to identify and classify various glomerular diseases. Here we report the application of newly developed helium ion scanning microscopy (HIM) to examine the glomerulopathy in a Col4a3 mutant/Alport syndrome mouse model. Our study revealed unprecedented details of glomerular abnormalities in Col4a3 mutants including distorted podocyte cell bodies and disorganized primary processes. Strikingly, we observed abundant filamentous microprojections arising from podocyte cell bodies and processes, and presence of unique bridging processes that connect the primary processes and foot processes in Alport mice. Furthermore, we detected an altered glomerular endothelium with disrupted sub-endothelial integrity. More importantly, we were able to clearly visualize the complex, three-dimensional podocyte and endothelial interface by HIM. Our study demonstrates that HIM provides nanometer resolution to uncover and rediscover critical ultrastructural characteristics of the glomerulopathy in Col4a3 mutant mice.

Histone Deacetylase Rpd3 Regulates Olfactory Projection Neuron Dendrite Targeting via the Transcription Factor Prospero

PubMed Central

Tea, Joy S.; Chihara, Takahiro; Luo, Liqun

2010-01-01

Compared to the mechanisms of axon guidance, relatively little is known about the transcriptional control of dendrite guidance. The Drosophila olfactory system with its stereotyped organization provides an excellent model to study the transcriptional control of dendrite wiring specificity. Each projection neuron (PN) targets its dendrites to a specific glomerulus in the antennal lobe and its axon stereotypically to higher brain centers. Using a forward genetic screen, we identified a mutation in Rpd3 that disrupts PN targeting specificity. Rpd3 encodes a class I histone deacetylase (HDAC) homologous to mammalian HDAC1 and HDAC2. Rpd3−/− PN dendrites that normally target to a dorsolateral glomerulus mistarget to medial glomeruli in the antennal lobe, and axons exhibit a severe overbranching phenotype. These phenotypes can be rescued by postmitotic expression of Rpd3 but not HDAC3, the only other class I HDAC in Drosophila. Furthermore, disruption of the atypical homeodomain transcription factor Prospero (Pros) yields similar phenotypes, which can be rescued by Pros expression in postmitotic neurons. Strikingly, overexpression of Pros can suppress Rpd3−/− phenotypes. Our study suggests a specific function for the general chromatin remodeling factor Rpd3 in regulating dendrite targeting in neurons, largely through the postmitotic action of the Pros transcription factor. PMID:20660276

Synaptic Spinules in the Olfactory Circuit of Drosophila melanogaster.

PubMed

Gruber, Lydia; Rybak, Jürgen; Hansson, Bill S; Cantera, Rafael

2018-01-01

Here we report on ultrastructural features of brain synapses in the fly Drosophila melanogaster and outline a perspective for the study of their functional significance. Images taken with the aid of focused ion beam-scanning electron microscopy (EM) at 20 nm intervals across olfactory glomerulus DA2 revealed that some synaptic boutons are penetrated by protrusions emanating from other neurons. Similar structures in the brain of mammals are known as synaptic spinules. A survey with transmission EM (TEM) disclosed that these structures are frequent throughout the antennal lobe. Detailed neuronal tracings revealed that spinules are formed by all three major types of neurons innervating glomerulus DA2 but the olfactory sensory neurons (OSNs) receive significantly more spinules than other olfactory neurons. Double-membrane vesicles (DMVs) that appear to represent material that has pinched-off from spinules are also most abundant in presynaptic boutons of OSNs. Inside the host neuron, a close association was observed between spinules, the endoplasmic reticulum (ER) and mitochondria. We propose that by releasing material into the host neuron, through a process triggered by synaptic activity and analogous to axonal pruning, synaptic spinules could function as a mechanism for synapse tagging, synaptic remodeling and neural plasticity. Future directions of experimental work to investigate this theory are proposed.

Extracellular purines' action on glomerular albumin permeability in isolated rat glomeruli: insights into the pathogenesis of albuminuria.

PubMed

Kasztan, Małgorzata; Piwkowska, Agnieszka; Kreft, Ewelina; Rogacka, Dorota; Audzeyenka, Irena; Szczepanska-Konkel, Mirosława; Jankowski, Maciej

2016-07-01

Purinoceptors (adrengeric receptors and P2 receptors) are expressed on the cellular components of the glomerular filtration barrier, and their activation may affect glomerular permeability to albumin, which may ultimately lead to albuminuria, a well-established risk factor for the progression of chronic kidney disease and development of cardiovascular diseases. We investigated the mechanisms underlying the in vitro and in vivo purinergic actions on glomerular filter permeability to albumin by measuring convectional albumin permeability (Palb) in a single isolated rat glomerulus based on the video microscopy method. Primary cultured rat podocytes were used for the analysis of Palb, cGMP accumulation, PKG-Iα dimerization, and immunofluorescence. In vitro, natural nucleotides (ATP, ADP, UTP, and UDP) and nonmetabolized ATP analogs (2-meSATP and ATP-γ-S) increased Palb in a time- and concentration-dependent manner. The effects were dependent on P2 receptor activation, nitric oxide synthase, and cytoplasmic guanylate cyclase. ATP analogs significantly increased Palb, cGMP accumulation, and subcortical actin reorganization in a PKG-dependent but nondimer-mediated route in cultured podocytes. In vivo, 2-meSATP and ATP-γ-S increased Palb but did not significantly affect urinary albumin excretion. Both agonists enhanced the clathrin-mediated endocytosis of albumin in podocytes. A product of adenine nucleotides hydrolysis, adenosine, increased the permeability of the glomerular barrier via adrenergic receptors in a dependent and independent manner. Our results suggest that the extracellular nucleotides that stimulate an increase of glomerular Palb involve nitric oxide synthase and cytoplasmic guanylate cyclase with actin reorganization in podocytes. Copyright © 2016 the American Physiological Society.

A novel assay to assess the effect of pharmaceutical compounds on the differentiation of podocytes.

PubMed

Kindt, Frances; Hammer, Elke; Kemnitz, Stefan; Blumenthal, Antje; Klemm, Paul; Schlüter, Rabea; Quaggin, Susan E; van den Brandt, Jens; Fuellen, Georg; Völker, Uwe; Endlich, Karlhans; Endlich, Nicole

2017-01-01

Therapeutic options for treating glomerulopathies, the main cause of chronic kidney disease, are limited. Podocyte dedifferentiation is a major event in the pathogenesis of glomerulopathies. The goal of the present study was, therefore, to develop an assay to monitor podocyte differentiation suitable for compound screening. We isolated and cultured glomeruli from transgenic mice, expressing cyan fluorescent protein (CFP) under the control of the promoter of nephrin, a marker of podocyte differentiation. Mean CFP fluorescence intensity per glomerulus (MFG) was determined by summation of all glomerular voxels from confocal z-stacks in the absence and presence of pharmaceutical compounds. In untreated cultured glomeruli, MFG remained fairly stable during the first 5 days, when foot processes were already effaced, and the level of many podocyte-specific proteins was only mildly affected, as revealed by proteomics. Between day 6 and 9, MFG decreased to almost zero. The decrease in MFG was paralleled by a decrease in CFP and nephrin expression, as determined by RT-PCR, western blots and proteomics. Puromycin aminonucleoside (PAN), which damages podocytes, concentration-dependently induced a complete loss of MFG. Dexamethasone (25 μM) and pioglitazone (10 μM) markedly attenuated the effect of 0.6 μg·mL -1 PAN on MFG. In summary, we established a novel assay to assess the effect of pharmaceutical compounds on the differentiation of podocytes in situ. Our assay is suitable for compound screening to identify drugs for the treatment of glomerulopathies. © 2016 The British Pharmacological Society.

A novel assay to assess the effect of pharmaceutical compounds on the differentiation of podocytes

PubMed Central

Kindt, Frances; Hammer, Elke; Kemnitz, Stefan; Blumenthal, Antje; Klemm, Paul; Schlüter, Rabea; Quaggin, Susan E; van den Brandt, Jens; Fuellen, Georg; Völker, Uwe; Endlich, Karlhans

2016-01-01

Background and Purpose Therapeutic options for treating glomerulopathies, the main cause of chronic kidney disease, are limited. Podocyte dedifferentiation is a major event in the pathogenesis of glomerulopathies. The goal of the present study was, therefore, to develop an assay to monitor podocyte differentiation suitable for compound screening. Experimental Approach We isolated and cultured glomeruli from transgenic mice, expressing cyan fluorescent protein (CFP) under the control of the promoter of nephrin, a marker of podocyte differentiation. Mean CFP fluorescence intensity per glomerulus (MFG) was determined by summation of all glomerular voxels from confocal z‐stacks in the absence and presence of pharmaceutical compounds. Key Results In untreated cultured glomeruli, MFG remained fairly stable during the first 5 days, when foot processes were already effaced, and the level of many podocyte‐specific proteins was only mildly affected, as revealed by proteomics. Between day 6 and 9, MFG decreased to almost zero. The decrease in MFG was paralleled by a decrease in CFP and nephrin expression, as determined by RT‐PCR, western blots and proteomics. Puromycin aminonucleoside (PAN), which damages podocytes, concentration‐dependently induced a complete loss of MFG. Dexamethasone (25 μM) and pioglitazone (10 μM) markedly attenuated the effect of 0.6 μg·mL−1 PAN on MFG. Conclusion and Implications In summary, we established a novel assay to assess the effect of pharmaceutical compounds on the differentiation of podocytes in situ. Our assay is suitable for compound screening to identify drugs for the treatment of glomerulopathies. PMID:27858997

Maternal nutrient restriction in sheep: hypertension and decreased nephron number in offspring at 9 months of age.

PubMed

Gilbert, Jeffrey S; Lang, Alvin L; Grant, Angela R; Nijland, Mark J

2005-05-15

Pregnant ewes were fed either a 50% nutrient-restricted (NR; n= 8) or a control 100% (C; n= 8) diet from day 28 to day 78 of gestation (dGA; term = 150 dGA). Lambs were born naturally, and fed to appetite throughout the study period. At 245 +/- 1 days postnatal age (DPNA), offspring were instrumented for blood pressure measurements, with tissue collection at 270 DPNA. Protein expression was assessed using Western blot, glomerulus number determined via acid maceration and hormone changes by radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA). NR lambs had higher mean arterial pressure (MAP; 89.0 +/- 6.6 versus 73.4 +/- 1.6 mmHg; P < 0.05), fewer renal glomeruli (57.8 +/- 23.8 versus 64.6 +/- 19.3 x 10(4); P < 0.05), increased expression of angiotensin converting enzyme (ACE) in the renal cortex (942 +/- 130 versus 464 +/- 60 arbitrary pixel units (apu); P < 0.03), and increased angiotensin II receptor AT2 expression in the renal medulla (63.3 +/- 12.1 versus 19.5 +/- 44.2 x 10(4) apu; P < 0.03). All data are presented as mean +/-S.E.M. The present data indicate that global maternal nutrient restriction (50%) during early to mid-gestation impairs renal nephrogenesis, increases MAP, and alters expression of AT2 and ACE without an associated change in birth weight. These data demonstrate the existence of a critical window of fetal susceptibility during early to mid-gestation that alters kidney development and blood pressure regulation in later life.

Amelioration of hyperglycaemia and its associated complications by finger millet ( Eleusine coracana L.) seed coat matter in streptozotocin-induced diabetic rats.

PubMed

Shobana, Shanmugam; Harsha, Mysore R; Platel, Kalpana; Srinivasan, Krishnapura; Malleshi, Nagappa G

2010-12-01

Finger millet (Eleusine coracana) is extensively cultivated and consumed in India and Africa. The millet seed coat is a rich source of dietary fibre and phenolic compounds. The effect of feeding a diet containing 20% finger millet seed coat matter (SCM) was examined in streptozotocin-induced diabetic rats. Diabetic rats maintained on the millet SCM diet (diabetic experimental (DE) group) for 6 weeks exhibited a lesser degree of fasting hyperglycaemia and partial reversal of abnormalities in serum albumin, urea and creatinine compared with the diabetic control (DC) group. The DE group of rats excreted comparatively lesser amounts of glucose, protein, urea and creatinine and was accompanied by improved body weights compared with their corresponding controls. Hypercholesterolaemia and hypertriacylglycerolaemia associated with diabetes were also notably reversed in the DE group. Slit lamp examination of the eye lens revealed an immature subcapsular cataract with mild lenticular opacity in the DE group of rats compared to the mature cataract with significant lenticular opacity and corneal vascularisation in the DC group. Lower activity of lens aldose reductase, serum advanced glycation end products and blood glycosylated Hb levels were observed in the DE group. The millet SCM feeding showed pronounced ameliorating effects on kidney pathology as reflected by near normal glomerular and tubular structures and lower glomerular filtration rate compared with the shrunken glomerulus, tubular vacuolations in the DC group. Thus, the present animal study evidenced the hypoglycaemic, hypocholesterolaemic, nephroprotective and anti-cataractogenic properties of finger millet SCM, suggesting its utility as a functional ingredient in diets for diabetics.

[The contribution of endogenous vasodilators to the control of glomerular hemodynamics].

PubMed

Arima, S; Ito, S; Abe, K

1994-06-01

Preglomerular afferent (Af-) and postglomerular efferent arterioles (Ef-Arts) are crucial vascular segments in the control of glomerular hemodynamics. However, their vascular reactivity is not fully understood. We examined: 1) their responses to angiotensin II (AII) or norepinephrine (NE), and 2) the possible modulatory roles of nitric oxide (NO) and prostaglandins (PGs) in these responses. Rabbit Af- or Ef-Arts were microperfused in vitro. Ef-Arts were perfused in either the orthograde direction from the distal end of Af-Arts through the glomerulus (OP) or the retrograde direction from its distal end to eliminate the influence of the glomerulus (RP). Although AII and NE constricted both arterioles in a dose-dependent manner, sensitivity to AII was higher in Ef-Arts. AII began to cause significant (P < 0.01) constriction from 10(-9) M (11 +/- 3%, n = 11) in Af-Arts, and from 10(-11) M in Ef-Arts (OP; 11 +/- 4%, n = 9. RP; 10 +/- 2%, n = 5). In addition, both AII and NE produced stronger constriction of Ef-Arts in RP than OP; AII at 10(-8) M or NE at 10(-6) M decreased the diameter by 35 +/- 4% or 25 +/- 4% in OP and 74 +/- 4% or 62 +/- 7% in RP. NO synthesis inhibitor nitro-L-arginine (L-NAME; 10(-4) M) increased the sensitivity of Af-Art to AII without affecting the reactivity of Ef-Art; in L-NAME-pretreated Af-Arts, AII began to cause significant constriction from 10(-10) M (14 +/- 4%, n = 9, P < 0.01). Thus, L-NAME-pretreatment significantly decreased the differences in sensitivity to AII between Af- and Ef-Arts without affecting different vascular responses between OP and RP. Indomethacin (5 x 10(-5) M) significantly augmented the AII- or NE-induced Ef-Art constriction only in OP; AII at 10(-8) M or NE at 10(-6) M decreased the diameter by 72 +/- 5% (n = 8) or 48 +/- 3% (n = 7). Thus, indomethacin-pretreatment markedly diminished the differences in responses between OP and RP. These results suggest that 1) NO modulates AII action only in the Af-Art, contributing to the difference in sensitivity to AII between Af- and Ef-Art, and 2) the glomerulus controls vascular reactivity of the downstream Ef-Art by releasing PGs.

Pathophysiologic Implications of Reduced Podocyte Number in a Rat Model of Progressive Glomerular Injury

PubMed Central

Macconi, Daniela; Bonomelli, Maria; Benigni, Ariela; Plati, Tiziana; Sangalli, Fabio; Longaretti, Lorena; Conti, Sara; Kawachi, Hiroshi; Hill, Prue; Remuzzi, Giuseppe; Remuzzi, Andrea

2006-01-01

Changes in podocyte number or density have been suggested to play an important role in renal disease progression. Here, we investigated the temporal relationship between glomerular podocyte number and development of proteinuria and glomerulosclerosis in the male Munich Wistar Fromter (MWF) rat. We also assessed whether changes in podocyte number affect podocyte function and focused specifically on the slit diaphragm-associated protein nephrin. Age-matched Wistar rats were used as controls. Estimation of podocyte number per glomerulus was determined by digital morphometry of WT1-positive cells. MWF rats developed moderate hypertension, massive proteinuria, and glomerulosclerosis with age. Glomerular hypertrophy was already observed at 10 weeks of age and progressively increased thereafter. By contrast, mean podocyte number per glomerulus was lower than normal in young animals and further decreased with time. As a consequence, the capillary tuft volume per podocyte was more than threefold increased in older rats. Electron microscopy showed important changes in podocyte structure of MWF rats, with expansion of podocyte bodies surrounding glomerular filtration membrane. Glomerular nephrin expression was markedly altered in MWF rats and inversely correlated with both podocyte loss and proteinuria. Our findings suggest that reduction in podocyte number is an important determinant of podocyte dysfunction and progressive impairment of the glomerular permselectivity that lead to the development of massive proteinuria and ultimately to renal scarring. PMID:16400008

[Clinical and pathological features of Alport syndrome in children].

PubMed

Zhu, Chun-Hua; Huang, Song-Ming; Wu, Hong-Mei; Bao, Hua-Ying; Chen, Ying; Han, Yuan; Zhao, Fei; Zhang, Ai-Hua; Zhang, Wei-Zhen

2010-03-01

To study the clinical and pathological features of Alport syndrome in children. The clinical and histopathological data of 10 hospitalized children with Alport syndrome from February 2007 to February 2009 were retrospectively reviewed. There were 7 males and 3 females, with the age ranging from 2 years to 6 years and 7 months (mean 3 years and 2 months). Five of 10 cases had positive family history. X-linked dominant inheritance Alport syndrome was diagnosed in 8 cases, and autosomal recessive inheritance Alport syndrome in 2 cases. Recurrent gross hematuria was found in 5 cases, hematuria and proteinuria in 3 cases, massive proteinuria in 1 case, and nephritic syndrome in 1 case. Under the light microscope, 8 cases presented with mesangial proliferation glomerulonephritis, and 2 cases with focal segmental glomerulosclerosis. Immunofluorescence assay showed that all cases had IgM deposition in glomerulus. Only 1 case showed typical glomerular basement membrane (GBM) pathological changes. All cases showed abnormal alpha-chain distribution in renal collagen IV. The children with Alport syndrome have diverse clinical manifestations. Characteristic histopathological presentations could not be found under a light microscope, mesangial proliferation glomerulonephritis is the dominant pathological change, and IgM deposition in glomerulus is common. The GBM pathological change in children is not common. Immunofluorescence assay of alpha-chain in collagen IV is needed for the diagnosis of Alport syndrome.

[Development of the Human Olfactory Bulbs in the Prenatal Ontogenesis: an Immunochistochemical Study with Markers of Presynaptic Terminals (anti-SNAP-25, -Synapsin-I, -Synaptophysin)].

PubMed

Kharlamova, A S; Barabanov, V M; Saveliev, S V

2015-01-01

We provide the data of the olfactory bulbs (OB) development in the human fetuses on the stages from 8 week to birth. Immunochistochemical markers of presynaptic terminals (anti-SNAP-25, -synapsin-I, -synaptophysin) were used to evaluate the maturation of the OB. Differentiation of the OB layers begins from periphery, which implicitly evidences that growth of the olfactory nerves fibers induses not only anatomical differentiation of the OB, but also differentiation of its functional layers. The sites of the developing glomerulus are revealed using the immunochistochemical prosedure on the stage before distinct glomerulus can be identified with common histological procedure. OB conductive system demonstrates immunoreactivity with the antibodies to the presynaptic proteins on the all stages from 10-11 weeks of fetus development. Four stages of the OB development are described. All functional layers of the OB are mature at the 22-weeks stage. Further differentiation of the OB neuroblasts, including lamina formation of the internal granular leyer, glomerular layer development, OB growth continue after 20-22 weeks stage until 38-40 weeks of the fetus develoment. Patterns of the immunoreactivity with antibodies to SNAP-25, synapsin-I and synaptophysin are completely appropriate to those of adult's OB on the 38-40 weeks of the prenatal development. Complete maturity of the human OB is achived at 38-40 weeks of the prenatal development.

Rosiglitazone reduces renal and plasma markers of oxidative injury and reverses urinary metabolite abnormalities in the amelioration of diabetic nephropathy.

PubMed

Zhang, Hongyu; Saha, Jharna; Byun, Jaeman; Schin, MaryLee; Lorenz, Matthew; Kennedy, Robert T; Kretzler, Matthias; Feldman, Eva L; Pennathur, Subramaniam; Brosius, Frank C

2008-10-01

Recent studies suggest that thiazolidinediones ameliorate diabetic nephropathy (DN) independently of their effect on hyperglycemia. In the current study, we confirm and extend these findings by showing that rosiglitazone treatment prevented the development of DN and reversed multiple markers of oxidative injury in DBA/2J mice made diabetic by low-dose streptozotocin. These diabetic mice developed a 14.2-fold increase in albuminuria and a 53% expansion of renal glomerular extracellular matrix after 12 wk of diabetes. These changes were largely abrogated by administration of rosiglitazone beginning 2 wk after the completion of streptozotocin injections. Rosiglitazone had no effect on glycemic control. Rosiglitazone had similar effects on insulin-treated diabetic mice after 24 wk of diabetes. Podocyte loss and glomerular fibronectin accumulation, other markers of early DN, were prevented by rosiglitazone in both 12- and 24-wk diabetic models. Surprisingly, glomerular GLUT1 levels did not increase and nephrin levels did not decrease in the diabetic animals; neither changed with rosiglitazone. Plasma and kidney markers of protein oxidation and lipid peroxidation were significantly elevated in the 24-wk diabetic animals despite insulin treatment and were reduced to near-normal levels by rosiglitazone. Finally, urinary metabolites were markedly altered by diabetes. Of 1,988 metabolite features identified by electrospray ionization time of flight mass spectrometry, levels of 56 were altered more than twofold in the urine of diabetic mice. Of these, 21 were returned to normal by rosiglitazone. Thus rosiglitazone has direct effects on the renal glomerulus to reduce reactive oxygen species accumulation to prevent type 1 diabetic mice from development of DN.

TGF-β–Activated Kinase 1 Is Crucial in Podocyte Differentiation and Glomerular Capillary Formation

PubMed Central

Lee, So-Young; Wang, Zhibo; Ding, Yan; Haque, Nadeem; Zhang, Jiwang; Zhou, Jing

2014-01-01

TGF-β–activated kinase 1 (TAK1) is a key intermediate in signal transduction induced by TGF-β or inflammatory cytokines, such as TNF-α and IL-1, which are potent inducers of podocyte injury responses that lead to proteinuria and glomerulosclerosis. Nevertheless, little is known about the physiologic and pathologic roles of TAK1 in podocytes. To examine the in vivo role of TAK1, we generated podocyte-specific Tak1 knockout mice (Nphs2-Cre+:Tak1fx/fx; Tak1∆/∆). Targeted deletion of Tak1 in podocytes resulted in perinatal lethality, with approximately 50% of animals dying soon after birth and 90% of animals dying within 1 week of birth. Tak1∆/∆ mice developed proteinuria from P1 and exhibited delayed glomerulogenesis and reduced expression of Wilms’ tumor suppressor 1 and nephrin in podocytes. Compared with Tak1fx/fx mice, Tak1∆/∆ mice exhibited impaired formation of podocyte foot processes that caused disruption of the podocyte architecture with prominent foot process effacement. Intriguingly, Tak1∆/∆ mice displayed increased expression of vascular endothelial growth factor within the glomerulus and abnormally enlarged glomerular capillaries. Furthermore, 4- and 7-week-old Tak1∆/∆ mice with proteinuria had increased collagen deposition in the mesangium and the adjacent tubulointerstitial area. Thus, loss of Tak1 in podocytes is associated with the development of proteinuria and glomerulosclerosis. Taken together, our data show that TAK1 regulates the expression of Wilms’ tumor suppressor 1, nephrin, and vascular endothelial growth factor and that TAK1 signaling has a crucial role in podocyte differentiation and attainment of normal glomerular microvasculature during kidney development and glomerular filtration barrier homeostasis. PMID:24652804

Deterioration of glomerular endothelial surface layer and the alteration in the renal function after a growth promoter boldenone injection in rabbits.

PubMed

Alm-Eldeen, A; Tousson, E

2012-05-01

Boldenone is an anabolic steroid developed for veterinary use. Recently, it is used by bodybuilders in both off-season and precontest, where it is well known for increasing vascularity while preparing for a bodybuilding contest. However, the side effect of this steroid on the human health is still unclear. Therefore, the present study was designed to investigate the possible effect of the growth promoter, boldenone undecylenate, on the function and structure of the rabbit's kidneys. A total of 36 adult New Zealand rabbits were divided into 4 groups. Control group includes animals that were injected intramuscularly with olive oil and dissected after 3 weeks. Three experimental groups include animals that receive one, two and three intramuscular injections of 5 mg/kg body weight boldenone, and dissected after 3, 6, and 9 weeks, respectively, and the interval of each dose of boldenone was 3 weeks. The biochemical analysis of the blood serum of treated rabbit showed a significant increase in the total protein, urea and creatinine concentrations, with a significant decrease in albumin/globulin (A/G) ratio. At the same time, a significant glomerulus mass reduction that accompanied with the expression of CD34, a marker for endothelial cells deterioration, was also determined. The incidence of the glomerulosclerosis was significantly increased compared with the control group (0.46 ± 0.05, p < 0.05). The glomerulosclerosis scores were 1.32 ± 0.10, 2.14 ± 0.11 and 3.02 ± 0.09 in groups 2, 3 and 4, respectively. These findings suggest that misuse of the boldenone undecylenate may contribute to the occurrence of a chronic renal injury that may lead to a progressive renal failure.

Therapeutic targeting of aldosterone: a novel approach to the treatment of glomerular disease

PubMed Central

Brem, Andrew S.; Gong, Rujun

2015-01-01

Numerous studies have established a role for mineralocorticoids in the development of renal fibrosis. Originally, the research focus for mineralocorticoid-induced fibrosis was on the collecting duct, where “classical” mineralocorticoid receptors (MR) involved with electrolyte transport are present. Epithelial cells in this segment can, under selected circumstances, also respond to MR activation by initiating pro-fibrotic pathways. More recently, “non-classical” MR have been described in kidney cells not associated with electrolyte transport including mesangial cells and podocytes within the glomerulus. Activation of MR in these cells appears to lead to glomerular sclerosis. Mechanistically, aldosterone induces excess production of reactive oxygen species (ROS) and oxidative stress in glomerular cells through activation of NADPH oxidase. In mesangial cells, aldosterone also has pro-apoptotic, mitogenic, and pro-fibrogenic effects, all of which potentially promote active remodeling and expansion of the mesangium. While mitochondrial dysfunction seems to mediate the aldosterone-induced mesangial apoptosis, the ROS dependent EGFR transactivation is likely responsible for aldosterone-induced mesangial mitosis and proliferation. In podocytes, mitochondrial dysfunction elicited by oxidative stress is an early event associated with aldosterone-induced podocyte injury. Both the p38MAPK signaling and the redox sensitive glycogen synthase kinase (GSK) 3β pathways are centrally implicated in aldosterone-induced podocyte death. Aldosterone-induced GSK3β over-activity could potentially cause hyperphosphorylation and over-activation of putative GSK3β substrates, including structural components of the mitochondrial permeability transition (MPT) pore, all of which lead to cell injury and death. Clinically, proteinuria significantly decreases when aldosterone inhibitors are included in the treatment of many glomerular diseases further supporting the view that mineralocorticoids are important players in glomerular pathology. PMID:25671776

Characteristics of microRNAs enriched in specific cell types and primary tissue types in solid organs.

PubMed

Kriegel, Alison J; Liu, Yong; Liu, Pengyuan; Baker, Maria Angeles; Hodges, Matthew R; Hua, Xing; Liang, Mingyu

2013-12-01

Knowledge of miRNA expression and function in specific cell types in solid organs is limited because of difficulty in obtaining appropriate specimens. We used laser capture microdissection to obtain nine tissue regions from rats, including the nucleus of the solitary tract, hypoglossal motor nucleus, ventral respiratory column/pre-Bötzinger complex, and midline raphe nucleus from the brain stem, myocardium and coronary artery from the heart, and glomerulus, proximal convoluted tubule, and medullary thick ascending limb from the kidney. Each tissue region consists of or is enriched for a specific cell type. Differential patterns of miRNA expression obtained by deep sequencing of minute amounts of laser-captured cells were highly consistent with data obtained from real-time PCR analysis. miRNA expression patterns correctly clustered the specimens by tissue regions and then by primary tissue types (neural, muscular, or epithelial). The aggregate difference in miRNA profiles between tissue regions that contained the same primary tissue type was as large as one-half of the aggregate difference between primary tissue types. miRNAs differentially expressed between primary tissue types are more likely to be abundant miRNAs, while miRNAs differentially expressed between tissue regions containing the same primary tissue type were distributed evenly across the abundance spectrum. The tissue type-enriched miRNAs were more likely to target genes enriched for specific functional categories compared with either cell type-enriched miRNAs or randomly selected miRNAs. These data indicate that the role of miRNAs in determining characteristics of primary tissue types may be different than their role in regulating cell type-specific functions in solid organs.

IGF-1, IGFBP-3 and ALS in adult patients with chronic kidney disease.

PubMed

Lepenies, Julia; Wu, Zida; Stewart, Paul M; Strasburger, Christian J; Quinkler, Marcus

2010-04-01

Insulin-like growth factor I (IGF-1) is for the most part bound in a ternary complex with IGF-binding protein-3 (IGFBP-3) and acid-labile subunit (ALS). This ternary complex is a storage form of IGF-1 in blood and passes not through the renal glomerulus. Little information is available in regard to the components of the ternary complex in adult renal disease. To investigate levels of serum IGF-1, IGFBP-3 and ALS in relation to renal function and extent of proteinuria. We measured IGF-1, IGFBP-3 and ALS concentrations in 137 patients who were investigated due to proteinuria and/or haematuria and/or renal impairment. The patients received renal biopsies and the histological diagnosis was documented. Urinary albumin excretion and relevant clinical parameter were evaluated. IGF-1 showed a highly positive correlation to IGFBP-3 and ALS, and the latter to IGFBP-3. IGF-1, IGFBP-3 and ALS decreased with increasing age. IGF-1 and IGFBP-3 showed no significant change depending on the creatinine clearance. However, ALS decreased with decreasing renal function. In patients with heavy proteinuria ALS levels, but not IGF-1 and IGFBP-3 levels, decreased significantly. Patients with chronic ischaemic renal damage and diabetic glomerulopathy showed higher IGF-1 and IGFBP-3 levels compared to patients with thin glomerular basement membrane disease despite their older age. IGF-1 and IGFBP-3 levels seem to be independent of renal function and severity of proteinuria. However, ALS levels are altered in renal failure and nephrotic syndrome, which may be due to increased renal loss or diminished hepatic production or both. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Disruptive chemical doping in a ferritin-based iron oxide nanoparticle to decrease r2 and enhance detection with T1-weighted MRI.

PubMed

Clavijo Jordan, M Veronica; Beeman, Scott C; Baldelomar, Edwin J; Bennett, Kevin M

2014-01-01

Inorganic doping was used to create flexible, paramagnetic nanoparticle contrast agents for in vivo molecular magnetic resonance imaging (MRI) with low transverse relaxivity (r2). Most nanoparticle contrast agents formed from superparamagnetic metal oxides are developed with high r2. While sensitive, they can have limited in vivo detection due to a number of constraints with T2 or T2*-weighted imaging. T1-weighted imaging is often preferred for molecular MRI, but most T1-shortening agents are small chelates with low metal payload or are nanoparticles that also shorten T2 and limit the range of concentrations detectable with T1-weighting. Here we used tungsten and iron deposition to form doped iron oxide crystals inside the apoferritin cavity to form a WFe nanoparticle with a disordered crystal and un-coupled atomic magnetic moments. The atomic magnetic moments were thus localized, resulting in a principally paramagnetic nanoparticle. The WFe nanoparticles had no coercivity or saturation magnetization at 5 K and sweeping up to ± 20,000 Oe, while native ferritin had a coercivity of 3000 Oe and saturation at ± 20,000 Oe. This tungsten-iron crystal paramagnetism resulted in an increased WFe particle longitudinal relaxivity (r1) of 4870 mm(-1) s(-1) and a reduced transverse relaxivity (r2) of 9076 mm(-1) s(-1) compared with native ferritin. The accumulation of the particles was detected with T1-weighted MRI in concentrations from 20 to 400 nm in vivo, both injected in the rat brain and targeted to the rat kidney glomerulus. The WFe apoferritin nanoparticles were not cytotoxic up to 700 nm particle concentrations, making them potentially important for targeted molecular MRI. Copyright © 2014 John Wiley & Sons, Ltd.

ER stress and basement membrane defects combine to cause glomerular and tubular renal disease resulting from Col4a1 mutations in mice

PubMed Central

Jones, Frances E.; Bailey, Matthew A.; Murray, Lydia S.; Lu, Yinhui; McNeilly, Sarah; Schlötzer-Schrehardt, Ursula; Lennon, Rachel; Sado, Yoshikazu; Brownstein, David G.; Mullins, John J.; Kadler, Karl E.; Van Agtmael, Tom

2016-01-01

ABSTRACT Collagen IV is a major component of basement membranes, and mutations in COL4A1, which encodes collagen IV alpha chain 1, cause a multisystemic disease encompassing cerebrovascular, eye and kidney defects. However, COL4A1 renal disease remains poorly characterized and its pathomolecular mechanisms are unknown. We show that Col4a1 mutations in mice cause hypotension and renal disease, including proteinuria and defects in Bowman's capsule and the glomerular basement membrane, indicating a role for Col4a1 in glomerular filtration. Impaired sodium reabsorption in the loop of Henle and distal nephron despite elevated aldosterone levels indicates that tubular defects contribute to the hypotension, highlighting a novel role for the basement membrane in vascular homeostasis by modulation of the tubular response to aldosterone. Col4a1 mutations also cause diabetes insipidus, whereby the tubular defects lead to polyuria associated with medullary atrophy and a subsequent reduction in the ability to upregulate aquaporin 2 and concentrate urine. Moreover, haematuria, haemorrhage and vascular basement membrane defects confirm an important vascular component. Interestingly, although structural and compositional basement membrane defects occurred in the glomerulus and Bowman's capsule, no tubular basement membrane defects were detected. By contrast, medullary atrophy was associated with chronic ER stress, providing evidence for cell-type-dependent molecular mechanisms of Col4a1 mutations. These data show that both basement membrane defects and ER stress contribute to Col4a1 renal disease, which has important implications for the development of treatment strategies for collagenopathies. PMID:26839400

Mixed organic solvents induce renal injury in rats.

PubMed

Qin, Weisong; Xu, Zhongxiu; Lu, Yizhou; Zeng, Caihong; Zheng, Chunxia; Wang, Shengyu; Liu, Zhihong

2012-01-01

To investigate the injury effects of organic solvents on kidney, an animal model of Sprague-Dawley (SD) rats treated with mixed organic solvents via inhalation was generated and characterized. The mixed organic solvents consisted of gasoline, dimethylbenzene and formaldehyde (GDF) in the ratio of 2:2:1, and were used at 12,000 PPM to treat the rats twice a day, each for 3 hours. Proteinuria appeared in the rats after exposure for 5-6 weeks. The incidences of proteinuria in male and female rats after exposure for 12 weeks were 43.8% (7/16) and 25% (4/16), respectively. Urinary N-Acetyl-β-(D)-Glucosaminidase (NAG) activity was increased significantly after exposure for 4 weeks. Histological examination revealed remarkable injuries in the proximal renal tubules, including tubular epithelial cell detachment, cloud swelling and vacuole formation in the proximal tubular cells, as well as proliferation of parietal epithelium and tubular reflux in glomeruli. Ultrastructural examination found that brush border and cytoplasm of tubular epithelial cell were dropped, that tubular epithelial cells were partially disintegrated, and that the mitochondria of tubular epithelial cells were degenerated and lost. In addition to tubular lesions, glomerular damages were also observed, including segmental foot process fusion and loss of foot process covering on glomerular basement membrane (GBM). Immunofluorescence staining indicated that the expression of nephrin and podocin were both decreased after exposure of GDF. In contrast, increased expression of desmin, a marker of podocyte injury, was found in some areas of a glomerulus. TUNEL staining showed that GDF induced apoptosis in tubular cells and glomerular cells. These studies demonstrate that GDF can induce both severe proximal tubular damage and podocyte injury in rats, and the tubular lesions appear earlier than that of glomeruli.

Mixed Organic Solvents Induce Renal Injury in Rats

PubMed Central

Qin, Weisong; Xu, Zhongxiu; Lu, Yizhou; Zeng, Caihong; Zheng, Chunxia; Wang, Shengyu; Liu, Zhihong

2012-01-01

To investigate the injury effects of organic solvents on kidney, an animal model of Sprague-Dawley (SD) rats treated with mixed organic solvents via inhalation was generated and characterized. The mixed organic solvents consisted of gasoline, dimethylbenzene and formaldehyde (GDF) in the ratio of 2∶2:1, and were used at 12,000 PPM to treat the rats twice a day, each for 3 hours. Proteinuria appeared in the rats after exposure for 5–6 weeks. The incidences of proteinuria in male and female rats after exposure for 12 weeks were 43.8% (7/16) and 25% (4/16), respectively. Urinary N-Acetyl-β-(D)-Glucosaminidase (NAG) activity was increased significantly after exposure for 4 weeks. Histological examination revealed remarkable injuries in the proximal renal tubules, including tubular epithelial cell detachment, cloud swelling and vacuole formation in the proximal tubular cells, as well as proliferation of parietal epithelium and tubular reflux in glomeruli. Ultrastructural examination found that brush border and cytoplasm of tubular epithelial cell were dropped, that tubular epithelial cells were partially disintegrated, and that the mitochondria of tubular epithelial cells were degenerated and lost. In addition to tubular lesions, glomerular damages were also observed, including segmental foot process fusion and loss of foot process covering on glomerular basement membrane (GBM). Immunofluorescence staining indicated that the expression of nephrin and podocin were both decreased after exposure of GDF. In contrast, increased expression of desmin, a marker of podocyte injury, was found in some areas of a glomerulus. TUNEL staining showed that GDF induced apoptosis in tubular cells and glomerular cells. These studies demonstrate that GDF can induce both severe proximal tubular damage and podocyte injury in rats, and the tubular lesions appear earlier than that of glomeruli. PMID:23029287

Macroglomeruli for fruit odors change blend preference in Drosophila

NASA Astrophysics Data System (ADS)

Ibba, Irene; Angioy, Anna Maria; Hansson, Bill S.; Dekker, Teun

2010-12-01

The olfactory circuitry of Drosophila melanogaster is becoming increasingly clear. However, how olfactory processing translates into appropriate behavioral responses is still poorly understood. Using a sibling species approach, we tested how a perturbation in the olfactory circuitry affects odor preference. In a previous study, we found that the sibling species of D. melanogaster, the specialist D. sechellia, overrepresents a sensillum, ab3, the A neuron of which is sensitive to hexanoate esters, characteristic of the species' sole host, the Morinda citrifolia fruit. Concordantly, the corresponding glomerulus, DM2, is enlarged. In this study, we found that the ab3B neuron, the expansion of which was previously assumed to be pleiotropic and of no ecological significance, is in fact tuned to another morinda fruit volatile, 2-heptanone (HP). Axons of this neuron type arborize in a second enlarged glomerulus. In behavioral experiments we tested how this has affected the fly's odor preference. We demonstrate that D. sechellia has a reversed preference for the key ligands of these macroglomeruli, especially at high concentrations. Whereas D. melanogaster was repelled by high concentrations of these odors, D. sechellia was highly attracted. This was the case for odors presented singly, but more notably for blends thereof. Our study indicates that relatively simple changes, such as a shift in sensillar abundance, and concordant shifts in glomerular size, can distort the resulting olfactory code, and can lead to saltatory shifts in odor preference. D. sechellia has exploited this to align its olfactory preference with its ecological niche.

Ultrastructure of the central subnucleus of the nucleus tractus solitarii and the esophageal afferent terminals in the rat.

PubMed

Hayakawa, Tetsu; Takanaga, Akinori; Tanaka, Koichi; Maeda, Seishi; Seki, Makoto

2003-03-01

The central subnucleus of the nucleus tractus solitarii (ceNTS) receives afferent projections from the esophageal wall and projects to the nucleus ambiguus, thus serving as a relay nucleus for peristalsis of the esophagus. Here we examine the synaptic organization of the ceNTS, and its esophageal afferents by using transganglionic anterograde transport of cholera toxin-conjugated horseradish peroxidase (CT-HRP). When CT-HRP was injected into the subdiaphragmatic esophagus, many anterogradely labeled terminals were found only in the ceNTS. The ceNTS was composed of round or oval-shaped, small neurons (14.7x8.7 micro m) containing sparse organelles and an irregularly shaped nucleus. The average number of axosomatic terminals was only 1.3 per section cut through the nucleolus. Most of them (92%) contained round vesicles and formed asymmetric synaptic contacts (Gray's type I), and a few (8%) contained pleomorphic vesicles and formed symmetric synaptic contacts (Gray's type II). All anterogradely labeled terminals contacted dendrites but not the neuronal somata. The labeled terminals were large (2.55+/-0.07 micro m) and exclusively Gray's type I. More than half of them (60%) contacted small dendrites (less than 1 micro m in diameter), and contained dense-cored vesicles. More than 40% of the labeled terminals contacted two to four dendrites, thus forming a synaptic glomerulus. Sometimes a labeled terminal that contacted an unlabeled terminal by an adherent junction was found within the glomerulus. The large terminals and these complex synaptic relations appeared to characterize the esophageal afferent projections in the ceNTS.

Adiponectin Enhances the Responsiveness of the Olfactory System

PubMed Central

Loch, Diana; Heidel, Christian; Breer, Heinz; Strotmann, Jörg

2013-01-01

The peptide hormone adiponectin is secreted by adipose tissue and the circulating concentration is reversely correlated with body fat mass; it is considered as starvation signal. The observation that mature sensory neurons of the main olfactory epithelium express the adiponectin receptor 1 has led to the concept that adiponectin may affect the responsiveness of the olfactory system. In fact, electroolfactogram recordings from olfactory epithelium incubated with exogenous adiponectin resulted in large amplitudes upon odor stimulation. To determine whether the responsiveness of the olfactory sensory neurons was enhanced, we have monitored the odorant-induced expression of the immediate early gene Egr1. It was found that in an olfactory epithelium incubated with nasally applied adiponectin the number of Egr1 positive cells was significantly higher compared to controls, suggesting that adiponectin rendered the olfactory neurons more responsive to an odorant stimulus. To analyze whether the augmented responsiveness of sensory neurons was strong enough to elicit a higher neuronal activity in the olfactory bulb, the number of activated periglomerular cells of a distinct glomerulus was determined by monitoring the stimulus-induced expression of c-fos. The studies were performed using the transgenic mOR256-17-IRES-tauGFP mice which allowed to visualize the corresponding glomerulus and to stimulate with a known ligand. The data indicate that upon exposure to 2,3-hexanedione in adiponectin-treated mice the number of activated periglomerular neurons was significantly increased compared to controls. The results of this study indicate that adiponectin increases the responsiveness of the olfactory system, probably due to a higher responsiveness of olfactory sensory neurons. PMID:24130737

Automated renal histopathology: digital extraction and quantification of renal pathology

NASA Astrophysics Data System (ADS)

Sarder, Pinaki; Ginley, Brandon; Tomaszewski, John E.

2016-03-01

The branch of pathology concerned with excess blood serum proteins being excreted in the urine pays particular attention to the glomerulus, a small intertwined bunch of capillaries located at the beginning of the nephron. Normal glomeruli allow moderate amount of blood proteins to be filtered; proteinuric glomeruli allow large amount of blood proteins to be filtered. Diagnosis of proteinuric diseases requires time intensive manual examination of the structural compartments of the glomerulus from renal biopsies. Pathological examination includes cellularity of individual compartments, Bowman's and luminal space segmentation, cellular morphology, glomerular volume, capillary morphology, and more. Long examination times may lead to increased diagnosis time and/or lead to reduced precision of the diagnostic process. Automatic quantification holds strong potential to reduce renal diagnostic time. We have developed a computational pipeline capable of automatically segmenting relevant features from renal biopsies. Our method first segments glomerular compartments from renal biopsies by isolating regions with high nuclear density. Gabor texture segmentation is used to accurately define glomerular boundaries. Bowman's and luminal spaces are segmented using morphological operators. Nuclei structures are segmented using color deconvolution, morphological processing, and bottleneck detection. Average computation time of feature extraction for a typical biopsy, comprising of ~12 glomeruli, is ˜69 s using an Intel(R) Core(TM) i7-4790 CPU, and is ~65X faster than manual processing. Using images from rat renal tissue samples, automatic glomerular structural feature estimation was reproducibly demonstrated for 15 biopsy images, which contained 148 individual glomeruli images. The proposed method holds immense potential to enhance information available while making clinical diagnoses.

The glial investment of the adult and developing antennal lobe of Drosophila

PubMed Central

Oland, Lynne A.; Biebelhausen, John P.; Tolbert, Leslie P.

2009-01-01

In recent years, the Drosophila olfactory system, with its unparalleled opportunities for genetic dissection of development and functional organization, has been used to study the development of central olfactory neurons and the molecular basis of olfactory coding. The results of these studies have been interpreted in the absence of a detailed understanding of the steps in maturation of glial cells in the antennal lobe. Here, we present a high-resolution study of the glia associated with olfactory glomeruli in adult and developing antennal lobes. The study provides a basis for comparison of findings in Drosophila with those in the moth Manduca sexta that indicate a critical role for glia in antennal lobe development. Using flies expressing GFP under a Nervana2 driver to visualize glia for confocal microscopy, and probing at higher resolution with the electron microscope, we find that glial development in Drosophila differs markedly from that in moths: glial cell bodies remain in a rind around the glomerular neuropil; glial processes ensheathe axon bundles in the nerve layer but likely contribute little to axonal sorting; their processes insinuate between glomeruli only very late and then form only a sparse, open network around each glomerulus; and glial processes invade the synaptic neuropil. Taking our results in the context of previous studies, we conclude that glial cells in the developing Drosophila antennal lobe are unlikely to play a strong role in either axonal sorting or glomerulus stabilization and that in the adult, glial processes do not electrically isolate glomeruli from their neighbors. PMID:18537134

Significant association between renal function and area of amyloid deposition in kidney biopsy specimens in both AA amyloidosis associated with rheumatoid arthritis and AL amyloidosis.

PubMed

Kuroda, Takeshi; Tanabe, Naohito; Hasegawa, Eriko; Wakamatsu, Ayako; Nozawa, Yukiko; Sato, Hiroe; Nakatsue, Takeshi; Wada, Yoko; Ito, Yumi; Imai, Naofumi; Ueno, Mitsuhiro; Nakano, Masaaki; Narita, Ichiei

2017-06-01

The kidney is a major target organ for systemic amyloidosis, which results in proteinuria and an elevated serum creatinine level. The clinical manifestations and precursor proteins of amyloid A (AA) and light-chain (AL) amyloidosis are different, and the renal damage due to amyloid deposition also seems to differ. The purpose of this study was to clarify haw the difference in clinical features between AA and AL amyloidosis are explained by the difference in the amount and distribution of amyloid deposition in the renal tissues. A total of 119 patients participated: 58 patients with an established diagnosis of AA amyloidosis (AA group) and 61 with AL amyloidosis (AL group). We retrospectively investigated the correlation between clinical data, pathological manifestations, and the area occupied by amyloid in renal biopsy specimens. In most of the renal specimens the percentage area occupied by amyloid was less than 10%. For statistical analyses, the percentage area of amyloid deposition was transformed to a common logarithmic value (Log 10 %amyloid). The results of sex-, age-, and Log 10 %amyloid-adjusted analyses showed that systolic blood pressure (SBP) was higher in the AA group. In terms of renal function parameters, serum creatinine, creatinine clearance (Ccr) and estimated glomerular filtration rate (eGFR) indicated significant renal impairment in the AA group, whereas urinary protein indicated significant renal impairment in the AL group. Pathological examinations revealed amyloid was predominantly deposited at glomerular basement membrane (GBM) and easily transferred to the mesangial area in the AA group, and it was predominantly deposited at in the AL group. The degree of amyloid deposition in the glomerular capillary was significantly more severe in AL group. The frequency of amyloid deposits in extraglomerular mesangium was not significantly different between the two groups, but in AA group, the degree amyloid deposition was significantly more severe, and the deposition pattern in the glomerulus was nodular. Nodular deposition in extraglomerular mesangium leads to renal impairment in AA group. There are significant differences between AA and AL amyloidosis with regard to the renal function, especially in terms of Ccr, eGFR and urinary protein, even after Log10%amyloid was adjusted; showing that these inter-group differences in renal function would not be depend on the amount of renal amyloid deposits. These differences could be explained by the difference in distribution and morphological pattern of amyloid deposition in the renal tissue.

Up-Regulation of Connexin43 in Glomerular Podocytes in Response to Injury

PubMed Central

Yaoita, Eishin; Yao, Jian; Yoshida, Yutaka; Morioka, Tetsuo; Nameta, Masaaki; Takata, Takuma; Kamiie, Jun-ichi; Fujinaka, Hidehiko; Oite, Takashi; Yamamoto, Tadashi

2002-01-01

Podocyte injury or podocyte loss in the renal glomerulus has been proposed as the crucial mechanism in the development of focal segmental glomerulosclerosis. However, it is poorly understood how podocytes respond to injury. In this study, glomerular expression of connexin43 (Cx43) gap junction protein was examined at both protein and transcript levels in an experimental model of podocyte injury, puromycin aminonucleoside (PAN) nephrosis. A striking increase in the number of immunoreactive dots with anti-Cx43 antibody was demonstrated along the glomerular capillary wall in the early to nephrotic stage of PAN nephrosis. The conspicuous change was not detected in the other areas including the mesangium and Bowman’s capsule. Immunoelectron microscopy showed that the immunogold particles for Cx43 along the capillary wall were localized predominantly at the cell-cell contact sites of podocytes. Consistently, Western blotting and ribonuclease protection assay revealed a distinct increase of Cx43 protein, phosphorylation, and transcript in glomeruli during PAN nephrosis. The changes were detected by 6 hours after PAN injection. These findings indicate that the increase of Cx43 expression is one of the earliest responses that have ever been reported in podocyte injury. To show the presence of functional gap junctional intercellular communication (GJIC) in podocytes, GJIC was assessed in podocytes in the primary culture by transfer of fluorescent dye, Lucifer yellow, after a single-cell microinjection. Diffusion of the dye into adjacent cells was observed frequently in the cultured podocytes, but scarcely in cultured parietal epithelial cells of Bowman’s capsule, which was compatible with their Cx43 staining. Thus, it is concluded that Cx43-mediated GJIC is present between podocytes, suggesting that podocytes may respond to injury as an integrated epithelium on a glomerulus rather than individually as a separate cell. PMID:12414508

NITROGEN RETENTION IN THE BLOOD IN EXPERIMENTAL ACUTE NEPHRITIS OF THE CAT

PubMed Central

Folin, Otto; Karsner, Howard T.; Denis, W.

1912-01-01

It will be seen that uranium nephritis, which involves both tubules and glomeruli, the former more markedly than the latter, produces a marked accumulation of nitrogen in the blood. Chromate nephritis, which involves almost exclusively the tubules, produces only moderate retention of nitrogen. Cantharidin nephritis which involves both tubules and glomeruli, the latter more severely than does uranium, produces a marked accumulation of nitrogen, beginning early and persisting for a considerable period. The experiments were controlled by testing the blood of normal cats kept under the same conditions, these animals showing only slight variations from day to day. This general statement is in accordance with the physiological classification of these nephritides except that the retention in uranium occurs at an early stage, where, according to the physiological studies of Schlayer and his associates, and of Pearce, Hill, and Eisenbrey, the vascular changes have not as yet appeared. It must be noticed that in the three types of nephritis that form the subject of this investigation, anatomical study shows the glomerulus to be distinctly involved in the two forms where accumulation of nitrogen in the blood is most marked, a condition indicating that although almost pure tubular involvement produces only moderate accumulation, the additional involvement of the glomerulus is extremely important in leading to a retention of nitrogenous waste products. The accumulation of non-protein nitrogen in the blood and tissues is not large when compared with the total intake or elimination of nitrogen, and consequently it is practically impossible by means of ordinary nitrogen equilibrium experiments to demonstrate the fact of the retention, to say nothing of determining the degree of accumulation of waste products accompanying nephritis. That both can be demonstrated by the method employed in this research is clearly shown by the figures recorded ablove. PMID:19867613

NITROGEN RETENTION IN THE BLOOD IN EXPERIMENTAL ACUTE NEPHRITIS OF THE CAT.

PubMed

Folin, O; Karsner, H T; Denis, W

1912-12-01

It will be seen that uranium nephritis, which involves both tubules and glomeruli, the former more markedly than the latter, produces a marked accumulation of nitrogen in the blood. Chromate nephritis, which involves almost exclusively the tubules, produces only moderate retention of nitrogen. Cantharidin nephritis which involves both tubules and glomeruli, the latter more severely than does uranium, produces a marked accumulation of nitrogen, beginning early and persisting for a considerable period. The experiments were controlled by testing the blood of normal cats kept under the same conditions, these animals showing only slight variations from day to day. This general statement is in accordance with the physiological classification of these nephritides except that the retention in uranium occurs at an early stage, where, according to the physiological studies of Schlayer and his associates, and of Pearce, Hill, and Eisenbrey, the vascular changes have not as yet appeared. It must be noticed that in the three types of nephritis that form the subject of this investigation, anatomical study shows the glomerulus to be distinctly involved in the two forms where accumulation of nitrogen in the blood is most marked, a condition indicating that although almost pure tubular involvement produces only moderate accumulation, the additional involvement of the glomerulus is extremely important in leading to a retention of nitrogenous waste products. The accumulation of non-protein nitrogen in the blood and tissues is not large when compared with the total intake or elimination of nitrogen, and consequently it is practically impossible by means of ordinary nitrogen equilibrium experiments to demonstrate the fact of the retention, to say nothing of determining the degree of accumulation of waste products accompanying nephritis. That both can be demonstrated by the method employed in this research is clearly shown by the figures recorded ablove.

ET-1 increases reactive oxygen species following hypoxia and high-salt diet in the mouse glomerulus.

PubMed

Heimlich, J B; Speed, J S; Bloom, C J; O'Connor, P M; Pollock, J S; Pollock, D M

2015-03-01

This study was designed to determine whether ET-1 derived from endothelial cells contributes to oxidative stress in the glomerulus of mice subjected to a high-salt diet and/or hypoxia. C57BL6/J control mice or vascular endothelial cell ET-1 knockout (VEET KO) mice were subjected to 3-h exposure to hypoxia (8% O₂) and/or 2 weeks of high-salt diet (4% NaCl) prior to metabolic cage assessment of renal function and isolation of glomeruli for the determination of reactive oxygen species (ROS). In control mice, hypoxia significantly increased urinary protein excretion during the initial 24 h, but only in animals on a high-salt diet. Hypoxia increased glomerular ET-1 mRNA expression in control, but not in vascular endothelial cell ET-1 knockout (VEET KO) mice. Under normoxic conditions, mice on a high-salt diet had approx. 150% higher glomerular ET-1 mRNA expression compared with a normal-salt diet (P < 0.05). High-salt diet administration significantly increased glomerular ROS production in flox control, but not in glomeruli isolated from VEET KO mice. In C57BL6/J mice, the ETA receptor-selective antagonist, ABT-627, significantly attenuated the increase in glomerular ROS production produced by high-salt diet. In addition, chronic infusion of C57BL6/J mice with a subpressor dose of ET-1 (osmotic pumps) significantly increased the levels of glomerular ROS that were prevented by ETA antagonist treatment. These data suggest that both hypoxia and a high-salt diet increase glomerular ROS production via endothelial-derived ET-1-ETA receptor activation and provide a potential mechanism for ET-1-induced nephropathy. © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Alterations of type IV collagen alpha chains in patients with chronic acquired glomerulopathies: mRNA levels, protein expression and urinary loss.

PubMed

Sanna-Cherchi, Simone; Carnevali, Maria Luisa; Martorana, Davide; Cravedi, Paolo; Maggiore, Umberto; Alinovi, Rossella; Bovino, Achiropita; Mattei, Silvia; Orlandini, Guido; Gatti, Rita; Savi, Mario; Sado, Yoshikazu; Neri, Tauro M; Allegri, Landino

2007-01-01

Type IV collagen is a major structural component of the normal kidney glomerulus. However, its role in chronic acquired glomerulopathies has been only partially elucidated. Urinary levels of col(IV)alpha1, col(IV)alpha3 and col(IV)alpha5 collagen chains were analyzed in 107 patients with chronic acquired glomerulopathies. In a subgroup of 33 patients, tissue mRNA levels, protein expression and urinary excretion were evaluated for all col(IV)alpha chains, from col(IV)alpha1 to col(IV)alpha5. The renal specimens were examined to get a semiquantitative score of the acute and chronic activity of the histological lesions. Urines obtained from 13 healthy subjects and 10 normal renal tissue samples were used as controls. Urinary levels of col(IV)alpha1, col(IV)alpha3, col(IV)alpha5 chains were significantly higher in patients than in controls [p < 0.01 for all], while only col(IV)alpha1 and col(IV)alpha3 urinary excretion correlated with the degree of chronic histological damage [col(IV)alpha1 R = 0.44, p < 0.001; col(IV)alpha3: R = 0.47, p < 0.001]. Compared with controls, patients showed a renal expression of mRNA for col(IV)alpha5 chain significantly higher [p = 0.001], while having a significantly lower protein expression of col(IV)alpha3, col(IV)alpha4 and col(IV)alpha5 chains [p < 0.01 for all]. Patients with chronic acquired glomerulopathies show important alterations in the col(IV)alpha chain network mimicking some molecular features of the X-linked Alport's syndrome. Further studies are needed to show whether urinary levels of the col(IV)alpha chains may be used as markers for monitoring renal injury. Copyright 2007 S. Karger AG, Basel.

Histological, molecular and biochemical detection of renal injury after Echis pyramidum snake envenomation in rats

PubMed Central

Al-Johany, Awadh M.; Al-Sadoon, Mohamed K.; Abdel Moneim, Ahmed E.; Bauomy, Amira A.; Diab, Marwa S.M.

2014-01-01

Nephrotoxicity is a common sign of snake envenomation. The present work aimed to clarify the effect of intraperitoneal injection of 1/8 LD50 and 1/4 LD50 doses of Echis pyramidum snake venom on the renal tissue of rats after 2, 4 and 6 h from envenomation. Histopathological examination showed intense dose and time dependent abnormalities, including swelling glomerulus and tubular necrosis and damage as well as signs of intertubular medullary hemorrhage at early stages of envenomation. However, at late stages of envenomation by any of the doses under investigation, no intact renal corpuscles were recorded and complete lysis in renal corpuscles with ruptured Bowman’s capsules was observed. Immunohistochemistry by immunohistochemical staining was used to test the protein expression of Bax in renal tissue of rats. The result showed that the expression of Bax in renal tissue sections of envenomated rats was increased according to dose and time-dependant manner. The isolation of DNA from the renal cells of envenomed rats pointed out to the occurrence of DNA fragmentation, which is another indicator for renal tissue injury especially after 6 h of 1/4 LD50 of E. pyramidum envenomation. Oxidative stress biomarkers malondialdehyde and nitrite/nitrate levels, antioxidant parameters; glutathione, total antioxidant capacity and catalase were assayed in renal tissue homogenates. The venom induced significant increase in the levels of malondialdehyde and nitrite/nitrate while the levels of glutathione, total antioxidant capacity and catalase were significantly decreased, especially after 6 h of envenomation. The results revealed that the E. pyramidum induced dose and time-dependant significant disturbances in the physiological parameters in the kidney. We conclude that the use of the immunohistochemical techniques, the detection of DNA integrity and oxidative stress marker estimations are more specific tools that can clarify cellular injury and could point out to the defense activity of the renal tissue at envenomation. PMID:25972751

Citral alleviates an accelerated and severe lupus nephritis model by inhibiting the activation signal of NLRP3 inflammasome and enhancing Nrf2 activation.

PubMed

Ka, Shuk-Man; Lin, Jung-Chen; Lin, Tsai-Jung; Liu, Feng-Cheng; Chao, Louis Kuoping; Ho, Chen-Lung; Yeh, Li-Tzu; Sytwu, Huey-Kang; Hua, Kuo-Feng; Chen, Ann

2015-11-19

Lupus nephritis (LN) is a major complication of systemic lupus erythematosus. NLRP3 inflammasome activation, reactive oxygen species (ROS) and mononuclear leukocyte infiltration in the kidney have been shown to provoke the acceleration and deterioration of LN, such as accelerated and severe LN (ASLN). Development of a novel therapeutic remedy based on these molecular events to prevent the progression of the disease is clinically warranted. Citral (3,7-dimethyl-2,6-octadienal), a major active compound in a Chinese herbal medicine Litsea cubeba, was used to test its renoprotective effects in a lipopolysaccharide (LPS)-induced mouse ASLN model by examining NLRP3 inflammasome activation, ROS and COX-2 production as well as Nrf2 activation. The analysis of mechanisms of action of Citral also involved its effects on IL-1β secretion and signaling pathways of NLRP3 inflammasome in LPS-primed peritoneal macrophages or J774A macrophages. Attenuated proteinuria, renal function impairment, and renal histopathology, the latter including intrinsic cell proliferation, cellular crescents, neutrophil influx, fibrinoid necrosis in the glomerulus, and peri-glomerular infiltration of mononuclear leukocytes as well as glomerulonephritis activity score were observed in Citral-treated ASLN mice. In addition, Citral inhibited NLRP3 inflammasome activation and levels of ROS, NAD(P)H oxidase subunit p47(phox), or COX-2, and it enhanced the activation of nuclear factor E2-related factor 2 (Nrf2). In LPS-primed macrophages, Citral reduced ATP-induced IL-1β secretion and caspase-1 activation, but did not affect LPS-induced NLRP3 protein expression. Our data show that Citral alleviates the mouse ASLN model by inhibition of the activation signal, but not the priming signal, of NLRP3 inflammasome and enhanced activation of Nrf2 antioxidant signaling.

The blood-cerebrospinal fluid barrier: structure and functional significance.

PubMed

Johanson, Conrad E; Stopa, Edward G; McMillan, Paul N

2011-01-01

The choroid plexus (CP) of the blood-CSF barrier (BCSFB) displays fundamentally different properties than blood-brain barrier (BBB). With brisk blood flow (10 × brain) and highly permeable capillaries, the human CP provides the CNS with a high turnover rate of fluid (∼400,000 μL/day) containing micronutrients, peptides, and hormones for neuronal networks. Renal-like basement membranes in microvessel walls and underneath the epithelium filter large proteins such as ferritin and immunoglobulins. Type IV collagen (α3, α4, and α5) in the subepithelial basement membrane confers kidney-like permselectivity. As in the glomerulus, so also in CP, the basolateral membrane utrophin A and colocalized dystrophin impart structural stability, transmembrane signaling, and ion/water homeostasis. Extensive infoldings of the plasma-facing basal labyrinth together with lush microvilli at the CSF-facing membrane afford surface area, as great as that at BBB, for epithelial solute and water exchange. CSF formation occurs by basolateral carrier-mediated uptake of Na+, Cl-, and HCO3-, followed by apical release via ion channel conductance and osmotic flow of water through AQP1 channels. Transcellular epithelial active transport and secretion are energized and channeled via a highly dense organelle network of mitochondria, endoplasmic reticulum, and Golgi; bleb formation occurs at the CSF surface. Claudin-2 in tight junctions helps to modulate the lower electrical resistance and greater permeability in CP than at BBB. Still, ratio analyses of influx coefficients (Kin) for radiolabeled solutes indicate that paracellular diffusion of small nonelectrolytes (e.g., urea and mannitol) through tight junctions is restricted; molecular sieving is proportional to solute size. Protein/peptide movement across BCSFB is greatly limited, occurring by paracellular leaks through incomplete tight junctions and low-capacity transcellular pinocytosis/exocytosis. Steady-state concentration ratios, CSF/plasma, ranging from 0.003 for IgG to 0.80 for urea, provide insight on plasma solute penetrability, barrier permeability, and CSF sink action to clear substances from CNS.

REPAIR EFFECTS OF UMBILICAL CORD MESENCHYMAL STEM CELLS ON PODOCYTE DAMAGE OF IgA NEPHROPATHY.

PubMed

Zhang, D W; Qiu, H; Mei, Y M; Fu, H; Zheng, H G

2015-01-01

This study aimed to explore the influence of umbilical cord mesenchymal stem cells (UMSC) on stem cell homing and glomerular mesangial cell (GMC) after intravenous injection performed on mice tails with IgA nephropathy (IgAN) and its possible mechanism, which provide a new way and theoretical basis for the application of stem cell transplantation (SCT) in kidney disease treatment. Specific pathogen free (SPF) male Kunming mice were randomly divided into groups. A complex method applying bovine serum albumin (BSA) gavage, hypodermic injection of CCl4 and lipopolysaccharide (LPS) was used for building IgAN mice model. In addition, vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF) and cluster of differentiation (CD) 44 were observed by Masson staining and detected with immunohistochemistry (IHC) to confirm homing and location of mesenchymal stem cells (MSCs). Moreover, Western Blot was used for detecting VEGF and CTGF so as to explore the possible mechanism of applying UMSC in treating IgAN. Masson staining indicated that fibrosis degree of MSCs in treatment group was significantly lower than in negative control group after stem cell treatment. Routine urine test explained that proteinuria in treatment group were (7.15±0.31), (4.87±0.22), (2.95±0.16) g/24 h and (12.00±1.38) g/24 h in model group (P less than 0.05). MSCs were observed to be located in glomerulus and renal interstitium by IHC detection of CD44 and IHC qualitative observation of VEGF and CTGF had different positive expressions in three groups. Furthermore, different expressions of VEGF and CTGF were observed quantitatively by Western Blot. Fibrosis degree of renal tissue relieves, hematuresis and proteinuria eases and IgAN symptoms obviously improve after UMSC treatment, which hints that the treatment of HUMSC has protective effect on IgAN mice model.

Febuxostat ameliorates diabetic renal injury in a streptozotocin-induced diabetic rat model.

PubMed

Lee, Hong-Joo; Jeong, Kyung Hwan; Kim, Yang Gyun; Moon, Joo Young; Lee, Sang Ho; Ihm, Chun Gyoo; Sung, Ji Youn; Lee, Tae Won

2014-01-01

Oxidative stress and inflammation are known to play central roles in the development of diabetic nephropathy (DN). Febuxostat is a novel non-purine xanthine oxidase (XO)-specific inhibitor developed to treat hyperuricemia. In this study, we investigated whether febuxostat could ameliorate DN via renoprotective mechanisms such as alleviation of oxidative stress and anti-inflammatory actions. Male Sprague-Dawley rats were divided into three groups: a normal group, a diabetes group (DM group), and a febuxostat-treated diabetes group (DM+Fx group). We administered 5 mg/kg of febuxostat to experimental rats for 7 weeks and evaluated clinical and biochemical parameters and XO and xanthine dehydrogenase (XDH) activity in hepatic tissue. The degree of oxidative stress and extent of inflammation were evaluated from urine samples and renal tissue collected from each group. Diabetic rats (DM and DM+Fx groups) had higher blood glucose and kidney weight relative to body weight than normal rats. Albuminuria was significantly reduced in febuxostat-treated diabetic rats compared with untreated diabetic rats. Quantitative analysis showed that hepatic XO and XDH activities were higher in the DM groups, but decreased after treatment with febuxostat. Urinary 8-OHdG concentrations and renal cortical nitrotyrosine also indicated reduced oxidative stress in the DM+Fx group relative to the DM group. The number of ED-1-stained cells in the glomerulus and tubule of diabetic renal tissue decreased in febuxostat-treated diabetic rats relative to that of non-treated diabetic rats. Diabetic rats also expressed higher transcript levels of inflammatory genes (E-selectin and VCAM-1), an inflammation-induced enzyme (COX-2), and inflammatory mediators (ED-1 and NF-κB) than control rats; expression of these genes was significantly reduced by treatment with febuxostat. Febuxostat prevents diabetic renal injury such as albuminuria. This renoprotective effect appears to be due to attenuation of the inflammatory and oxidative effects of diabetes-induced renal damage through inhibition of XO and XDH activities. © 2014 S. Karger AG, Basel.

Fourier-based quantification of renal glomeruli size using Hough transform and shape descriptors.

PubMed

Najafian, Sohrab; Beigzadeh, Borhan; Riahi, Mohammad; Khadir Chamazkoti, Fatemeh; Pouramir, Mahdi

2017-11-01

Analysis of glomeruli geometry is important in histopathological evaluation of renal microscopic images. Due to the shape and size disparity of even glomeruli of same kidney, automatic detection of these renal objects is not an easy task. Although manual measurements are time consuming and at times are not very accurate, it is commonly used in medical centers. In this paper, a new method based on Fourier transform following usage of some shape descriptors is proposed to detect these objects and their geometrical parameters. Reaching the goal, a database of 400 regions are selected randomly. 200 regions of which are part of glomeruli and the other 200 regions are not belong to renal corpuscles. ROC curve is used to decide which descriptor could classify two groups better. f_measure, which is a combination of both tpr (true positive rate) and fpr (false positive rate), is also proposed to select optimal threshold for descriptors. Combination of three parameters (solidity, eccentricity, and also mean squared error of fitted ellipse) provided better result in terms of f_measure to distinguish desired regions. Then, Fourier transform of outer edges is calculated to form a complete curve out of separated region(s). The generality of proposed model is verified by use of cross validation method, which resulted tpr of 94%, and fpr of 5%. Calculation of glomerulus' and Bowman's space with use of the algorithm are also compared with a non-automatic measurement done by a renal pathologist, and errors of 5.9%, 5.4%, and 6.26% are resulted in calculation of Capsule area, Bowman space, and glomeruli area, respectively. Having tested different glomeruli with various shapes, the experimental consequences show robustness and reliability of our method. Therefore, it could be used to illustrate renal diseases and glomerular disorders by measuring the morphological changes accurately and expeditiously. Copyright © 2017 Elsevier B.V. All rights reserved.

Histological, molecular and biochemical detection of renal injury after Echis pyramidum snake envenomation in rats.

PubMed

Al-Johany, Awadh M; Al-Sadoon, Mohamed K; Abdel Moneim, Ahmed E; Bauomy, Amira A; Diab, Marwa S M

2015-05-01

Nephrotoxicity is a common sign of snake envenomation. The present work aimed to clarify the effect of intraperitoneal injection of 1/8 LD50 and 1/4 LD50 doses of Echis pyramidum snake venom on the renal tissue of rats after 2, 4 and 6 h from envenomation. Histopathological examination showed intense dose and time dependent abnormalities, including swelling glomerulus and tubular necrosis and damage as well as signs of intertubular medullary hemorrhage at early stages of envenomation. However, at late stages of envenomation by any of the doses under investigation, no intact renal corpuscles were recorded and complete lysis in renal corpuscles with ruptured Bowman's capsules was observed. Immunohistochemistry by immunohistochemical staining was used to test the protein expression of Bax in renal tissue of rats. The result showed that the expression of Bax in renal tissue sections of envenomated rats was increased according to dose and time-dependant manner. The isolation of DNA from the renal cells of envenomed rats pointed out to the occurrence of DNA fragmentation, which is another indicator for renal tissue injury especially after 6 h of 1/4 LD50 of E. pyramidum envenomation. Oxidative stress biomarkers malondialdehyde and nitrite/nitrate levels, antioxidant parameters; glutathione, total antioxidant capacity and catalase were assayed in renal tissue homogenates. The venom induced significant increase in the levels of malondialdehyde and nitrite/nitrate while the levels of glutathione, total antioxidant capacity and catalase were significantly decreased, especially after 6 h of envenomation. The results revealed that the E. pyramidum induced dose and time-dependant significant disturbances in the physiological parameters in the kidney. We conclude that the use of the immunohistochemical techniques, the detection of DNA integrity and oxidative stress marker estimations are more specific tools that can clarify cellular injury and could point out to the defense activity of the renal tissue at envenomation.

Molecular genetics of familial hematuric diseases.

PubMed

Deltas, Constantinos; Pierides, Alkis; Voskarides, Konstantinos

2013-12-01

The familial hematuric diseases are a genetically heterogeneous group of monogenic conditions, caused by mutations in one of several genes. The major genes involved are the following: (i) the collagen IV genes COL4A3/A4/A5 that are expressed in the glomerular basement membranes (GBM) and are responsible for the most frequent forms of microscopic hematuria, namely Alport syndrome (X-linked or autosomal recessive) and thin basement membrane nephropathy (TBMN). (ii) The FN1 gene, expressed in the glomerulus and responsible for a rare form of glomerulopathy with fibronectin deposits (GFND). (iii) CFHR5 gene, a recently recognized regulator of the complement alternative pathway and mutated in a recently revisited form of inherited C3 glomerulonephritis (C3GN), characterized by isolated C3 deposits in the absence of immune complexes. A hallmark feature of all conditions is the age-dependent penetrance and a broad phenotypic heterogeneity in the sense that subsets of patients progress to added proteinuria or proteinuria and chronic renal failure that may or may not lead to end-stage kidney disease (ESKD) anywhere between the second and seventh decade of life. In addition to other excellent laboratory tools that assist the clinician in reaching the correct diagnosis, the molecular analysis emerges as the gold standard in establishing the diagnosis in many cases of doubt due to equivocal findings that complicate the differential diagnosis. Recent work led to the description of candidate genetic modifiers which confer a variable risk for progressing to chronic renal failure when co-inherited on the background of a primary glomerulopathy. Finally, more families are still waiting to be studied and more genes to be mapped and cloned that are responsible for other forms of heritable hematuric diseases. The study of such genes and their protein products will likely shed more light on the structure and function of the glomerular filtration barrier and other important glomerular components.

Differential Recognition Preferences of the Three Src Homology 3 (SH3) Domains from the Adaptor CD2-associated Protein (CD2AP) and Direct Association with Ras and Rab Interactor 3 (RIN3)*

PubMed Central

Rouka, Evgenia; Simister, Philip C.; Janning, Melanie; Kumbrink, Joerg; Konstantinou, Tassos; Muniz, João R. C.; Joshi, Dhira; O'Reilly, Nicola; Volkmer, Rudolf; Ritter, Brigitte; Knapp, Stefan; von Delft, Frank; Kirsch, Kathrin H.; Feller, Stephan M.

2015-01-01

CD2AP is an adaptor protein involved in membrane trafficking, with essential roles in maintaining podocyte function within the kidney glomerulus. CD2AP contains three Src homology 3 (SH3) domains that mediate multiple protein-protein interactions. However, a detailed comparison of the molecular binding preferences of each SH3 remained unexplored, as well as the discovery of novel interactors. Thus, we studied the binding properties of each SH3 domain to the known interactor Casitas B-lineage lymphoma protein (c-CBL), conducted a peptide array screen based on the recognition motif PxPxPR and identified 40 known or novel candidate binding proteins, such as RIN3, a RAB5-activating guanine nucleotide exchange factor. CD2AP SH3 domains 1 and 2 generally bound with similar characteristics and specificities, whereas the SH3-3 domain bound more weakly to most peptide ligands tested yet recognized an unusually extended sequence in ALG-2-interacting protein X (ALIX). RIN3 peptide scanning arrays revealed two CD2AP binding sites, recognized by all three SH3 domains, but SH3-3 appeared non-functional in precipitation experiments. RIN3 recruited CD2AP to RAB5a-positive early endosomes via these interaction sites. Permutation arrays and isothermal titration calorimetry data showed that the preferred binding motif is Px(P/A)xPR. Two high-resolution crystal structures (1.65 and 1.11 Å) of CD2AP SH3-1 and SH3-2 solved in complex with RIN3 epitopes 1 and 2, respectively, indicated that another extended motif is relevant in epitope 2. In conclusion, we have discovered novel interaction candidates for CD2AP and characterized subtle yet significant differences in the recognition preferences of its three SH3 domains for c-CBL, ALIX, and RIN3. PMID:26296892

Automated quantification of renal interstitial fibrosis for computer-aided diagnosis: A comprehensive tissue structure segmentation method.

PubMed

Tey, Wei Keat; Kuang, Ye Chow; Ooi, Melanie Po-Leen; Khoo, Joon Joon

2018-03-01

Interstitial fibrosis in renal biopsy samples is a scarring tissue structure that may be visually quantified by pathologists as an indicator to the presence and extent of chronic kidney disease. The standard method of quantification by visual evaluation presents reproducibility issues in the diagnoses. This study proposes an automated quantification system for measuring the amount of interstitial fibrosis in renal biopsy images as a consistent basis of comparison among pathologists. The system extracts and segments the renal tissue structures based on colour information and structural assumptions of the tissue structures. The regions in the biopsy representing the interstitial fibrosis are deduced through the elimination of non-interstitial fibrosis structures from the biopsy area and quantified as a percentage of the total area of the biopsy sample. A ground truth image dataset has been manually prepared by consulting an experienced pathologist for the validation of the segmentation algorithms. The results from experiments involving experienced pathologists have demonstrated a good correlation in quantification result between the automated system and the pathologists' visual evaluation. Experiments investigating the variability in pathologists also proved the automated quantification error rate to be on par with the average intra-observer variability in pathologists' quantification. Interstitial fibrosis in renal biopsy samples is a scarring tissue structure that may be visually quantified by pathologists as an indicator to the presence and extent of chronic kidney disease. The standard method of quantification by visual evaluation presents reproducibility issues in the diagnoses due to the uncertainties in human judgement. An automated quantification system for accurately measuring the amount of interstitial fibrosis in renal biopsy images is presented as a consistent basis of comparison among pathologists. The system identifies the renal tissue structures through knowledge-based rules employing colour space transformations and structural features extraction from the images. In particular, the renal glomerulus identification is based on a multiscale textural feature analysis and a support vector machine. The regions in the biopsy representing interstitial fibrosis are deduced through the elimination of non-interstitial fibrosis structures from the biopsy area. The experiments conducted evaluate the system in terms of quantification accuracy, intra- and inter-observer variability in visual quantification by pathologists, and the effect introduced by the automated quantification system on the pathologists' diagnosis. A 40-image ground truth dataset has been manually prepared by consulting an experienced pathologist for the validation of the segmentation algorithms. The results from experiments involving experienced pathologists have demonstrated an average error of 9 percentage points in quantification result between the automated system and the pathologists' visual evaluation. Experiments investigating the variability in pathologists involving samples from 70 kidney patients also proved the automated quantification error rate to be on par with the average intra-observer variability in pathologists' quantification. The accuracy of the proposed quantification system has been validated with the ground truth dataset and compared against the pathologists' quantification results. It has been shown that the correlation between different pathologists' estimation of interstitial fibrosis area has significantly improved, demonstrating the effectiveness of the quantification system as a diagnostic aide. Copyright © 2017 Elsevier B.V. All rights reserved.

[Localization of NADPH-diaphorase in the brain of the shore crab Hemigrapsus sanguineus].

PubMed

Kotsiuba, E P

2005-01-01

The presence and localization of NADPH-diaphorase in the cerebral ganglion of the shore crab Hemigrapsus sanguineus was investigated with histochemical and electron histochemical methods. The reactivity of this enzyme was found in the deutrocerebrum, mainly in neuropils of olfactory lobes, the lateral antennular neuropil, a laterodorsal group of cells, and in the oculomotor nerve nucleus. Ultrastructural localization of the enzyme was detected in neurons on the perinuclear membrane, and in membranes of endoplasmic reticulum, in mitochondria and cytosol. The enzyme was found in axons of the antennular nerve, and in terminals of receptor axons in the glomerulus. The obtained data testify to participation of NO in perception and processing of the olfactory information.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Feng; Zhang, Yuanyuan; Wang, Qingzhu

Objective: This study was designed to investigate the protective effect of forkhead transcription factor O1 (FoxO1) on podocyte injury in rats with diabetic nephropathy. Methods: Streptozotocin-induced diabetic rats were served as DM group, while DM rats transfected with blank lentiviral vectors (LV-pSC-GFP) or lentiviral vectors carrying constitutively active FoxO1 (LV-CA-FoxO1) were served as LV-NC group or LV-CA group, respectively. The control group (NG) consisted of uninduced rats that received an injection of diluent buffer. At 2, 4, and 8 weeks after transfection, the levels of urine albumin, blood glucose, blood urea nitrogen, serum creatinine and urine podocalyxin were measured. Real-timemore » PCR and western blotting were performed to measure mRNA and protein levels of FoxO1, podocalyxin, nephrin, and desmin in renal cortex. In addition, light and electron microscopy were used to detect structural changes in the glomerulus and podocytes. Results: Compared with the rats in LV-NC and DM groups, LV-CA rats showed a significant increase in FoxO1 mRNA and protein levels and a distinct decrease in urine albumin, blood urea nitrogen, and serum creatinine (except at the two-week time point) levels (p < 0.05). Podocalyxin and nephrin mRNA and protein levels increased (p < 0.05), whereas desmin mRNA and protein levels decreased (p < 0.05). Pathological changes in glomerulus were also ameliorated in LV-CA group. Conclusions: Upregulating expression of FoxO1 by transduction with recombinant lentivirus ameliorates podocyte injury in diabetic rats. - Highlights: • The structures and functions of podocytes were impaired in STZ-induced diabetic rats. • Constitutively active FoxO1 ameliorates structure injury and preserves function of podocytes in diabetic rats. • FoxO1 may alleviate the pathological changes associated with diabetic nephropathy.« less

Validation of a Three-Dimensional Method for Counting and Sizing Podocytes in Whole Glomeruli

PubMed Central

van der Wolde, James W.; Schulze, Keith E.; Short, Kieran M.; Wong, Milagros N.; Bensley, Jonathan G.; Cullen-McEwen, Luise A.; Caruana, Georgina; Hokke, Stacey N.; Li, Jinhua; Firth, Stephen D.; Harper, Ian S.; Nikolic-Paterson, David J.; Bertram, John F.

2016-01-01

Podocyte depletion is sufficient for the development of numerous glomerular diseases and can be absolute (loss of podocytes) or relative (reduced number of podocytes per volume of glomerulus). Commonly used methods to quantify podocyte depletion introduce bias, whereas gold standard stereologic methodologies are time consuming and impractical. We developed a novel approach for assessing podocyte depletion in whole glomeruli that combines immunofluorescence, optical clearing, confocal microscopy, and three-dimensional analysis. We validated this method in a transgenic mouse model of selective podocyte depletion, in which we determined dose-dependent alterations in several quantitative indices of podocyte depletion. This new approach provides a quantitative tool for the comprehensive and time-efficient analysis of podocyte depletion in whole glomeruli. PMID:26975438

A diffuse mixed histiocytic-lymphocytic lymphoma associated with immunological abnormalities.

PubMed

Syrjänen, K J

1979-01-01

A diffuse generalized lymphoma histologically classified as mixed histiocytic-lymphocytic type and associated with profound immunologie abnormalities is reported. The patient had an autoimmune hemolytic anemia, an autoimmune thrombocytopenia, polyclonally increased IgG and IgM, polyclonal secretion of kappa and lamda chains into urine, very low serum complement C3 and antibodies against glomerulus and smooth muscle. When studied with the modern surface-marker techniques, the lesion was found to be composed of entirely lymphoid cells of the B-lymphocyte series. The proper classification of this tumor could be a primitive immunoblastic sarcoma. The relationship of the present tumor to the non-neoplastic angioimmunoblastic lymphadenopathia is discussed. The necessity of applying the surface-marker techniques in the classification of malignant lymphomas is emphasized.

Parallel processing of afferent olfactory sensory information

PubMed Central

Vaaga, Christopher E.

2016-01-01

Key points The functional synaptic connectivity between olfactory receptor neurons and principal cells within the olfactory bulb is not well understood.One view suggests that mitral cells, the primary output neuron of the olfactory bulb, are solely activated by feedforward excitation.Using focal, single glomerular stimulation, we demonstrate that mitral cells receive direct, monosynaptic input from olfactory receptor neurons.Compared to external tufted cells, mitral cells have a prolonged afferent‐evoked EPSC, which serves to amplify the synaptic input.The properties of presynaptic glutamate release from olfactory receptor neurons are similar between mitral and external tufted cells.Our data suggest that afferent input enters the olfactory bulb in a parallel fashion. Abstract Primary olfactory receptor neurons terminate in anatomically and functionally discrete cortical modules known as olfactory bulb glomeruli. The synaptic connectivity and postsynaptic responses of mitral and external tufted cells within the glomerulus may involve both direct and indirect components. For example, it has been suggested that sensory input to mitral cells is indirect through feedforward excitation from external tufted cells. We also observed feedforward excitation of mitral cells with weak stimulation of the olfactory nerve layer; however, focal stimulation of an axon bundle entering an individual glomerulus revealed that mitral cells receive monosynaptic afferent inputs. Although external tufted cells had a 4.1‐fold larger peak EPSC amplitude, integration of the evoked currents showed that the synaptic charge was 5‐fold larger in mitral cells, reflecting the prolonged response in mitral cells. Presynaptic afferents onto mitral and external tufted cells had similar quantal amplitude and release probability, suggesting that the larger peak EPSC in external tufted cells was the result of more synaptic contacts. The results of the present study indicate that the monosynaptic afferent input to mitral cells depends on the strength of odorant stimulation. The enhanced spiking that we observed in response to brief afferent input provides a mechanism for amplifying sensory information and contrasts with the transient response in external tufted cells. These parallel input paths may have discrete functions in processing olfactory sensory input. PMID:27377344

Dense Deposit Disease and C3 Glomerulopathy

PubMed Central

Barbour, Thomas D.; Pickering, Matthew C.; Terence Cook, H.

2013-01-01

Summary C3 glomerulopathy refers to those renal lesions characterized histologically by predominant C3 accumulation within the glomerulus, and pathogenetically by aberrant regulation of the alternative pathway of complement. Dense deposit disease is distinguished from other forms of C3 glomerulopathy by its characteristic appearance on electron microscopy. The extent to which dense deposit disease also differs from other forms of C3 glomerulopathy in terms of clinical features, natural history, and outcomes of treatment including renal transplantation is less clear. We discuss the pathophysiology of C3 glomerulopathy, with evidence for alternative pathway dysregulation obtained from affected individuals and complement factor H (Cfh)-deficient animal models. Recent linkage studies in familial C3 glomerulopathy have shown genomic rearrangements in the Cfh-related genes, for which the novel pathophysiologic concept of Cfh deregulation has been proposed. PMID:24161036

Kidney Dysplasia

MedlinePlus

... Disease Ectopic Kidney Medullary Sponge Kidney Kidney Dysplasia Kidney Dysplasia What is kidney dysplasia? Kidney dysplasia is a condition in which ... Kidney dysplasia in one kidney What are the kidneys and what do they do? The kidneys are ...

Renal damages after extracorporeal shock wave lithotripsy evaluated by Gd-DTPA-enhanced dynamic magnetic resonance imaging.

PubMed

Umekawa, T; Kohri, K; Yamate, T; Amasaki, N; Ishikawa, Y; Takada, M; Iguchi, M; Kurita, T

1992-01-01

Renal damages after extracorporeal shock wave lithotripsy (ESWL) were evaluated by magnetic resonance imaging (MRI) including Gd-DTPA-enhanced dynamic MRI in 37 patients with renal stone by spin echo methods (T1 and T2-weighted scan) and small tip angle gradient echo method (T2-weighted scan). Sixty-eight percent of the patients had changes in the MRI findings after ESWL. The frequently observed findings were perirenal fluid collection (38%), loss of corticomedullary junction (35%), and increased signal intensity of muscle and other adjacent tissue (34%). Preoperative Gd-DTPA-enhanced dynamic MRI showed low intensity band which suggests Gd-DTPA secretion from the glomerulus into the renal tubulus. In all cases the low intensity band became unclear after ESWL because of renal contusion due to ESWL. MRI, including Gd-DTPA-enhanced dynamic MRI, is considered to be a good procedure for evaluation of renal damages due to ESWL.

Cell biology of mesangial cells: the third cell that maintains the glomerular capillary.

PubMed

Kurihara, Hidetake; Sakai, Tatsuo

2017-03-01

The renal glomerulus consists of glomerular endothelial cells, podocytes, and mesangial cells, which cooperate with each other for glomerular filtration. We have produced monoclonal antibodies against glomerular cells in order to identify different types of glomerular cells. Among these antibodies, the E30 clone specifically recognizes the Thy1.1 molecule expressed on mesangial cells. An injection of this antibody into rats resulted in mesangial cell-specific injury within 15 min, and induced mesangial proliferative glomerulonephritis in a reproducible manner. We examined the role of mesangial cells in glomerular function using several experimental tools, including an E30-induced nephritis model, mesangial cell culture, and the deletion of specific genes. Herein, we describe the characterization of E30-induced nephritis, formation of the glomerular capillary network, mesangial matrix turnover, and intercellular signaling between glomerular cells. New molecules that are involved in a wide variety of mesangial cell functions are also introduced.

Lateral presynaptic inhibition mediates gain control in an olfactory circuit.

PubMed

Olsen, Shawn R; Wilson, Rachel I

2008-04-24

Olfactory signals are transduced by a large family of odorant receptor proteins, each of which corresponds to a unique glomerulus in the first olfactory relay of the brain. Crosstalk between glomeruli has been proposed to be important in olfactory processing, but it is not clear how these interactions shape the odour responses of second-order neurons. In the Drosophila antennal lobe (a region analogous to the vertebrate olfactory bulb), we selectively removed most interglomerular input to genetically identified second-order olfactory neurons. Here we show that this broadens the odour tuning of these neurons, implying that interglomerular inhibition dominates over interglomerular excitation. The strength of this inhibitory signal scales with total feedforward input to the entire antennal lobe, and has similar tuning in different glomeruli. A substantial portion of this interglomerular inhibition acts at a presynaptic locus, and our results imply that this is mediated by both ionotropic and metabotropic receptors on the same nerve terminal.

PMab-52: Specific and Sensitive Monoclonal Antibody Against Cat Podoplanin for Immunohistochemistry.

PubMed

Yamada, Shinji; Itai, Shunsuke; Nakamura, Takuro; Yanaka, Miyuki; Saidoh, Noriko; Chang, Yao-Wen; Handa, Saori; Harada, Hiroyuki; Kagawa, Yumiko; Ichii, Osamu; Konnai, Satoru; Kaneko, Mika K; Kato, Yukinari

2017-10-01

Podoplanin (PDPN) is expressed in several normal tissues, such as lymphatic endothelial cells, podocytes of renal glomerulus, and type I alveolar cells of lung. PDPN activates platelet aggregation by binding to C-type lectin-like receptor-2 (CLEC-2) on platelet. Although monoclonal antibodies (mAbs) against human PDPN, mouse PDPN, rat PDPN, rabbit PDPN, dog PDPN, and bovine PDPN have been established, anticat PDPN (cPDPN) mAbs have not been developed. In this study, we immunized mice with Chinese hamster ovary (CHO)-K1 cell lines expressing cPDPN, and developed anti-cPDPN mAbs. One of the clones, PMab-52 (IgM, kappa), detected cPDPN specifically in flow cytometry and Western blot analysis. PMab-52 is also useful for detecting feline squamous cell carcinoma cells in immunohistochemical analysis. PMab-52 is expected to be useful for investigating the function of cPDPN in feline carcinomas.

Ectopic Kidney

MedlinePlus

... Ectopic Kidney Medullary Sponge Kidney Kidney Dysplasia Ectopic Kidney What is an ectopic kidney? An ectopic kidney is a birth defect in ... has an ectopic kidney. 1 What are the kidneys and what do they do? The kidneys are ...

Simple Kidney Cysts

MedlinePlus

... Solitary Kidney Your Kidneys & How They Work Simple Kidney Cysts What are simple kidney cysts? Simple kidney cysts are abnormal, fluid-filled ... that form in the kidneys. What are the kidneys and what do they do? The kidneys are ...

Pathways to nephron loss starting from glomerular diseases-insights from animal models.

PubMed

Kriz, Wilhelm; LeHir, Michel

2005-02-01

Studies of glomerular diseases in animal models show that progression toward nephron loss starts with extracapillary lesions, whereby podocytes play the central role. If injuries remain bound within the endocapillary compartment, they will undergo recovery or be repaired by scaring. Degenerative, inflammatory and dysregulative mechanisms leading to nephron loss are distinguished. In addition to several other unique features, the dysregulative mechanisms leading to collapsing glomerulopathy are particular in that glomeruli and tubules are affected in parallel. In contrast, in degenerative and inflammatory diseases, tubular injury is secondary to glomerular lesions. In both of the latter groups of diseases, the progression starts in the glomerulus with the loss of the separation between the tuft and Bowman's capsule by forming cell bridges (parietal cells and/or podocytes) between the glomerular and the parietal basement membranes. Cell bridges develop into tuft adhesions to Bowman's capsule, which initiate the formation of crescents, either by misdirected filtration (proteinaceous crescents) or by epithelial cell proliferation (cellular crescents). Crescents may spread over the entire circumference of the glomerulus and, via the glomerulotubular junction, may extend onto the tubule. Two mechanisms concerning the transfer of a glomerular injury onto the tubulointerstitium are discussed: (1) direct encroachment of extracapillary lesions and (2) protein leakage into tubular urine, resulting in injury to the tubule and the interstitium. There is evidence that direct encroachment is the crucial mechanism. Progression of chronic renal disease is underlain by a vicious cycle which passes on the damage from lost and/or damaged nephrons to so far healthy nephrons. Presently, two mechanisms are discussed: (1) the loss of nephrons leads to compensatory mechanisms in the remaining nephrons (glomerular hypertension, hyperfiltration, hypertrophy) which increase their vulnerability to any further challenge (overload hypothesis); and (2) a proteinuric glomerular disease leads, by some way or another, to tubulointerstitial inflammation and fibrosis, accounting for the further deterioration of renal function (fibrosis hypothesis). So far, no convincing evidence has been published that in primary glomerular diseases fibrosis is harmful to healthy nephrons. The potential of glomerular injuries to regenerate or to be repaired by scaring is limited. The only option for extracapillary injuries with tuft adhesion is repair by formation of a segmental adherent scar (i.e., segmental glomerulosclerosis).

Identified Serotonergic Modulatory Neurons Have Heterogeneous Synaptic Connectivity within the Olfactory System of Drosophila.

PubMed

Coates, Kaylynn E; Majot, Adam T; Zhang, Xiaonan; Michael, Cole T; Spitzer, Stacy L; Gaudry, Quentin; Dacks, Andrew M

2017-08-02

Modulatory neurons project widely throughout the brain, dynamically altering network processing based on an animal's physiological state. The connectivity of individual modulatory neurons can be complex, as they often receive input from a variety of sources and are diverse in their physiology, structure, and gene expression profiles. To establish basic principles about the connectivity of individual modulatory neurons, we examined a pair of identified neurons, the "contralaterally projecting, serotonin-immunoreactive deutocerebral neurons" (CSDns), within the olfactory system of Drosophila Specifically, we determined the neuronal classes providing synaptic input to the CSDns within the antennal lobe (AL), an olfactory network targeted by the CSDns, and the degree to which CSDn active zones are uniformly distributed across the AL. Using anatomical techniques, we found that the CSDns received glomerulus-specific input from olfactory receptor neurons (ORNs) and projection neurons (PNs), and networkwide input from local interneurons (LNs). Furthermore, we quantified the number of CSDn active zones in each glomerulus and found that CSDn output is not uniform, but rather heterogeneous, across glomeruli and stereotyped from animal to animal. Finally, we demonstrate that the CSDns synapse broadly onto LNs and PNs throughout the AL but do not synapse upon ORNs. Our results demonstrate that modulatory neurons do not necessarily provide purely top-down input but rather receive neuron class-specific input from the networks that they target, and that even a two cell modulatory network has highly heterogeneous, yet stereotyped, pattern of connectivity. SIGNIFICANCE STATEMENT Modulatory neurons often project broadly throughout the brain to alter processing based on physiological state. However, the connectivity of individual modulatory neurons to their target networks is not well understood, as modulatory neuron populations are heterogeneous in their physiology, morphology, and gene expression. In this study, we use a pair of identified serotonergic neurons within the Drosophila olfactory system as a model to establish a framework for modulatory neuron connectivity. We demonstrate that individual modulatory neurons can integrate neuron class-specific input from their target network, which is often nonreciprocal. Additionally, modulatory neuron output can be stereotyped, yet nonuniform, across network regions. Our results provide new insight into the synaptic relationships that underlie network function of modulatory neurons. Copyright © 2017 the authors 0270-6474/17/377318-14$15.00/0.

Kidney Facts

MedlinePlus

... Page Transplant Living > Kidney KIDNEY TRANSPLANT LEARNING CENTER Kidney The kidneys are a vital organ in the ... your body. Location of the kidneys How the kidney works Your kidneys play a vital role in ...

Solitary Kidney

MedlinePlus

... Solitary Kidney Your Kidneys & How They Work Solitary Kidney What is a solitary kidney? When a person has only one kidney or ... ureter are removed (bottom right). What are the kidneys and what do they do? The kidneys are ...

Incidence of kidney stones in kidney transplant recipients: A systematic review and meta-analysis

PubMed Central

Cheungpasitporn, Wisit; Thongprayoon, Charat; Mao, Michael A; Kittanamongkolchai, Wonngarm; Jaffer Sathick, Insara J; Dhondup, Tsering; Erickson, Stephen B

2016-01-01

AIM To evaluate the incidence and characteristics of kidney stones in kidney transplant recipients. METHODS A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from the inception of the databases through March 2016. Studies assessing the incidence of kidney stones in kidney transplant recipients were included. We applied a random-effects model to estimate the incidence of kidney stones. RESULTS Twenty one studies with 64416 kidney transplant patients were included in the analyses to assess the incidence of kidney stones after kidney transplantation. The estimated incidence of kidney stones was 1.0% (95%CI: 0.6%-1.4%). The mean duration to diagnosis of kidney stones after kidney transplantation was 28 ± 22 mo. The mean age of patients with kidney stones was 42 ± 7 years. Within reported studies, approximately 50% of kidney transplant recipients with kidney stones were males. 67% of kidney stones were calcium-based stones (30% mixed CaOx/CaP, 27%CaOx and 10%CaP), followed by struvite stones (20%) and uric acid stones (13%). CONCLUSION The estimated incidence of kidney stones in patients after kidney transplantation is 1.0%. Although calcium based stones are the most common kidney stones after transplantation, struvite stones (also known as “infection stones”) are not uncommon in kidney transplant recipients. These findings may impact the prevention and clinical management of kidney stones after kidney transplantation. PMID:28058231

Predicting kidney disease progression in patients with acute kidney injury after cardiac surgery.

PubMed

Mizuguchi, K Annette; Huang, Chuan-Chin; Shempp, Ian; Wang, Justin; Shekar, Prem; Frendl, Gyorgy

2018-06-01

The study objective was to identify patients who are likely to develop progressive kidney dysfunction (acute kidney disease) before their hospital discharge after cardiac surgery, allowing targeted monitoring of kidney function in this at-risk group with periodic serum creatinine measurements. Risks of progression to acute kidney disease (a state in between acute kidney injury and chronic kidney disease) were modeled from acute kidney injury stages (Kidney Disease: Improving Global Outcomes) in patients undergoing cardiac surgery. A modified Poisson regression with robust error variance was used to evaluate the association between acute kidney injury stages and the development of acute kidney disease (defined as doubling of creatinine 2-4 weeks after surgery) in this observational study. Acute kidney disease occurred in 4.4% of patients with no preexisting kidney disease and 4.8% of patients with preexisting chronic kidney disease. Acute kidney injury predicted development of acute kidney disease in a graded manner in which higher stages of acute kidney injury predicted higher relative risk of progressive kidney disease (area under the receiver operator characteristic curve = 0.82). This correlation persisted regardless of baseline kidney function (P < .001). Of note, development of acute kidney disease was associated with higher mortality and need for renal replacement therapy. The degree of acute kidney injury can identify patients who will have a higher risk of progression to acute kidney disease. These patients may benefit from close follow-up of renal function because they are at risk of progressing to chronic kidney disease or end-stage renal disease. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

42 CFR 486.328 - Condition: Reporting of data.

Code of Federal Regulations, 2011 CFR

2011-10-01

...: (1) Kidneys procured. Each kidney recovered will be counted individually. En bloc kidneys recovered will count as two kidneys procured. (2) Kidneys transplanted. Each kidney transplanted will be counted individually. En bloc kidney transplants will be counted as two kidneys transplanted. (3) Extra-renal organs...

42 CFR 486.328 - Condition: Reporting of data.

Code of Federal Regulations, 2010 CFR

2010-10-01

...: (1) Kidneys procured. Each kidney recovered will be counted individually. En bloc kidneys recovered will count as two kidneys procured. (2) Kidneys transplanted. Each kidney transplanted will be counted individually. En bloc kidney transplants will be counted as two kidneys transplanted. (3) Extra-renal organs...

Kidney Disease Basics

MedlinePlus

... My Kidneys Fail? Clinical Trials What Is Chronic Kidney Disease? Chronic kidney disease (CKD) means your kidneys ... work, be active, and enjoy life. Will my kidneys get better? Kidney disease is often “progressive”, which ...

Past, present and future of kidney paired donation transplantation in India

PubMed Central

Kute, Vivek B; Patel, Himanshu V; Shah, Pankaj R; Modi, Pranjal R; Shah, Veena R; Rizvi, Sayyed J; Pal, Bipin C; Modi, Manisha P; Shah, Priya S; Varyani, Umesh T; Wakhare, Pavan S; Shinde, Saiprasad G; Ghodela, Vijay A; Patel, Minaxi H; Trivedi, Varsha B; Trivedi, Hargovind L

2017-01-01

One third of healthy willing living kidney donors are rejected due to ABO blood group incompatibility and donor specific antibody. This increases pre-transplant dialysis duration leading to increased morbidity and mortality on the kidney transplantation waiting list. Over the last decade kidney paired donation is most rapidly increased source of living kidney donors. In a kidney transplantation program dominated by living donor kidney transplantation, kidney paired donation is a legal and valid alternative strategy to increase living donor kidney transplantation. This is more useful in countries with limited resources where ABO incompatible kidney transplantation or desensitization protocol is not feasible because of costs/infectious complications and deceased donor kidney transplantation is in initial stages. The matching allocation, ABO blood type imbalance, reciprocity, simultaneity, geography were the limitation for the expansion of kidney paired donation. Here we describe different successful ways to increase living donor kidney transplantation through kidney paired donation. Compatible pairs, domino chain, combination of kidney paired donation with desensitization or ABO incompatible transplantation, international kidney paired donation, non-simultaneous, extended, altruistic donor chain and list exchange are different ways to expand the donor pool. In absence of national kidney paired donation program, a dedicated kidney paired donation team will increase access to living donor kidney transplantation in individual centres with team work. Use of social networking sites to expand donor pool, HLA based national kidney paired donation program will increase quality and quantity of kidney paired donation transplantation. Transplant centres should remove the barriers to a broader implementation of multicentre, national kidney paired donation program to further optimize potential of kidney paired donation to increase transplantation of O group and sensitized patients. This review assists in the development of similar programs in other developing countries. PMID:28507916

Past, present and future of kidney paired donation transplantation in India.

PubMed

Kute, Vivek B; Patel, Himanshu V; Shah, Pankaj R; Modi, Pranjal R; Shah, Veena R; Rizvi, Sayyed J; Pal, Bipin C; Modi, Manisha P; Shah, Priya S; Varyani, Umesh T; Wakhare, Pavan S; Shinde, Saiprasad G; Ghodela, Vijay A; Patel, Minaxi H; Trivedi, Varsha B; Trivedi, Hargovind L

2017-04-24

One third of healthy willing living kidney donors are rejected due to ABO blood group incompatibility and donor specific antibody. This increases pre-transplant dialysis duration leading to increased morbidity and mortality on the kidney transplantation waiting list. Over the last decade kidney paired donation is most rapidly increased source of living kidney donors. In a kidney transplantation program dominated by living donor kidney transplantation, kidney paired donation is a legal and valid alternative strategy to increase living donor kidney transplantation. This is more useful in countries with limited resources where ABO incompatible kidney transplantation or desensitization protocol is not feasible because of costs/infectious complications and deceased donor kidney transplantation is in initial stages. The matching allocation, ABO blood type imbalance, reciprocity, simultaneity, geography were the limitation for the expansion of kidney paired donation. Here we describe different successful ways to increase living donor kidney transplantation through kidney paired donation. Compatible pairs, domino chain, combination of kidney paired donation with desensitization or ABO incompatible transplantation, international kidney paired donation, non-simultaneous, extended, altruistic donor chain and list exchange are different ways to expand the donor pool. In absence of national kidney paired donation program, a dedicated kidney paired donation team will increase access to living donor kidney transplantation in individual centres with team work. Use of social networking sites to expand donor pool, HLA based national kidney paired donation program will increase quality and quantity of kidney paired donation transplantation. Transplant centres should remove the barriers to a broader implementation of multicentre, national kidney paired donation program to further optimize potential of kidney paired donation to increase transplantation of O group and sensitized patients. This review assists in the development of similar programs in other developing countries.

Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor

ClinicalTrials.gov

2018-06-19

Adult Kidney Wilms Tumor; Beckwith-Wiedemann Syndrome; Childhood Kidney Wilms Tumor; Diffuse Hyperplastic Perilobar Nephroblastomatosis; Hemihypertrophy; Rhabdoid Tumor of the Kidney; Stage I Kidney Wilms Tumor; Stage II Kidney Wilms Tumor; Stage III Kidney Wilms Tumor; Stage IV Kidney Wilms Tumor; Stage V Kidney Wilms Tumor

Kidney pain (image)

MedlinePlus

A kidney stone is a solid piece of material that forms in a kidney. Kidney stones may be the size of sand or ... A kidney stone is a solid piece of material that forms in a kidney. Kidney stones may be the ...

Current organ allocation disadvantages kidney alone recipients over combined organ recipients.

PubMed

Martin, Michael S; Hagan, Michael E; Granger, Darla K

2016-03-01

The United Network for Organ Sharing began including the Kidney Donor Profile Index (KDPI) March 26, 2012 and began a new allocation scheme December 1, 2014. Kidney donors from our organ procurement organization from March 2012 to December 2014 were reviewed. The KDPIs of all 919 kidney only transplants were compared with all 102 kidney/extrarenal transplants. The average KDPI for kidney alone allografts was 47 (range 1 to 100) (standard deviation = 25.83) vs 27 for kidney/extrarenal kidneys (range 1 to 82) (standard deviation = 20.16) (P < .001, t test). Multivariate analysis including in- vs out-of-state recipient, donor body mass index, and donation after cardiac death vs brain-dead donor showed significantly lower KDPI for kidney/extrarenal transplants. Kidney/extrarenal organs have decreased graft survival compared with kidneys transplanted alone. In this sample, 21% of lower KDPI kidneys were allocated as kidney/extrarenal organs. This disadvantages those waiting for a kidney alone. Attention to the outcomes of kidneys transplanted with extrarenal organs is needed. Copyright © 2016 Elsevier Inc. All rights reserved.

Kidney (Renal) Failure

MedlinePlus

... News Physician Resources Professions Site Index A-Z Kidney Failure Kidney failure, also known as renal failure, ... evaluated? How is kidney failure treated? What is kidney (renal) failure? The kidneys are designed to maintain ...

Amyloidosis and Kidney Disease

MedlinePlus

... Solitary Kidney Your Kidneys & How They Work Amyloidosis & Kidney Disease What is amyloidosis? Amyloidosis is a rare ... the organs and tissues affected. What are the kidneys and what do they do? The kidneys are ...

Kidney Versus Combined Kidney and Liver Transplantation in Young People With Autosomal Recessive Polycystic Kidney Disease: Data From the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant (ESPN/ERA-EDTA) Registry.

PubMed

Mekahli, Djalila; van Stralen, Karlijn J; Bonthuis, Marjolein; Jager, Kitty J; Balat, Ayşe; Benetti, Elisa; Godefroid, Nathalie; Edvardsson, Vidar O; Heaf, James G; Jankauskiene, Augustina; Kerecuk, Larissa; Marinova, Svetlana; Puteo, Flora; Seeman, Tomas; Zurowska, Aleksandra; Pirenne, Jacques; Schaefer, Franz; Groothoff, Jaap W

2016-11-01

The choice for either kidney or combined liver-kidney transplantation in young people with kidney failure and liver fibrosis due to autosomal recessive polycystic kidney disease (ARPKD) can be challenging. We aimed to analyze the characteristics and outcomes of transplantation type in these children, adolescents, and young adults. Cohort study. We derived data for children, adolescents, and young adults with ARPKD with either kidney or combined liver-kidney transplants for 1995 to 2012 from the ESPN/ERA-EDTA Registry, a European pediatric renal registry collecting data from 36 European countries. Liver transplantation. Transplantation and patient survival. 202 patients with ARPKD aged 19 years or younger underwent transplantation after a median of 0.4 (IQR, 0.0-1.4) years on dialysis therapy at a median age of 9.0 (IQR, 4.1-13.7) years. 32 (15.8%) underwent combined liver-kidney transplantation, 163 (80.7%) underwent kidney transplantation, and 7 (3.5%) were excluded because transplantation type was unknown. Age- and sex-adjusted 5-year patient survival posttransplantation was 95.5% (95% CI, 92.4%-98.8%) overall: 97.4% (95% CI, 94.9%-100.0%) for patients with kidney transplantation in contrast to 87.0% (95% CI, 75.8%-99.8%) with combined liver-kidney transplantation. The age- and sex-adjusted risk for death after combined liver-kidney transplantation was 6.7-fold (95% CI, 1.8- to 25.4-fold) greater than after kidney transplantation (P=0.005). Five-year death-censored kidney transplant survival following combined liver-kidney and kidney transplantation was similar (92.1% vs 85.9%; P=0.4). No data for liver disease of kidney therapy recipients. Combined liver-kidney transplantation in ARPKD is associated with increased mortality compared to kidney transplantation in our large observational study and was not associated with improved 5-year kidney transplant survival. Long-term follow-up of both kidney and liver involvement are needed to better delineate the optimal transplantation strategy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Treatment Methods for Kidney Failure: Transplantation

MedlinePlus

... Right Financial Help for Treatment of Kidney Failure Kidney Transplant Some people with kidney failure may be ... transplant . What is the process for getting a kidney transplant? If you want a kidney transplant, the ...

Chronic Kidney Diseases

MedlinePlus

... Safe Videos for Educators Search English Español Chronic Kidney Diseases KidsHealth / For Kids / Chronic Kidney Diseases What's ... re talking about your kidneys. What Are the Kidneys? Your kidneys are tucked under your lower ribs ...

Kidney Transplantation: MedlinePlus Health Topic

MedlinePlus

... as They Affect Physical Fitness: A Physical Therapist's Point of View (National Kidney Foundation) Solitary Kidney (National Institute of Diabetes and Digestive and Kidney Diseases) Travel Tips: A Guide for Kidney Patients (National Kidney ...

BARTERING FOR A COMPATIBLE KIDNEY USING YOUR INCOMPATIBLE, LIVE KIDNEY DONOR: LEGAL AND ETHICAL ISSUES RELATED TO KIDNEY CHAINS.

PubMed

Tenenbaum, Evelyn M

2016-01-01

Kidney chains are a recent and novel method of increasing the number of available kidneys for transplantation and have the potential to save thousands of lives. However, because they are novel, kidney chains do not fit neatly within existing legal and ethicalframeworks, raising potential barriers to their full implementation. Kidney chains are an extension of paired kidney donation, which began in the United States in 2000. Paired kidney donations allow kidney patients with willing, but incompatible, donors to swap donors to increase the number of donor/recipient pairs and consequently, the number of transplants. More recently, transplant centers have been using non-simultaneous, extended, altruistic donor ("NEAD") kidney chains--which consist of a sequence of donations by incompatible donors--to further expand the number of donations. This Article fully explains paired kidney donation and kidney chains and focuses on whether NEAD chains are more coercive than traditional kidney donation to a family member or close friend and whether NEAD chains violate the National Organ Transplant Act's prohibition on the transfer of organs for valuable consideration.

Unique molecular changes in kidney allografts after simultaneous liver-kidney compared with solitary kidney transplantation.

PubMed

Taner, Timucin; Park, Walter D; Stegall, Mark D

2017-05-01

Kidney allografts transplanted simultaneously with liver allografts from the same donor are known to be immunologically privileged. This is especially evident in recipients with high levels of donor-specific anti-HLA antibodies. Here we investigated the mechanisms of liver's protective impact using gene expression in the kidney allograft. Select solitary kidney transplant or simultaneous liver-kidney transplant recipients were retrospectively reviewed and separated into four groups: 16 cross-match negative kidney transplants, 15 cross-match positive kidney transplants, 12 cross-match negative simultaneous liver-kidney transplants, and nine cross-match-positive simultaneous liver-kidney transplants. Surveillance biopsies of cross-match-positive kidney transplants had increased expression of genes associated with donor-specific antigens, inflammation, and endothelial cell activation compared to cross-match-negative kidney transplants. These changes were not found in cross-match-positive simultaneous liver-kidney transplant biopsies when compared to cross-match-negative simultaneous liver-kidney transplants. In addition, simultaneously transplanting a liver markedly increased renal expression of genes associated with tissue integrity/metabolism, regardless of the cross-match status. While the expression of inflammatory gene sets in cross-match-positive simultaneous liver-kidney transplants was not completely reduced to the level of cross-match-negative kidney transplants, the downstream effects of donor-specific anti-HLA antibodies were blocked. Thus, simultaneous liver-kidney transplants can have a profound impact on the kidney allograft, not only by decreasing inflammation and avoiding endothelial cell activation in cross-match-positive recipients, but also by increasing processes associated with tissue integrity/metabolism by unknown mechanisms. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Collagen IV Diseases: A Focus on the Glomerular Basement Membrane in Alport Syndrome

PubMed Central

Cosgrove, Dominic; Liu, Shiguang

2016-01-01

Alport syndrome is the result of mutations in any of three type IV collagen genes, COL4A3, COL4A4, or COL4A5. Because the three collagen chains form heterotrimers, there is an absence of all three proteins in the basement membranes where they are expressed. In the glomerulus, the mature glomerular basement membrane type IV collagen network, normally comprised of two separate networks, α3(IV)/α4(IV)/α5(IV) and α1(IV)/α2(IV), is comprised entirely of collagen α1(IV)/α2. This review addresses the current state of our knowledge regarding the consequence of this change in basement membrane composition, including both the direct, via collagen receptor binding, and indirect, regarding influences on glomerular biomechanics. The state of our current understanding regarding mechanisms of glomerular disease initiation and progression will be examined, as will the current state of the art regarding emergent therapeutic approaches to slow or arrest glomerular disease in Alport patients. PMID:27576055

Non-redundant coding of aversive odours in the main olfactory pathway

PubMed Central

Dewan, Adam; Pacifico, Rodrigo; Zhan, Ross; Rinberg, Dmitry; Bozza, Thomas

2013-01-01

Many species are critically dependent on olfaction for survival. In the main olfactory system of mammals, odours are detected by sensory neurons which express a large repertoire of canonical odorant receptors (ORs) and a much smaller repertoire of Trace Amine-Associated Receptors (TAARs)1–4. Odours are encoded in a combinatorial fashion across glomeruli in the main olfactory bulb, with each glomerulus corresponding to a different receptor5–7. The degree to which individual receptor genes contribute to odour perception is unclear. Here we show that genetic deletion of the olfactory TAAR gene family, or even a single TAAR gene, eliminates aversion that mice display to low concentrations of volatile amines and to the odour of predator urine. Our findings identify a role for the TAARs in olfaction, namely in the high-sensitivity detection of innately aversive odours. In addition, our data reveal that aversive amines are represented in a non-redundant fashion, and that individual main olfactory receptor genes can contribute significantly to odour perception. PMID:23624375

Non-redundant coding of aversive odours in the main olfactory pathway.

PubMed

Dewan, Adam; Pacifico, Rodrigo; Zhan, Ross; Rinberg, Dmitry; Bozza, Thomas

2013-05-23

Many species are critically dependent on olfaction for survival. In the main olfactory system of mammals, odours are detected by sensory neurons that express a large repertoire of canonical odorant receptors and a much smaller repertoire of trace amine-associated receptors (TAARs). Odours are encoded in a combinatorial fashion across glomeruli in the main olfactory bulb, with each glomerulus corresponding to a specific receptor. The degree to which individual receptor genes contribute to odour perception is unclear. Here we show that genetic deletion of the olfactory Taar gene family, or even a single Taar gene (Taar4), eliminates the aversion that mice display to low concentrations of volatile amines and to the odour of predator urine. Our findings identify a role for the TAARs in olfaction, namely, in the high-sensitivity detection of innately aversive odours. In addition, our data reveal that aversive amines are represented in a non-redundant fashion, and that individual main olfactory receptor genes can contribute substantially to odour perception.

A novel role of HIF-1α/PROX-1/LYVE-1 axis on tissue regeneration after renal ischaemia/reperfusion in mice.

PubMed

Meng, Fanwei

2018-04-10

Renal ischaemia reperfusion (I/R) is a common clinical condition with a high morbidity and mortality rate. To date, I/R-induced renal injury remains an ineffective treatment. We hypothesis that angiogenesis and lymphangiogenesis markers, prospero homeobox-1 (PROX-1) and lymphatic endothelial hyaluronan receptor-1 (LYVE-1), are critical during I/R. Kunming mice were subjected to I/R and observed for the following eight consecutive days. Pathology analysis and protein distribution were detected by H&E staining, immunohistochemistry and immunofluorescence confocal analysis. After I/R treatment, renal pathology was changed. HIF-1α was induced in the early stage and colocalisation with PROX-1 mainly in the renal tubular region, whereas PROX-1 and LYVE-1 were colocalised in the glomerulus of the endothelial region. In this study, we revealed HIF-1α/PROX-1/LVYE-1 axis dynamic changes in different regions after I/R and demonstrated for the first time it activates during I/R repair.

Familial Risks of Kidney Failure in Sweden: A Nationwide Family Study

PubMed Central

Akrawi, Delshad Saleh; Li, Xinjun; Sundquist, Jan; Sundquist, Kristina; Zöller, Bengt

2014-01-01

Background The value of family history as a risk factor for kidney failure has not been determined in a nationwide setting. Aim This nationwide family study aimed to determine familial risks for kidney failure in Sweden. Methods The Swedish multi-generation register on 0–78-year-old subjects were linked to the Swedish patient register and the Cause of death register for 1987–2010. Individuals diagnosed with acute kidney failure (n = 10063), chronic kidney failure (n = 18668), or unspecified kidney failure (n = 3731) were included. Kidney failure patients with cystic kidney disease, congenital kidney and urinary tract malformations, urolithiasis, and rare inherited kidney syndromes, and hyperoxaluria were excluded. Standardized incidence ratios (SIRs) were calculated for individuals whose parents/siblings were diagnosed with kidney failure compared to those whose parents or siblings were not. Results The concordant (same disease) familial risks (sibling/parent history) were increased for chronic kidney failure SIR = 2.02 (95% confidence interval, CI 1.90–2.14) but not for acute kidney failure SIR = 1.08 (95% CI 0.94–1.22) and for unspecified kidney failure SIR = 1.25 (95% CI 0.94–1.63). However, the discordant (different disease) familial risk for acute kidney failure SIR = 1.19 (95% CI 1.06–1.32) and unspecified kidney failure SIR = 1.63 (95% CI 1.40–1.90) was significantly increased in individuals with a family history of chronic kidney failure. The familial risk for chronic kidney failure was similar for males SIR = 2.04 (95% CI 1.90–2.20) and females SIR = 1.97 (95% CI 1.78–2.17). Familial risks for chronic kidney failure were highest at age of 10–19 years SIR = 6.33 (95% CI 4.16–9.22). Conclusions The present study shows that family history is an important risk factor for chronic kidney failure but to a lower degree for acute kidney failure and unspecified kidney failure. PMID:25423475

Concise Review: Kidney Generation with Human Pluripotent Stem Cells.

PubMed

Morizane, Ryuji; Miyoshi, Tomoya; Bonventre, Joseph V

2017-11-01

Chronic kidney disease (CKD) is a worldwide health care problem, resulting in increased cardiovascular mortality and often leading to end-stage kidney disease, where patients require kidney replacement therapies such as hemodialysis or kidney transplantation. Loss of functional nephrons contributes to the progression of CKD, which can be attenuated but not reversed due to inability to generate new nephrons in human adult kidneys. Human pluripotent stem cells (hPSCs), by virtue of their unlimited self-renewal and ability to differentiate into cells of all three embryonic germ layers, are attractive sources for kidney regenerative therapies. Recent advances in stem cell biology have identified key signals necessary to maintain stemness of human nephron progenitor cells (NPCs) in vitro, and led to establishment of protocols to generate NPCs and nephron epithelial cells from human fetal kidneys and hPSCs. Effective production of large amounts of human NPCs and kidney organoids will facilitate elucidation of developmental and pathobiological pathways, kidney disease modeling and drug screening as well as kidney regenerative therapies. We summarize the recent studies to induce NPCs and kidney cells from hPSCs, studies of NPC expansion from mouse and human embryonic kidneys, and discuss possible approaches in vivo to regenerate kidneys with cell therapies and the development of bioengineered kidneys. Stem Cells 2017;35:2209-2217. © 2017 AlphaMed Press.

40 CFR 180.518 - Pyrimethanil; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Cattle, kidney 2.5 Cattle, meat 0.01 Cattle, meat byproducts, except kidney 0.01 Goat, fat 0.01 Goat, kidney 2.5 Goat, meat 0.01 Goat, meat byproducts, except kidney 0.01 Horse, fat 0.01 Horse, kidney 2.5 Horse, meat 0.01 Horse, meat byproducts, except kidney 0.01 Sheep, fat 0.01 Sheep, kidney 2.5 Sheep...

40 CFR 180.518 - Pyrimethanil; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Cattle, kidney 2.5 Cattle, meat 0.01 Cattle, meat byproducts, except kidney 0.01 Goat, fat 0.01 Goat, kidney 2.5 Goat, meat 0.01 Goat, meat byproducts, except kidney 0.01 Horse, fat 0.01 Horse, kidney 2.5 Horse, meat 0.01 Horse, meat byproducts, except kidney 0.01 Sheep, fat 0.01 Sheep, kidney 2.5 Sheep...

[Banff score changes in kidneys from marginal donors].

PubMed

Borda, Bernadett; Szederkényi, Edit; Ottlakán, Aurél; Kemény, Éva; Szabó, Viktor; Hódi, Zoltán; Lázár, György

2016-02-21

Despite an increase in the number of cadaver donors and the number of overall organ transplantations, the dramatic increase in the waiting list makes it necessary to reconsider donor criteria. The authors examined whether differences could exist in the function and/or morphology of transplanted kidneys originated from marginal and ideal donors one and five years after transplantation. Kidney function and histopathologic findings were analysed and compared one and 5 years after transplantation in 97 patients having marginal donor kidneys and 178 patients who received ideal donor kidneys. Serum creatinine level was significantly higher (p = 0.0001) and estimated glomerular filtration rate was significantly lower (p = 0.003) in patients having marginal donor kidneys as compared to those with ideal donor kidneys 5 years after transplantation. Morphological changes in the transplanted kidneys such as tubulitis (p = 0.014) and interstitial inflammation (p = 0.025) were significantly more frequently present in patients with marginal donor kidneys than in those with ideal donor kidneys one year after transplantation. Despite an absence of differences in kidney function one year after kidney transplantation between patients having marginal and ideal donor kidneys, morphologic differences in the transplanted kidneys can be detected between the two groups of patients.

Temporal Analysis of Market Competition and Density in Renal Transplantation Volume and Outcome.

PubMed

Adler, Joel T; Yeh, Heidi; Markmann, James F; Nguyen, Louis L

2016-03-01

Kidney transplant centers are distributed unevenly throughout 58 donor service areas (DSAs) in the United States. Market competition and transplant center density may affect transplantation access and outcomes. We evaluated the role of spatial organization of transplant centers in conjunction with market competition in the conduct of kidney transplantation. The Scientific Registry of Transplant Recipients was queried for market characteristics associated with kidney transplantation between 2003 and 2012. Market competition was calculated using the Herfindahl Hirschman Index. Kidney transplant centers were geocoded to measure spatial organization by the average nearest neighbor (ANN) method. Kidney quality was assessed by kidney donor risk index. A hierarchical negative binomial mixed effects model tested the relationship between market characteristics and annual kidney transplants by DSA. About 152,071 kidney transplants were performed at 229 adult kidney transplant centers in 58 DSAs. Greater market competition was associated with kidney transplant center spatial clustering (P < 0.001). In multivariable analysis, more kidney transplant centers (incidence rate ratio [IRR], 1.04; P = 0.005), 100 more new listings (IRR, 1.02; P = 0.003), 100 more deceased donors (IRR, 1.23; P < 0.001), 100 more new dialysis registrants (IRR, 1.01; P < 0.001), and higher kidney donor risk index (IRR, 1.98; P < 0.001) were associated with increased kidney transplants. After controlling for market characteristics, larger numbers of kidney transplant centers were associated with more kidney transplants and increased utilization of deceased donor kidneys. This underlines the importance of understanding geography as well as competition in improving access to kidney transplantation.

Kidney disease - resources

MedlinePlus

Resources - kidney disease ... The following organizations are good resources for information on kidney disease: National Institute of Diabetes and Digestive and Kidney Disease -- www.niddk.nih.gov/health-information/kidney- ...

40 CFR 180.275 - Chlorothalonil; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., kidney 0.5 Cattle, meat byproducts, except kidney 0.05 Cattle, meat 0.03 Goat, fat 0.1 Goat, kidney 0.5 Goat, meat byproducts, except kidney 0.05 Goat, meat 0.03 Hog, fat 0.1 Hog, kidney 0.5 Hog, meat byproducts, except kidney 0.05 Hog, meat 0.03 Horse, fat 0.1 Horse, kidney 0.5 Horse, meat byproducts, except...

Novel Approach to Estimate Kidney and Cyst Volumes using Mid-Slice Magnetic Resonance Images in Polycystic Kidney Disease

PubMed Central

Bae, Kyongtae T; Tao, Cheng; Wang, Jinhong; Kaya, Diana; Wu, Zhiyuan; Bae, Junu T; Chapman, Arlene B; Torres, Vicente E; Grantham, Jared J; Mrug, Michal; Bennett, William M; Flessner, Michael F; Landsittel, Doug P

2013-01-01

Objective To evaluate whether kidney and cyst volumes can be accurately estimated based on limited area measurements from MR images of patients with autosomal dominant polycystic kidney disease (ADPKD). Materials and Methods MR coronal images of 178 ADPKD participants from the Consortium for Radiologic Imaging Studies of ADPKD (CRISP) were analyzed. For each MR image slice, we measured kidney and renal cyst areas using stereology and region-based thresholding methods, respectively. The kidney and cyst ‘observed’ volumes were calculated by summing up the area measurements of all the slices covering the kidney. To estimate the volume, we selected a coronal mid-slice in each kidney and multiplied its area by the total number of slices (‘PANK2’ for kidney and ‘PANC2’ for cyst). We then compared the kidney and cyst volumes predicted from PANK2 and PANC2, respectively, to the corresponding observed volumes, using a linear regression analysis. Results The kidney volume predicted from PANK2 correlated extremely well with the observed kidney volume: R2=0.994 for right and 0.991 for left kidney. The linear regression coefficient multiplier to PANK2 that best fit the kidney volume was 0.637 (95%CI: 0.629–0.644) for right and 0.624 (95%CI: 0.616–0.633) for left kidney. The correlation between the cyst volume predicted from PANC2 and the observed cyst volume was also very high: R2=0.984 for right and 0.967 for left kidney. The least squares linear regression coefficient for PANC2 was 0.637 (95%CI: 0.624–0.649) for right and 0.608 (95%CI: 0.591–0.625) for left kidney. Conclusion Kidney and cyst volumes can be closely approximated by multiplying the product of the mid-slice area measurement and the total number of slices in the coronal MR images of ADPKD kidneys by 0.61–0.64. This information will help save processing time needed to estimate total kidney and cyst volumes of ADPKD kidneys. PMID:24107679

Pediatric Inflammatory Bowel Diseases: Should We Be Looking for Kidney Abnormalities?

PubMed

Lauritzen, Didde; Andreassen, Bente Utoft; Heegaard, Niels Henrik H; Klinge, Lone Gabriels; Walsted, Anne-Mette; Neland, Mette; Nielsen, Rasmus Gaardskær; Wittenhagen, Per

2018-04-26

Kidney disease has been reported in adults with inflammatory bowel disease (IBD) and is regarded an extraintestinal manifestation or more rarely a side effect of the medical treatment. In this cross-sectional study we describe the extent of kidney pathology in a cohort of 56 children with IBD. Blood and urine samples were analyzed for markers of kidney disease and ultrasonography was performed to evaluate pole-to-pole kidney length. We found that 25% of the patients had either previously reported kidney disease or ultrasonographic signs of chronic kidney disease. The median kidney size compared with normal children was significantly reduced. In a multivariate linear mixed model, small kidneys significantly correlated with the use of infliximab, whereas the use of enteral nutritional therapy was associated with larger kidneys. Children with IBD are at risk of chronic kidney disease, and the risk seems to be increased with the severity of the disease.

Epidemiology of Kidney Discard from Expanded Criteria Donors Undergoing Donation after Circulatory Death.

PubMed

Singh, Sunita K; Kim, S Joseph

2016-02-05

The broader use of combined expanded criteria donor and donation after circulatory death (ECD/DCD) kidneys may help expand the deceased donor pool. The purpose of our study was to evaluate discard rates of kidneys from ECD/DCD donors and factors associated with discard. ECD/DCD donors and kidneys were evaluated from January 1, 2000 to March 31, 2011 using data from the Scientific Registry of Transplant Recipients. The kidney donor risk index was calculated for all ECD/DCD kidneys. Multivariable logistic regression models were used to determine risk factors for discarding both donor kidneys. The Kaplan-Meier product limit method and the log-rank statistic were used to assess the cumulative probability of graft failure for transplants from ECD/DCD donors where the mate kidney was discarded versus both kidneys were used. There were 896 ECD/DCD donors comprising 1792 kidneys. Both kidneys were discarded in 44.5% of donors, whereas 51.0% of all available kidneys were discarded. The kidney donor risk index scores were higher among donors of discarded versus transplanted kidneys (median, 1.82; interquartile range, 1.60, 2.07 versus median, 1.67; interquartile range, 1.49, 1.87, respectively; P<0.001); however, the distributions showed considerable overlap. The adjusted odds ratios for discard were higher among donors who were older, diabetic, AB blood type, and hepatitis C positive. The cumulative probabilities of total graft failure at 1, 3, and 5 years were 17.3%, 36.5%, and 55.4% versus 13.8%, 24.7%, and 40.5% among kidneys from donors where only one versus both kidneys were transplanted, respectively (log rank P=0.04). Our study shows a significantly higher discard rate for ECD/DCD kidneys versus prior reports. Some discarded ECD/DCD kidneys may be acceptable for transplantation. Additional studies are needed to evaluate the factors that influence decision making around the use of ECD/DCD kidneys. Copyright © 2016 by the American Society of Nephrology.

Epidemiology of Kidney Discard from Expanded Criteria Donors Undergoing Donation after Circulatory Death

PubMed Central

Singh, Sunita K.

2016-01-01

Background and objectives The broader use of combined expanded criteria donor and donation after circulatory death (ECD/DCD) kidneys may help expand the deceased donor pool. The purpose of our study was to evaluate discard rates of kidneys from ECD/DCD donors and factors associated with discard. Design, setting, participants, & measurements ECD/DCD donors and kidneys were evaluated from January 1, 2000 to March 31, 2011 using data from the Scientific Registry of Transplant Recipients. The kidney donor risk index was calculated for all ECD/DCD kidneys. Multivariable logistic regression models were used to determine risk factors for discarding both donor kidneys. The Kaplan–Meier product limit method and the log-rank statistic were used to assess the cumulative probability of graft failure for transplants from ECD/DCD donors where the mate kidney was discarded versus both kidneys were used. Results There were 896 ECD/DCD donors comprising 1792 kidneys. Both kidneys were discarded in 44.5% of donors, whereas 51.0% of all available kidneys were discarded. The kidney donor risk index scores were higher among donors of discarded versus transplanted kidneys (median, 1.82; interquartile range, 1.60, 2.07 versus median, 1.67; interquartile range, 1.49, 1.87, respectively; P<0.001); however, the distributions showed considerable overlap. The adjusted odds ratios for discard were higher among donors who were older, diabetic, AB blood type, and hepatitis C positive. The cumulative probabilities of total graft failure at 1, 3, and 5 years were 17.3%, 36.5%, and 55.4% versus 13.8%, 24.7%, and 40.5% among kidneys from donors where only one versus both kidneys were transplanted, respectively (log rank P=0.04). Conclusions Our study shows a significantly higher discard rate for ECD/DCD kidneys versus prior reports. Some discarded ECD/DCD kidneys may be acceptable for transplantation. Additional studies are needed to evaluate the factors that influence decision making around the use of ECD/DCD kidneys. PMID:26668028

Kidney Transplant

MedlinePlus

... Events Advocacy Donate A to Z Health Guide Kidney Transplant Print Email When your kidneys fail, treatment ... doctor, nurse and family members. What is a kidney transplant? When you get a kidney transplant, a ...

Kidney Failure

MedlinePlus

... store Donate Now Give Monthly Give In Honor Kidney Failure (ESRD) Causes, Symptoms, & Treatments www.kidneyfund.org > ... Disaster preparedness Kidney failure/ESRD diet What causes kidney failure? In most cases, kidney failure is caused ...

Kidney Problems

MedlinePlus

... our e-newsletter! Aging & Health A to Z Kidney Problems Basic Facts & Information The kidneys are two ... kidney (renal) diseases are called nephrologists . What are Kidney Diseases? For about one-third of older people, ...

Disposition and metabolism of codeine after single and chronic doses in one poor and seven extensive metabolisers.

PubMed

Chen, Z R; Somogyi, A A; Reynolds, G; Bochner, F

1991-04-01

1. The pharmacokinetics, metabolism and partial clearances of codeine to morphine, norcodeine and codeine-6-glucuronide after single (30 mg) and chronic (30 mg 8 h for seven doses) administration of codeine were studied in eight subjects (seven extensive and one poor metaboliser of dextromethorphan). Codeine, codeine-6-glucuronide, morphine and norcodeine were measured by high performance liquid chromatographic assays. 2. After the single dose, the time to achieve maximum plasma codeine concentrations was 0.97 +/- 0.31 h (mean +/- s.d.) and for codeine-6-glucuronide it was 1.28 +/- 0.49 h. The plasma AUC of codeine-6-glucuronide was 15.8 +/- 4.5 times higher than that of codeine. The AUC of codeine in saliva was 3.4 +/- 1.1 times higher than that in plasma. The elimination half-life of codeine was 3.2 +/- 0.3 h and that of codeine-6-glucuronide was 3.2 +/- 0.9 h. 3. The renal clearance of codeine was 183 +/- 59 ml min-1 and was inversely correlated with urine pH (r = 0.81). These data suggest that codeine undergoes filtration at the glomerulus, tubular secretion and passive reabsorption. The renal clearance of codeine-6-glucuronide was 55 +/- 21 ml min-1, and was not correlated with urine pH. Its binding to human plasma was less than 10%. These data suggest that codeine-6-glucuronide undergoes filtration at the glomerulus and tubular reabsorption. This latter process is unlikely to be passive. 4. After chronic dosing, the pharmacokinetics of codeine and codeine-6-glucuronide were not significantly different from the single dose pharmacokinetics. 5. After the single dose, 86.1 +/- 11.4% of the dose was recovered in urine, of which 59.8 +/- 10.3% was codeine-6-glucuronide, 7.1 +/- 1.1% was total morphine, 6.9 +/- 2.1% was total norcodeine and 11.8 +/- 3.9% was unchanged codeine. These recoveries were not significantly different (P greater than 0.05) after chronic administration. 6. After the single dose, the partial clearance to morphine was 137 +/- 31 ml min-1 in the seven extensive metabolisers and 8 ml min-1 in the poor metaboliser; to norcodeine the values were 103 +/- 33 ml min-1 and 90 ml min-1; to codeine-6-glucuronide the values were 914 +/- 129 ml min-1 and 971 ml min-1; and intrinsic clearance was 1568 +/- 103 ml min-1 and 1450 ml min-1. These values were not significantly (P greater than 0.05) altered by chronic administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Chronic Kidney Disease (CKD)

MedlinePlus

... Donate Now Give Monthly Give In Honor Chronic kidney disease (CKD) www.kidneyfund.org > Kidney Disease > Chronic ... Kidney-friendly diet for CKD What causes chronic kidney disease (CKD)? Anyone can get CKD. Some people ...

About Chronic Kidney Disease

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... Donate A to Z Health Guide About Chronic Kidney Disease Tweet Share Print Email Chronic kidney disease ( ... about Glomerular Filtration Rate (GFR) What is chronic kidney disease (CKD)? Chronic kidney disease includes conditions that ...

Nephrectomy (Kidney Removal)

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... nephrectomy is needed because of other kidney diseases. Kidney function Most people have two kidneys — fist-sized ... and the disease that prompted the surgery? Monitoring kidney function Most people can function well with only ...

Injury - kidney and ureter

MedlinePlus

... injury of the kidney; Bruised kidney; Ureteral injury; Pre-renal failure - injury, Post-renal failure - injury; Kidney ... or falling blood pressure Signs of kidney failure Tests that may be done include: Abdominal CT scan ...

Evolution of Acute Kidney Injury and Its Association With Systemic Hemodynamics in Children With Fluid-Refractory Septic Shock.

PubMed

Deep, Akash; Sagar, Hiremath; Goonasekera, Chulananda; Karthikeyan, Palaniswamy; Brierley, Joe; Douiri, Abdel

2018-07-01

There are no studies in pediatrics evaluating the progression of acute kidney injury in septic shock. We investigated the evolution of sepsis-associated acute kidney injury and its association with systemic hemodynamics in children with fluid-refractory septic shock. Prospective cohort study. PICU of a tertiary care hospital. All patients with fluid-refractory septic shock (n = 61) between September 2010 and February 2014. Hemodynamic variables using noninvasive ultrasound cardiac output monitor were measured at admission and 6 hourly thereafter till 48 hours. We used the Kidney Disease: Improving Global Outcomes criteria to define and stage acute kidney injury. Associations between various hemodynamic variables and development of acute kidney injury were evaluated. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury and was compared with no acute kidney injury or stage 1 acute kidney injury. Severe acute kidney injury developed in 29.5% (n = 18) of the 61 children with fluid-refractory septic shock, whereas 43 patients (70.49%) had either no or stage 1 acute kidney injury. Most patients who developed acute kidney injury did so within the first 48 hours of PICU admission. Severe acute kidney injury conferred a three-fold increased risk of death by day 28 (hazard ratio, 3.23; 95% CI, 1.52-6.67; p = 0.002), longer ICU stay, and increased duration of mechanical ventilation. Central venous pressure at presentation was higher in severe acute kidney injury by 5 cm H2O. Highest lactate in the first 24 hours of PICU admission, low diastolic blood pressure, low systemic vascular resistance index at admission were associated with severe acute kidney injury. This model reliably predicted stage 2/3 acute kidney injury by day 3 with area under the curve equals to 94%; 95% CI, 88.3-99.99. None of the other hemodynamic variables showed any association with severe acute kidney injury. Manifestations of sepsis-associated acute kidney injury often occur early after PICU admission and is associated with increased morbidity and mortality. There is a need to develop a predictive model in septic shock which could facilitate early detection of acute kidney injury.

Tolvaptan and Kidney Pain in Patients With Autosomal Dominant Polycystic Kidney Disease: Secondary Analysis From a Randomized Controlled Trial

PubMed Central

Casteleijn, Niek F.; Blais, Jaime D.; Chapman, Arlene B.; Czerwiec, Frank S.; Devuyst, Olivier; Higashihara, Eiji; Leliveld, Anna M.; Ouyang, John; Perrone, Ronald D.; Torres, Vicente E.; Gansevoort, Ron T.

2017-01-01

Background Kidney pain is a common complication in patients with autosomal dominant polycystic kidney disease (ADPKD), and data from the TEMPO 3:4 trial suggested that tolvaptan, a vasopressin V2 receptor antagonist, may have a positive effect on kidney pain in this patient group. Because pain is difficult to measure, the incidence of kidney pain leading to objective medical interventions was used in the present study to assess pain. Study Design Secondary analysis from a randomized controlled trial. Setting & Participants Patients with ADPKD with preserved kidney function. Intervention Tolvaptan or placebo. Outcomes Kidney pain events defined by objective medical interventions. Measurements Kidney pain events were recorded and independently adjudicated. Incidence of a first kidney pain event was assessed overall and categorized into 5 subgroups according to severity. Results Of 1,445 participating patients (48.4% women; mean age, 39 ± 7 [SD] years; mean estimated glomerular filtration rate, 81 ± 22 mL/min/1.73 m2; median total kidney volume, 1,692 [IQR, 750–7,555] mL), 50.9% reported a history of kidney pain at baseline. History of urinary tract infections, kidney stones, or hematuria (all P < 0.001) and female sex (P < 0.001) were significantly associated with history of kidney pain. Tolvaptan use resulted in a significantly lower incidence of kidney pain events when compared to placebo: 10.1% versus 16.8% (P < 0.001), with a risk reduction of 36% (HR, 0.64; 95% CI, 0.48–0.86). The reduction in pain event incidence by tolvaptan was found in all groups irrespective of pain severity and was independent of predisposing factors (P for interaction > 0.05). The effect of tolvaptan was explained at least in part by a decrease in incidence of urinary tract infections, kidney stones, and hematuria when compared to placebo. Limitations Trial has specific inclusion criteria for total kidney volume and kidney function. Conclusions Tolvaptan decreased the incidence of kidney pain events independent of patient characteristics predisposing for kidney pain and possibly in part due to reductions in ADPKD-related complications. PMID:27856088

Risk of chronic and end stage kidney disease in patients with nephrolithiasis.

PubMed

Shoag, Jonathan; Halpern, Joshua; Goldfarb, David S; Eisner, Brian H

2014-11-01

We examine kidney stone disease as a potential risk factor for chronic kidney disease, end stage kidney disease and treatment with dialysis. The NHANES (National Health and Nutrition Examination Survey) 2007-2010 database was interrogated for patients with a history of kidney stones. Demographics and comorbid conditions including age, gender, body mass index, diabetes, hemoglobin A1c, hypertension, gout and smoking were also assessed. Multivariate analysis adjusting for patient demographics and comorbidities was performed to assess differences in the prevalence of chronic kidney disease and treatment with dialysis between the 2 groups. History of nephrolithiasis was assessed with the question, "Have you ever had kidney stones?" Chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 ml/minute/1.73 m(2) and/or a urinary albumin-to-creatinine ratio greater than 30 mg/gm. Statistical calculations were performed using Stata® software with determinations of p values and 95% CI where appropriate. The study included an analysis of 5,971 NHANES participants for whom data on chronic kidney disease and kidney stones were available, of whom 521 reported a history of kidney stones. On multivariate analysis a history of kidney stones was associated with chronic kidney disease and treatment with dialysis (OR 1.50, 1.10-2.04, p = 0.013 and OR 2.37, 1.13-4.96, p = 0.025, respectively). This difference appeared to be driven by women, where a history of kidney stones was associated with a higher prevalence of chronic kidney disease (OR 1.76, 1.13-2.763, p = 0.016) and treatment with dialysis (OR 3.26, 1.48-7.16, p = 0.004). There was not a significant association between kidney stone history and chronic kidney disease or treatment with dialysis in men. Kidney stone history is associated with an increased risk of chronic kidney disease and treatment with dialysis among women even after adjusting for comorbid conditions. Large scale prospective studies are needed to further characterize the relationship between nephrolithiasis and chronic kidney disease. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Averting the legacy of kidney disease--focus on childhood.

PubMed

Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

2016-03-01

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and chronic kidney disease in later childhood or in adult life. Children born early or who are small-for-date newborns have a relatively increased risk for the development of chronic kidney disease later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced chronic kidney disease in childhood; there is evidence that children fare better than adults if they receive kidney replacement therapy including dialysis and transplant, whereas only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers, and caregivers about the needs and possibilities surrounding kidney disease in childhood. Copyright © 2016 World Kidney Day 2016 Steering Committee. Published by Elsevier Inc. All rights reserved.

Kidney transplantation after previous liver transplantation: analysis of the organ procurement transplant network database.

PubMed

Gonwa, Thomas A; McBride, Maureen A; Mai, Martin L; Wadei, Hani M

2011-07-15

Patients after liver transplant have a high incidence of chronic kidney disease and end-stage renal disease (ESRD). We investigated kidney transplantation after liver transplantation using the Organ Procurement Transplant Network database. The Organ Procurement Transplant Network database was queried for patients who received kidney transplantation after previous liver transplantation. These patients were compared with patients who received primary kidney transplantation alone during the same time period. Between 1997 and 2008, 157,086 primary kidney transplants were performed. Of these, 680 deceased donor kidney transplants and 410 living donor kidney transplants were performed in previous recipients of liver transplants. The number of kidney after liver transplants performed each year has increased from 37 per year to 124 per year in 2008. The time from liver transplant to kidney transplant increased from 8.2 to 9.0 years for living donor transplants and from 5.4 to 9.6 years for deceased donor. The 1, 3, and 5 year actuarial graft survival in both living donor kidney after liver transplant and deceased donor kidney after liver transplant are less than the kidney transplant alone patients. However, the death-censored graft survivals are equal. The patient survival is also less but is similar to what would be expected in liver transplant recipients who did not have ESRD. In 2008, kidney after liver transplantation represented 0.9% of the total kidney alone transplants performed in the United States. Kidney transplantation is an appropriate therapy for selected patients who develop ESRD after liver transplantation.

Kidney Disease

MedlinePlus

... Staying Safe Videos for Educators Search English Español Kidney Disease KidsHealth / For Teens / Kidney Disease What's in ... Coping With Kidney Conditions Print What Do the Kidneys Do? You might never think much about some ...

(Re)Building a Kidney

PubMed Central

Carroll, Thomas J.; Cleaver, Ondine; Gossett, Daniel R.; Hoshizaki, Deborah K.; Hubbell, Jeffrey A.; Humphreys, Benjamin D.; Jain, Sanjay; Jensen, Jan; Kaplan, David L.; Kesselman, Carl; Ketchum, Christian J.; Little, Melissa H.; McMahon, Andrew P.; Shankland, Stuart J.; Spence, Jason R.; Valerius, M. Todd; Wertheim, Jason A.; Wessely, Oliver; Zheng, Ying; Drummond, Iain A.

2017-01-01

(Re)Building a Kidney is a National Institute of Diabetes and Digestive and Kidney Diseases-led consortium to optimize approaches for the isolation, expansion, and differentiation of appropriate kidney cell types and the integration of these cells into complex structures that replicate human kidney function. The ultimate goals of the consortium are two-fold: to develop and implement strategies for in vitro engineering of replacement kidney tissue, and to devise strategies to stimulate regeneration of nephrons in situ to restore failing kidney function. Projects within the consortium will answer fundamental questions regarding human gene expression in the developing kidney, essential signaling crosstalk between distinct cell types of the developing kidney, how to derive the many cell types of the kidney through directed differentiation of human pluripotent stem cells, which bioengineering or scaffolding strategies have the most potential for kidney tissue formation, and basic parameters of the regenerative response to injury. As these projects progress, the consortium will incorporate systematic investigations in physiologic function of in vitro and in vivo differentiated kidney tissue, strategies for engraftment in experimental animals, and development of therapeutic approaches to activate innate reparative responses. PMID:28096308

Utilization of Deceased Donor Kidneys to Initiate Living Donor Chains.

PubMed

Melcher, M L; Roberts, J P; Leichtman, A B; Roth, A E; Rees, M A

2016-05-01

We propose that some deceased donor (DD) kidneys be allocated to initiate nonsimultaneous extended altruistic donor chains of living donor (LD) kidney transplants to address, in part, the huge disparity between patients on the DD kidney waitlist and available donors. The use of DD kidneys for this purpose would benefit waitlisted candidates in that most patients enrolled in kidney paired donation (KPD) systems are also waitlisted for a DD kidney transplant, and receiving a kidney through the mechanism of KPD will decrease pressure on the DD pool. In addition, a LD kidney usually provides survival potential equal or superior to that of DD kidneys. If KPD chains that are initiated by a DD can end in a donation of an LD kidney to a candidate on the DD waitlist, the quality of the kidney allocated to a waitlisted patient is likely to be improved. We hypothesize that a pilot program would show a positive impact on patients of all ethnicities and blood types. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Reconstruction and Analysis of Human Kidney-Specific Metabolic Network Based on Omics Data

PubMed Central

Zhang, Ai-Di; Dai, Shao-Xing; Huang, Jing-Fei

2013-01-01

With the advent of the high-throughput data production, recent studies of tissue-specific metabolic networks have largely advanced our understanding of the metabolic basis of various physiological and pathological processes. However, for kidney, which plays an essential role in the body, the available kidney-specific model remains incomplete. This paper reports the reconstruction and characterization of the human kidney metabolic network based on transcriptome and proteome data. In silico simulations revealed that house-keeping genes were more essential than kidney-specific genes in maintaining kidney metabolism. Importantly, a total of 267 potential metabolic biomarkers for kidney-related diseases were successfully explored using this model. Furthermore, we found that the discrepancies in metabolic processes of different tissues are directly corresponding to tissue's functions. Finally, the phenotypes of the differentially expressed genes in diabetic kidney disease were characterized, suggesting that these genes may affect disease development through altering kidney metabolism. Thus, the human kidney-specific model constructed in this study may provide valuable information for the metabolism of kidney and offer excellent insights into complex kidney diseases. PMID:24222897

Transport of organic anions and cations in murine embryonic kidney development and in serially-reaggregated engineered kidneys

PubMed Central

Lawrence, Melanie L.; Chang, C-Hong; Davies, Jamie A.

2015-01-01

Recent advances in renal tissue engineering have shown that dissociated, early renogenic tissue from the developing embryo can self-assemble into morphologically accurate kidney-like organs arranged around a central collecting duct tree. In order for such self-assembled kidneys to be useful therapeutically or as models for drug screening, it is necessary to demonstrate that they are functional. One of the main functional characteristics of mature kidneys is transport of organic anions and cations into and out of the proximal tubule. Here, we show that the transport function of embryonic kidneys allowed to develop in culture follows a developmental time-course that is comparable to embryonic kidney development in vivo. We also demonstrate that serially-reaggregated engineered kidneys can transport organic anions and cations through specific uptake and efflux channels. These results support the physiological relevance of kidneys grown in culture, a commonly used model for kidney development and research, and suggest that serially-reaggregated kidneys self-assembled from separated cells have some functional characteristics of intact kidneys. PMID:25766625

Kidney Stones (For Parents)

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... Staying Safe Videos for Educators Search English Español Kidney Stones KidsHealth / For Parents / Kidney Stones What's in ... other treatments to help remove the stones. How Kidney Stones Form It's the kidneys' job to remove ...

Chronic Kidney Disease and Medicines

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... If My Kidneys Fail? Clinical Trials Managing Chronic Kidney Disease If you have chronic kidney disease (CKD), ... hard, but it’s worthwhile. Ten ways to manage kidney disease Control your blood pressure Meet your blood ...

High Blood Pressure and Kidney Disease

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... Your Kidneys & How They Work High Blood Pressure & Kidney Disease What is high blood pressure? Blood pressure ... have their blood pressure checked. What are the kidneys and what do they do? The kidneys are ...

Kidney Biopsy

MedlinePlus

... Series Urinary Tract Imaging Urodynamic Testing Virtual Colonoscopy Kidney Biopsy What is a kidney biopsy? A kidney biopsy is a procedure that ... performs procedures using imaging equipment Why is a kidney biopsy performed? A health care provider will perform ...

Autophagy and kidney inflammation

PubMed Central

Kimura, Tomonori; Isaka, Yoshitaka; Yoshimori, Tamotsu

2017-01-01

ABSTRACT Inflammation plays a pivotal role in pathophysiological processes of kidney diseases. Macroautophagy/autophagy plays multiple roles in inflammatory responses, and the regulation of inflammation by autophagy has great potential as a treatment for damaged kidneys. A growing body of evidence suggests autophagy protects kidney from versatile kidney inflammatory insults, including those that are acute, chronic, metabolic, and aging-related. It is noteworthy that, in kidney, mitophagy is active, and damaged lysosomes are removed by autophagy. In this mode, autophagy suppresses inflammation to protect the kidney. Systemic inflammation also affects the kidney via pro-inflammatory cytokines and infiltration of inflammatory cells, and autophagy also has a regulatory role in systemic inflammation. This review focuses on the roles of autophagy in kidney diseases and aging through inflammation, and discusses the potential usage of autophagy as an inflammatory modulator for the treatment of kidney diseases. PMID:28441075

Autophagy and kidney inflammation.

PubMed

Kimura, Tomonori; Isaka, Yoshitaka; Yoshimori, Tamotsu

2017-06-03

Inflammation plays a pivotal role in pathophysiological processes of kidney diseases. Macroautophagy/autophagy plays multiple roles in inflammatory responses, and the regulation of inflammation by autophagy has great potential as a treatment for damaged kidneys. A growing body of evidence suggests autophagy protects kidney from versatile kidney inflammatory insults, including those that are acute, chronic, metabolic, and aging-related. It is noteworthy that, in kidney, mitophagy is active, and damaged lysosomes are removed by autophagy. In this mode, autophagy suppresses inflammation to protect the kidney. Systemic inflammation also affects the kidney via pro-inflammatory cytokines and infiltration of inflammatory cells, and autophagy also has a regulatory role in systemic inflammation. This review focuses on the roles of autophagy in kidney diseases and aging through inflammation, and discusses the potential usage of autophagy as an inflammatory modulator for the treatment of kidney diseases.

Factors affecting willingness to receive a kidney transplant among minority patients at an urban safety-net hospital: a cross-sectional survey.

PubMed

Ilori, Titilayo O; Enofe, Nosayaba; Oommen, Anju; Odewole, Oluwaseun; Ojo, Akinlolu; Plantinga, Laura; Pastan, Stephen; Echouffo-Tcheugui, Justin B; McClellan, William

2015-11-21

In the US, African Americans (AAs) are four times more likely to develop end stage renal disease (ESRD) but half as likely to receive a kidney transplant as whites. Patient interest in kidney transplantation is a fundamental step in the kidney transplant referral process. Our aim was to determine the factors associated with the willingness to receive a kidney transplant among chronic kidney disease (CKD) patients in a predominantly minority population. CKD patients from an outpatient nephrology clinic at a safety-net hospital (n = 213) participated in a cross-sectional survey from April to June, 2013 to examine the factors associated with willingness to receive a kidney transplant among a predominantly minority population. The study questionnaire was developed from previously published literature. Multivariable logistic regression analysis was used to determine factors associated with willingness to undergo a kidney transplant. Respondents were primarily AAs (91.0%), mostly female (57.6%) and middle aged (51.6%). Overall, 53.9% of participants were willing to undergo a kidney transplant. Willingness to undergo a kidney transplant was associated with a positive perception towards living kidney donation (OR 7.31, 95% CI: 1.31-40.88), willingness to attend a class about kidney transplant (OR = 7.15, CI: 1.76-29.05), perception that a kidney transplant will improve quality of life compared to dialysis (OR = 5.40, 95% CI: 1.97-14.81), and obtaining information on kidney transplant from other sources vs. participant's physician (OR =3.30, 95% CI: 1.13-9.67), when compared with their reference groups. It is essential that the quality of life benefits of kidney transplantation be known to individuals with CKD to increase their willingness to undergo kidney transplantation. Availability of multiple sources of information and classes on kidney transplantation may also contribute to willingness to undergo kidney transplantation, especially among AAs.

CT volumetry is superior to nuclear renography for prediction of residual kidney function in living donors.

PubMed

Barbas, Andrew S; Li, Yanhong; Zair, Murtuza; Van, Julie A; Famure, Olusegun; Dib, Martin J; Laurence, Jerome M; Kim, S Joseph; Ghanekar, Anand

2016-09-01

Living kidney donor evaluation commonly includes nuclear renography to assess split kidney function and computed tomography (CT) scan to evaluate anatomy. To streamline donor workup and minimize exposure to radioisotopes, we sought to assess the feasibility of using proportional kidney volume from CT volumetry in lieu of nuclear renography. We examined the correlation between techniques and assessed their ability to predict residual postoperative kidney function following live donor nephrectomy. In a cohort of 224 live kidney donors, we compared proportional kidney volume derived by CT volumetry with split kidney function derived from nuclear renography and found only modest correlation (left kidney R(2) =26.2%, right kidney R(2) =26.7%). In a subset of 88 live kidney donors with serum creatinine measured 6 months postoperatively, we compared observed estimated glomerular filtration rate (eGFR) at 6 months with predicted eGFR from preoperative imaging. Compared to nuclear renography, CT volumetry more closely approximated actual observed postoperative eGFR for Chronic Kidney Disease Epidemiology Collaboration (J-test: P=.02, Cox-Pesaran test: P=.01) and Mayo formulas (J-test: P=.004, Cox-Pesaran test: P<.001). These observations support the use of CT volumetry for estimation of split kidney function in healthy individuals with normal kidney function and morphology. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sodium lactate improves renal microvascular thrombosis compared to sodium bicarbonate and 0.9% NaCl in a porcine model of endotoxic shock: an experimental randomized open label controlled study.

PubMed

Duburcq, Thibault; Durand, Arthur; Tournoys, Antoine; Gnemmi, Viviane; Gmyr, Valery; Pattou, François; Jourdain, Mercedes; Tamion, Fabienne; Besnier, Emmanuel; Préau, Sebastien; Parmentier-Decrucq, Erika; Mathieu, Daniel; Poissy, Julien; Favory, Raphaël

2018-02-14

Sodium lactate seemed to improve fluid balance and avoid fluid overload. The objective of this study was to determine if these beneficial effects can be at least partly explained by an improvement in disseminated intravascular coagulation (DIC)-associated renal microvascular thrombosis. Ancillary work of an interventional randomized open label controlled experimental study. Fifteen female "Large White" pigs (2 months old) were challenged with intravenous infusion of E. coli endotoxin. Three groups of five animals were randomly assigned to receive different fluids: a treatment group received sodium lactate 11.2% (SL group); an isotonic control group received 0.9% NaCl (NC group); a hypertonic control group, with the same amount of osmoles and sodium than SL group, received sodium bicarbonate 8.4% (SB group). Glomerular filtration rate (GFR) markers, coagulation and inflammation parameters were measured over a 5-h period. Immediately after euthanasia, kidneys were withdrawn for histological study. Statistical analysis was performed with nonparametric tests and the Dunn correction for multiple comparisons. A p < 0.05 was considered significant. The direct immunofluorescence study revealed that the percentage of capillary sections thrombosed in glomerulus were significantly lesser in SL group [5 (0-28) %] compared to NC [64 (43-79) %, p = 0.01] and SB [64 (43-79), p = 0.03] groups. Alterations in platelet count and fibrinogen level occurred earlier and were significantly more pronounced in both control groups compared to SL group (p < 0.05 at 210 and 300 min). The increase in thrombin-antithrombin complexes was significantly higher in NC [754 (367-945) μg/mL; p = 0.03] and SB [463 (249-592) μg/mL; p = 0.03] groups than in SL group [176 (37-265) μg/mL]. At the end of the experiment, creatinine clearance was significantly higher in SL group [55.46 (30.07-67.85) mL/min] compared to NC group [1.52 (0.17-27.67) mL/min, p = 0.03]. In this study, we report that sodium lactate improves DIC-associated renal microvascular thrombosis and preserves GFR. These findings could at least partly explain the better fluid balance observed with sodium lactate infusion.

Exposure to sub-acute doses of fipronil and buprofezin in combination or alone induces biochemical, hematological, histopathological and genotoxic damage in common carp (Cyprinus carpio L.).

PubMed

Qureshi, Irfan Zia; Bibi, Asia; Shahid, Sana; Ghazanfar, Madiha

2016-10-01

Use of pesticides or insecticides can be highly toxic to aquatic life forms due to leaching and agricultural runoff, rains or flood. Fipronil (FP) is a GABA receptor inhibitor, while buprofezin (BPFN) is an insect growth regulator. Presently, we exposed groups of aquaria acclimated carp fish (Cyprinus carpio) for 96h to sub-lethal concentrations of fipronil (400μgL(-1); 9.15×10(-7)molL(-1)) and buprofezin (BPFN, 100mgL(-1); 1.072×10(-6)molL(-1)) singly or in combination. The extent of damage was assessed at biochemical, hematological, molecular biological and histopathological level. Results obtained in treated fish were compared statistically with those of control non-treated fish and also among treatment groups. Significance level was p<0.05. Compared to control, serum total protein and globulin concentrations decreased significantly (p<0.0001) in fish treated with FP; while albumin concentration remained unaltered with all treatments. Glucose concentration decreased significantly (p<0.002) in fish treated with FP. In contrast, combined FP+BPFN treatment and BPFN treatment caused insignificant elevation of glucose concentration. Hematological assessment demonstrated significant decrease in red blood cell and thrombocyte counts, hemoglobin concentration and hematocrit percent; while white blood cell count showed an increase in all treatment groups (p<0.0001). Blood smears from pesticide treated fish revealed aberrant erythrocyte morphologies which included necrosis, micronuclear formation and hyperchromatosis. DNA laddering assay carried out on whole blood demonstrated excessive smear formation in combined FP+BPFN and BPFN treatment groups but no smear formation was noticeable in FP treated fish. Compared to control, whole blood DNA content increased significantly in the combined FP+BPFN and BPFN treatment groups (p<0.001 and p<0.009). With all treatments histopathological changes observed in the gills were: epithelial uplifting and necrosis of lamellae, lamellar atrophy, disruption of cartilaginous core, fusion and disorganization of lamellae and telangiectasia. In liver these were: karyorrhexis, hepatocellular hypertrophy, nuclear hypertrophy, melanomacrophage aggregates and central vein contraction, while in the kidney: deterioration of glomerulus and dilatation of Bowman's space, dilatation of renal tubules, thyroidisation, altered tubular lumen, nuclear hypertrophy, cellular atrophy, and cellular necrosis were the outcome. Our study revealed that FP and BPFN produce highly toxic effects on fish when given in combination or singly. To our knowledge, this is the first report on toxicity caused by FP and BPFN in single and combined state. Copyright © 2016 Elsevier B.V. All rights reserved.

Qi-Dan Fang ameliorates adriamycin-induced nephrotic syndrome rat model by enhancing renal function and inhibiting podocyte injury.

PubMed

Wu, Jun-Biao; Ye, Shu-Fang; Liang, Chun-Ling; Li, Yu-Cui; Yu, Ying-Jia; Lai, Jie-Mei; Lin, Hui; Zheng, Jie; Zhou, Jiu-Yao

2014-02-12

Nephrotic syndrome (NS) is a clinical syndrome with a variety of causes, mainly characterized by heavy proteinuria. Podocyte injury plays a key role in proteinuria, one of the principal means for the control of NS is to prevent podocyte injury. Qi-Dan Fang consists of two of the most extensively applied herbal remedies among Traditional Chinese Medicine (TCM) (Radix Astragali Mongolici and Radix Salviae Miltiorrhizae, with a weight ratio of 5:1) which are specifically used for the treatment of various kidney diseases. In previous studies, we found that Qi-Dan Fang provides improvement to patients with adriamycin-induced nephrotic syndrome by alleviating proteinuria and serum lipid. The aim of this study is to study the efficiency of Qi-Dan Fang on NS model rat with renal dysfunction and podocyte injury, something which has not been carried out yet. The rats were divided into Normal, Model, Jin Gui Shen Qi Pill (4.12 g/kg), Qi-Dan Fang (3.09, 6.17 and 12.34 g/kg/d) groups, they were each given a single tail intravenous injection of Adriamycin (6.0 mg/kg) except for the Normal group and were orally administered dosages of Qi-Dian Fang and Jin Gui Shen Qi pills once daily for 7 weeks. Following the treatment, the content of cystation C (CysC), blood urea nitrogen (BUN), serum creatinine (Scr) were measured with an autobiochemical analyser. The pathomorphological changes to the glomeruli, the mRNA expressions of nephrin, podocin, CD2AP genes and p53, bax, bcl-2 proteins expressions were also carried out to probe the effects of Qi-Dan Fang. (1) Qi-Dan Fang treatment raised the level of CysC in blood serum while lowering the content of BUN and Scr in the adriamycin-induced nephrotic syndrome rat model; (2) Long-term administration of Qi-Dan Fang was able to ameliorate pathomorphological change of glomeruli and repair the organization structure of Glomerulus; (3) Qi-Dan Fang could increase the mRNA expression of nephrin, podocin and CD2AP genes, down-regulate the expression of p53, bax proteins, while increased bcl-2 protein to protect the podocyte and restore Glomerular selective filtration function. Results of our present studies reveal that Qi-Dan Fang is able to enhance renal function, inhibit podocyte injury to provide improvements to the Adriamycin-induced nephrotic syndrome. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Outcome Measures Used to Report Kidney Function in Studies Investigating Surgical Management of Kidney Tumours: A Systematic Review.

PubMed

Ellis, Robert J; Cho, Yeoungjee; Del Vecchio, Sharon J; McStea, Megan; Morais, Christudas; Coombes, Jeff S; Wood, Simon T; Gobe, Glenda C; Francis, Ross S

2018-05-01

Most practice decisions relevant to preserving kidney function in patients managed surgically for kidney tumours are driven by observational studies. A wide range of outcome measures are used in these studies, which reduces comparability and increases the risk of reporting bias. To comprehensively and succinctly describe the outcomes used to evaluate kidney function in studies evaluating surgical management of kidney tumours. Electronic search of the PubMed database was conducted to identify studies with at least one measure of kidney function in patients managed surgically for kidney tumours, published between January 2000 and September 2017. Abstracts were initially screened for eligibility. Full texts of articles were then evaluated in more detail for inclusion. A narrative synthesis of the evidence was conducted. A total of 312 studies, involving 127905 participants, were included in this review. Most were retrospective (n=274) studies and conducted in a single centre (n=264). Overall, 78 unique outcome measures were identified, which were grouped into six outcome categories. Absolute postoperative kidney function (n=187), relative kidney function (n=181), and postoperative chronic kidney disease (n=131) were most frequently reported. Kidney function was predominantly quantified using estimated glomerular filtration rate or creatinine clearance (n=255), most using the modification of diet in renal disease equation (n=182). Only 70 studies provided rationale for specific outcome measures used. There is significant variability in the reporting and quantification of kidney function in studies evaluating patients managed surgically for kidney tumours. A standardised approach to measuring and reporting kidney function will increase the effectiveness of outcomes reported and improve relevance of research findings within a clinical context. Although we know that the removal of a kidney can reduce kidney function, clinical significance of various approaches is a matter of debate. This article demonstrates significant variability in the way kidney function was reported across all studies of patients with kidney cancer undergoing surgery, indicating a need for standardisation. Copyright © 2018 European Association of Urology. All rights reserved.

Klotho and activin A in kidney injury: plasma Klotho is maintained in unilateral obstruction despite no upregulation of Klotho biosynthesis in the contralateral kidney.

PubMed

Nordholm, Anders; Mace, Maria L; Gravesen, Eva; Hofman-Bang, Jacob; Morevati, Marya; Olgaard, Klaus; Lewin, Ewa

2018-05-01

In a new paradigm of etiology related to chronic kidney disease-mineral and bone disorder (CKD-MBD), kidney injury may cause induction of factors in the injured kidney that are released into the circulation and thereby initiate and maintain renal fibrosis and CKD-MBD. Klotho is believed to ameliorate renal fibrosis and CKD-MBD, while activin A might have detrimental effects. The unilateral ureter obstruction (UUO) model is used here to examine this concept by investigating early changes related to renal fibrosis in the obstructed kidney, untouched contralateral kidney, and vasculature which might be affected by secreted factors from the obstructed kidney, and comparing with unilateral nephrectomized controls (UNX). Obstructed kidneys showed early Klotho gene and protein depletion, whereas plasma Klotho increased in both UUO and UNX rats, indicating an altered metabolism of Klotho. Contralateral kidneys had no compensatory upregulation of Klotho and maintained normal expression of the examined fibrosis-related genes, as did remnant UNX kidneys. UUO caused upregulation of transforming growth factor-β and induction of periostin and activin A in obstructed kidneys without changes in the contralateral kidneys. Plasma activin A doubled in UUO rats after 10 days while no changes were seen in UNX rats, suggesting secretion of activin A from the obstructed kidney with potentially systemic effects on CKD-MBD. As such, increased aortic sclerostin was observed in UUO rats compared with UNX and normal controls. The present results are in line with the new paradigm and show very early vascular effects of unilateral kidney fibrosis, supporting the existence of a new kidney-vasculature axis.

Use and Outcomes of Kidneys from Donation after Circulatory Death Donors in the United States.

PubMed

Gill, John; Rose, Caren; Lesage, Julie; Joffres, Yayuk; Gill, Jagbir; O'Connor, Kevin

2017-12-01

Donation after circulatory death (DCD) donors are an important source of kidneys for transplantation, but DCD donor transplantation is less common in the United States than in other countries. In this study of national data obtained between 2008 and 2015, recovery of DCD kidneys varied substantially among the country's 58 donor service areas, and 25% of DCD kidneys were recovered in only four donor service areas. Overall, 20% of recovered DCD kidneys were discarded, varying from 3% to 33% among donor service areas. Compared with kidneys from neurologically brain dead (NBD) donors, DCD kidneys had a higher adjusted odds ratio of discard that varied from 1.25 (95% confidence interval [95% CI], 1.16 to 1.34) in kidneys with total donor warm ischemic time (WIT) of 10-26 minutes to 2.67 (95% CI, 2.34 to 3.04) in kidneys with total donor WIT >48 minutes. Among the 12,831 DCD kidneys transplanted, kidneys with WIT≤48 minutes had survival similar to that of NBD kidneys. DCD kidneys with WIT>48 minutes had a higher risk of allograft failure (hazard ratio, 1.23; 95% CI, 1.07 to 1.41), but this risk was limited to kidneys with cold ischemia time (CIT) >12 hours. We conclude that donor service area-level variation in the recovery and discard of DCD kidneys is large. Additional national data collection is needed to understand the potential to increase DCD donor transplantation in the United States. Strategies to minimize cold ischemic injury may safely allow increased use of DCD kidneys with WIT>48 minutes. Copyright © 2017 by the American Society of Nephrology.

Knowledge of Kidney Donation Among Care Givers in Two Tertiary Hospitals in Southwest Nigeria.

PubMed

Adejumo, Oluseyi A; Solarin, Adaobi U; Abiodun, Moses T; Akinbodewa, Ayodeji A

2017-05-01

One of the major challenges of kidney transplantation is shortage of kidney donors. Care givers (CGs) are potential kidney donors, but the majority of them are unwilling to donate due to inadequate knowledge on kidney donation. This study evaluated the knowledge of kidney donation and its determinants among CGs in two tertiary hospitals in Southwest Nigeria. This was a cross-sectional study that was carried out in the Kidney Care Centre (KCC), Ondo and Babcock University Teaching Hospital (BUTH), Ilishan-Remo using a self-administered pretested questionnaire that assessed knowledge of kidney donation and its determinants. Pvalue of <0.05 was taken as significant. A total of 244 respondents participated in the study. The majority were below 40 years, married, and female. The proportion of respondents with adequate knowledge of kidney donation was 63.4%. More respondents from BUTH compared to KCC had adequate knowledge of kidney donation (80% vs. 46.7%, P ≤ 0.001). Similarly, the mean knowledge score was higher in respondents from BUTH (P ≤ 0.001). Factors that determined knowledge of kidney donation were female gender (AOR: 3.43, 95% CI: 1.25-9.40, P = 0.02) and social class (AOR: 1.22, 95% CI: 0.50-2.95, P ≤ 0.001). There was positive correlation between knowledge of kidney donation among the respondents from both hospitals and their willingness to donate kidneys (r = 0.439, P ≤ 0.001). Knowledge of kidney donation was better among BUTH's respondents. Gender and social class were predictors of knowledge of kidney donation. Improving knowledge of kidney donation may improve willingness to donate among the public. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Successful Dual Kidney Transplantation After Hypothermic Oxygenated Perfusion of Discarded Human Kidneys

PubMed Central

Ravaioli, Matteo; De Pace, Vanessa; Comai, Giorgia; Busutti, Marco; Gaudio, Massimo Del; Amaduzzi, Annalisa; Cucchetti, Alessandro; Siniscalchi, Antonio; La Manna, Gaetano; D’Errico, Antonietta A.D.; Pinna, Antonio Daniele

2017-01-01

Patient: Female, 58 Final Diagnosis: Nephroangiosclerosis Symptoms: Renal failure Medication: — Clinical Procedure: Resuscitation of grafts by hypothermic oxygenated perfusion Specialty: Transplantology Objective: Challenging differential diagnosis Background: The recovery of discarded human kidneys has increased in recent years and impels to use of unconventional organ preservation strategies that improve graft function. We report the first case of human kidneys histologically discarded and transplanted after hypothermic oxygenated perfusion (HOPE). Case Report: Marginal kidneys from a 78-year-old woman with brain death were declined by Italian transplant centers due to biopsy score (right kidney: 6; left kidney: 7). We recovered and preserved both kidneys through HOPE and we revaluated their use for transplantation by means of perfusion parameters. The right kidney was perfused for 1 h 20 min and the left kidney for 2 h 30 min. During organ perfusion, the renal flow increased progressively. We observed an increase of 34% for the left kidney (median flow 52 ml/min) and 50% for the right kidney (median flow 24 ml/min). Both kidneys had low perfusate’s lactate levels. We used perfusion parameters as important determinants of the organ discard. Based on our previous organ perfusion experience, the increase of renal flow and the low level of lactate following 1 h of HOPE lead us to declare both kidneys as appropriate for dual kidney transplantation (DKT). No complications were reported during the transplant and in the post-transplant hospital stay. The recipient had immediate graft function and serum creatinine value of 0.95 mg/dL at 3 months post-transplant. Conclusions: HOPE provides added information in the organ selection process and may improve graft quality of marginal kidneys. PMID:28928357

Comparison of the morphometric features of the left and right horse kidneys: a stereological approach.

PubMed

Bolat, D; Bahar, S; Tipirdamaz, S; Selcuk, M L

2013-12-01

The aims of this study were to determine the total volume of the horse kidney and volume fractions of its functional subcomponents (cortex, medulla, renal pelvis) using stereological methods and investigate any possible difference in the functional subcomponents of the right and left kidneys that may arise from differences in shape. The study was carried out on the kidneys of 5 horses of different breed and sex. The weight of the kidneys was measured by a digital scale, and kidney volume was calculated by Archimedes' principle. Total kidney volume and volume fractions of subcomponents of the right and left kidneys were estimated by the Cavalieri's principle. The weights of the right and left kidneys were 550 ± 25 g and 585 ± 23 g, respectively. The volumes of the right and left kidneys estimated using the Cavalieri method were 542 ± 46 ml and 581 ± 29 ml. The relative organ weight of the kidneys was calculated as 1:330. The densities of the right and left kidneys were determined to be 1.01 and 1.00, respectively. The mean volume fractions of the cortex, medulla and renal pelvis were determined as 55.6, 42.7 and 1.7 in both kidneys. No statistically significant difference existed between morphometric data pertaining to the right and left kidneys (P > 0.05). To determine precisely whether differences in shape cause any difference in the functional subcomponents of the right and left kidneys requires further investigation of differences in the number of microscopically functional unit of the kidney such as renal glomeruli and nephrons. © 2013 Blackwell Verlag GmbH.

Complete staghorn calculus in polycystic kidney disease: infection is still the cause

PubMed Central

2013-01-01

Background Kidney stones in patients with autosomal dominant polycystic kidney disease are common, regarded as the consequence of the combination of anatomic abnormality and metabolic risk factors. However, complete staghorn calculus is rare in polycystic kidney disease and predicts a gloomy prognosis of kidney. For general population, recent data showed metabolic factors were the dominant causes for staghorn calculus, but for polycystic kidney disease patients, the cause for staghorn calculus remained elusive. Case presentation We report a case of complete staghorm calculus in a polycystic kidney disease patient induced by repeatedly urinary tract infections. This 37-year-old autosomal dominant polycystic kidney disease female with positive family history was admitted in this hospital for repeatedly upper urinary tract infection for 3 years. CT scan revealed the existence of a complete staghorn calculus in her right kidney, while there was no kidney stone 3 years before, and the urinary stone component analysis showed the composition of calculus was magnesium ammonium phosphate. Conclusion UTI is an important complication for polycystic kidney disease and will facilitate the formation of staghorn calculi. As staghorn calculi are associated with kidney fibrosis and high long-term renal deterioration rate, prompt control of urinary tract infection in polycystic kidney disease patient will be beneficial in preventing staghorn calculus formation. PMID:24070202

Complete staghorn calculus in polycystic kidney disease: infection is still the cause.

PubMed

Mao, Zhiguo; Xu, Jing; Ye, Chaoyang; Chen, Dongping; Mei, Changlin

2013-08-01

Kidney stones in patients with autosomal dominant polycystic kidney disease are common, regarded as the consequence of the combination of anatomic abnormality and metabolic risk factors. However, complete staghorn calculus is rare in polycystic kidney disease and predicts a gloomy prognosis of kidney. For general population, recent data showed metabolic factors were the dominant causes for staghorn calculus, but for polycystic kidney disease patients, the cause for staghorn calculus remained elusive. We report a case of complete staghorm calculus in a polycystic kidney disease patient induced by repeatedly urinary tract infections. This 37-year-old autosomal dominant polycystic kidney disease female with positive family history was admitted in this hospital for repeatedly upper urinary tract infection for 3 years. CT scan revealed the existence of a complete staghorn calculus in her right kidney, while there was no kidney stone 3 years before, and the urinary stone component analysis showed the composition of calculus was magnesium ammonium phosphate. UTI is an important complication for polycystic kidney disease and will facilitate the formation of staghorn calculi. As staghorn calculi are associated with kidney fibrosis and high long-term renal deterioration rate, prompt control of urinary tract infection in polycystic kidney disease patient will be beneficial in preventing staghorn calculus formation.

When Your Child Needs a Kidney Transplant

MedlinePlus

... Search English Español When Your Child Needs a Kidney Transplant KidsHealth / For Parents / When Your Child Needs ... to monitor their new kidney function. About the Kidneys Kidneys are bean-shaped organs located near the ...

Kidney biomimicry--a rediscovered scientific field that could provide hope to patients with kidney disease.

PubMed

Stenvinkel, Peter; Johnson, Richard J

2013-11-01

Most studies on kidney disease have relied on classic experimental studies in mice and rats or clinical studies in humans. From such studies much understanding of the physiology and pathophysiology of kidney disease has been obtained. However, breakthroughs in the prevention and treatment of kidney diseases have been relatively few, and new approaches to fight kidney disease are needed. Here we discuss kidney biomimicry as a new approach to understand kidney disease. Examples are given of how various animals have developed ways to prevent or respond to kidney failure, how to protect themselves from hypoxia or oxidative stress and from the scourge of hyperglycemia. We suggest that investigation of evolutionary biology and comparative physiology might provide new insights for the prevention and treatment of kidney disease. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

Mechanisms of "kidney governing bones" theory in traditional Chinese medicine.

PubMed

Ju, Dahong; Liu, Meijie; Zhao, Hongyan; Wang, Jun

2014-09-01

Studies conducted by our group on the mechanism of "kidney governing bones" theory in traditional Chinese medicine (TCM) are reviewed in this paper. Conclusions can be summarized as follows. (1) Neuroendocrine-immune network (NIN)-osteoclast regulatory pathway OPG-RANKL-RANK is one of the mechanisms of "kidney governing bones." Although kidney-reinforcing therapy is regarded as one of the holistic regulatory mechanisms of the body, characteristic holistic regulation in TCM can be reflected through nonselective regulation of the NIN during kidney reinforcement therapy, which can be used to treat osteoporosis through microadjustments in the microenvironment of the bone marrow. (2) Marrow exhaustion in TCM, which is the state wherein lipocytes in the bone marrow increase whereas other cells decrease, serves as the pathogenesis of osteoporosis brought about by failure of the "kidney governing bones." (3) The kidney in TCM can be regarded as a complex system comprising multiple functional units in the body, including the unit "governing bones." Kidney deficiency refers to a deficiency in only one or more units of the kidney system and not the whole system itself, which explains the kidney-reinforcing effect of many herbs; some herbs can treat osteoporosis, but some cannot. Although both classified as kidney-reinforcing agents, the former can resolve failure of the "kidney governing bones" unit while the latter regulates the failure of other units in the kidney system. Despite the current understanding on "kidney governing bones" theory, the mechanism of "kidney governing bones" remains complicated and unresolved. Thus, further studies in this area are warranted.

Would you sell a kidney in a regulated kidney market? Results of an exploratory study.

PubMed

Rid, A; Bachmann, L M; Wettstein, V; Biller-Andorno, N

2009-09-01

It is often claimed that a regulated kidney market would significantly reduce the kidney shortage, thus saving or improving many lives. Data are lacking, however, on how many people would consider selling a kidney in such a market. A survey instrument, developed to assess behavioural dispositions to and attitudes about a hypothetical regulated kidney market, was given to Swiss third-year medical students. Respondents' (n = 178) median age was 23 years. Their socioeconomic status was high or middle (94.6%). 48 (27%) considered selling a kidney in a regulated kidney market, of whom 31 (66%) would sell only to overcome a particularly difficult financial situation. High social status and male gender was the strongest predictor of a disposition to sell. 32 of all respondents (18%) supported legalising a regulated kidney market. This attitude was not associated with a disposition to sell a kidney. 5 respondents (2.8%) endorsed a market and considered providing a kidney to a stranger if and only if paid. 4 of those 5 would sell only under financial duress. Current understanding of a regulated kidney market is insufficient. It is unclear whether a regulated market would result in a net gain of kidneys. Most possible kidney vendors would only sell in a particularly difficult financial situation, raising concerns about the validity of consent and inequities in the provision of organs. Further empirical and normative analysis of these issues is required. Any calls to implement and evaluate a regulated kidney market in pilot studies are therefore premature.

Definition and Facts for Kidney Stones in Adults

MedlinePlus

... Eating, Diet, & Nutrition Clinical Trials Definition & Facts for Kidney Stones What are kidney stones? Kidney stones are hard, pebble-like pieces ... stone may get stuck along the way. Do kidney stones have another name? The scientific name for ...

40 CFR 180.497 - Clofencet; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

... commodities: Commodities Parts per million Cattle, fat 0.04 Cattle, kidney 10.0 Cattle, meat byproducts, except kidney 0.5 Cattle, meat 0.15 Egg 1.0 Goat, fat 0.04 Goat, kidney 10.0 Goat, meat byproducts, except kidney 0.5 Goat, meat 0.15 Hog, fat 0.04 Hog, kidney 10.0 Hog, meat byproducts, except kidney 0.5...

40 CFR 180.497 - Clofencet; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

... commodities: Commodities Parts per million Cattle, fat 0.04 Cattle, kidney 10.0 Cattle, meat byproducts, except kidney 0.5 Cattle, meat 0.15 Egg 1.0 Goat, fat 0.04 Goat, kidney 10.0 Goat, meat byproducts, except kidney 0.5 Goat, meat 0.15 Hog, fat 0.04 Hog, kidney 10.0 Hog, meat byproducts, except kidney 0.5...

40 CFR 180.506 - Cyclanilide; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

... byproducts, except kidney 0.2 Cattle, kidney 2.0 Cotton, undelinted seed 0.60 Cotton, gin byproducts 25.0 Goat, fat 0.10 Goat, meat 0.02 Goat, meat byproducts, except kidney 0.20 Goat, kidney 2.0 Horse, fat 0.10 Horse, meat 0.02 Horse, meat byproducts, except kidney 0.20 Horse, kidney 2.0 Hog, fat 0.10 Hog...

40 CFR 180.506 - Cyclanilide; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

... byproducts, except kidney 0.2 Cattle, kidney 2.0 Cotton, undelinted seed 0.60 Cotton, gin byproducts 25.0 Goat, fat 0.10 Goat, meat 0.02 Goat, meat byproducts, except kidney 0.20 Goat, kidney 2.0 Horse, fat 0.10 Horse, meat 0.02 Horse, meat byproducts, except kidney 0.20 Horse, kidney 2.0 Hog, fat 0.10 Hog...

40 CFR 180.205 - Paraquat; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., kidney 0.5 Cattle, meat 0.05 Cattle, meat byproducts, except kidney 0.05 Coffee, bean, green 0.05 Corn... Goat, kidney 0.5 Goat, meat 0.05 Goat, meat byproducts, except kidney 0.05 Grain, aspirated fractions..., kidney 0.5 Hog, meat 0.05 Hog, meat byproducts, except kidney 0.05 Hop, dried cones 0.5 Horse, fat 0.05...

Kidney function and plasma copeptin levels in healthy kidney donors and autosomal dominant polycystic kidney disease patients.

PubMed

Zittema, Debbie; van den Berg, Else; Meijer, Esther; Boertien, Wendy E; Muller Kobold, Anneke C; Franssen, Casper F M; de Jong, Paul E; Bakker, Stephan J L; Navis, Gerjan; Gansevoort, Ron T

2014-09-05

Plasma copeptin, a marker of arginine vasopressin, is elevated in patients with autosomal dominant polycystic kidney disease and predicts disease progression. It is unknown whether elevated copeptin levels result from decreased kidney clearance or as compensation for impaired concentrating capacity. Data from patients with autosomal dominant polycystic kidney disease and healthy kidney donors before and after donation were used, because after donation, overall GFR decreases with a functionally normal kidney. Data were obtained between October of 2008 and January of 2012 from healthy kidney donors who visited the institution for routine measurements predonation and postdonation and patients with autosomal dominant polycystic kidney disease who visited the institution for kidney function measurement. Plasma copeptin levels were measured using a sandwich immunoassay, GFR was measured as (125)I-iothalamate clearance, and urine concentrating capacity was measured as urine-to-plasma ratio of urea. In patients with autosomal dominant polycystic kidney disease, total kidney volume was measured with magnetic resonance imaging. Patients with autosomal dominant polycystic kidney disease (n=122, age=40 years, men=56%) had significantly higher copeptin levels (median=6.8 pmol/L; interquartile range=3.4-15.7 pmol/L) compared with donors (n=134, age=52 years, men=49%) both predonation and postdonation (median=3.8 pmol/L; interquartile range=2.8-6.3 pmol/L; P<0.001; median=4.4 pmol/L; interquartile range=3.6-6.1 pmol/L; P<0.001). In donors, copeptin levels did not change after donation, despite a significant fall in GFR (from 105 ± 17 to 66 ± 10; P<0.001). Copeptin and GFR were significantly associated in patients with autosomal dominant polycystic kidney disease (β=-0.45, P<0.001) but not in donors. In patients with autosomal dominant polycystic kidney disease, GFR and total kidney volume were both associated significantly with urine-to-plasma ratio of urea (β=0.84, P<0.001; β=-0.51, P<0.001, respectively). On the basis of the finding in donors that kidney clearance is not a main determinant of plasma copeptin levels, it was hypothesized that, in patients with autosomal dominant polycystic kidney disease, kidney damage and associated impaired urine concentration capacity determine copeptin levels. Copyright © 2014 by the American Society of Nephrology.

Measuring kidney patients' motivation to pursue living donor kidney transplant: development of stage of change, decisional balance and self-efficacy measures.

PubMed

Waterman, Amy D; Robbins, Mark L; Paiva, Andrea L; Peipert, John D; Davis, LaShara A; Hyland, Shelley S; Schenk, Emily A; Baldwin, Kari A; Amoyal, Nicole R

2015-02-01

While educational interventions to increase patient motivation to pursue living donor kidney transplant have shown success in increasing living donor kidney transplant rates, there are no validated, theoretically consistent measures of Stage of Change, a measure of readiness to pursue living donor kidney transplant; Decisional Balance, a weighted assessment of living donor kidney transplant's advantages/disadvantages; and Self-Efficacy, a measure of belief that patients can pursue living donor kidney transplant in difficult circumstances. This study developed and validated measures of these three constructs. In two independent samples of kidney patients (N 1 = 279 and N 2 = 204), results showed good psychometric properties and support for their use in the assessment of living donor kidney transplant interventions. © The Author(s) 2013.

40 CFR 180.573 - Tepraloxydim; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Parts per million Cattle, fat 0.15 Cattle, kidney 0.50 Cattle, meat 0.20 Cattle, meat byproducts, except kidney 0.20 Egg 0.20 Goat, fat 0.15 Goat, kidney 0.50 Goat, meat 0.20 Goat, meat byproducts, except kidney 0.20 Hog, fat 0.15 Hog, kidney 0.50 Hog, meat 0.20 Hog, meat byproducts, except kidney 0.20 Horse...

40 CFR 180.573 - Tepraloxydim; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Parts per million Cattle, fat 0.15 Cattle, kidney 0.50 Cattle, meat 0.20 Cattle, meat byproducts, except kidney 0.20 Egg 0.20 Goat, fat 0.15 Goat, kidney 0.50 Goat, meat 0.20 Goat, meat byproducts, except kidney 0.20 Hog, fat 0.15 Hog, kidney 0.50 Hog, meat 0.20 Hog, meat byproducts, except kidney 0.20 Horse...

Kidneys at Higher Risk of Discard: Expanding the Role of Dual Kidney Transplantation

PubMed Central

Tanriover, B.; Mohan, S.; Cohen, D. J.; Radhakrishnan, J.; Nickolas, T. L.; Stone, P. W.; Tsapepas, D. S.; Crew, R. J.; Dube, G. K.; Sandoval, P. R.; Samstein, B.; Dogan, E.; Gaston, R. S.; Tanriover, J. N.; Ratner, L. E.; Hardy, M. A.

2014-01-01

Half of the recovered expanded criteria donor (ECD) kidneys are discarded in the United States. A new kidney allocation system offers kidneys at higher risk of discard, Kidney Donor Profile Index (KDPI) >85%, to a wider geographic area to promote broader sharing and expedite utilization. Dual kidney transplantation (DKT) based on the KDPI is a potential option to streamline allocation of kidneys which otherwise would have been discarded. To assess the clinical utility of the KDPI in kidneys at higher risk of discard, we analyzed the OPTN/UNOS Registry that included the deceased donor kidneys recovered between 2002 and 2012. The primary outcomes were allograft survival, patient survival and discard rate based on different KDPI categories (<80%, 80–90% and >90%). Kidneys with KDPI >90% were associated with increased odds of discard (OR = 1.99, 95% CI 1.74–2.29) compared to ones with KDPI <80%. DKTs of KDPI >90% were associated with lower overall allograft failure (HR = 0.74, 95% CI 0.62–0.89) and better patient survival (HR = 0.79, 95% CI 0.64–0.98) compared to single ECD kidneys with KDPI >90%. Kidneys at higher risk of discard may be offered in the up-front allocation system as a DKT. Further modeling and simulation studies are required to determine a reasonable KDPI cutoff percentile. PMID:24472195

Hyperuricemia, Acute and Chronic Kidney Disease, Hypertension, and Cardiovascular Disease: Report of a Scientific Workshop Organized by the National Kidney Foundation.

PubMed

Johnson, Richard J; Bakris, George L; Borghi, Claudio; Chonchol, Michel B; Feldman, David; Lanaspa, Miguel A; Merriman, Tony R; Moe, Orson W; Mount, David B; Sanchez Lozada, Laura Gabriella; Stahl, Eli; Weiner, Daniel E; Chertow, Glenn M

2018-06-01

Urate is a cause of gout, kidney stones, and acute kidney injury from tumor lysis syndrome, but its relationship to kidney disease, cardiovascular disease, and diabetes remains controversial. A scientific workshop organized by the National Kidney Foundation was held in September 2016 to review current evidence. Cell culture studies and animal models suggest that elevated serum urate concentrations can contribute to kidney disease, hypertension, and metabolic syndrome. Epidemiologic evidence also supports elevated serum urate concentrations as a risk factor for the development of kidney disease, hypertension, and diabetes, but differences in methodologies and inpacts on serum urate concentrations by even subtle changes in kidney function render conclusions uncertain. Mendelian randomization studies generally do not support a causal role of serum urate in kidney disease, hypertension, or diabetes, although interpretation is complicated by nonhomogeneous populations, a failure to consider environmental interactions, and a lack of understanding of how the genetic polymorphisms affect biological mechanisms related to urate. Although several small clinical trials suggest benefits of urate-lowering therapies on kidney function, blood pressure, and insulin resistance, others have been negative, with many trials having design limitations and insufficient power. Thus, whether uric acid has a causal role in kidney and cardiovascular diseases requires further study. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Kidney injury molecule-1 and microalbuminuria levels in Zambian population: biomarkers of kidney injury.

PubMed

Zulu, Mildred; Kaile, Trevor; Kantenga, Timothy; Chileshe, Chisanga; Nkhoma, Panji; Sinkala, Musalula

2016-01-01

Kidney injury affects renal excretion of plasma analytes and metabolic waste products with grave pathologic consequences. Early detection, thus of kidney injury is essential for injury specific intervention that may avert permanent renal damage and delay progression of kidney injury. We aimed to evaluate Kidney Injury Molecule-1 (KIM-1) and Microalbuminuria (MAU), as biomarkers of kidney injury, in comparison with creatinine. We compared the levels of urine MAU, urine KIM-1 and other plasma biochemical tests in specimens from 80 individuals with and without kidney disease. We found no difference in KIM-1 levels between the kidney disease group (2.82± 1.36ng/mL) and controls (3.29 ± 1.14ng/mL), p = 0.122. MAU was higher in participants with kidney disease (130.809± 84.744 µg/mL) than the controls (15.983± 20.442µg/mL), p ?0.001. KIM-1 showed a weak negative correlation with creatinine (r = -0.279, p = 0.09), whereas MAU was positively correlated with creatinine in participants with kidney disease with statistical significance (r = 0.556, p = 0.001). The study demonstrated that in Zambian setting MAU and creatinine are sensitive biomarkers in the diagnosis of kidney damage. We moreover propose further evaluation of KIM-1 as a biomarker of kidney injury.

Kidney injury molecule-1 and microalbuminuria levels in Zambian population: biomarkers of kidney injury

PubMed Central

Zulu, Mildred; Kaile, Trevor; Kantenga, Timothy; Chileshe, Chisanga; Nkhoma, Panji; Sinkala, Musalula

2016-01-01

Introduction Kidney injury affects renal excretion of plasma analytes and metabolic waste products with grave pathologic consequences. Early detection, thus of kidney injury is essential for injury specific intervention that may avert permanent renal damage and delay progression of kidney injury. We aimed to evaluate Kidney Injury Molecule-1 (KIM-1) and Microalbuminuria (MAU), as biomarkers of kidney injury, in comparison with creatinine. Methods We compared the levels of urine MAU, urine KIM-1 and other plasma biochemical tests in specimens from 80 individuals with and without kidney disease. Results We found no difference in KIM-1 levels between the kidney disease group (2.82± 1.36ng/mL) and controls (3.29 ± 1.14ng/mL), p = 0.122. MAU was higher in participants with kidney disease (130.809± 84.744 µg/mL) than the controls (15.983± 20.442µg/mL), p ?0.001. KIM-1 showed a weak negative correlation with creatinine (r = -0.279, p = 0.09), whereas MAU was positively correlated with creatinine in participants with kidney disease with statistical significance (r = 0.556, p = 0.001). Conclusion The study demonstrated that in Zambian setting MAU and creatinine are sensitive biomarkers in the diagnosis of kidney damage. We moreover propose further evaluation of KIM-1 as a biomarker of kidney injury. PMID:27642395

BHD-associated kidney cancer exhibits unique molecular characteristics and a wide variety of variants in chromatin remodeling genes.

PubMed

Hasumi, Hisashi; Furuya, Mitsuko; Tatsuno, Kenji; Yamamoto, Shogo; Baba, Masaya; Hasumi, Yukiko; Isono, Yasuhiro; Suzuki, Kae; Jikuya, Ryosuke; Otake, Shinji; Muraoka, Kentaro; Osaka, Kimito; Hayashi, Narihiko; Makiyama, Kazuhide; Miyoshi, Yasuhide; Kondo, Keiichi; Nakaigawa, Noboru; Kawahara, Takashi; Izumi, Koji; Teranishi, Junichi; Yumura, Yasushi; Uemura, Hiroji; Nagashima, Yoji; Metwalli, Adam R; Schmidt, Laura S; Aburatani, Hiroyuki; Linehan, W Marston; Yao, Masahiro

2018-05-14

Birt-Hogg-Dubé (BHD) syndrome is a hereditary kidney cancer syndrome, which predisposes patients to develop kidney cancer, cutaneous fibrofolliculomas and pulmonary cysts. The responsible gene FLCN is a tumor suppressor for kidney cancer which plays an important role in energy homeostasis through the regulation of mitochondrial oxidative metabolism. However, the process by which FLCN-deficiency leads to renal tumorigenesis is unclear. In order to clarify molecular pathogenesis of BHD-associated kidney cancer, we conducted whole-exome sequencing analysis using next-generation sequencing technology as well as metabolite analysis using LC/MS and GC/MS. Whole-exome sequencing analysis of BHD-associated kidney cancer revealed that copy number variations (CNV) of BHD-associated kidney cancer are considerably different from those already reported in sporadic cases. In somatic variant analysis, very few variants were commonly observed in BHD-associated kidney cancer; however, variants in chromatin remodeling genes were frequently observed in BHD-associated kidney cancer (17/29 tumors, 59%). Metabolite analysis of BHD-associated kidney cancer revealed metabolic reprogramming towards upregulated redox regulation which may neutralize reactive oxygen species potentially produced from mitochondria with increased respiratory capacity under FLCN-deficiency. BHD-associated kidney cancer displays unique molecular characteristics which are completely different from sporadic kidney cancer, providing mechanistic insight into tumorigenesis under FLCN-deficiency as well as a foundation for development of novel therapeutics for kidney cancer.

Chronic epithelial kidney injury molecule-1 expression causes murine kidney fibrosis.

PubMed

Humphreys, Benjamin D; Xu, Fengfeng; Sabbisetti, Venkata; Grgic, Ivica; Movahedi Naini, Said; Wang, Ningning; Chen, Guochun; Xiao, Sheng; Patel, Dhruti; Henderson, Joel M; Ichimura, Takaharu; Mou, Shan; Soeung, Savuth; McMahon, Andrew P; Kuchroo, Vijay K; Bonventre, Joseph V

2013-09-01

Acute kidney injury predisposes patients to the development of both chronic kidney disease and end-stage renal failure, but the molecular details underlying this important clinical association remain obscure. We report that kidney injury molecule-1 (KIM-1), an epithelial phosphatidylserine receptor expressed transiently after acute injury and chronically in fibrotic renal disease, promotes kidney fibrosis. Conditional expression of KIM-1 in renal epithelial cells (Kim1(RECtg)) in the absence of an injury stimulus resulted in focal epithelial vacuolization at birth, but otherwise normal tubule histology and kidney function. By 4 weeks of age, Kim1(RECtg) mice developed spontaneous and progressive interstitial kidney inflammation with fibrosis, leading to renal failure with anemia, proteinuria, hyperphosphatemia, hypertension, cardiac hypertrophy, and death, analogous to progressive kidney disease in humans. Kim1(RECtg) kidneys had elevated expression of proinflammatory monocyte chemotactic protein-1 (MCP-1) at early time points. Heterologous expression of KIM-1 in an immortalized proximal tubule cell line triggered MCP-1 secretion and increased MCP-1-dependent macrophage chemotaxis. In mice expressing a mutant, truncated KIM-1 polypeptide, experimental kidney fibrosis was ameliorated with reduced levels of MCP-1, consistent with a profibrotic role for native KIM-1. Thus, sustained KIM-1 expression promotes kidney fibrosis and provides a link between acute and recurrent injury with progressive chronic kidney disease.

Older kidneys donor transplantation: five years' experience without biopsy and using clinical laboratory and macroscopic anatomy evaluation.

PubMed

Santangelo, M; Zuccaro, M; De Rosa, P; Tammaro, V; Grassia, S; Federico, S; Ciotola, A L; Spinosa, G; Renda, A

2007-01-01

The exponential increase in organ demand is not associated with a similar increase of available kidneys. This emergency led to expanded criteria to consider a kidney transplantable. The aim of this retrospective study was to explain our use of older donor kidneys without biopsy. Between 2000 and 2005, 58 older kidneys were harvested: 27 were transplanted in our center; 13 were discarded; and 18 were transplanted in other centers. We considered 3 factors to define kidney quality: macroscopic anatomy, multiple factors linked to the donor, and clinical-laboratory data. After transplantation, we observed the patients for at least 1 year and up to 6 years. At 1 year, 24/27 (89%) patients had a functional kidney, 2 patients showed an initial renal failure and 1 patient lost the kidney. At maximum follow-up, 19 patients (70%) had functional kidneys, 4 with initial renal failure. These results compared with the kidneys harvested using Standard Donor Kidney Criteria are acceptable. Obviously we need long-term follow-up to increase, the amount of data and obtain a definitive outcome. Biopsy is the gold standard for the definition of an older kidney's quality. When a biopsy is not feasible, the study of the macroscopic anatomy the kidney's donor and of some donor's parameters represent an acceptable biopsy alternative, being able to rescue some organs that would be otherwise lost.

Kidney (Renal Cell) Cancer—Patient Version

Cancer.gov

Kidney cancer can develop in adults and children. The main types of kidney cancer are renal cell cancer, transitional cell cancer, and Wilms tumor. Certain inherited conditions increase the risk of kidney cancer. Start here to find information on kidney cancer treatment, research, and statistics.

Long term follow up of kidney donors with asymptomatic renal stones.

PubMed

Serur, David; Charlton, Marian; Juluru, Krishna; Salama, Gayle; Locastro, Eve; Bretzlaff, Gretchen; Hartono, Choli

2017-08-01

Patients with asymptomatic kidney stones have a high rate of progression to becoming symptomatic kidney stones when followed for several years. Small kidney stones are often found incidentally on imaging when evaluating patients for kidney donation, and there is a concern that after nephrectomy, the donor may become symptomatic and incur damage to the remaining kidney. We reviewed kidney donors at our institution with asymptomatic stones and surveyed them several years after donation to see if the stones became clinically active. © 2017 Asian Pacific Society of Nephrology.

Mononuclear phagocyte subpopulations in the mouse kidney.

PubMed

George, James F; Lever, Jeremie M; Agarwal, Anupam

2017-04-01

Mononuclear phagocytes are the most common cells in the kidney associated with immunity and inflammation. Although the presence of these cells in the kidney has been known for decades, the study of mononuclear phagocytes in the context of kidney function and dysfunction is still at an early stage. The purpose of this review is to summarize the present knowledge regarding classification of these cells in the mouse kidney and to identify relevant questions that would further advance the field and potentially lead to new opportunities for treatment of acute kidney injury and other kidney diseases.

What We Do and Do Not Know About Women and Kidney Diseases; Questions Unanswered and Answers Unquestioned: Reflection on World Kidney Day and International Woman’s Day

PubMed Central

Piccoli, Giorgina B.; Alrukhaimi, Mona; Liu, Zhi-Hong; Zakharova, Elena; Levin, Adeera

2018-01-01

Background: Chronic kidney disease affects approximately 10% of the world’s adult population: It is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women’s Day in 2018 coincide, thus giving an occasion to reflect on open questions on the importance of kidney health in women for the present and the future generations. Objectives: In this review, we summarize some aspects that are unique to women’s kidney health, offering an opportunity to reflect on the importance of women’s health and specifically their kidney health, on the community, and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Findings: Girls and women, who make up approximately 50% of the world’s population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is not only a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for childbearing, and on the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. Conclusion: Improving knowledge on women, kidney health, and kidney disease, may be a way to improve outcomes of kidney diseases worldwide. PMID:29552348

Association between Organ Procurement Organization Social Network Centrality and Kidney Discard and Transplant Outcomes1

PubMed Central

Butala, Neel M.; King, Marissa D.; Reitsma, William; Formica, Richard N.; Abt, Peter L.; Reese, Peter P.; Parikh, Chirag R.

2015-01-01

Background Given growth in kidney transplant waitlists and discard rates, donor kidney acceptance is an important problem. We used network analysis to examine whether organ procurement organization (OPO) network centrality affects discard and outcomes. Methods We identified 106,160 deceased-donor kidneys recovered for transplant from 2000–2010 in SRTR. We constructed the transplant network by year with each OPO representing a node and each kidney-sharing relationship between OPOs representing a directed tie between nodes. Primary exposures were the number of different OPOs to which an OPO has given a kidney or from which an OPO has received a kidney in year preceding procurement year. Primary outcomes were discard, cold-ischemia time, delayed graft function, and 1-year graft loss. We used multivariable regression, restricting analysis to the 50% of OPOs with highest discard and stratifying remaining OPOs by kidney volume. Models controlled for kidney donor risk index, waitlist time, and kidney pumping. Results An increase in one additional OPO to which a kidney was given by a procuring OPO in a year was associated with 1.4% lower likelihood of discard for a given kidney (odds ratio, 0.986; 95% confidence interval, 0.974-0.998) among OPOs procuring high kidney volume, but 2% higher likelihood of discard (OR:1.021, CI:1.006, 1.037) among OPOs procuring low kidney volume, with mixed associations with recipient outcomes. Conclusions Our study highlights the value of network analysis in revealing how broader kidney sharing is associated with levels of organ acceptance. We conclude interventions to promote broader inter-OPO sharing could be developed to reduce discard for a subset of OPOs. PMID:26102610

Early Outcomes of the New UK Deceased Donor Kidney Fast-Track Offering Scheme.

PubMed

Callaghan, Chris J; Mumford, Lisa; Pankhurst, Laura; Baker, Richard J; Bradley, J Andrew; Watson, Christopher J E

2017-12-01

The UK Kidney Fast-Track Scheme (KFTS) was introduced in 2012 to identify kidneys at high risk of discard and to rapidly facilitate transplantation. A retrospective analysis of kidneys transplanted through the KFTS was undertaken. UK Transplant Registry data were collected on deceased donor kidneys implanted between November 1, 2012, and April 30, 2015, (donation after brain death [DBD] donors) and March 1, 2013, and April 30, 2015 (donation after circulatory death [DCD] donors). Posttransplant outcomes included 1-year estimated glomerular filtration rate and death-censored graft survival (DCGS). Over the study period, 523 deceased donor kidneys were transplanted through the KFTS and 4174 via the standard National Kidney Allocation Scheme (NKAS). Kidneys in the KFTS were more likely to be from older diabetic donors, had a higher frequency of poor ex vivo perfusion, had longer cold ischemic times, and were transplanted into older recipients. One-year DCGS of KFTS and NKAS DBD donor kidneys was similar (94% vs 95%; P = 0.70), but for DCD donor kidneys, DCGS was lower in those allocated via the KFTS (91% versus 95%; P = 0.04). Median 1-year estimated glomerular filtration rate for DBD donor kidneys was lower in those allocated via the KFTS (49 vs 52 mL/min per 1.73 m; P = 0.01), but for DCD kidneys, there was no difference (45 vs 48 mL/min per 1.73 m; P = 0.10). Although KFTS kidneys have less favorable donor, graft, and recipient risk factors than NKAS kidneys, short-term graft and patient outcomes are acceptable. National schemes that identify and rapidly offer kidneys at high risk of discard may contribute to minimizing the unnecessary discard of organs.

Acute Kidney Injury in Pediatric Severe Sepsis: An Independent Risk Factor for Death and New Disability.

PubMed

Fitzgerald, Julie C; Basu, Rajit K; Akcan-Arikan, Ayse; Izquierdo, Ledys M; Piñeres Olave, Byron E; Hassinger, Amanda B; Szczepanska, Maria; Deep, Akash; Williams, Duane; Sapru, Anil; Roy, Jason A; Nadkarni, Vinay M; Thomas, Neal J; Weiss, Scott L; Furth, Susan

2016-12-01

The prevalence of septic acute kidney injury and impact on functional status of PICU survivors are unknown. We used data from an international prospective severe sepsis study to elucidate functional outcomes of children suffering septic acute kidney injury. Secondary analysis of patients in the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study: acute kidney injury was defined on the study day using Kidney Disease Improving Global Outcomes definitions. Patients with no acute kidney injury or stage 1 acute kidney injury ("no/mild acute kidney injury") were compared with those with stage 2 or 3 acute kidney injury ("severe acute kidney injury"). The primary outcome was a composite of death or new moderate disability at discharge defined as a Pediatric Overall Performance Category score of 3 or higher and increased by 1 from baseline. One hundred twenty-eight PICUs in 26 countries. Children with severe sepsis in the Sepsis PRevalence, OUtcomes, and Therapies study. None. One hundred two (21%) of 493 patients had severe acute kidney injury. More than twice as many patients with severe acute kidney injury died or developed new moderate disability compared with those with no/mild acute kidney injury (64% vs 30%; p < 0.001). Severe acute kidney injury was independently associated with death or new moderate disability (adjusted odds ratio, 2.5; 95% CI, 1.5-4.2; p = 0.001) after adjustment for age, region, baseline disability, malignancy, invasive mechanical ventilation, albumin administration, and the pediatric logistic organ dysfunction score. In a multinational cohort of critically ill children with severe sepsis and high mortality rates, septic acute kidney injury is independently associated with further increased death or new disability.

A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Webb, Carol F., E-mail: carol-webb@omrf.org; Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK; Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK

Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights:more » • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development.« less

Clinico-pathological features of kidney disease in diabetic cases.

PubMed

Furuichi, Kengo; Shimizu, Miho; Okada, Hirokazu; Narita, Ichiei; Wada, Takashi

2018-03-21

Diabetic kidney disease is the major cause of end-stage kidney disease in developed countries. However, the onset of kidney disorder and the progression pattern of kidney dysfunction and proteinuria greatly vary cases by cases. Therefore, risk classification with clinical data and pathological findings is important. Recent clinico-pathological study with kidney biopsy samples from diabetic patients revealed that pathological changes of diabetic nephropathy are characteristic and have special impacts on prognosis in each clinical stage. Moreover, comparison of the clinico-pathological findings of diabetic nephropathy with hypertensive nephrosclerosis revealed that there are few differences in their pathological findings in cases with low albuminuria and preserved estimated glomerular filtration rate (eGFR). Because it is so difficult to clearly distinguish pure kidney lesions caused by diabetes and kidney lesions due to effects other than diabetes, it is vital that these overlapped pathological findings be confirmed on kidney biopsy in cases of early stage diabetes. Further research is warranted regarding the pathogenesis of diabetic nephropathy and indication of kidney biopsy in diabetic cases.

Should We Formulate an Incentivized Model Facilitating Kidney Donation from Living Donors? A Focus on Turkey's Current System.

PubMed

Avci, Ercan

2018-04-23

Kidney transplantation is a lifesaving medical treatment. However, very high demand for kidneys with low kidney donation causes a black market that exploits patients' desperation and donors' vulnerability. The current kidney donation programs fail to produce promising results to avoid illegal and unethical kidney trafficking and commercialism. Even though the primary goal of kidney donation is to increase the number of deceased organ donations, in some countries, like Turkey, due to religious or cultural concerns, it is impossible to supply adequate deceased kidney donations. In this view, the aim of this paper is to examine kidney trafficking in the scope of Turkey's current organ donation system and propose a new model, named the Incentivized Kidney Donation Model (IKDM), to increase kidney donation from living donors. The model encompasses the following benefits offered to kidney donors; lifetime health insurance, exemptions from copayments/contribution shares, priority when receiving an organ, priority when finding a job, income tax exemptions for salaried employees, and free or discounted public utilities. This normative model has the potential to promote donors' altruistic acts as well as the solidarity and loyalty among members of a society without violating ethical values and internationally accepted principles. © 2018 John Wiley & Sons Ltd.

Automatic detection of kidney in 3D pediatric ultrasound images using deep neural networks

NASA Astrophysics Data System (ADS)

Tabrizi, Pooneh R.; Mansoor, Awais; Biggs, Elijah; Jago, James; Linguraru, Marius George

2018-02-01

Ultrasound (US) imaging is the routine and safe diagnostic modality for detecting pediatric urology problems, such as hydronephrosis in the kidney. Hydronephrosis is the swelling of one or both kidneys because of the build-up of urine. Early detection of hydronephrosis can lead to a substantial improvement in kidney health outcomes. Generally, US imaging is a challenging modality for the evaluation of pediatric kidneys with different shape, size, and texture characteristics. The aim of this study is to present an automatic detection method to help kidney analysis in pediatric 3DUS images. The method localizes the kidney based on its minimum volume oriented bounding box) using deep neural networks. Separate deep neural networks are trained to estimate the kidney position, orientation, and scale, making the method computationally efficient by avoiding full parameter training. The performance of the method was evaluated using a dataset of 45 kidneys (18 normal and 27 diseased kidneys diagnosed with hydronephrosis) through the leave-one-out cross validation method. Quantitative results show the proposed detection method could extract the kidney position, orientation, and scale ratio with root mean square values of 1.3 +/- 0.9 mm, 6.34 +/- 4.32 degrees, and 1.73 +/- 0.04, respectively. This method could be helpful in automating kidney segmentation for routine clinical evaluation.

Histopathologic Findings of Potential Kidney Donors With Asymptomatic Microscopic Hematuria: Impact on Donation.

PubMed

Hassan, E A; Ali, T Z; Abdulbaki, A; Ibrahim, I A; Almanae, H M; Aleid, H A

2017-10-01

Isolated microscopic hematuria (IMH) is not uncommon in potential kidney donors. The aim was to study the kidney biopsy findings of potential kidney donors with IMH and the impact of the histopathologic diagnoses on the decision to accept or decline such donors from kidney donation. In this retrospective study, all the potential kidney donors with IMH were identified from the medical records of patients who underwent kidney biopsies between January 2010 and December 2016. Forty-five such individuals were identified. The mean age of these potential donors was 32.6 years and 76% were male. All of them had normal blood pressure and no significant proteinuria. Seventeen (38%) biopsies showed histopathologic abnormalities; thin basement membrane disease (n = 13; 28%) was the most common cause followed by immunoglobulin (Ig)A nephropathy (n = 4; 9%). Donors with abnormal biopsy findings were excluded from donation. However, 62% of the potential donors had normal kidney biopsy findings and were accepted for kidney donation. IMH justifies extensive work-up including kidney biopsy to identify donors who may have underlying significant glomerular pathology excluding them from kidney donation. On the other hand, kidney biopsy also helps in accepting the donors if it does not show significant abnormality. Copyright © 2017 Elsevier Inc. All rights reserved.

Advanced Donation Programs and Deceased Donor-Initiated Chains-2 Innovations in Kidney Paired Donation.

PubMed

Wall, Anji E; Veale, Jeffrey L; Melcher, Marc L

2017-12-01

Kidney paired donation (KPD) strategies have facilitated compatible living-donor kidney transplants for end-stage renal disease patients with willing but incompatible living donors. Success has inspired further innovations that expand opportunities for kidney-paired donation. Two such innovations are the advanced donation strategy in which a donor provides a kidney before their recipient is matched, or even in need of, a kidney transplant, and deceased donor initiated chains in which chains are started with deceased donors rather than altruistic living donors. Although these innovations may expand KPD, they raise several ethical issues. Specific concerns raised by advanced donation include the management of uncertainty, the extent of donor and recipient consent, the scope of the obligation that the organization has to the kidney exchange paired recipient, the naming of alternative recipients, and the potential to unfairly advantage the recipient. Use of deceased donors for chain-initiating kidneys raises ethical issues concerning the consent process for each involved party, the prioritization of deceased donor kidneys, the allocation of chain ending kidneys, and the value of a living donor kidney versus a deceased donor kidney. We outline each ethical issue and discuss how it can be conceptualized and managed so that these KPD innovations programs are ultimately successful.

History of kidney stones as a possible risk factor for chronic kidney disease.

PubMed

Vupputuri, Suma; Soucie, J Michael; McClellan, William; Sandler, Dale P

2004-03-01

The incidence of treated end-stage renal disease has increased progressively in the United States over the past several decades. It has been suggested that kidney stones may be a contributing factor for a small percentage of these patients. We conducted a case-control study utilizing 548 hospital cases and 514 age, race and gender-matched community controls. The main outcome measure was diagnosis of chronic kidney disease, assessed by comprehensive chart review. History of kidney stones and other co-variables were obtained during telephone interviews. This study revealed 16.8% of cases and 6.4% of controls with reported history of kidney stones. The odds ratios (adjusted for confounding variables) for chronic kidney disease (overall), diabetic nephropathy and interstitial nephritis for patients with kidney stones were 1.9 (95% CI: 1.1, 3.3), 2.5 (95% CI: 0.87, 7.0) and 3.4 (95% CI: 1.5, 7.4), respectively. After stratifying by hypertensive status this increased risk persisted only for study participants reporting no history of hypertension. Kidney stones may play a role in the development of chronic kidney disease. Our study suggests that the prevention of kidney stones may be a means of delaying the onset of chronic kidney disease, however, further studies are needed to make conclusive recommendations.

Automated kidney morphology measurements from ultrasound images using texture and edge analysis

NASA Astrophysics Data System (ADS)

Ravishankar, Hariharan; Annangi, Pavan; Washburn, Michael; Lanning, Justin

2016-04-01

In a typical ultrasound scan, a sonographer measures Kidney morphology to assess renal abnormalities. Kidney morphology can also help to discriminate between chronic and acute kidney failure. The caliper placements and volume measurements are often time consuming and an automated solution will help to improve accuracy, repeatability and throughput. In this work, we developed an automated Kidney morphology measurement solution from long axis Ultrasound scans. Automated kidney segmentation is challenging due to wide variability in kidney shape, size, weak contrast of the kidney boundaries and presence of strong edges like diaphragm, fat layers. To address the challenges and be able to accurately localize and detect kidney regions, we present a two-step algorithm that makes use of edge and texture information in combination with anatomical cues. First, we use an edge analysis technique to localize kidney region by matching the edge map with predefined templates. To accurately estimate the kidney morphology, we use textural information in a machine learning algorithm framework using Haar features and Gradient boosting classifier. We have tested the algorithm on 45 unseen cases and the performance against ground truth is measured by computing Dice overlap, % error in major and minor axis of kidney. The algorithm shows successful performance on 80% cases.

42 CFR 409.18 - Services related to kidney transplantations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Services related to kidney transplantations. 409.18... Access Hospital Services § 409.18 Services related to kidney transplantations. (a) Kidney transplants. Medicare pays for kidney transplantation surgery only if performed in a renal transplantation center...

42 CFR 409.18 - Services related to kidney transplantations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 2 2011-10-01 2011-10-01 false Services related to kidney transplantations. 409.18... Access Hospital Services § 409.18 Services related to kidney transplantations. (a) Kidney transplants. Medicare pays for kidney transplantation surgery only if performed in a renal transplantation center...

Kidney function after off-pump or on-pump coronary artery bypass graft surgery: a randomized clinical trial.

PubMed

Garg, Amit X; Devereaux, P J; Yusuf, Salim; Cuerden, Meaghan S; Parikh, Chirag R; Coca, Steven G; Walsh, Michael; Novick, Richard; Cook, Richard J; Jain, Anil R; Pan, Xiangbin; Noiseux, Nicolas; Vik, Karel; Stolf, Noedir A; Ritchie, Andrew; Favaloro, Roberto R; Parvathaneni, Sirish; Whitlock, Richard P; Ou, Yongning; Lawrence, Mitzi; Lamy, Andre

2014-06-04

Most acute kidney injury observed in the hospital is defined by sudden mild or moderate increases in the serum creatinine concentration, which may persist for several days. Such acute kidney injury is associated with lower long-term kidney function. However, it has not been demonstrated that an intervention that reduces the risk of such acute kidney injury better preserves long-term kidney function. To characterize the risk of acute kidney injury with an intervention in a randomized clinical trial and to determine if there is a difference between the 2 treatment groups in kidney function 1 year later. The Coronary Artery Bypass Grafting Surgery Off- or On-pump Revascularisation Study (CORONARY) enrolled 4752 patients undergoing first isolated coronary artery bypass graft (CABG) surgery at 79 sites in 19 countries. Patients were randomized to receive CABG surgery either with a beating-heart technique (off-pump) or with cardiopulmonary bypass (on-pump). From January 2010 to November 2011, 2932 patients (from 63 sites in 16 countries) from CORONARY were enrolled into a kidney function substudy to record serum creatinine concentrations during the postoperative period and at 1 year. The last 1-year serum creatinine concentration was recorded on January 18, 2013. Acute kidney injury within 30 days of surgery (≥50% increase in serum creatinine concentration from prerandomization concentration) and loss of kidney function at 1 year (≥20% loss in estimated glomerular filtration rate from prerandomization level). Off-pump (n = 1472) vs on-pump (n = 1460) CABG surgery reduced the risk of acute kidney injury (17.5% vs 20.8%, respectively; relative risk, 0.83 [95% CI, 0.72-0.97], P = .01); however, there was no significant difference between the 2 groups in the loss of kidney function at 1 year (17.1% vs 15.3%, respectively; relative risk, 1.10 [95% CI, 0.95-1.29], P = .23). Results were consistent with multiple alternate continuous and categorical definitions of acute kidney injury or kidney function loss, and in the subgroup with baseline chronic kidney disease. Use of off-pump compared with on-pump CABG surgery reduced the risk of postoperative acute kidney injury, without evidence of better preserved kidney function with off-pump CABG surgery at 1 year. In this setting, an intervention that reduced the risk of mild to moderate acute kidney injury did not alter longer-term kidney function. clinicaltrials.gov Identifier: NCT00463294.

Clazakizumab in Highly-HLA Sensitized Patients Awaiting Renal Transplant

ClinicalTrials.gov

2018-05-08

Kidney Failure, Chronic; End-Stage Renal Disease; Transplant Glomerulopathy; Transplant;Failure,Kidney; Kidney Transplant Failure and Rejection; Antibody-mediated Rejection; Kidney Transplant; Complications

42 CFR 410.48 - Kidney disease education services.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 2 2011-10-01 2011-10-01 false Kidney disease education services. 410.48 Section... Kidney disease education services. (a) Definitions. As used in this section: Kidney disease patient education services means face-to-face educational services provided to patients with Stage IV chronic kidney...

Mononuclear phagocyte subpopulations in the mouse kidney

PubMed Central

George, James F.; Lever, Jeremie M.

2017-01-01

Mononuclear phagocytes are the most common cells in the kidney associated with immunity and inflammation. Although the presence of these cells in the kidney has been known for decades, the study of mononuclear phagocytes in the context of kidney function and dysfunction is still at an early stage. The purpose of this review is to summarize the present knowledge regarding classification of these cells in the mouse kidney and to identify relevant questions that would further advance the field and potentially lead to new opportunities for treatment of acute kidney injury and other kidney diseases. PMID:28100500

Women and Kidney Disease: Reflections on World Kidney Day 2018.

PubMed

Piccoli, Giorgina B; Alrukhaimi, Mona; Liu, Zhi-Hong; Zakharova, Elena; Levin, Adeera

2018-01-01

World Kidney Day and International Women's Day 2018 are commemorated on the same day (March 8), an opportunity to highlight the importance of women's health, and particularly, their kidney health. On its 13th anniversary, World Kidney Day promotes affordable and equitable access to health education, health care, and prevention for all women and girls in the world. In this article, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide. Copyright© by the American Nephrology Nurses Association.

Kidney Disease and the Nexus of Chronic Kidney Disease and Acute Kidney Injury: The Role of Novel Biomarkers as Early and Accurate Diagnostics.

PubMed

Yerramilli, Murthy; Farace, Giosi; Quinn, John; Yerramilli, Maha

2016-11-01

Chronic kidney disease (CKD) and acute kidney injury (AKI) are interconnected and the presence of one is a risk for the other. CKD is an important predictor of AKI after exposure to nephrotoxic drugs or major surgery, whereas persistent or repetitive injury could result in the progression of CKD. This brings new perspectives to the diagnosis and monitoring of kidney diseases highlighting the need for a panel of kidney-specific biomarkers that reflect functional as well as structural damage and recovery, predict potential risk and provide prognosis. This article discusses the kidney-specific biomarkers, symmetric dimethylarginine (SDMA), clusterin, cystatin B, and inosine. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of Kidney Donors: Core Curriculum 2018.

PubMed

Sawinski, Deirdre; Locke, Jayme E

2018-05-01

Nearly 100,000 patients are waiting for a kidney transplant, yet each year only 11,000 undergo transplantation with a deceased donor kidney. Annual death rates among waitlist registrants range from 5% to 15%; many die before receiving a transplant. Not surprisingly, registrants turn to family and friends to become living kidney donors on their behalf. Living kidney donor selection practices aim to quantify lifetime risk for kidney failure based on a candidate's predonation demographic and health characteristics. It has been established that estimated lifetime risk for kidney failure varies considerably based on predonation comorbid conditions, and as such, it is of paramount importance that potential living donor candidates undergo proper medical, surgical, and psychosocial screening before donation. This installment of AJKD's Core Curriculum in Nephrology provides readers with the tools necessary for proper evaluation of living kidney donor candidates. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Environmental pollution and kidney diseases.

PubMed

Xu, Xin; Nie, Sheng; Ding, Hanying; Hou, Fan Fan

2018-05-01

The burden of disease and death attributable to environmental pollution is becoming a public health challenge worldwide, especially in developing countries. The kidney is vulnerable to environmental pollutants because most environmental toxins are concentrated by the kidney during filtration. Given the high mortality and morbidity of kidney disease, environmental risk factors and their effect on kidney disease need to be identified. In this Review, we highlight epidemiological evidence for the association between kidney disease and environmental pollutants, including air pollution, heavy metal pollution and other environmental risk factors. We discuss the potential biological mechanisms that link exposure to environmental pollutants to kidney damage and emphasize the contribution of environmental pollution to kidney disease. Regulatory efforts should be made to control environmental pollution and limit individual exposure to preventable or avoidable environmental risk. Population studies with accurate quantification of environmental exposure in polluted regions, particularly in developing countries, might aid our understanding of the dose-response relationship between pollutants and kidney diseases.

World Kidney Day 2016 Averting The Legacy of Kidney Disease-Focus On Childhood.

PubMed

Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

2016-03-01

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. © 2016 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Emergence of an Israel faith-based community organization facilitating live donor kidney transplantation.

PubMed

Wasser, Walter G; Boner, Geoffrey; Koslowsky, Meni; Lazar, Adi

2018-06-07

The 2014 Consensus Conference on Best Practices in Living Kidney Donations recognized live donor kidney transplantation as the best treatment for late-stage kidney disease, yielding superior graft and patient survival, improved quality of life, fewer requirements for dialysis and increased cost-effectiveness compared to deceased donor kidney transplantation. Yet in spite of the excellent results of living kidney donation, the annual number of living kidney donors is declining in many countries, including the United States. In Israel, a non-profit organization, Matnat Chaim ("Gift of Life" in Hebrew), a faith-based initiative, has emerged as a major force for arranging living donor kidney transplantation mainly by facilitating altruistic living unrelated donor transplantation. A retrospective review of the records of live kidney donations facilitated by the Matnat Chaim organization and referred to Israel transplant centers, since the organization's inception in 2009, was performed and compared to published data from the Israel Ministry of Health. Matnat Chaim has facilitated 494 live kidney donations since its founding in February 2009 until the end of 2017. Of the 124 live kidney transplants performed in 2016, 111 (90%) were shown to be altruistic and unrelated. This large number of donations was associated with a doubling of the total number of kidney transplantations, performed in Israel (data published by the Israel Ministry of Health). The success of an Israel community organization in the promotion of kidney transplantation may serve as a model for other religious and non-religious communities worldwide.

Effects of Platelet-Rich Plasma (PRP) on a Model of Renal Ischemia-Reperfusion in Rats.

PubMed

Martín-Solé, Oriol; Rodó, Joan; García-Aparicio, Lluís; Blanch, Josep; Cusí, Victoria; Albert, Asteria

2016-01-01

Renal ischemia-reperfusion injury is a major cause of acute renal failure, causing renal cell death, a permanent decrease of renal blood flow, organ dysfunction and chronic kidney disease. Platelet-rich plasma (PRP) is an autologous product rich in growth factors, and therefore able to promote tissue regeneration and angiogenesis. This product has proven its efficacy in multiple studies, but has not yet been tested on kidney tissue. The aim of this work is to evaluate whether the application of PRP to rat kidneys undergoing ischemia-reperfusion reduces mid-term kidney damage. A total of 30 monorrenal Sprague-Dawley male rats underwent renal ischemia-reperfusion for 45 minutes. During ischemia, PRP (PRP Group, n = 15) or saline solution (SALINE Group, n = 15) was administered by subcapsular renal injection. Control kidneys were the contralateral organs removed immediately before the start of ischemia in the remaining kidneys. Survival, body weight, renal blood flow on Doppler ultrasound, kidney weight, kidney volume, blood biochemistry and histopathology were determined for all subjects and kidneys, as applicable. Correlations between these variables were searched for. The PRP Group showed significantly worse kidney blood flow (p = 0.045) and more histopathological damage (p<0.0001). Correlations were found between body weight, kidney volume, kidney weight, renal blood flow, histology, and serum levels of creatinine and urea. Our study provides the first evidence that treatment with PRP results in the deterioration of the kidney's response to ischemia-reperfusion injury.

World Kidney Day 2016: averting the legacy of kidney disease-focus on childhood.

PubMed

Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

2016-04-01

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. Sociedad Argentina de Pediatría.

Editorial: World Kidney Day 2016: Averting the Legacy of Kidney Disease--Focus on Childhood.

PubMed

Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

2016-01-01

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have a relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults if they receive kidney replacement therapy including dialysis and transplantation, although only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers, and caregivers about the needs and possibilities surrounding kidney disease in childhood. Copyright © 2016. Published by Elsevier Inc.

World Kidney Day 2016: Averting the legacy of kidney disease-focus on childhood.

PubMed

Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

2016-03-01

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early, or who are small-for-date newborns, have a relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy-makers, and caregivers about the needs and possibilities surrounding kidney disease in childhood.

Kidney Disease Among Registered Métis Citizens of Ontario: A Population-Based Cohort Study

PubMed Central

Hayward, Jade S.; McArthur, Eric; Nash, Danielle M.; Sontrop, Jessica M.; Russell, Storm J.; Khan, Saba; Walker, Jennifer D.; Nesrallah, Gihad E.; Sood, Manish M.; Garg, Amit X.

2017-01-01

Background: Indigenous peoples in Canada have higher rates of kidney disease than non-Indigenous Canadians. However, little is known about the risk of kidney disease specifically in the Métis population in Canada. Objective: To compare the prevalence of chronic kidney disease and incidence of acute kidney injury and end-stage kidney disease among registered Métis citizens in Ontario and a matched sample from the general Ontario population. Design: Population-based, retrospective cohort study using data from the Métis Nation of Ontario’s Citizenship Registry and administrative databases. Setting: Ontario, Canada; 2003-2013. Patients: Ontario residents ≥18 years. Measurements: Prevalence of chronic kidney disease and incidence of acute kidney injury and end-stage kidney disease. Secondary outcomes among patients hospitalized with acute kidney injury included non-recovery of kidney function and mortality within 1 year of discharge. Methods: Database codes and laboratory values were used to determine study outcomes. Métis citizens were matched (1:4) to Ontario residents on age, sex, and area of residence. The analysis included 12 229 registered Métis citizens and 48 916 adults from the general population. Results: We found the prevalence of chronic kidney disease was slightly higher among Métis citizens compared with the general population (3.1% vs 2.6%, P = 0.002). The incidence of acute kidney injury was 1.2 per 1000 person-years in both Métis citizens and the general population (P = 0.54). Of those hospitalized with acute kidney injury, outcomes were similar among Métis citizens and the general population except 1-year mortality, which was higher for Métis citizens (24.5% vs 15.3%, P = 0.03). The incidence of end-stage kidney disease did not differ between groups (<3.0 per 10 000 person-years, P = 0.73). Limitations: The Métis Nation of Ontario Citizenship Registry only captures about 20% of Métis people in Ontario. Administrative health care codes used to identify kidney disease are highly specific but have low sensitivity. Conclusions: Rates of kidney disease were similar or slightly higher for Métis citizens in Ontario compared with the matched general population. PMID:28491337

Acute kidney failure

MedlinePlus

Kidney failure; Renal failure; Renal failure - acute; ARF; Kidney injury - acute ... There are many possible causes of kidney damage. They include: ... cholesterol (cholesterol emboli) Decreased blood flow due to very ...

Cadmium, mercury, and lead in kidney cortex of living kidney donors: Impact of different exposure sources,

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barregard, Lars, E-mail: lars.barregard@amm.gu.se; Fabricius-Lagging, Elisabeth; Lundh, Thomas

Background: Most current knowledge on kidney concentrations of nephrotoxic metals like cadmium (Cd), mercury (Hg), or lead (Pb) comes from autopsy studies. Assessment of metal concentrations in kidney biopsies from living subjects can be combined with information about exposure sources like smoking, diet, and occupation supplied by the biopsied subjects themselves. Objectives: To determine kidney concentrations of Cd, Hg, and Pb in living kidney donors, and assess associations with common exposure sources and background factors. Methods: Metal concentrations were determined in 109 living kidney donors aged 24-70 years (median 51), using inductively coupled plasma-mass spectrometry (Cd and Pb) and coldmore » vapor atomic fluorescence spectrometry (Hg). Smoking habits, occupation, dental amalgam, fish consumption, and iron stores were evaluated. Results: The median kidney concentrations were 12.9 {mu}g/g (wet weight) for cadmium, 0.21 {mu}g/g for mercury, and 0.08 {mu}g/g for lead. Kidney Cd increased by 3.9 {mu}g/g for a 10 year increase in age, and by 3.7 {mu}g/g for an extra 10 pack-years of smoking. Levels in non-smokers were similar to those found in the 1970s. Low iron stores (low serum ferritin) in women increased kidney Cd by 4.5 {mu}g/g. Kidney Hg increased by 6% for every additional amalgam surface, but was not associated with fish consumption. Lead was unaffected by the background factors surveyed. Conclusions: In Sweden, kidney Cd levels have decreased due to less smoking, while the impact of diet seems unchanged. Dental amalgam is the main determinant of kidney Hg. Kidney Pb levels are very low due to decreased exposure.« less

The risk of kidney cancer in patients with kidney stones: a systematic review and meta-analysis.

PubMed

Cheungpasitporn, W; Thongprayoon, C; O'Corragain, O A; Edmonds, P J; Ungprasert, P; Kittanamongkolchai, W; Erickson, S B

2015-03-01

The objective of this meta-analysis was to evaluate the association between a history of kidney stones and kidney cancer. A literature search was performed from inception until June 2014. Studies that reported odds ratios or hazard ratios comparing the risk of renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) of the upper urinary tract in patients with the history of kidney stones versus those without the history of kidney stones were included. Pooled risk ratios (RRs) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. Seven studies were included in our analysis to assess the association between a history of kidney stones and RCC. The pooled RR of RCC in patients with kidney stones was 1.76 (95% CI, 1.24-2.49). The subgroup analysis found that the history of kidney stones was associated with increased RCC risk only in males (RR, 1.41 [95% CI, 1.11-1.80]), but not in females (RR, 1.13 [95% CI, 0.86-1.49]). Five studies were selected to assess the association between a history of kidney stones and TCC. The pooled RR of TCC in patients with kidney stones was 2.14 (95% CI, 1.35-3.40). Our study demonstrates a significant increased risk of RCC and TCC in patients with prior kidney stones. However, the increased risk of RCC was noted only in male patients. This finding suggests that a history of kidney stones is associated with kidney cancer and may impact clinical management and cancer surveillance. © The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Improvement in hypertension in patients with diabetes mellitus after kidney/pancreas transplantation.

PubMed

Elliott, M D; Kapoor, A; Parker, M A; Kaufman, D B; Bonow, R O; Gheorghiade, M

2001-07-31

Hypertension persists in many patients with diabetes mellitus after kidney transplantation. However, the impact of control of diabetes as well as kidney failure on hypertension by combined kidney and pancreas transplantation has not been studied. Between March 1993 and August 1998, 111 patients with type 1 diabetes mellitus underwent successful pancreas transplantation (108 kidney/pancreas transplantation) and another 28 patients with type 1 diabetes mellitus underwent isolated kidney transplantation. Blood pressure measurements and all antihypertensive medications were determined for both groups before transplantation and at 1, 3, 6, and 12 months and at the most recent outpatient evaluation after transplantation. At baseline, the mean blood pressure was 151/88 and 151/83 mm Hg for the kidney/pancreas and isolated kidney transplant patients, respectively. The mean blood pressure decreased to 134/77 mm Hg 1 month after kidney/pancreas transplantation (P<0.001) and decreased further to 126/70 mm Hg (P<0.001) at a mean follow-up of 18 months. This reduction in blood pressure after transplantation occurred despite a decrease in antihypertensive medications and the institution of immunosuppressive agents. At 1 month after kidney/pancreas transplantation, the average number of antihypertensive medications per patient was 0.9+/-1.0, compared with 2.5+/-1.1 before surgery (P<0.001). At 18 months after transplantation, 34% of patients were both normotensive (blood pressure

Comparative anatomical study of the kidney position in amniotes using the origin of the renal artery as a landmark.

PubMed

Yokota, Eri; Kawashima, Tomokazu; Ohkubo, Fumie; Sasaki, Hiroshi

2005-03-01

The anatomical relationship between the kidney position and its arterial supply was investigated in 21 mammals, 1 bird, and 3 reptiles (n = 1 for each species) and in 43 human cadavers. The following observations were made. (1) Although the right kidney was located caudal to the left kidney in 29 out of 43 human cadavers (67.4%), the origin of the right renal artery from the aorta was located cranial to the origin of the left renal artery in 36 human cadavers (83.7%). Therefore, the relative positions of the kidneys do not correspond with the relative origins of the renal arteries in humans. (2) Among the mammals that were examined, the position of the kidney and the branching level of the renal artery on the right side were usually cranial to those on the left side. (3) In the bird and most reptiles that were examined, kidneys were typically located in the pelvic region and were supplied by segmental arterial branches. These results suggest that the right kidney and its arterial supply are generally located cranial to the left kidney in phylogeny of mammals. While the presence of a human accessory renal artery in 9 out of 86 sides (10.5%) and a cranial origin of the left renal artery relative to the right renal artery in 7 out of 43 cadavers (16.3%), shows some variation in the arterial supply to the kidneys, the origin of the renal arteries can generally be used as phylogenetic landmarks indicating the relative positions of the kidneys. Hence, from an ontological perspective, the human right kidney may be initially situated cranial to the left kidney during the early stages of development. Thereafter, the human right kidney may shift downwards secondary.

Alterations in apparent diffusion coefficient values of the kidney during the cardiac cycle: Evaluation with ECG-triggered diffusion-weighted MR imaging.

PubMed

Ito, Katsuyoshi; Hayashida, Minoru; Kanki, Akihiko; Yamamoto, Akira; Tamada, Tsutomu; Yoshida, Koji; Tanabe, Masahiro

2018-05-17

To evaluate dynamic changes in apparent diffusion coefficient (ADC) values of the kidney at different time points during the cardiac cycle using electrocardiographic (ECG)-triggered diffusion-weighted MR imaging in normal subjects, and to elucidate the differences in ADC values between the right and left kidneys during a cardiac cycle. The study was approved by our institutional review board and informed consent was obtained from subjects. Twenty healthy volunteers who underwent ECG-triggered diffusion-weighted MR imaging of the kidney were included. The differences in ADC values of each kidney during different cardiac phases were compared. Additionally, the differences in maximum and minimum ADC values between the right and left kidney were also evaluated. ADC values in the right and left kidney changed significantly during the cardiac cycle (P < 0.00001). Maximum and minimum ADC values during the cardiac cycle of the left kidney were significantly higher (P = 0.026 and 0.017, respectively) than those of the right kidney. Maximum ADC value in the left kidney had a significantly strong positive correlation with the left renal vein ratio (r = 0.83, P < 0.00001). In the right kidney, maximum ADC showed a weakly positive correlation with the diameter of the right renal vein (r = 0.45, P = 0.048). ADC values of the kidney obtained using ECG-triggered diffusion-weighted MR imaging change significantly during the cardiac cycle. Maximum (systolic) ADC during the cardiac cycle of the left kidney was significantly higher than that of the right kidney, probably due to the anatomical difference in the renal vein. Copyright © 2018 Elsevier Inc. All rights reserved.

APOL1 Oligomerization as the Key Mediator of Kidney Disease in African Americans

DTIC Science & Technology

2015-10-01

kidney disease that accounts for the high rate of kidney disease in African Americans. This work is based on the hypothesize that APOL1 kidney disease...microscopy- based approaches. 15. SUBJECT TERMS Kidney, ESRD, APOL1, African American 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER...is based on the hypothesize that APOL1 kidney disease in African Americans results from abnormal aggregation of the APOL1 risk variant protein in an

Attitudes toward kidney donation.

PubMed Central

Aghanwa, H. S.; Akinsola, A.; Akinola, D. O.; Makanjuola, R. O. A.

2003-01-01

The Renal Unit of Obafemi Awolowo University Teaching Hospital Ile-Ife in Southwest Nigeria intends commencing a kidney transplantation program. This cross-sectional study aimed at examining the willingness of Nigerians to be living-related kidney donors. Three hundred and sixteen Nigerians (96 first-degree relatives of end-stage renal disease patients, 69 rural dwellers and 151 health workers) were interviewed regarding their willingness to donate kidneys using an interview schedule designed to elicit socio-demographic information, knowledge about kidney transplantation and attitude toward kidney donation. Sixty-two percent of health workers, 52.1% of the patients' relatives and 27.1% of rural dwellers expressed willingness to donate. Higher proportions of health workers and patients' relatives--compared with the rural dwellers--were willing to donate a kidney to their children, full-siblings and parents (P<0.05). The level of awareness about kidney transplantation was highest among health workers and least among rural dwellers (P<0.001). Altruism was the primary motivation for those willing to donate a kidney. The most important reason for refusal to donate was fear of adverse health consequences. Among the rural dwellers, never-married persons were more willing than the married to donate (P<0.05). Programs aimed at increasing awareness about the safety of kidney donation, reducing adverse beliefs about kidney donation, and encouraging altruistic tendencies will increase the availability of kidney donors. PMID:12934871

MELAS Syndrome and Kidney Disease Without Fanconi Syndrome or Proteinuria: A Case Report.

PubMed

Rudnicki, Michael; Mayr, Johannes A; Zschocke, Johannes; Antretter, Herwig; Regele, Heinz; Feichtinger, René G; Windpessl, Martin; Mayer, Gert; Pölzl, Gerhard

2016-12-01

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) represents one of the most frequent mitochondrial disorders. The majority of MELAS cases are caused by m.3243A>G mutation in the mitochondrial MT-TL1 gene, which encodes the mitochondrial tRNA Leu(UUR) . Kidney involvement usually manifests as Fanconi syndrome or focal segmental glomerulosclerosis. We describe a patient with MELAS mutation, cardiomyopathy, and chronic kidney disease without Fanconi syndrome, proteinuria, or hematuria. While the patient was waitlisted for heart transplantation, her kidney function deteriorated from an estimated glomerular filtration rate of 33 to 20mL/min/1.73m 2 within several months. Kidney biopsy was performed to distinguish decreased kidney perfusion from intrinsic kidney pathology. Histologic examination of the biopsy specimen showed only a moderate degree of tubular atrophy and interstitial fibrosis, but quantitative analysis of the m.3243A>G mitochondrial DNA mutation revealed high heteroplasmy levels of 89% in the kidney. Functional assessment showed reduced activity of mitochondrial enzymes in kidney tissue, which was confirmed by immunohistology. In conclusion, we describe an unusual case of MELAS syndrome with chronic kidney disease without apparent proteinuria or tubular disorders associated with Fanconi syndrome, but widespread interstitial fibrosis and a high degree of heteroplasmy of the MELAS specific mutation and low mitochondrial activity in the kidney. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Averting the legacy of kidney disease - Focus on childhood.

PubMed

Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

2016-03-01

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

Averting the legacy of kidney disease: focus on childhood.

PubMed

Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

2016-04-01

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

Averting the legacy of kidney disease - focus on childhood.

PubMed

Ingelfinger, J R; Kalantar-Zadeh, K; Schaefer, F

2016-01-01

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, in that the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease as a consequence of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, although only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that the World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

Averting the Legacy of Kidney Disease: Focus on Childhood.

PubMed

Ingelfinger, J R; Kalantar-Zadeh, K; Schaefer, F

2016-01-01

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policymakers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

Averting the legacy of kidney disease: focus on childhood.

PubMed

Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

2016-06-01

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

Averting the legacy of kidney disease - focus on childhood.

PubMed

Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

2016-04-08

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group amongst children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertensionand CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely to help to detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, whilst only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic oreconomic circumstances. Our hope is that World Kidney Day will inform the general public, policymakers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

Averting the Legacy of Kidney Disease - Focus on Childhood.

PubMed

Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

2016-04-01

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

Averting the legacy of kidney disease-focus on childhood.

PubMed

Ingelfinger, Julie R; Schaefer, Franz; Kalantar-Zadeh, Kamyar

2016-03-01

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

Decellularized Human Kidney Cortex Hydrogels Enhance Kidney Microvascular Endothelial Cell Maturation and Quiescence.

PubMed

Nagao, Ryan J; Xu, Jin; Luo, Ping; Xue, Jun; Wang, Yi; Kotha, Surya; Zeng, Wen; Fu, Xiaoyun; Himmelfarb, Jonathan; Zheng, Ying

2016-10-01

The kidney peritubular microvasculature is highly susceptible to injury from drugs and toxins, often resulting in acute kidney injury and progressive chronic kidney disease. Little is known about the process of injury and regeneration of human kidney microvasculature, resulting from the lack of appropriate kidney microvascular models that can incorporate the proper cells, extracellular matrices (ECMs), and architectures needed to understand the response and contribution of individual vascular components in these processes. In this study, we present methods to recreate the human kidney ECM (kECM) microenvironment by fabricating kECM hydrogels derived from decellularized human kidney cortex. The majority of native matrix proteins, such as collagen-IV, laminin, and heparan sulfate proteoglycan, and their isoforms were preserved in similar proportions as found in normal kidneys. Human kidney peritubular microvascular endothelial cells (HKMECs) became more quiescent when cultured on this kECM gel compared with culture on collagen-I-assessed using phenotypic, genotypic, and functional assays; whereas human umbilical vein endothelial cells became stimulated on kECM gels. We demonstrate for the first time that human kidney cortex can form a hydrogel suitable for use in flow-directed microphysiological systems. Our findings strongly suggest that selecting the proper ECM is a critical consideration in the development of vascularized organs on a chip and carries important implications for tissue engineering of all vascularized organs.

Trends in Hospitalizations for Acute Kidney Injury - United States, 2000-2014.

PubMed

Pavkov, Meda E; Harding, Jessica L; Burrows, Nilka R

2018-03-16

Acute kidney injury is a sudden decrease in kidney function with or without kidney damage, occurring over a few hours or days. Diabetes, hypertension, and advanced age are primary risk factors for acute kidney injury. It is increasingly recognized as an in-hospital complication of sepsis, heart conditions, and surgery (1,2). Its most severe stage requires treatment with dialysis. Acute kidney injury is also associated with higher likelihood of long-term care, incidence of chronic kidney disease and hospital mortality, and health care costs (1,2). Although a number of U.S. studies have indicated an increasing incidence of dialysis-treated acute kidney injury since the late 1990s (3), no data are available on national trends in diabetes-related acute kidney injury. To estimate diabetes- and nondiabetes-related acute kidney injury trends, CDC analyzed 2000-2014 data from the National Inpatient Sample (NIS) (4) and the National Health Interview Survey (NHIS) (5). Age-standardized rates of acute kidney injury hospitalizations increased by 139% (from 23.1 to 55.3 per 1,000 persons) among adults with diagnosed diabetes, and by 230% (from 3.5 to 11.7 per 1,000 persons) among those without diabetes. Improving both patient and provider awareness that diabetes, hypertension, and advancing age are frequently associated with acute kidney injury might reduce its occurrence and improve management of the underlying diseases in an aging population.

A Re-evaluation of Discarded Deceased Donor Kidneys in the UK: Are Usable Organs Still Being Discarded?

PubMed

Mittal, Shruti; Adamusiak, Anna; Horsfield, Catherine; Loukopoulos, Ioannis; Karydis, Nikolaos; Kessaris, Nicos; Drage, Martin; Olsburgh, Jonathon; Watson, Christopher Je; Callaghan, Chris J

2017-07-01

A significant proportion of procured deceased donor kidneys are subsequently discarded. The UK Kidney Fast-Track Scheme (KFTS) was introduced in 2012, enabling kidneys at risk of discard to be simultaneously offered to participating centers. We undertook an analysis of discarded kidneys to determine if unnecessary organ discard was still occurring since the KFTS was introduced. Between April and June 2015, senior surgeons independently inspected 31 consecutive discarded kidneys from throughout the United Kingdom. All kidneys were biopsied. Organs were categorized as usable, possibly usable pending histology, or not usable for implantation. After histology reports were available, final assessments of usability were made. There were 19 donors (6 donations after brain death, 13 donations after circulatory death), with a median (range) donor age of 67 (29-83) years and Kidney Donor Profile Index of 93 (19-100). Reasons for discard were variable. Only 3 discarded kidneys had not entered the KFTS. After initial assessment postdiscard, 11 kidneys were assessed as usable, with 9 kidneys thought to be possibly usable. Consideration of histological data reduced the number of kidneys thought usable to 10 (10/31; 32%). The KFTS scheme is successfully identifying organs at high risk of discard, though potentially transplantable organs are still being discarded. Analyses of discarded organs are essential to identify barriers to organ utilization and develop strategies to reduce unnecessary discard.

Kidney Tests

MedlinePlus

... taking out waste products and making urine. Kidney tests check to see how well your kidneys are working. They include blood, urine, and imaging tests. Early kidney disease usually does not have signs ...

75 FR 3741 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-22

... Diabetes and Digestive and Kidney Diseases; Notice of Meetings Pursuant to section 10(d) of the Federal... Digestive and Kidney Diseases Initial Review Group; Kidney, Urologic and Hematologic Diseases D Subcommittee..., [email protected] . Name of Committee: National Institute of Diabetes and Digestive and Kidney...

78 FR 9063 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-07

... Diabetes and Digestive and Kidney Diseases; Notice of Meetings Pursuant to section 10(d) of the Federal... Digestive and Kidney Diseases Initial Review Group; Kidney, Urologic and Hematologic Diseases D Subcommittee... . Name of Committee: National Institute of Diabetes and Digestive and Kidney Diseases Initial Review...

76 FR 24897 - National Institute of Diabetes And Digestive and Kidney Diseases; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-03

... Diabetes And Digestive and Kidney Diseases; Notice of Meeting Pursuant to section 10(d) of the Federal... Digestive and Kidney Diseases Initial Review Group, Kidney, Urologic and Hematologic Diseases D Subcommittee..., Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases...

78 FR 22273 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-15

... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Acute Kidney Injury. Date: June 6, 2013..., Kidney Diseases, Urology and Hematology Research, National Institutes of Health, HHS) Dated: April 9...

75 FR 56119 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-15

... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, Fellowships in Digestive Diseases and... Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis Panel. Kidney Disease Ancillary...

75 FR 56117 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-15

... Diabetes and Digestive and Kidney Diseases; Notice of Meetings Pursuant to section 10(d) of the Federal... Digestive and Kidney Diseases Initial Review Group, Kidney, Urologic and Hematologic Diseases D Subcommittee.... [email protected] . Name of Committee: National Institute of Diabetes and Digestive and Kidney...

77 FR 28890 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-16

... Diabetes and Digestive and Kidney Diseases Notice of Meetings Pursuant to section 10(d) of the Federal... Digestive and Kidney Diseases Initial Review Group; Kidney, Urologic and Hematologic Diseases D Subcommittee..., [email protected] . Name of Committee: National Institute of Diabetes and Digestive and Kidney...

77 FR 6130 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-07

... Diabetes and Digestive and Kidney Diseases Notice of Closed Meeting Pursuant to section 10(d) of the... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Cellular Biology of Kidney Function and... Research; 93.849, Kidney Diseases, Urology and Hematology Research, National Institutes of Health, HHS...

9 CFR 310.19 - Inspection of kidneys.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Inspection of kidneys. 310.19 Section... INSPECTION AND CERTIFICATION POST-MORTEM INSPECTION § 310.19 Inspection of kidneys. An employee of the establishment shall open the kidney capsule and expose the kidneys of all livestock at the time of slaughter for...

9 CFR 310.19 - Inspection of kidneys.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Inspection of kidneys. 310.19 Section... INSPECTION AND CERTIFICATION POST-MORTEM INSPECTION § 310.19 Inspection of kidneys. An employee of the establishment shall open the kidney capsule and expose the kidneys of all livestock at the time of slaughter for...

78 FR 38997 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-28

... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Time-Sensitive Obesity Research. Date... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the... Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Kidney Disease Ancillary...

75 FR 63495 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-15

... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, Kidney Diseases in Children Ancillary... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, DDK-C Conflicts. Date: November 16, 2010...

CD74 in Kidney Disease

PubMed Central

Valiño-Rivas, Lara; Baeza-Bermejillo, Ciro; Gonzalez-Lafuente, Laura; Sanz, Ana Belen; Ortiz, Alberto; Sanchez-Niño, Maria Dolores

2015-01-01

CD74 (invariant MHC class II) regulates protein trafficking and is a receptor for macrophage migration inhibitory factor (MIF) and d-dopachrome tautomerase (d-DT/MIF-2). CD74 expression is increased in tubular cells and/or glomerular podocytes and parietal cells in human metabolic nephropathies, polycystic kidney disease, graft rejection and kidney cancer and in experimental diabetic nephropathy and glomerulonephritis. Stressors like abnormal metabolite (glucose, lyso-Gb3) levels and inflammatory cytokines increase kidney cell CD74. MIF activates CD74 to increase inflammatory cytokines in podocytes and tubular cells and proliferation in glomerular parietal epithelial cells and cyst cells. MIF overexpression promotes while MIF targeting protects from experimental glomerular injury and kidney cysts, and interference with MIF/CD74 signaling or CD74 deficiency protected from crescentic glomerulonephritis. However, CD74 may protect from interstitial kidney fibrosis. Furthermore, CD74 expression by stressed kidney cells raises questions about the kidney safety of cancer therapy strategies delivering lethal immunoconjugates to CD74-expressing cells. Thus, understanding CD74 biology in kidney cells is relevant for kidney therapeutics. PMID:26441987

Endoplasmic Reticulum Stress in Ischemic and Nephrotoxic Acute Kidney Injury.

PubMed

Yan, Mingjuan; Shu, Shaoqun; Guo, Chunyuan; Tang, Chengyuan; Dong, Zheng

2018-06-12

Acute kidney injury is a medical condition characterized by kidney damage with a rapid decline of renal function, which is associated with high mortality and morbidity. Recent research has further established an intimate relationship between acute kidney injury and chronic kidney disease. Perturbations of kidney cells in acute kidney injury result in the accumulation of unfolded and misfolded proteins in the endoplasmic reticulum, leading to unfolded protein response or endoplasmic reticulum stress. In this review, we analyze the role and regulation of endoplasmic reticulum stress in acute kidney injury triggered by renal ischemia-reperfusion and cisplatin nephrotoxicity. The balance between the two major components of unfolded protein response, the adaptive pathway and the apoptotic pathway, plays a critical role in determining the cell fate in endoplasmic reticulum stress. The adaptive pathway is evoked to attenuate translation, induce chaperones, maintain protein homeostasis, and promote cell survival. Prolonged endoplasmic reticulum stress activates the apoptotic pathway, resulting in the elimination of dysfunctional cells. Therefore, regulating ER stress in kidney cells may provide a therapeutic target in acute kidney injury.

On the occasion of world kidney day 2016; work together to better protect the kidney

PubMed Central

Nasri, Hamid; Rafieian-Kopaei, Mahmoud

2016-01-01

Context: World kidney day is a yearly global alertness and education ceremony, held on the second Thursday in March. Evidence Acquisition: Directory of open access journals (DOAJ), EMBASE, Google Scholar, PubMed, EBSCO, and Web of Science have been searched. Results: Once again we reached to March 14, the world kidney day of 2016. This is the 10th anniversary of world kidney day, a program of the International Society of Nephrology (ISN) and the International Federation of Kidney Foundations (IFKF). World kidney day first began in 2006 and the worldwide campaign highlights a specific theme each year. The theme for 2015 was to invite everybody to drink a glass of water and give one, too, to celebrate their kidneys. This is a symbolic action to memorize that kidneys are vital organs and that they might be cared. Conclusions: It is a manner to make individuals more conscious about their lifestyle choices. In this year, world kidney day will be celebrated on Thursday March 10, 2016. The theme for 2016 will highlight on renal disease and children. PMID:27047805

On the occasion of world kidney day 2016; work together to better protect the kidney.

PubMed

Nasri, Hamid; Rafieian-Kopaei, Mahmoud

2016-01-01

World kidney day is a yearly global alertness and education ceremony, held on the second Thursday in March. Directory of open access journals (DOAJ), EMBASE, Google Scholar, PubMed, EBSCO, and Web of Science have been searched. Once again we reached to March 14, the world kidney day of 2016. This is the 10th anniversary of world kidney day, a program of the International Society of Nephrology (ISN) and the International Federation of Kidney Foundations (IFKF). World kidney day first began in 2006 and the worldwide campaign highlights a specific theme each year. The theme for 2015 was to invite everybody to drink a glass of water and give one, too, to celebrate their kidneys. This is a symbolic action to memorize that kidneys are vital organs and that they might be cared. It is a manner to make individuals more conscious about their lifestyle choices. In this year, world kidney day will be celebrated on Thursday March 10, 2016. The theme for 2016 will highlight on renal disease and children.

The science of Stewardship: due diligence for kidney donors and kidney function in living kidney donation--evaluation, determinants, and implications for outcomes.

PubMed

Poggio, Emilio D; Braun, William E; Davis, Connie

2009-10-01

Living kidney donor transplantation is now a common treatment for ESRD because it provides excellent outcomes to transplant recipients and is considered a safe procedure for prospective donors. The short- and long-term safety of prospective donors is paramount to the continued success of this procedure. Whereas the initial experiences with living kidney donors mostly included the healthiest, the increase in the need for organs and the changing demographic characteristics of the general population have subtly reshaped the suitability for donation. Kidney function assessment is a critical component of the evaluation of prospective donors; therefore, special emphasis is usually placed on this aspect of the evaluation. At the same time, consideration of kidney function after donation is important because it assists with the determination of renal health in donors. This review summarizes the process of predonation kidney function assessment, determinants of pre- and postdonation renal function, and, importantly, the potential implications of kidney function to the long-term outcomes of kidney donors.

Cerebral Small Vessel Disease and Chronic Kidney Disease

PubMed Central

2015-01-01

Chronic kidney disease, defined by a decreased glomerular filtration rate or albuminuria, is recognized as a major global health burden, mainly because it is an established risk factor for cardiovascular and cerebrovascular diseases. The magnitude of the effect of chronic kidney disease on incident stroke seems to be higher in persons of Asian ethnicity. Since the kidney and brain share unique susceptibilities to vascular injury due to similar anatomical and functional features of small artery diseases, kidney impairment can be predictive of the presence and severity of cerebral small vessel diseases. Chronic kidney disease has been reported to be associated with silent brain infarcts, cerebral white matter lesions, and cerebral microbleeds, independently of vascular risk factors. In addition, chronic kidney disease affects cognitive function, partly via the high prevalence of cerebral small vessel diseases. Retinal artery disease also has an independent relationship with chronic kidney disease and cognitive impairment. Stroke experts are no longer allowed to be ignorant of chronic kidney disease. Close liaison between neurologists and nephrologists can improve the management of cerebral small vessel diseases in kidney patients. PMID:25692105

Kidney School

MedlinePlus

... copies? Read our licensing agreement Living Successfully with Kidney Disease People with kidney disease can live long ... Listen Printing multiple copies? Read our licensing agreement Kidneys: How They Work, How They Fail, What You ...

Kidney stones

MedlinePlus Videos and Cool Tools

... kidneys, ureters, bladder and urethra. Within each kidney, urine flows from the outer cortex to the inner ... The renal pelvis is the funnel through which urine exits the kidney and enters the ureter. As ...

Creatinine - urine

MedlinePlus

... test can be used for the following: To evaluate how well the kidneys are working As part ... the tubule cells Kidney failure Too little blood flow to the kidneys, damage to filtering units Kidney ...

Kidney Diseases

MedlinePlus

... until you go to the bathroom. Most kidney diseases attack the nephrons. This damage may leave kidneys ... medicines. You have a higher risk of kidney disease if you have diabetes, high blood pressure, or ...

Bone and mineral disorders after kidney transplantation: therapeutic strategies

PubMed Central

Molnar, Miklos Z.; Naser, Mohamed S.; Rhee, Connie M.; Kalantar-Zadeh, Kamyar; Bunnapradist, Suphamai

2017-01-01

Mineral and bone diseases (MBD) are common in patients with chronic kidney disease who undergo kidney transplantation. The incidence, types and severity of MBD varies according to the duration of chronic kidney disease, presence of comorbid conditions and intake of certain medications. Moreover, multiple types of pathology may be responsible for MBD. After successful reversal of uremia by kidney transplantation, many bone and mineral disorders improve, while immunosuppression, other medications, and new and existing comorbidities may result in new or worsening MBD. Chronic kidney disease is also common after kidney transplantation and may impact bone and mineral disease. In this article, we reviewed the prevalence, pathophysiology, and impact of MBD on post-transplant outcomes. We also discussed the diagnostic approach; immunosuppression management and potential treatment of MBD in kidney transplant recipients. PMID:24462303

Peptide-induced prostaglandin biosynthesis in the renal-vein-constricted kidney

PubMed Central

Myers, Stuart I.; Zipser, Robert; Needleman, Philip

1981-01-01

The ipsilateral kidney was removed from a rabbit 48h after unilateral partial renal-vein-constriction and was perfused with Krebs–Henseleit media at 37°C. Hourly administration of a fixed dose of bradykinin to the renal-vein-constricted kidney demonstrated a marked time-dependent increase in the release of bioassayable prostaglandin E2 and thromboxane A2 into the venous effluent as compared with the response of the contralateral control kidney. The renal-vein-constricted kidney produced up to 60 times more prostaglandin E2 in response to bradykinin after 6h of perfusion as compared with the contralateral kidney; thromboxane A2 was not demonstratable in the contralateral kidney. Inhibition of protein synthesis de novo in the perfused renal-vein-constricted kidney with cycloheximide lessened the hormone-stimulated increase in prostaglandin E2 by 94% and in thromboxane A2 by 90% at 6h of perfusion. Covalent acetylation of the renal cyclo-oxygenase by prior oral administration of aspirin to the rabbit inhibited initial bradykinin-stimulated prostaglandin E2 biosynthesis 71% at 1h of perfusion. However, there was total recovery from aspirin in the renal-vein-constricted kidney by 2h of perfusion after bradykinin stimulation. Total cyclo-oxygenase activity as measured by [14C]arachidonate metabolism to labelled prostaglandins by renal cortical and renal medullary microsomal fractions prepared from 6h-perfused kidneys demonstrated that renal-vein-constricted kidney-cortical cyclo-oxygenase activity was significantly greater than the contralateral-kidney-cortical conversion, whereas medullary arachidonate metabolism was comparable in both the renal-vein-constricted kidney and contralateral kidney. These data suggest that perfusion of a renal-vein-constricted kidney initiates a time-dependent induction of synthesis of prostaglandin-producing enzymes, which appear to be primarily localized in the renal cortex. The presence of the synthetic capacity to generate very potent vasodilator and vasoconstrictor prostaglandins in the renal cortex suggests that these substances could mediate or modulate changes in renal vascular resistance in pathological states. PMID:6798974

Prevalence of chronic kidney disease among patients undergoing transradial percutaneous coronary interventions.

PubMed

Hossain, Mohammad A; Quinlan, Amy; Heck-Kanellidis, Jennifer; Calderon, Dawn; Patel, Tejas; Gandhi, Bhavika; Patel, Shrinil; Hetavi, Mahida; Costanzo, Eric J; Cosentino, James; Patel, Chirag; Dewan, Asa; Kuo, Yen-Hong; Salman, Loay; Vachharajani, Tushar J

2018-07-01

While transradial approach to conduct percutaneous coronary interventions offers multiple advantages, the procedure can cause radial artery damage and occlusion. Because radial artery is the preferred site for the creation of an arteriovenous fistula to provide dialysis, patients with chronic kidney disease are particularly dependent on radial artery for their long-term survival. In this retrospective study, we investigated the prevalence of chronic kidney disease in patients undergoing coronary interventions via radial artery. Stage of chronic kidney disease was based on estimated glomerular filtration rate and National Kidney Foundation - Kidney Disease Outcomes Quality Initiative guidelines. A total of 497 patients undergoing transradial percutaneous coronary interventions were included. Over 70.4% (350/497) of the patients had chronic kidney disease. Stage II chronic kidney disease was observed in 243 (69%) patients (estimated glomerular filtration rate = 76.0 ± 8.4 mL/min). Stage III was observed in 93 (27%) patients (estimated glomerular filtration rate = 49 ± 7.5 mL/min). Stage IV chronic kidney disease was observed in 5 (1%) patients (estimated glomerular filtration rate = 25.6 ± 4.3 mL/min) and Stage V chronic kidney disease was observed in 9 (3%) patients (estimated glomerular filtration rate = 9.3 ± 3.5 mL/min). Overall, 107 of 350 patients (30%) had advanced chronic kidney disease, that is, stage III-V chronic kidney disease. Importantly, 14 of the 107 (13%) patients had either stage IV or V chronic kidney disease. This study finds that nearly one-third of the patients undergoing transradial percutaneous coronary interventions have advanced chronic kidney disease. Because many of these patients may require dialysis, the use of radial artery to conduct percutaneous coronary interventions must be carefully considered in chronic kidney disease population.

Generation of a Three-Dimensional Kidney Structure from Pluripotent Stem Cells.

PubMed

Yoshimura, Yasuhiro; Taguchi, Atsuhiro; Nishinakamura, Ryuichi

2017-01-01

The kidney is a vital organ that has an important role in the maintenance of homeostasis by fluid volume regulation and waste product excretion. This role cannot be performed without the three-dimensional (3D) structure of the kidney. Therefore, it is important to generate the 3D structure of the kidney when inducing functional kidney tissue or the whole organ from pluripotent stem cells. In this chapter, we describe the detailed methods to induce kidney progenitor cells from pluripotent stem cells, which are based on embryological development. We also provide a method to generate 3D kidney tissue with vascularized glomeruli upon transplantation.

Chronic kidney disease

MedlinePlus

Kidney failure - chronic; Renal failure - chronic; Chronic renal insufficiency; Chronic kidney failure; Chronic renal failure ... Chronic kidney disease (CKD) slowly gets worse over months or years. You may not notice any symptoms for some ...

Reestablishment of radiographic kidney size in Miniature Schnauzer dogs

PubMed Central

SOHN, Jungmin; YUN, Sookyung; LEE, Jeosoon; CHANG, Dongwoo; CHOI, Mincheol; YOON, Junghee

2016-01-01

Kidney size may be altered in renal diseases, and the detection of kidney size alteration has diagnostic and prognostic values. We hypothesized that radiographic kidney size, the kidney length to the second lumbar vertebra (L2) length ratio, in normal Miniature Schnauzer dogs may be overestimated due to their shorter vertebral length. This study was conducted to evaluate radiographic and ultrasonographic kidney size and L2 length in clinically normal Miniature Schnauzers and other dog breeds to evaluate the effect of vertebral length on radiographic kidney size and to reestablish radiographic kidney size in normal Miniature Schnauzers. Abdominal radiographs and ultrasonograms from 49 Miniature Schnauzers and 54 other breeds without clinical evidence of renal disease and lumbar vertebral abnormality were retrospectively evaluated. Radiographic kidney size, in the Miniature Schnauzer (3.31 ± 0.26) was significantly larger than that in other breeds (2.94 ± 0.27). Relative L2 length, the L2 length to width ratio, in the Miniature Schnauzer (1.11 ± 0.06) was significantly shorter than that in other breeds (1.21 ± 0.09). However, ultrasonographic kidney sizes, kidney length to aorta diameter ratios, were within or very close to normal range both in the Miniature Schnauzer (6.75 ± 0.67) and other breeds (7.16 ± 1.01). Thus, Miniature Schnauzer dogs have breed-specific short vertebrae and consequently a larger radiographic kidney size, which was greater than standard reference in normal adult dogs. Care should be taken when evaluating radiographic kidney size in Miniature Schnauzers to prevent falsely diagnosed renomegaly. PMID:27594274

Increasing access to kidney transplantation in countries with limited resources: the Indian experience with kidney paired donation.

PubMed

Kute, Vivek B; Vanikar, Aruna V; Shah, Pankaj R; Gumber, Manoj R; Patel, Himanshu V; Engineer, Divyesh P; Modi, Pranjal R; Shah, Veena R; Trivedi, Hargovind L

2014-10-01

According to the Indian chronic kidney disease registry, in 2010 only 2% of end stage kidney disease patients were managed with kidney transplantation, 37% were managed with dialysis and 61% were treated conservatively without renal replacement therapy. In countries like India, where a well-organized deceased donor kidney transplantation program is not available, living donor kidney transplantation is the major source of organs for kidney transplantation. The most common reason to decline a donor for directed living donation is ABO incompatibility, which eliminates up to one third of the potential living donor pool. Because access to transplantation with human leukocyte antigen (HLA)-desensitization protocols and ABO incompatible transplantation is very limited due to high costs and increased risk of infections from more intense immunosuppression, kidney paired donation (KPD) promises hope to a growing number of end stage kidney disease patients. KPD is a rapidly growing and cost-effective living donor kidney transplantation strategy for patients who are incompatible with their healthy, willing living donor. In principle, KPD is feasible for any centre that performs living donor kidney transplantation. In transplant centres with a large living donor kidney transplantation program KPD does not require extra infrastructure, decreases waiting time, avoids transplant tourism and prevents commercial trafficking. Although KPD is still underutilized in India, it has been performed more frequently in recent times. To substantially increase donor pool and transplant rates, transplant centres should work together towards a national KPD program and frame a uniform acceptable allocation policy. © 2014 Asian Pacific Society of Nephrology.

Impact of chronic kidney disease stage on lower-extremity arthroplasty.

PubMed

Deegan, Brian F; Richard, Raveesh D; Bowen, Thomas R; Perkins, Robert M; Graham, Jove H; Foltzer, Michael A

2014-07-01

End-stage renal disease and dialysis is commonly associated with poor outcomes after joint replacement surgery. The goal of this study was to evaluate postoperative complications in patients with less advanced chronic kidney disease undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA). Patients who underwent THA or TKA between 2004 and 2011 with stage 1, 2, or 3 chronic kidney disease were retrospectively reviewed via an electronic medical record. The authors compared 377 patients who had stage 1 to 2 chronic kidney disease with 402 patients who had stage 3 chronic kidney disease. No significant differences in 90-day readmission or revision rates were found between the stage 1 to 2 and stage 3 patient groups. For patients with stage 3 chronic kidney disease, the overall mortality rate was greater than that in patients with stage 1 to 2 chronic kidney disease. However, when adjusted for comorbid disease, no significant increases were seen in joint infection, readmission, or early revision between patients with stage 1 to 2 chronic kidney disease vs patients with stage 3 chronic kidney disease. The overall incidence of infection was high (3.5%) but far less than reported for patients with end-stage renal disease, dialysis, and kidney transplant. In conclusion, patients with stage 1, 2, or 3 chronic kidney disease may have a higher than expected rate of prosthetic joint infection (3.5%) after total joint arthroplasty. Patients with stage 3 chronic kidney disease are at higher risk for postoperative mortality compared with those with lesser stages of kidney disease. Copyright 2014, SLACK Incorporated.

Influence of CT-based depth correction of renal scintigraphy in evaluation of living kidney donors on side selection and postoperative renal function: is it necessary to know the relative renal function?

PubMed

Weinberger, Sarah; Klarholz-Pevere, Carola; Liefeldt, Lutz; Baeder, Michael; Steckhan, Nico; Friedersdorff, Frank

2018-03-22

To analyse the influence of CT-based depth correction in the assessment of split renal function in potential living kidney donors. In 116 consecutive living kidney donors preoperative split renal function was assessed using the CT-based depth correction. Influence on donor side selection and postoperative renal function of the living kidney donors were analyzed. Linear regression analysis was performed to identify predictors of postoperative renal function. A left versus right kidney depth variation of more than 1 cm was found in 40/114 donors (35%). 11 patients (10%) had a difference of more than 5% in relative renal function after depth correction. Kidney depth variation and changes in relative renal function after depth correction would have had influence on side selection in 30 of 114 living kidney donors. CT depth correction did not improve the predictability of postoperative renal function of the living kidney donor. In general, it was not possible to predict the postoperative renal function from preoperative total and relative renal function. In multivariate linear regression analysis, age and BMI were identified as most important predictors for postoperative renal function of the living kidney donors. Our results clearly indicate that concerning the postoperative renal function of living kidney donors, the relative renal function of the donated kidney seems to be less important than other factors. A multimodal assessment with consideration of all available results including kidney size, location of the kidney and split renal function remains necessary.

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

PubMed Central

Wang, Xuexiang; Johnson, Ashley C.; Williams, Jan M.; White, Tiffani; Chade, Alejandro R.; Zhang, Jie; Liu, Ruisheng; Roman, Richard J.; Lee, Jonathan W.; Kyle, Patrick B.; Solberg-Woods, Leah

2015-01-01

Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%–75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. PMID:25349207

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model.

PubMed

Wang, Xuexiang; Johnson, Ashley C; Williams, Jan M; White, Tiffani; Chade, Alejandro R; Zhang, Jie; Liu, Ruisheng; Roman, Richard J; Lee, Jonathan W; Kyle, Patrick B; Solberg-Woods, Leah; Garrett, Michael R

2015-07-01

Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%-75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. Copyright © 2015 by the American Society of Nephrology.

Analysis of the Results of ABO-Incompatible Kidney Transplantation: In Comparison with ABO-Compatible Kidney Transplantation

PubMed Central

Jeon, Byung Joo; Seong, Youl Keun; Han, Bo Hyun

2010-01-01

Purpose The number of patients waiting for kidney transplantation is incessantly increasing, but the number of cadaveric kidney transplantations or ABO-compatible donors is so insufficient that ABO-incompatible kidney transplantation is being performed as an alternative. There are overseas studies and research showing that the 5-year survival rate and 5-year graft survival rate of ABO-incompatible kidney transplantation are not much different from those of ABO-compatible kidney transplantation. However, domestic research on the subject is rare. Therefore, we report the results of 22 ABO-incompatible kidney transplantation cases performed in our hospital. Materials and Methods This research was from 22 patients in our hospital who underwent ABO-incompatible kidney transplantation from 15 February 2007 to 20 May 2010. Results As yet, there have been no donor graft losses and no deaths after transplantation. The results of the two groups were analyzed by analysis of covariance of the creatinine value of the recipients at 6 months after the operation, corrected for the preoperative value in order to statistically identify whether there were differences in renal function after the operation between ABO-compatible and ABO-incompatible kidney transplantation. The results of the analysis of covariance showed no statistical difference in renal function after the operation between the two groups. Conclusions Even though there were not many cases, our initial results for ABO-incompatible kidney transplantation were positive. Considering the increasing number of patients waiting for kidney transplantation, longer-term domestic research studies of ABO-incompatible kidney transplantation are necessary. PMID:21221208

Reestablishment of radiographic kidney size in Miniature Schnauzer dogs.

PubMed

Sohn, Jungmin; Yun, Sookyung; Lee, Jeosoon; Chang, Dongwoo; Choi, Mincheol; Yoon, Junghee

2017-01-10

Kidney size may be altered in renal diseases, and the detection of kidney size alteration has diagnostic and prognostic values. We hypothesized that radiographic kidney size, the kidney length to the second lumbar vertebra (L2) length ratio, in normal Miniature Schnauzer dogs may be overestimated due to their shorter vertebral length. This study was conducted to evaluate radiographic and ultrasonographic kidney size and L2 length in clinically normal Miniature Schnauzers and other dog breeds to evaluate the effect of vertebral length on radiographic kidney size and to reestablish radiographic kidney size in normal Miniature Schnauzers. Abdominal radiographs and ultrasonograms from 49 Miniature Schnauzers and 54 other breeds without clinical evidence of renal disease and lumbar vertebral abnormality were retrospectively evaluated. Radiographic kidney size, in the Miniature Schnauzer (3.31 ± 0.26) was significantly larger than that in other breeds (2.94 ± 0.27). Relative L2 length, the L2 length to width ratio, in the Miniature Schnauzer (1.11 ± 0.06) was significantly shorter than that in other breeds (1.21 ± 0.09). However, ultrasonographic kidney sizes, kidney length to aorta diameter ratios, were within or very close to normal range both in the Miniature Schnauzer (6.75 ± 0.67) and other breeds (7.16 ± 1.01). Thus, Miniature Schnauzer dogs have breed-specific short vertebrae and consequently a larger radiographic kidney size, which was greater than standard reference in normal adult dogs. Care should be taken when evaluating radiographic kidney size in Miniature Schnauzers to prevent falsely diagnosed renomegaly.

Use of Readily Accessible Inflammatory Markers to Predict Diabetic Kidney Disease.

PubMed

Winter, Lauren; Wong, Lydia A; Jerums, George; Seah, Jas-Mine; Clarke, Michele; Tan, Sih Min; Coughlan, Melinda T; MacIsaac, Richard J; Ekinci, Elif I

2018-01-01

Diabetic kidney disease is a common complication of type 1 and type 2 diabetes and is the primary cause of end-stage renal disease in developed countries. Early detection of diabetic kidney disease will facilitate early intervention aimed at reducing the rate of progression to end-stage renal disease. Diabetic kidney disease has been traditionally classified based on the presence of albuminuria. More recently estimated glomerular filtration rate has also been incorporated into the staging of diabetic kidney disease. While albuminuric diabetic kidney disease is well described, the phenotype of non-albuminuric diabetic kidney disease is now widely accepted. An association between markers of inflammation and diabetic kidney disease has previously been demonstrated. Effector molecules of the innate immune system including C-reactive protein, interleukin-6, and tumor necrosis factor-α are increased in patients with diabetic kidney disease. Furthermore, renal infiltration of neutrophils, macrophages, and lymphocytes are observed in renal biopsies of patients with diabetic kidney disease. Similarly high serum neutrophil and low serum lymphocyte counts have been shown to be associated with diabetic kidney disease. The neutrophil-lymphocyte ratio is considered a robust measure of systemic inflammation and is associated with the presence of inflammatory conditions including the metabolic syndrome and insulin resistance. Cross-sectional studies have demonstrated a link between high levels of the above inflammatory biomarkers and diabetic kidney disease. Further longitudinal studies will be required to determine if these readily available inflammatory biomarkers can accurately predict the presence and prognosis of diabetic kidney disease, above and beyond albuminuria, and estimated glomerular filtration rate.

APOL1 Oligomerization as the Key Mediator of Kidney Disease in African Americans

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-14-1-0333 TITLE: APOL1 Oligomerization as the Key Mediator of Kidney Disease in African Americans PRINCIPAL INVESTIGATOR...SUBTITLE APOL1 Oligomerization as the Key Mediator of Kidney Disease in African Americans 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER...treating, kidney disease, in particular the APOL1- associated form of kidney disease that accounts for the high rate of kidney disease in African Americans

APOL1 Oligomerization as the Key Mediator of Kidney Disease in African Americans

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-14-1-0334 TITLE: APOL1 Oligomerization as the Key Mediator of Kidney Disease in African Americans PRINCIPAL INVESTIGATOR...SUBTITLE APOL1 Oligomerization as the Key Mediator of Kidney Disease in African Americans 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...treating, kidney disease, in particular the APOL1- associated form of kidney disease that accounts for the high rate of kidney disease in African Americans

Studying Kidney Disease Using Tissue and Genome Engineering in Human Pluripotent Stem Cells.

PubMed

Garreta, Elena; González, Federico; Montserrat, Núria

2018-01-01

Kidney morphogenesis and patterning have been extensively studied in animal models such as the mouse and zebrafish. These seminal studies have been key to define the molecular mechanisms underlying this complex multistep process. Based on this knowledge, the last 3 years have witnessed the development of a cohort of protocols allowing efficient differentiation of human pluripotent stem cells (hPSCs) towards defined kidney progenitor populations using two-dimensional (2D) culture systems or through generating organoids. Kidney organoids are three-dimensional (3D) kidney-like tissues, which are able to partially recapitulate kidney structure and function in vitro. The current possibility to combine state-of-the art tissue engineering with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated systems 9 (Cas9)-mediated genome engineering provides an unprecedented opportunity for studying kidney disease with hPSCs. Recently, hPSCs with genetic mutations introduced through CRISPR/Cas9-mediated genome engineering have shown to produce kidney organoids able to recapitulate phenotypes of polycystic kidney disease and glomerulopathies. This mini review provides an overview of the most recent advances in differentiation of hPSCs into kidney lineages, and the latest implementation of the CRISPR/Cas9 technology in the organoid setting, as promising platforms to study human kidney development and disease. © 2017 S. Karger AG, Basel.

Chronic Kidney Disease in Kidney Stone Formers

PubMed Central

Krambeck, Amy E.; Lieske, John C.

2011-01-01

Summary Recent population studies have found symptomatic kidney stone formers to be at increased risk for chronic kidney disease (CKD). Although kidney stones are not commonly identified as the primary cause of ESRD, they still may be important contributing factors. Paradoxically, CKD can be protective against forming kidney stones because of the substantial reduction in urine calcium excretion. Among stone formers, those with rare hereditary diseases (cystinuria, primary hyperoxaluria, Dent disease, and 2,8 dihydroxyadenine stones), recurrent urinary tract infections, struvite stones, hypertension, and diabetes seem to be at highest risk for CKD. The primary mechanism for CKD from kidney stones is usually attributed to an obstructive uropathy or pyelonephritis, but crystal plugs at the ducts of Bellini and parenchymal injury from shockwave lithotripsy may also contribute. The historical shift to less invasive surgical management of kidney stones has likely had a beneficial impact on the risk for CKD. Among potential kidney donors, past symptomatic kidney stones but not radiographic stones found on computed tomography scans were associated with albuminuria. Kidney stones detected by ultrasound screening have also been associated with CKD in the general population. Further studies that better classify CKD, better characterize stone formers, more thoroughly address potential confounding by comorbidities, and have active instead of passive follow-up to avoid detection bias are needed. PMID:21784825

Survival of Kidney Retransplant Compared With First Kidney Transplant: A Report From Southern Iran.

PubMed

Roozbeh, Jamshid; Malekmakan, Leila; Monavarian, Mehri; Daneshian, Arghavan; Karimi, Zeynab

2016-11-18

Kidney retransplant is increasingly performed, but patient survival is controversial. The aim of this study was to evaluate the outcomes of patients with second kidney grafts and compare survival rates of recipients with first and second kidney transplant procedures. This was a retrospective study analyzing records from the Shiraz University of Medical Sciences transplant ward. Survival rates of retrans?lanted patients were compared with a randomly selected group of first kidney recipients. Factors related to retransplant survival were evaluated. Data were analyzed by SPSS version 16.0, and P < .05 was consi?ered as significant. This study included 200 patients with first kidney transplants and 68 patients with kidney retransplants. We found that 1-, 3-, 5-, and 7-year graft survival rates were 91.9%, 87.2% ,86.3%, and 86.3% among retransplanted patients versus 98.3%, 95.4%, 90.2%, and 88.7% among the first transplant group (P = .130). Hospital stay duration after transplant, kidney rejection rate during hospitalization, delayed graft function, and creatinine levels at discharge were significantly associated with survival in retransplanted patients (P < .05). Kidney retransplants can yield desirable outcomes and is the treatment of choice in patients who have lost their graft. Careful screening for risk factors should be consider for obtaining better results in second kidney transplant procedures.

Kidney Cancer

MedlinePlus

... common cancers in the United States. Cancer Home Kidney Cancer Language: English (US) Español (Spanish) Recommend on ... work with the chemical trichloroethylene. What Are the Kidneys? The body has two kidneys, one on each ...

Automated Segmentation of Kidneys from MR Images in Patients with Autosomal Dominant Polycystic Kidney Disease

PubMed Central

Kim, Youngwoo; Ge, Yinghui; Tao, Cheng; Zhu, Jianbing; Chapman, Arlene B.; Torres, Vicente E.; Yu, Alan S.L.; Mrug, Michal; Bennett, William M.; Flessner, Michael F.; Landsittel, Doug P.

2016-01-01

Background and objectives Our study developed a fully automated method for segmentation and volumetric measurements of kidneys from magnetic resonance images in patients with autosomal dominant polycystic kidney disease and assessed the performance of the automated method with the reference manual segmentation method. Design, setting, participants, & measurements Study patients were selected from the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease. At the enrollment of the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease Study in 2000, patients with autosomal dominant polycystic kidney disease were between 15 and 46 years of age with relatively preserved GFRs. Our fully automated segmentation method was on the basis of a spatial prior probability map of the location of kidneys in abdominal magnetic resonance images and regional mapping with total variation regularization and propagated shape constraints that were formulated into a level set framework. T2–weighted magnetic resonance image sets of 120 kidneys were selected from 60 patients with autosomal dominant polycystic kidney disease and divided into the training and test datasets. The performance of the automated method in reference to the manual method was assessed by means of two metrics: Dice similarity coefficient and intraclass correlation coefficient of segmented kidney volume. The training and test sets were swapped for crossvalidation and reanalyzed. Results Successful segmentation of kidneys was performed with the automated method in all test patients. The segmented kidney volumes ranged from 177.2 to 2634 ml (mean, 885.4±569.7 ml). The mean Dice similarity coefficient ±SD between the automated and manual methods was 0.88±0.08. The mean correlation coefficient between the two segmentation methods for the segmented volume measurements was 0.97 (P<0.001 for each crossvalidation set). The results from the crossvalidation sets were highly comparable. Conclusions We have developed a fully automated method for segmentation of kidneys from abdominal magnetic resonance images in patients with autosomal dominant polycystic kidney disease with varying kidney volumes. The performance of the automated method was in good agreement with that of manual method. PMID:26797708

Automated Segmentation of Kidneys from MR Images in Patients with Autosomal Dominant Polycystic Kidney Disease.

PubMed

Kim, Youngwoo; Ge, Yinghui; Tao, Cheng; Zhu, Jianbing; Chapman, Arlene B; Torres, Vicente E; Yu, Alan S L; Mrug, Michal; Bennett, William M; Flessner, Michael F; Landsittel, Doug P; Bae, Kyongtae T

2016-04-07

Our study developed a fully automated method for segmentation and volumetric measurements of kidneys from magnetic resonance images in patients with autosomal dominant polycystic kidney disease and assessed the performance of the automated method with the reference manual segmentation method. Study patients were selected from the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease. At the enrollment of the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease Study in 2000, patients with autosomal dominant polycystic kidney disease were between 15 and 46 years of age with relatively preserved GFRs. Our fully automated segmentation method was on the basis of a spatial prior probability map of the location of kidneys in abdominal magnetic resonance images and regional mapping with total variation regularization and propagated shape constraints that were formulated into a level set framework. T2-weighted magnetic resonance image sets of 120 kidneys were selected from 60 patients with autosomal dominant polycystic kidney disease and divided into the training and test datasets. The performance of the automated method in reference to the manual method was assessed by means of two metrics: Dice similarity coefficient and intraclass correlation coefficient of segmented kidney volume. The training and test sets were swapped for crossvalidation and reanalyzed. Successful segmentation of kidneys was performed with the automated method in all test patients. The segmented kidney volumes ranged from 177.2 to 2634 ml (mean, 885.4±569.7 ml). The mean Dice similarity coefficient ±SD between the automated and manual methods was 0.88±0.08. The mean correlation coefficient between the two segmentation methods for the segmented volume measurements was 0.97 (P<0.001 for each crossvalidation set). The results from the crossvalidation sets were highly comparable. We have developed a fully automated method for segmentation of kidneys from abdominal magnetic resonance images in patients with autosomal dominant polycystic kidney disease with varying kidney volumes. The performance of the automated method was in good agreement with that of manual method. Copyright © 2016 by the American Society of Nephrology.

77 FR 6131 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-07

... Diabetes and Digestive and Kidney Diseases Notice of Closed Meetings Pursuant to section 10(d) of the... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; PAR09-247 Ancillary Studies in... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; George M. O'Brien Kidney Research Core...

78 FR 14312 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-05

... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the... Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; George M. O'Brien Kidney..., Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases...

Neurocognitive Outcomes in Children with Chronic Kidney Disease: Current Findings and Contemporary Endeavors

ERIC Educational Resources Information Center

Gerson, Arlene C.; Butler, Robert; Moxey-Mims, Marva; Wentz, Alicia; Shinnar, Shlomo; Lande, Marc B.; Mendley, Susan R.; Warady, Bradley A.; Furth, Susan L.; Hooper, Stephen R.

2006-01-01

Given the rise in chronic kidney disease (CKD) in both children and adults, CKD has recently been targeted as a public health priority. Childhood onset kidney disease is generally a noncurable and progressive condition that leads to kidney failure by early adulthood. Fortunately, improved identification of kidney problems allows for early…

42 CFR 413.202 - Organ procurement organization (OPO) cost for kidneys sent to foreign countries or transplanted...

Code of Federal Regulations, 2011 CFR

2011-10-01

... kidneys sent to foreign countries or transplanted in patients other than Medicare beneficiaries. 413.202... (OPO) cost for kidneys sent to foreign countries or transplanted in patients other than Medicare beneficiaries. An OPO's total costs for all kidneys is reduced by the costs associated with procuring kidneys...

42 CFR 413.202 - Organ procurement organization (OPO) cost for kidneys sent to foreign countries or transplanted...

Code of Federal Regulations, 2010 CFR

2010-10-01

... kidneys sent to foreign countries or transplanted in patients other than Medicare beneficiaries. 413.202... (OPO) cost for kidneys sent to foreign countries or transplanted in patients other than Medicare beneficiaries. An OPO's total costs for all kidneys is reduced by the costs associated with procuring kidneys...

Robotic assisted kidney transplantation

PubMed Central

Modi, Pranjal; Pal, Bipinchandra; Modi, Jayesh; Kumar, Suresh; Sood, Akshay; Menon, Mani

2014-01-01

Kidney transplantation is the standard of care for patients with end stage renal disease. While open surgery remains the gold standard, minimally invasive surgery has recently been introduced for the recipient undergoing kidney transplantation. We review the evolution of techniques of minimally invasive surgery for kidney transplantation with specific emphasis on technical aspects of robotic assisted kidney transplantation. PMID:25097315

Diabetic Kidney Problems

MedlinePlus

... too high. Over time, this can damage your kidneys. Your kidneys clean your blood. If they are damaged, waste ... in your blood instead of leaving your body. Kidney damage from diabetes is called diabetic nephropathy. It ...

Sexuality and Chronic Kidney Disease

MedlinePlus

... with kidney disease or kidney failure still enjoy sex? It's important to remember that people with kidney ... healthcare professional. What if I lose interest in sex? Your interest in sex may change when you ...

Percutaneous urinary procedures

MedlinePlus

... pass by itself or to be treated by going through the bladder to the kidney. Urine is leaking inside your body. The kidney stone is causing urinary tract infections . The kidney stone is damaging your kidney.

Donation, Not Disease! A Multiple-Hit Hypothesis on Development of Post-Donation Kidney Disease.

PubMed

Cheng, Xingxing S; Glassock, Richard J; Lentine, Krista L; Chertow, Glenn M; Tan, Jane C

2017-01-01

The risks following living kidney donation has been the subject of rigorous investigation in the past several decades. How to utilize the burgeoning new knowledge base to better the risk assessment, education, and health maintenance of donors is unclear. We review the physiologic and epidemiologic evidences on the post-donation state and submit a multiple-hit hypothesis to reconcile the finite elevation in risk of kidney disease after donation with the benign course of most kidney donors. The risk of end-stage kidney disease is higher in kidney donors compared to similarly healthy non-kidney donors. Nonetheless, post-donation kidney disease is uncommon and arises mostly in the setting of other "hits"-either a "first hit" present at birth or a "second hit" acquired later in life. The transplant community's focus should be directed toward (1) personalized risk assessment to inform consent before donation and (2) preventing and treating development of "second hits" following kidney donation.

Kidney Injury Molecule-1 Outperforms Traditional Biomarkers of Kidney Injury in Multi-site Preclinical Biomarker Qualification Studies

PubMed Central

Vaidya, Vishal S.; Ozer, Josef S.; Frank, Dieterle; Collings, Fitz B.; Ramirez, Victoria; Troth, Sean; Muniappa, Nagaraja; Thudium, Douglas; Gerhold, David; Holder, Daniel J.; Bobadilla, Norma A.; Marrer, Estelle; Perentes, Elias; Cordier, André; Vonderscher, Jacky; Maurer, Gérard; Goering, Peter L.; Sistare, Frank D.; Bonventre, Joseph V.

2010-01-01

Kidney toxicity accounts for a significant percentage of morbidity and drug candidate failure. Serum creatinine (SCr) and blood urea nitrogen (BUN) have been used to monitor kidney dysfunction for over a century but these markers are insensitive and non-specific. In multi-site preclinical rat toxicology studies the diagnostic performance of urinary kidney injury molecule-1 (Kim-1) was compared to traditional biomarkers as predictors of kidney tubular histopathologic changes, currently considered the “gold standard” of nephrotoxicity. In multiple models of kidney injury, urinary Kim-1 significantly outperformed SCr and BUN. The area under the receiver operating characteristic curve for Kim-1 was between 0.91 and 0.99 as compared to 0.79 to 0.9 for BUN and 0.73 to 0.85 for SCr. Thus urinary Kim-1 is the first injury biomarker of kidney toxicity qualified by the FDA and EMEA and is expected to significantly improve kidney safety monitoring. PMID:20458318

Model systems for the study of kidney development: use of the pronephros in the analysis of organ induction and patterning.

PubMed

Vize, P D; Seufert, D W; Carroll, T J; Wallingford, J B

1997-08-15

Most vertebrate organs, once formed, continue to perform the function for which they were generated until the death of the organism. The kidney is a notable exception to this rule. Vertebrates, even those that do not undergo metamorphosis, utilize a progression of more complex kidneys as they grow and develop. This is presumably due to the changing conditions to which the organism must respond to retain what Homer Smith referred to as our physiological freedom. To quote, "Recognizing that we have the kind of blood we have because we have the kind of kidneys we have, we must acknowledge that our kidneys constitute the major foundation of our physiological freedom. Only because they work the way they do has it become possible for us to have bones, muscles, glands, and brains. Superficially, it might be said that the function of the kidneys is to make urine; but in a more considered view one can say that the kidneys make the stuff of philosophy itself" ("From Fish to Philosopher," Little, Brown and Co., Boston, 1953). Different kidneys are used to make the stuff of philosophy at different stages of development depending on the age and needs of the organism, rather than the usual approach of simply making embryonic organs larger as the animal grows. Although evolution has provided the higher vertebrates with complex adult kidneys, they continue to utilize simple kidneys in embryogenesis. In lower vertebrates with simple adult kidneys, even more simple versions are used during early developmental stages. In this review the anatomy, development, and gene expression patterns of the embryonic kidney, the pronephros, will be described and compared to the more complex kidney forms. Despite some differences in anatomy, similar developmental pathways seem to be responsible for the induction and the response to induction in both evanescent and permanent kidney forms. Gene expression patterns can, therefore, be added to the morphological and functional data indicating that all forms of the kidney are closely related structures. Given the similarities between the development of simple and complex kidneys, the embryonic kidneys may be an ideal model system in which to investigate the genesis of multicomponent organ systems.

Kidney Failure and ESRD in the Atherosclerosis Risk in Communities (ARIC) Study: Comparing Ascertainment of Treated and Untreated Kidney Failure in a Cohort Study.

PubMed

Rebholz, Casey M; Coresh, Josef; Ballew, Shoshana H; McMahon, Blaithin; Whelton, Seamus P; Selvin, Elizabeth; Grams, Morgan E

2015-08-01

Linkage to the US Renal Data System (USRDS) registry commonly is used to identify end-stage renal disease (ESRD) cases, or kidney failure treated with dialysis or transplantation, but it underestimates the total burden of kidney failure. This study validates a kidney failure definition that includes both kidney failure treated and not treated by dialysis or transplantation. It compares kidney failure risk factors and outcomes using this broader definition with USRDS-identified ESRD risk factors and outcomes. Diagnostic test study with stratified random sampling of hospitalizations for chart review. Atherosclerosis Risk in Communities Study (n=11,530; chart review, n=546). USRDS-identified ESRD; treated or untreated kidney failure defined by USRDS-identified ESRD or International Classification of Diseases, Ninth or Tenth Revision, Clinical Modification (ICD-9-CM/ICD-10-CM) code for hospitalization or death. For ESRD, determination of permanent dialysis therapy or transplantation; for kidney failure, determination of permanent dialysis therapy, transplantation, or estimated glomerular filtration rate < 15 mL/min/1.73 m(2). During 13 years' median follow-up, 508 kidney failure cases were identified, including 173 (34.1%) from the USRDS registry. ESRD and kidney failure incidence were 1.23 and 3.66 cases per 1,000 person-years in the overall population and 1.35 and 6.59 cases per 1,000 person-years among participants older than 70 years, respectively. Other risk-factor associations were similar between ESRD and kidney failure, except diabetes and albuminuria, which were stronger for ESRD. Survivals at 1 and 5 years were 74.0% and 24.0% for ESRD and 59.8% and 31.6% for kidney failure, respectively. Sensitivity and specificity were 88.0% and 97.3% comparing the kidney failure ICD-9-CM/ICD-10-CM code algorithm to chart review; for USRDS-identified ESRD, sensitivity and specificity were 94.9% and 100.0%. Some medical charts were incomplete. A kidney failure definition including treated and untreated disease identifies more cases than linkage to the USRDS registry alone, particularly among older adults. Future studies might consider reporting both USRDS-identified ESRD and a more inclusive kidney failure definition. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Kidney Disease: Early Detection and Treatment

MedlinePlus

... Bar Home Current Issue Past Issues Special Section Kidney Disease: Early Detection and Treatment Past Issues / Winter ... called a "urine albumin-to-creatinine ratio." Treating Kidney Disease Kidney disease is usually a progressive disease, ...

9 CFR 318.5 - Requirements concerning procedures.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., and horn butts removed, and the heads then thoroughly cleaned. (e) Kidneys for use in the preparation... detached kidneys, including beef kidneys with detached kidney fat, shall be inspected before being used in...

9 CFR 318.5 - Requirements concerning procedures.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., and horn butts removed, and the heads then thoroughly cleaned. (e) Kidneys for use in the preparation... detached kidneys, including beef kidneys with detached kidney fat, shall be inspected before being used in...

Vitamins and Minerals in Kidney Disease

MedlinePlus

... Know Hyponatremia Selecting the right shoes for your workout Staying Fit With Kidney Disease The National Kidney ... 2017 National Kidney Foundation, Inc., 30 East 33rd Street, New York, NY 10016, 1-800-622-9010. ...

Mineral & Bone Disorder in Chronic Kidney Disease

MedlinePlus

... Kidney Disease Anemia in Chronic Kidney Disease Financial Help for Treatment of Kidney Failure Learning as much as you can about your treatment will help make you an important member of your health ...

Consensus Conference on Best Practices in Live Kidney Donation: Recommendations to Optimize Education, Access, and Care

PubMed Central

Rudow, Dianne LaPointe; Hays, Rebecca; Baliga, Prabhakar; Cohen, David J.; Cooper, Matthew; Danovitch, Gabriel M.; Dew, Mary Amanda; Gordon, Elisa J.; Mandelbrot, Didier A.; McGuire, Suzanne; Milton, Jennifer; Moore, Deonna R.; Morgieivich, Marie; Schold, Jesse D.; Segev, Dorry L.; Serur, David; Steiner, Robert W.; Tan, Jane C.; Waterman, Amy D.; Zavala, Edward Y.; Rodrigue, James R.

2015-01-01

Live donor kidney transplantation is the best treatment option for most patients with late-stage chronic kidney disease; however, the rate of living kidney donation has declined in the United States. A consensus conference was held June 5–6, 2014 to identify best practices and knowledge gaps pertaining to live donor kidney transplantation and living kidney donation. Transplant professionals, patients, and other key stakeholders discussed processes for educating transplant candidates and potential living donors about living kidney donation; efficiencies in the living donor evaluation process; disparities in living donation; and financial and systemic barriers to living donation. We summarize the consensus recommendations for best practices in these educational and clinical domains, future research priorities, and possible public policy initiatives to remove barriers to living kidney donation. PMID:25648884

Safe and ethical living kidney donation in Qatar: A national health system's approach.

PubMed

Asim, Muhammad; Al-Maslamani, Yousuf; Al-Malki, Hassan

2017-01-01

The increasing incidence of end-stage kidney disease in Qatar has led to growing demand for donor kidneys. The deceased donor kidney program has yet to achieve its full potential; hence, living kidney donation has been widely adopted as an appropriate alternative. The reliance on living kidney donors however, raises a number of social, ethical, and legal concerns surrounding informed consent, voluntarism, psychosocial evaluation, perioperative care, and long-term follow-up of living kidney donors. Many of these concerns become heightened in a multicultural, multilingual society within a Gulf country such as Qatar. This article provides an insight into the challenges that living kidney donation poses in a multiethnic society with significant socioeconomic divides. It also discusses the remedial measures that the Qatari government, healthcare authorities, and transplant community have adopted to address these issues.

Safe and ethical living kidney donation in Qatar: A national health system's approach

PubMed Central

Asim, Muhammad; Al-Maslamani, Yousuf; Al-Malki, Hassan

2017-01-01

The increasing incidence of end-stage kidney disease in Qatar has led to growing demand for donor kidneys. The deceased donor kidney program has yet to achieve its full potential; hence, living kidney donation has been widely adopted as an appropriate alternative. The reliance on living kidney donors however, raises a number of social, ethical, and legal concerns surrounding informed consent, voluntarism, psychosocial evaluation, perioperative care, and long-term follow-up of living kidney donors. Many of these concerns become heightened in a multicultural, multilingual society within a Gulf country such as Qatar. This article provides an insight into the challenges that living kidney donation poses in a multiethnic society with significant socioeconomic divides. It also discusses the remedial measures that the Qatari government, healthcare authorities, and transplant community have adopted to address these issues. PMID:28795019

Does size matter? Kidney transplant donor size determines kidney function among living donors

PubMed Central

Narasimhamurthy, Meenakshi; Smith, Lachlan M.; Machan, Jason T.; Reinert, Steven E.; Gohh, Reginald Y.; Dworkin, Lance D.; Merhi, Basma; Patel, Nikunjkumar; Beland, Michael D.

2017-01-01

Background Kidney donor outcomes are gaining attention, particularly as donor eligibility criteria continue to expand. Kidney size, a useful predictor of recipient kidney function, also likely correlates with donor outcomes. Although donor evaluation includes donor kidney size measurements, the association between kidney size and outcomes are poorly defined. Methods We examined the relationship between kidney size (body surface area-adjusted total volume, cortical volume and length) and renal outcomes (post-operative recovery and longer-term kidney function) among 85 kidney donors using general linear models and time-to-chronic kidney disease data. Results Donors with the largest adjusted cortical volume were more likely to achieve an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 over a median 24-month follow-up than those with smaller cortical volumes (P <0.001), had a shorter duration of renal recovery (1.3–2.2 versus 32.5 days) and started with a higher eGFR at pre-donation (107–110 versus 91 mL/min/1.73 m2) and immediately post-nephrectomy (∼63 versus 50–51 mL/min/1.73 m2). Similar findings were seen with adjusted total volume and length. Conclusions Larger kidney donors were more likely to achieve an eGFR ≥60 mL/min/1.73 m2 with renal recovery over a shorter duration due to higher pre-donation and initial post-nephrectomy eGFRs. PMID:28638611

Women and kidney disease: reflections on World Kidney Day 2018.

PubMed

Piccoli, Giorgina B; Alrukhaimi, Mona; Liu, Zhi-Hong; Zakharova, Elena; Levin, Adeera

2018-02-01

Chronic kidney disease affects ∼10% of the world's adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women's health, and specifically their kidney health, to the community and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women, so that we may apply those learnings more broadly. Girls and women, who make up ∼50% of the world's population, are important contributors to society as a whole and to their families. Gender differences continue to exist around the world in access to education, medical care and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, and also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for child bearing, and for the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we do and do not know about women, kidney health and kidney disease, and what we might learn in the future to improve outcomes worldwide.

Effects of Platelet-Rich Plasma (PRP) on a Model of Renal Ischemia-Reperfusion in Rats

PubMed Central

Martín-Solé, Oriol; Rodó, Joan; García-Aparicio, Lluís; Blanch, Josep; Cusí, Victoria; Albert, Asteria

2016-01-01

Renal ischemia-reperfusion injury is a major cause of acute renal failure, causing renal cell death, a permanent decrease of renal blood flow, organ dysfunction and chronic kidney disease. Platelet-rich plasma (PRP) is an autologous product rich in growth factors, and therefore able to promote tissue regeneration and angiogenesis. This product has proven its efficacy in multiple studies, but has not yet been tested on kidney tissue. The aim of this work is to evaluate whether the application of PRP to rat kidneys undergoing ischemia-reperfusion reduces mid-term kidney damage. A total of 30 monorrenal Sprague-Dawley male rats underwent renal ischemia-reperfusion for 45 minutes. During ischemia, PRP (PRP Group, n = 15) or saline solution (SALINE Group, n = 15) was administered by subcapsular renal injection. Control kidneys were the contralateral organs removed immediately before the start of ischemia in the remaining kidneys. Survival, body weight, renal blood flow on Doppler ultrasound, kidney weight, kidney volume, blood biochemistry and histopathology were determined for all subjects and kidneys, as applicable. Correlations between these variables were searched for. The PRP Group showed significantly worse kidney blood flow (p = 0.045) and more histopathological damage (p<0.0001). Correlations were found between body weight, kidney volume, kidney weight, renal blood flow, histology, and serum levels of creatinine and urea. Our study provides the first evidence that treatment with PRP results in the deterioration of the kidney’s response to ischemia-reperfusion injury. PMID:27551718

Averting the Legacy of Kidney Disease - Focus on Childhood.

PubMed

Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

2016-01-01

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. © 2016 S. Karger AG, Basel.

Averting the Legacy of Kidney Disease - Focus on Childhood.

PubMed

Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

2016-01-01

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. © 2016 S. Karger AG, Basel.

Averting the Legacy of Kidney Disease--Focus on Childhood.

PubMed

Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

2016-01-01

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. © 2016 S. Karger AG, Basel.

Revisiting double kidney transplantation: two kidneys provide better graft survival than one.

PubMed

Cruzado, J M; Fernandez, L; Riera, L; Bestard, O; Carrera, M; Torras, J; Gil Vernet, S; Melilli, E; Ngango, L; Grinyó, J M

2011-01-01

Double kidney transplantation is an accepted strategy to increase the donor pool. Regarding older donor kidneys, protocols for deciding to perform a dual or a single transplantation are mainly based on preimplantation biopsies. The aim of our study was to evaluate the long-term graft and patient survivals of our "Dual Kidney Transplant program." Patients who lost one of their grafts peritransplantation were used as controls. A total of 203 patients underwent kidney transplantation from December 1996 to January 2008 in our "old for old" renal transplantation program. We excluded 21 patients because of a nonfunctioning kidney, hyperacute rejection, or patient death with a functioning graft within the first month. Seventy-nine among 182 kidney transplantation the "old for old" program were dual kidney transplantation (DKT). Fifteen of 79 patients lost one of their kidney grafts (the uninephrectomized (UNX) UNX group). At 1 year, renal function was lower and proteinuria greater among the UNX than the DKT group. Patient survival was similar in both groups. However, death-censored graft survival was lower in UNX than DKT patients. The 5-year graft survival rate was 70% in UNX versus 93% in DKT cohorts (P = .04). In conclusion, taking into account the kidney shortage, our results may question whether the excellent transplant outcomes with DKT counter balance the reduced donor pool obviating acceptable transplant outcomes for more patients with single kidney transplantation. Copyright © 2011 Elsevier Inc. All rights reserved.

Ift25 is not a cystic kidney disease gene but is required for early steps of kidney development.

PubMed

Desai, Paurav B; San Agustin, Jovenal T; Stuck, Michael W; Jonassen, Julie A; Bates, Carlton M; Pazour, Gregory J

2018-06-01

Eukaryotic cilia are assembled by intraflagellar transport (IFT) where large protein complexes called IFT particles move ciliary components from the cell body to the cilium. Defects in most IFT particle proteins disrupt ciliary assembly and cause mid gestational lethality in the mouse. IFT25 and IFT27 are unusual components of IFT-B in that they are not required for ciliary assembly and mutant mice survive to term. The mutants die shortly after birth with numerous organ defects including duplex kidneys. Completely duplex kidneys result from defects in ureteric bud formation at the earliest steps of metanephric kidney development. Ureteric bud initiation is a highly regulated process involving reciprocal signaling between the ureteric epithelium and the overlying metanephric mesenchyme with regulation by the peri-Wolffian duct stroma. The finding of duplex kidney in Ift25 and Ift27 mutants suggests functions for these genes in regulation of ureteric bud initiation. Typically the deletion of IFT genes in the kidney causes rapid cyst growth in the early postnatal period. In contrast, the loss of Ift25 results in smaller kidneys, which show only mild tubule dilations that become apparent in adulthood. The smaller kidneys appear to result from reduced branching in the developing metanephric kidney. This work indicates that IFT25 and IFT27 are important players in the early development of the kidney and suggest that duplex kidney is part of the ciliopathy spectrum. Copyright © 2018 Elsevier B.V. All rights reserved.

Women and Kidney Disease: Reflections on World Kidney Day 2018.

PubMed

Piccoli, Giorgina B; Alrukhaimi, Mona; Liu, Zhi-Hong; Zakharova, Elena; Levin, Adeera

2018-03-01

: Chronic kidney disease aff ects approximately 10% of the world's adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus off ering an opportunity to refl ect on the importance of women's health and specifically their kidney health, on the community, and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world's population, are important contributors to society and their families. Sex diff erences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, off ering an opportunity for diagnosis of kidney disease, but also a state in which acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for child bearing, and on the fetus. Women have diff erent complications on dialysis than men and are more likely to be donors than recipients of kidney transplants.In this editorial, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.

Diagnosis of hyperthyroidism in cats with mild chronic kidney disease.

PubMed

Wakeling, J; Moore, K; Elliott, J; Syme, H

2008-06-01

In cats with concurrent hyperthyroidism and non-thyroidal illnesses such as chronic kidney disease, total thyroxine concentrations are often within the laboratory reference range (19 to 55 nmol/l). The objective of the study was to determine total thyroxine, free thyroxine and/or thyroid-stimulating hormone concentrations in cats with mild chronic kidney disease. Total thyroxine, free thyroxine and thyroid-stimulating hormone were measured in three groups. The hyperthyroidism-chronic kidney disease group (n=16) had chronic kidney disease and clinical signs compatible with hyperthyroidism but a plasma total thyroxine concentration within the reference range. These cats were subsequently confirmed to be hyperthyroid at a later date. The chronic kidney disease-only group (n=20) had chronic kidney disease but no signs of hyperthyroidism. The normal group (n=20) comprised clinically healthy senior (>8 years) cats. In 4 of 20 euthyroid chronic kidney disease cats, free thyroxine concentrations were borderline or high (> or =40 pmol/l). In the hyperthyroidism-chronic kidney disease group, free thyroxine was high in 15 of 16 cats, while thyroid-stimulating hormone was low in 16 of 16 cats. Most hyperthyroidism-chronic kidney disease cats (14 of 16) had total thyroxine greater than 30 nmol/l, whereas all the chronic kidney disease-only cats had total thyroxine less than 30 nmol/l. The combined measurement of free thyroxine with total thyroxine or thyroid-stimulating hormone may be of merit in the diagnosis of hyperthyroidism in cats with chronic kidney disease.

Risk of kidney stones with surgical intervention in living kidney donors.

PubMed

Thomas, S M; Lam, N N; Welk, B K; Nguan, C; Huang, A; Nash, D M; Prasad, G V R; Knoll, G A; Koval, J J; Lentine, K L; Kim, S J; Lok, C E; Garg, A X

2013-11-01

A kidney stone in a person with a solitary kidney requires urgent attention, which may result in surgical and/or hospital attention. We conducted a matched retrospective cohort study to determine if living kidney donors compared to healthy nondonors have a higher risk of: (i) kidney stones with surgical intervention, and (ii) hospital encounters for kidney stones. We reviewed all predonation charts for living kidney donations from 1992 to 2009 at five major transplant centers in Ontario, Canada, and linked this information to healthcare databases. We selected nondonors from the healthiest segment of the general population and matched 10 nondonors to every donor. Of the 2019 donors and 20 190 nondonors, none had evidence of kidney stones prior to cohort entry. Median follow-up time was 8.4 years (maximum 19.7 years; loss to follow-up <7%). There was no difference in the rate of kidney stones with surgical intervention in donors compared to nondonors (8.3 vs. 9.7 events/10 000 person-years; rate ratio 0.85; 95% confidence interval [CI] 0.47-1.53). Similarly there was no difference in the rate of hospital encounters for kidney stones (12.1 vs. 16.1 events/10 000 person-years; rate ratio 0.75; 95% CI 0.45-1.24). These interim results are reassuring for the safety of living kidney donation. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Anatomy guided automated SPECT renal seed point estimation

NASA Astrophysics Data System (ADS)

Dwivedi, Shekhar; Kumar, Sailendra

2010-04-01

Quantification of SPECT(Single Photon Emission Computed Tomography) images can be more accurate if correct segmentation of region of interest (ROI) is achieved. Segmenting ROI from SPECT images is challenging due to poor image resolution. SPECT is utilized to study the kidney function, though the challenge involved is to accurately locate the kidneys and bladder for analysis. This paper presents an automated method for generating seed point location of both kidneys using anatomical location of kidneys and bladder. The motivation for this work is based on the premise that the anatomical location of the bladder relative to the kidneys will not differ much. A model is generated based on manual segmentation of the bladder and both the kidneys on 10 patient datasets (including sum and max images). Centroid is estimated for manually segmented bladder and kidneys. Relatively easier bladder segmentation is followed by feeding bladder centroid coordinates into the model to generate seed point for kidneys. Percentage error observed in centroid coordinates of organs from ground truth to estimated values from our approach are acceptable. Percentage error of approximately 1%, 6% and 2% is observed in X coordinates and approximately 2%, 5% and 8% is observed in Y coordinates of bladder, left kidney and right kidney respectively. Using a regression model and the location of the bladder, the ROI generation for kidneys is facilitated. The model based seed point estimation will enhance the robustness of kidney ROI estimation for noisy cases.

Kidney regeneration and stem cells.

PubMed

Takaori, Koji; Yanagita, Motoko

2014-01-01

The kidney has the capacity to recover from ischemic and toxic insults. Although there has been debate about the origin of cells that replace injured epithelial cells, it is now widely recognized that intrinsic surviving tubular cells are responsible for the repair. On the other hand, the cells, which have stem cell-like characteristics, have been isolated in the kidney using various methods, but it remains unknown if these stem cells actually exist in the adult kidney and if they are involved in kidney regeneration. This review will focus on the pathophysiology of kidney regeneration and the contribution of renal stem cells. We also discuss possible therapeutic applications to kidney disease. Copyright © 2013 Wiley Periodicals, Inc.

40 CFR 180.518 - Pyrimethanil; tolerances for residues.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (pre-harvest and post-harvest) 14 Fruit, stone, group 12 10 Grape 5.0 Grape, raisin 8.0 Lemon... Cattle, kidney 2.5 Cattle, meat 0.01 Cattle, meat byproducts, except kidney 0.01 Goat, fat 0.01 Goat, kidney 2.5 Goat, meat 0.01 Goat, meat byproducts, except kidney 0.01 Horse, fat 0.01 Horse, kidney 2.5...

[The kidney transplantation from the ABO-incompatible donors].

PubMed

Goriaĭnov, V A; Kaabak, M M; Babenko, N N; Shishlo, L A; Morozova, M M; Ragimov, A A; Dashkova, N G; Salimov, É L

2012-01-01

The experience of 28 allotransplantations of ABO-incompatible kidneys was compared with the treatment results of 38 ABO-compatible renal transplantations. The transplanted kidney function, morphological changes of the transplanted kidney and the comparative analysis of actuary survival in both groups showed no significant difference. The results of the study prove the validity of the kidney transplantation from the ABO-incompatible donors.

Basics of kidney biopsy: A nephrologist's perspective

PubMed Central

Agarwal, S. K.; Sethi, S.; Dinda, A. K.

2013-01-01

The introduction of the kidney biopsy is one of the major events in the history of nephrology. Primary indications of kidney biopsy are glomerular hematuria/proteinuria with or without renal dysfunction and unexplained renal failure. Kidney biopsy is usually performed in prone position but in certain situations, supine and lateral positions may be required. Biopsy needles have changed with times from Vim–Silverman needle to Tru-cut needle to spring-loaded automatic gun. The procedure has also changed from blind bedside kidney biopsy to ultrasound marking to real-time ultrasound guidance to rarely computerized tomography guidance and laparoscopic and open biopsy. In very specific situations, transjugular kidney biopsy may be required. Most of the centers do kidney biopsy on short 1-day admission, whereas some take it as an outdoor procedure. For critical interpretation of kidney biopsy, adequate sample and clinical information are mandatory. Tissue needs to be stained with multiple stains for delineation of various components of kidney tissue. Many consider that electron microscopy (EM) is a must for all kidney biopsies, but facilities for EM are limited even in big centers. Sophisticated tests such as immunohistochemistry and in-situ hybridization are useful adjuncts for definitive diagnosis in certain situations. PMID:23960337

Postoperative acute kidney injury following intraoperative blood product transfusions during cardiac surgery.

PubMed

Kindzelski, Bogdan A; Corcoran, Philip; Siegenthaler, Michael P; Horvath, Keith A

2018-01-01

This study explored the nature of the association between intraoperative usage of red blood cell, fresh frozen plasma, cryoprecipitate or platelet transfusions and acute kidney injury. A total of 1175 patients who underwent cardiac surgery between 2008 and 2013 were retrospectively analyzed. We assessed the association between: (1) preoperative patient characteristics and acute kidney injury, (2) intraoperative blood product usage and acute kidney injury, (3) acute kidney injury and 30-day mortality or re-hospitalization. In our cohort of 1175 patients, 288 patients (24.5%) developed acute kidney injury. This included 162 (13.8%), 69 (5.9%) and 57 (4.9%) developing stage 1, stage 2 or stage 3 acute kidney injury, respectively. Increased red blood cell, fresh frozen plasma or platelet transfusions increased the odds of developing acute kidney injury. Specifically, every unit of red blood cells, fresh frozen plasma or platelets transfused was associated with an increase in the covariate-adjusted odds ratio of developing ⩾ stage 2 kidney injury of 1.18, 1.19 and 1.04, respectively. Intraoperative blood product transfusions were independently associated with an increased odds of developing acute kidney injury following cardiac surgery. Further randomized studies are needed to better define intraoperative transfusion criteria.

Successful outcome of transplant of kidneys recovered from a brain-dead liver transplant recipient: case report.

PubMed

Domagała, Piotr; Kwiatkowski, Artur; Drozdowski, Jakub; Ostrowski, Krzysztof; Wszola, Michal; Diuwe, Piotr; Durlik, Magdalena; Paczek, Leszek; Chmura, Andrzej

2012-12-01

Few reports describing the use of organs donated by transplant recipients have been published. In this case report, kidneys procured from a brain-dead liver recipient were transplanted successfully. A 21-year-old man was referred for liver transplant after an overdose of acetaminophen. The patient's kidney function was initially normal, with proper urine production and normal kidney laboratory parameters. On the third day after admission, the patient's kidney laboratory parameters became elevated and hepatic encephalopathy requiring mechanical ventilation developed. An orthotopic liver transplant was performed the next day. The patient did not recover consciousness, and brain death was diagnosed on the third day after the liver transplant surgery. The maximum serum concentration of creatinine was 5.8 mg/dL (513 μmol/L) before kidney recovery, and urine production was normal. The kidneys were recovered with organ-perfusion support and were preserved by using machine perfusion. The kidneys were transplanted into 2 male recipients. Twelve months after transplant, the recipients remained in good health with satisfactory kidney function. This case demonstrates that transplanting kidneys recovered from liver transplant recipients is possible and beneficial, thus expanding the pool of potential donors.

Whole kidney engineering for clinical translation.

PubMed

Kim, Ick-Hee; Ko, In Kap; Atala, Anthony; Yoo, James J

2015-04-01

Renal transplantation is currently the only definitive treatment for end-stage renal disease; however, this treatment is severely limited by the shortage of implantable kidneys. To address this shortcoming, development of an engineered, transplantable kidney has been proposed. Although current advances in engineering kidneys based on decellularization and recellularization techniques have offered great promises for the generation of functional kidney constructs, most studies have been conducted using rodent kidney constructs and short-term in-vivo evaluation. Toward clinical translations of this technique, several limitations need to be addressed. Human-sized renal scaffolds are desirable for clinical application, and the fabrication is currently feasible using native porcine and discarded human kidneys. Current progress in stem cell biology and cell culture methods have demonstrated feasibility of the use of embryonic stem cells, induced pluripotent stem cells, and primary renal cells as clinically relevant cell sources for the recellularization of renal scaffolds. Finally, approaches to long-term implantation of engineered kidneys are under investigation using antithrombogenic strategies such as functional reendothelialization of acellular kidney matrices. In the field of bioengineering, whole kidneys have taken a number of important initial steps toward clinical translations, but many challenges must be addressed to achieve a successful treatment for the patient with end-stage renal disease.

Endoplasmic reticulum stress in kidney function and disease.

PubMed

Taniguchi, Mai; Yoshida, Hiderou

2015-07-01

Recently, a number of papers have reported that endoplasmic reticulum (ER) stress is involved in the onset of various kidney diseases, but the pathological mechanisms responsible have not been clarified. In this review, we summarize recent findings on this issue and try to clarify the pathology of ER stress-induced kidney diseases. ER stress is evoked in various kidney diseases, including diabetic nephropathy, renal fibrosis, inflammation or osmolar contrast-induced renal injury, ischemia-reperfusion, genetic mutations of renal proteins, proteinuria and cyclosporine A treatment. In some cases, chemical chaperones, such as 4-phenylbutyrate and taurodeoxycholic acid, relieve the symptoms, indicating that ER stress-induced apoptosis of renal cells is one of the major causes of certain kidney diseases. Actually, the ER stress response provides protection against some kidney diseases, although the PERK-ATF4-CHOP pathway of the ER stress response is proapoptotic in some kidney diseases. The disposal of unfolded proteins by autophagy is also protective for some ER stress-induced kidney diseases. Because ER stress is a major cause of some kidney diseases, the ER stress response and autophagy, which deal with unfolded proteins that accumulate in the ER, are promising therapeutic targets in acute and chronic kidney diseases.

A Cost‐Benefit Analysis of Government Compensation of Kidney Donors

PubMed Central

McCormick, F.; Ojo, A.; Roberts, J. P.

2016-01-01

Abstract From 5000 to 10 000 kidney patients die prematurely in the United States each year, and about 100 000 more suffer the debilitating effects of dialysis, because of a shortage of transplant kidneys. To reduce this shortage, many advocate having the government compensate kidney donors. This paper presents a comprehensive cost‐benefit analysis of such a change. It considers not only the substantial savings to society because kidney recipients would no longer need expensive dialysis treatments—$1.45 million per kidney recipient—but also estimates the monetary value of the longer and healthier lives that kidney recipients enjoy—about $1.3 million per recipient. These numbers dwarf the proposed $45 000‐per‐kidney compensation that might be needed to end the kidney shortage and eliminate the kidney transplant waiting list. From the viewpoint of society, the net benefit from saving thousands of lives each year and reducing the suffering of 100 000 more receiving dialysis would be about $46 billion per year, with the benefits exceeding the costs by a factor of 3. In addition, it would save taxpayers about $12 billion each year. PMID:26474298

Pre-Treatment with Curcumin Ameliorates Cisplatin-Induced Kidney Damage by Suppressing Kidney Inflammation and Apoptosis in Rats.

PubMed

Soetikno, Vivian; Sari, Shinta Dewi Permata; Ul Maknun, Lulu; Sumbung, Nielda Kezia; Rahmi, Deliana Nur Ihsani; Pandhita, Bashar Adi Wahyu; Louisa, Melva; Estuningtyas, Ari

2018-06-26

In addition to oxidative stress, inflammation and apoptosis have an important role in the pathogenesis of cisplatin-induced kidney damage. This study aimed to investigate the molecular mechanisms of protective effects of curcumin against cisplatin-induced kidney inflammation and apoptosis in rats. Eighteen rats were equally divided into three groups; normal (0.5% CMC-Na), cisplatin (CDPP) (7 mg/kg i.p.), and cisplatin+curcumin (CMN100) groups. Curcumin was given at a dose of 100 mg/kg orally for nine days, starts one week before giving a single dose of cisplatin. Kidney and plasma were taken for analysis. Cisplatin challenged rats demonstrated kidney injury as shown by reduced creatinine clearance, increased of plasma BUN, plasma creatinine, and kidney MDA, decreased of kidney GSH levels, and kidney histopathology alterations. Also, cisplatin increased ERK1/2 phosphorylation and NF-κB expression, which subsequently increased mRNA expression of TNF-α, IL-6, KIM-1, NGAL, and Bax/Bcl-2 ratio as well as decreased mRNA expression of IL-10 in kidney tissues. Pre-treatment with curcumin significantly ameliorated inflammation and apoptosis induced by cisplatin. In addition, curcumin downregulated Ctr1 and OCT2 drug transporters as compared to cisplatin group. Histopathological examination furthers confirmed the kidney damage protection effect of curcumin. These data indicate that curcumin has nephroprotective properties against cisplatin-induced kidney damage in rats and this effect is associated with its anti-inflammatory and anti-apoptosis profiles, in addition to its antioxidant. Hence, curcumin may be useful for preventing kidney damage against cisplatin administration. © Georg Thieme Verlag KG Stuttgart · New York.

Utility of applying quality assessment tools for kidneys with KDPI ≥80

PubMed Central

Doshi, Mona D.; Reese, Peter P.; Hall, Isaac E.; Schröppel, Bernd; Ficek, Joseph; Formica, Richard N.; Weng, Francis L.; Hazs, Rick D.; Philbrook, Heather Thiessen; Parikh, Chirag

2016-01-01

Background Kidneys with “high” kidney donor profile index (KDPI) are often biopsied and pumped, yet frequently discarded. Methods In this multicenter study, we describe the characteristics and outcomes of kidneys with KDPI ≥80 that were procured from 338 deceased donors. We excluded donors with anatomical kidney abnormalities. Results Donors were categorized by the number of kidneys discarded: 1) none (n=154, 46%), 2) 1 discarded and 1 transplanted (n=48, 14%), 3) both discarded (n=136, 40%). Donors in group 3 were older, more often white, and had higher terminal creatinine and KDPI than group 1 (all p<0.05). Biopsy was performed in 92% of all kidneys, and 47% were pumped. Discard was associated with biopsy findings and 1st hour renal resistance. Kidney injury biomarker levels (NGAL, IL-18, and KIM-1 measured from donor urine at procurement and from perfusate soon after pump perfusion) were not different between groups. There was no significant difference in 1-year estimated glomerular filtration rate (eGFR) or graft failure between groups 1 and 2 (41.5±18 vs. 41.4±22 mL/min/1.73m2; p=0.97 and 9% vs. 10%; p=0.76). Conclusions Kidneys with KDPI ≥80 comprise the most resource consuming fraction of our donor kidney pool and have the highest rates of discard. Our data suggest that some discarded kidneys with KDPI ≥80 are viable; however, current tools and urine- and perfusate-biomarkers to identify these viable kidneys are not satisfactory. We need better methods to assess viability of kidneys with high KDPI. PMID:27490414

Incidence and characteristics of kidney stones in patients with horseshoe kidney: A systematic review and meta-analysis

PubMed Central

Pawar, Aditya S.; Thongprayoon, Charat; Cheungpasitporn, Wisit; Sakhuja, Ankit; Mao, Michael A.; Erickson, Stephen B.

2018-01-01

Introduction: The horseshoe kidney (HSK) is the most common type of renal fusion anomaly. The incidence and characteristics of kidney stones in patients with HSK are not well studied. The aim of this meta-analysis was to evaluate the incidence and types of kidney stones in patients with HSK. Methods: A systematic literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from the databases' inception through November 2016. Studies assessing the incidence and types of kidney stones in patients with HSK were included. We applied a random-effects model to estimate the incidence of kidney stones. The study protocol was registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42016052037). Results: A total of 14 observational studies with 943 patients (522 adults and 421 pediatric) with HSK were enrolled. The estimated pooled incidence of kidney stones was 36% (95% confidence interval [CI], 15%–59%) in adults with the HSK. Kidney stones were less common in pediatric patients with HSK with an estimated pooled incidence of 3% (95% CI, 2%–5%). The mean age of adult stone formers with HSK was 44.9 ± 6.2 years, and 75% were males. Within reported studies, 89.2% of kidney stones were calcium-based stones (64.2% calcium oxalate [CaOx], 18.8% calcium phosphate [CaP], and 6.2% mixed CaOx/CaP), followed by struvite stones (4.2%), uric acid stones (3.8%), and others (2.8%). Conclusions: Kidney stones are very common in adult patients with HSK with an estimated incidence of 36%. Calcium-based stones are the most prevalent kidney stones in adults with HSKs. These findings may impact the prevention and clinical management of kidney stones in patients with HSK. PMID:29416282

Donor-specific hypo-responsiveness occurs in simultaneous liver-kidney transplant recipients after the first year.

PubMed

Taner, Timucin; Gustafson, Michael P; Hansen, Michael J; Park, Walter D; Bornschlegl, Svetlana; Dietz, Allan B; Stegall, Mark D

2018-06-01

Kidney allografts of patients who undergo simultaneous liver-kidney transplantation incur less immune-mediated injury, and retain better function compared to other kidney allografts. To characterize the host alloimmune responses in 28 of these patients, we measured the donor-specific alloresponsiveness and phenotypes of peripheral blood cells after the first year. These values were then compared to those of 61 similarly immunosuppressed recipients of a solitary kidney or 31 recipients of liver allografts. Four multicolor, non-overlapping flow cytometry protocols were used to assess the immunophenotypes. Mixed cell cultures with donor or third party cells were used to measure cell proliferation and interferon gamma production. Despite a significant overlap, simultaneous liver-kidney transplant recipients had a lower overall frequency of circulating CD8 + , activated CD4 + and effector memory T cells, compared to solitary kidney transplant recipients. Simultaneous liver-kidney transplant recipient T cells had a significantly lower proliferative response to the donor cells compared to solitary kidney recipients (11.9 vs. 42.9%), although their response to third party cells was unaltered. The frequency of interferon gamma producing alloreactive T cells in simultaneous liver-kidney transplant recipients was significantly lower than that of solitary kidney transplant recipients. Flow cytometric analysis of the mixed cultures demonstrated that both alloreactive CD4 + and CD8 + compartments of the simultaneous liver-kidney transplant recipient circulating blood cells were smaller. Thus, the phenotypic and functional characteristics of the circulating blood cells of the simultaneous liver-kidney transplant recipients resembled those of solitary liver transplant recipients, and appear to be associated with donor-specific hypo-alloresponsiveness. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Women and kidney disease: reflections on World Kidney Day 2018: Kidney Health and Women's Health: a case for optimizing outcomes for present and future generations.

PubMed

Piccoli, Giorgina B; Alrukhaimi, Mona; Liu, Zhi-Hong; Zakharova, Elena; Levin, Adeera

2018-02-01

Chronic kidney disease (CKD) affects ∼10% of the world's adult population: it is one of the top 20 causes of death worldwide and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day coincide in 2018, thus offering an opportunity to reflect on the importance of women's health, and specifically their kidney health, on the community and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply these learnings more broadly. Girls and women, who make up ∼50% of the world's population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for the diagnosis of kidney disease, and also a state where acute and chronic kidney diseases may manifest and that may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for childbearing and on the fetus. Women have different complications on dialysis than men and are more likely to be donors than recipients of kidney transplants. In this editorial we focus on what we do and do not know about women, kidney health and kidney disease and what we might learn in the future to improve outcomes worldwide. © The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Diuretic renography in hydronephrosis: renal tissue tracer transit predicts functional course and thereby need for surgery.

PubMed

Schlotmann, Andreas; Clorius, John H; Clorius, Sandra N

2009-10-01

The recognition of those hydronephrotic kidneys which require therapy to preserve renal function remains difficult. We retrospectively compared the 'tissue tracer transit' (TTT) of (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG(3)) with 'response to furosemide stimulation' (RFS) and with 'single kidney function < 40%' (SKF < 40%) to predict functional course and thereby need for surgery. Fifty patients with suspected unilateral obstruction and normal contralateral kidney had 115 paired (baseline/follow-up) (99m)Tc-MAG(3) scintirenographies. Three predictions of the functional development were derived from each baseline examination: the first based on TTT (visually assessed), the second on RFS and the third on SKF < 40%. Each prediction also considered whether the patient had surgery. Possible predictions were 'better', 'worse' or 'stable' function. A comparison of SKF at baseline and follow-up verified the predictions. The frequency of correct predictions for functional improvement following surgery was 8 of 10 kidneys with delayed TTT, 9 of 22 kidneys with obstructive RFS and 9 of 21 kidneys with SKF < 40%; for functional deterioration without surgery it was 2 of 3 kidneys with delayed TTT, 3 of 20 kidneys with obstructive RFS and 3 of 23 kidneys with SKF < 40%. Without surgery 67 of 70 kidneys with timely TTT maintained function. Without surgery 0 of 9 kidneys with timely TTT but obstructive RFS and only 1 of 16 kidneys with timely TTT but SKF < 40% lost function. Delayed TTT appears to identify the need for therapy to preserve function of hydronephrotic kidneys, while timely TTT may exclude risk even in the presence of an obstructive RFS or SKF < 40%.

Synergistic Interaction of Hypertension and Diabetes in Promoting Kidney Injury and the Role of Endoplasmic Reticulum Stress.

PubMed

Wang, Zhen; do Carmo, Jussara M; Aberdein, Nicola; Zhou, Xinchun; Williams, Jan M; da Silva, Alexandre A; Hall, John E

2017-05-01

Diabetes mellitus and hypertension are major risk factors for chronic kidney injury, together accounting for >70% of end-stage renal disease. In this study, we assessed interactions of hypertension and diabetes mellitus in causing kidney dysfunction and injury and the role of endoplasmic reticulum (ER) stress. Hypertension was induced by aorta constriction (AC) between the renal arteries in 6-month-old male Goto-Kakizaki (GK) type 2 diabetic and control Wistar rats. Fasting plasma glucose averaged 162±11 and 87±2 mg/dL in GK and Wistar rats, respectively. AC produced hypertension in the right kidney (above AC) and near normal blood pressure in the left kidney (below AC), with both kidneys exposed to the same levels of glucose, circulating hormones, and neural influences. After 8 weeks of AC, blood pressure above the AC (and in the right kidney) increased from 109±1 to 152±5 mm Hg in GK rats and from 106±4 to 141±5 mm Hg in Wistar rats. The diabetic-hypertensive right kidneys in GK-AC rats had much greater increases in albumin excretion and histological injury compared with left kidneys (diabetes mellitus only) of GK rats or right kidneys (hypertension only) of Wistar-AC rats. Marked increases in ER stress and oxidative stress indicators were observed in diabetic-hypertensive kidneys of GK-AC rats. Inhibition of ER stress with tauroursodeoxycholic acid for 6 weeks reduced blood pressure (135±4 versus 151±4 mm Hg), albumin excretion, ER and oxidative stress, and glomerular injury, while increasing glomerular filtration rate in hypertensive-diabetic kidneys. These results suggest that diabetes mellitus and hypertension interact synergistically to promote kidney dysfunction and injury via ER stress. © 2017 American Heart Association, Inc.

Resistive index for kidney evaluation in normal and diseased cats.

PubMed

Tipisca, Vlad; Murino, Carla; Cortese, Laura; Mennonna, Giuseppina; Auletta, Luigi; Vulpe, Vasile; Meomartino, Leonardo

2016-06-01

The objectives were to determine the resistive index (RI) in normal cats and in cats with various renal diseases, and to evaluate the effect of age on RI. The subjects were cats that had ultrasonography (US) of the urinary tract and RI measurement at our centre between January 2003 and April 2014. Based on clinical evaluation, biochemical and haematological tests, urinalysis and US, the cats were classified as healthy or diseased. RI measurements were made from the interlobar or arcuate arteries. Data were analysed for differences between the right and the left kidney, the two sexes, different age groups in healthy cats, and between healthy and diseased cats. A total of 116 cats (68 males, 48 females) were included: 24 healthy and 92 diseased. In the healthy cats, RI (mean ± SD) differed significantly (P = 0.02) between the right kidney (0.54 ± 0.07) and the left kidney (0.59 ± 0.08). For the left kidney, RI was significantly higher in cats with chronic kidney disease (0.73 ± 0.12) and acute kidney injury (0.72 ± 0.08) (P = 0.0008). For the right kidney, RI was significantly higher in cats with chronic kidney disease (0.72 ± 0.11), acute kidney injury (0.74 ± 0.08), polycystic kidney disease (0.77 ± 0.11) and renal tumour (0.74 ± 0.001) (P <0.0001). There was no significant effect on RI value in either kidney in terms of age or sex. RI could be considered a valuable diagnostic tool in cats, useful in the differential diagnosis of diffuse renal diseases. While it does not change with the age of the cat, ultrasonographers should be aware that RI may differ between the two kidneys. © ISFM and AAFP 2015.

Kidney Stones in Children and Teens

MedlinePlus

... Issues Listen Español Text Size Email Print Share Kidney Stones in Children and Teens Page Content Article ... teen girls having the highest incidence. Types of Kidney Stones There are many different types of kidney ...

Kidney Cancer in Children

MedlinePlus

What is Kidney Cancer in Children? Kidney (renal) tumors are very rare in children. Still, the three most common renal tumors ... treatable and curable. What are the Types of Kidney Cancer in Children? Male urinary tract Medical Illustration ...

Treatment Option Overview (Wilms Tumor and Other Childhood Kidney Tumors)

MedlinePlus

... Kidney Cancer Research Wilms Tumor and Other Childhood Kidney Tumors Treatment (PDQ®)–Patient Version General Information About Wilms Tumor and Other Childhood Kidney Tumors Go to Health Professional Version Key Points ...

Chronic Kidney Disease

MedlinePlus

You have two kidneys, each about the size of your fist. Their main job is to filter your blood. They remove wastes and ... help control blood pressure, and make hormones. Chronic kidney disease (CKD) means that your kidneys are damaged ...

Chronic Kidney Disease - Multiple Languages

MedlinePlus

... Kidney Problems - العربية (Arabic) Bilingual PDF Health Information Translations Kidney Failure - العربية (Arabic) Bilingual PDF Health Information Translations Bosnian (bosanski) Expand Section Kidney Failure - bosanski (Bosnian) ...

Kidney cell electrophoresis

NASA Technical Reports Server (NTRS)

Todd, P.

1980-01-01

The following aspects of kidney cell electrophoresis are discussed: (1) the development and testing of electrophoresis solutions; (2) optimization of freezing and thawing; (3) procedures for evaluation of separated kidney cells; and (4) electrophoretic mobility characterization of kidney cells.

Kidney cell electrophoresis

NASA Technical Reports Server (NTRS)

Todd, P.

1979-01-01

A kidney cell electrophoresis technique is described in four parts: (1) the development and testing of electrophoresis solutions; (2) optimization of freezing and thawing; (3) procedures for evaluation of separated kidney cells; and (4) electrophoretic mobility characteristics of kidney cells.

Recent insights into C3 glomerulopathy

PubMed Central

Barbour, Thomas D.; Pickering, Matthew C.; Cook, H. Terence

2013-01-01

‘C3 glomerulopathy’ is a recent disease classification comprising several rare types of glomerulonephritis (GN), including dense deposit disease (DDD), C3 glomerulonephritis (C3GN) and CFHR5 nephropathy. These disorders share the key histological feature of isolated complement C3 deposits in the glomerulus. A common aetiology involving dysregulation of the alternative pathway (AP) of complement has been elucidated in the past decade, with genetic defects and/or autoantibodies able to be identified in a proportion of patients. We review the clinical and histological features of C3 glomerulopathy, relating these to underlying molecular mechanisms. The role of uncontrolled C3 activation in pathogenesis is emphasized, with important lessons from animal models. Methods, advantages and limitations of gene testing in the assessment of individuals or families with C3 glomerulopathy are discussed. While no therapy has yet been shown consistently effective, clinical evaluation of agents targeting specific components of the complement system is ongoing. However, limits to current knowledge regarding the natural history and the appropriate timing and duration of proposed therapies need to be addressed. PMID:23479095

IGF1-Dependent Synaptic Plasticity of Mitral Cells in Olfactory Memory during Social Learning.

PubMed

Liu, Zhihui; Chen, Zijun; Shang, Congping; Yan, Fei; Shi, Yingchao; Zhang, Jiajing; Qu, Baole; Han, Hailin; Wang, Yanying; Li, Dapeng; Südhof, Thomas C; Cao, Peng

2017-07-05

During social transmission of food preference (STFP), mice form long-term memory of food odors presented by a social partner. How does the brain associate a social context with odor signals to promote memory encoding? Here we show that odor exposure during STFP, but not unconditioned odor exposure, induces glomerulus-specific long-term potentiation (LTP) of synaptic strength selectively at the GABAergic component of dendrodendritic synapses of granule and mitral cells in the olfactory bulb. Conditional deletion of synaptotagmin-10, the Ca 2+ sensor for IGF1 secretion from mitral cells, or deletion of IGF1 receptor in the olfactory bulb prevented the socially relevant GABAergic LTP and impaired memory formation after STFP. Conversely, the addition of IGF1 to acute olfactory bulb slices elicited the GABAergic LTP in mitral cells by enhancing postsynaptic GABA receptor responses. Thus, our data reveal a synaptic substrate for a socially conditioned long-term memory that operates at the level of the initial processing of sensory information. Copyright © 2017 Elsevier Inc. All rights reserved.

Bendamustine-induced nephrogenic diabetes insipidus
.

PubMed

Derman, Benjamin A; Jain, Milli; McAninch, Elizabeth A; Gashti, Casey

2017-01-01

A 59-year-old man presented with polyuria and polydipsia immediately following his sixth cycle of rituximab and bendamustine for chronic lymphocytic leukemia. He initially compensated by increasing his oral fluid intake at home, but later developed septic shock and was admitted with orders to be kept nil per os (NPO). This prompted an episode of acute hypernatremia during which he exhibited continued polyuria with inappropriately dilute urine. Desmopressin challenge yielded no response in the urine osmolality, indicating a nephrogenic source of his diabetes insipidus (DI). He had no known exposure to other causative agents and had demonstrated a robust response to chemotherapy. The patient became eunatremic once oral intake was resumed and his infection was treated. Two months after presentation, he remained symptomatic. A trial with hydrochlorothiazide resulted in a significant increase in urine osmolality and subsequent decrease in urine output. To our knowledge, this is the first case of nephrogenic diabetes insipidus after rituximab and bendamustine exposure. We propose that bendamustine, similar to the alkylating agent ifosfamide, is toxic to the glomerulus and proximal tubule cells and is the most likely cause of the patient's nephrogenic DI.
.

Kidney stones: pathophysiology, diagnosis and management.

PubMed

Cunningham, Priscilla; Noble, Helen; Al-Modhefer, Abdul-Kadhum; Walsh, Ian

2016-11-10

The prevalence of kidney stones is increasing, and approximately 12 000 hospital admissions every year are due to this condition. This article will use a case study to focus on a patient diagnosed with a calcium oxalate kidney stone. It will discuss the affected structures in relation to kidney stones and describe the pathology of the condition. Investigations for kidney stones, differential diagnosis and diagnosis, possible complications and prognosis, will be discussed. Finally, a detailed account of management strategies for the patient with kidney stones will be given, looking at pain management, medical procedures and dietary interventions.

Chronic Kidney Disease Screening Methods and Its Implication for Malaysia: An in Depth Review

PubMed Central

Almualm, Yasmin; Huri, Hasniza Zaman

2015-01-01

Chronic Kidney Disease has become a public health problem, imposing heath, social and human cost on societies worldwide. Chronic Kidney Disease remains asymptomatic till late stage when intervention cannot stop the progression of the disease. Therefore, there is an urgent need to detect the disease early. Despite the high prevalence of Chronic Kidney Disease in Malaysia, screening is still lacking behind. This review discusses the strengths and limitations of current screening methods for Chronic Kidney Disease from a Malaysian point of view. Diabetic Kidney Disease was chosen as focal point as Diabetes is the leading cause of Chronic Kidney Disease in Malaysia. Screening for Chronic Kidney Disease in Malaysia includes a urine test for albuminuria and a blood test for serum creatinine. Recent literature indicates that albuminuria is not always present in Diabetic Kidney Disease patients and serum creatinine is only raised after substantial kidney damage has occurred. Recently, cystatin C was proposed as a potential marker for kidney disease but this has not been studied thoroughly in Malaysia. Glomerular Filtration Rate is the best method for measuring kidney function and is widely estimated using the Modification of Diet for Renal Disease equation. Another equation, the Chronic Kidney Disease Epidemiology Collaboration Creatinine equation was introduced in 2009. The new equation retained the precision and accuracy of the Modification of Diet for Renal Disease equation at GFR < 60ml/min/1.73m2, showed less bias and improved precision at GFR>60ml/min/1.73m2. In Asian countries, adding an ethnic coefficient to the equation enhanced its performance. In Malaysia, a multi-ethnic Asian population, the Chronic Kidney Disease Epidemiology Collaboration equation should be validated and the Glomerular Filtration Rate should be reported whenever serum creatinine is ordered. Reporting estimated Glomerular Filtration Rate will help diagnose patients who would have been otherwise missed if only albuminuria and serum creatinine are measured. PMID:25946939

Potential Use of Autologous Renal Cells from Diseased Kidneys for the Treatment of Renal Failure.

PubMed

George, Sunil K; Abolbashari, Mehran; Jackson, John D; Aboushwareb, Tamer; Atala, Anthony; Yoo, James J

2016-01-01

Chronic kidney disease (CKD) occurs when certain conditions cause the kidneys to gradually lose function. For patients with CKD, renal transplantation is the only treatment option that restores kidney function. In this study, we evaluated primary renal cells obtained from diseased kidneys to determine whether their normal phenotypic and functional characteristics are retained, and could be used for cell therapy. Primary renal cells isolated from both normal kidneys (NK) and diseased kidneys (CKD) showed similar phenotypic characteristics and growth kinetics. The expression levels of renal tubular cell markers, Aquaporin-1 and E-Cadherin, and podocyte-specific markers, WT-1 and Nephrin, were similar in both NK and CKD kidney derived cells. Using fluorescence- activated cell sorting (FACS), specific renal cell populations were identified and included proximal tubular cells (83.1% from NK and 80.3% from CKD kidneys); distal tubular cells (11.03% from NK and 10.9% from CKD kidneys); and podocytes (1.91% from NK and 1.78% from CKD kidneys). Ultra-structural analysis using scanning electron microscopy (SEM) revealed microvilli on the apical surface of cultured cells from NK and CKD samples. Moreover, transmission electron microscopy (TEM) analysis showed a similar organization of tight junctions, desmosomes, and other intracellular structures. The Na+ uptake characteristics of NK and CKD derived renal cells were also similar (24.4 mmol/L and 25 mmol/L, respectively) and no significant differences were observed in the protein uptake and transport characteristics of these two cell isolates. These results show that primary renal cells derived from diseased kidneys such as CKD have similar structural and functional characteristics to their counterparts from a normal healthy kidney (NK) when grown in vitro. This study suggests that cells derived from diseased kidney may be used as an autologous cell source for renal cell therapy, particularly in patients with CKD or end-stage renal disease (ESRD).

Chronic kidney disease screening methods and its implication for Malaysia: an in depth review.

PubMed

Almualm, Yasmin; Zaman Huri, Hasniza

2015-01-01

Chronic Kidney Disease has become a public health problem, imposing heath, social and human cost on societies worldwide. Chronic Kidney Disease remains asymptomatic till late stage when intervention cannot stop the progression of the disease. Therefore, there is an urgent need to detect the disease early. Despite the high prevalence of Chronic Kidney Disease in Malaysia, screening is still lacking behind. This review discusses the strengths and limitations of current screening methods for Chronic Kidney Disease from a Malaysian point of view. Diabetic Kidney Disease was chosen as focal point as Diabetes is the leading cause of Chronic Kidney Disease in Malaysia. Screening for Chronic Kidney Disease in Malaysia includes a urine test for albuminuria and a blood test for serum creatinine. Recent literature indicates that albuminuria is not always present in Diabetic Kidney Disease patients and serum creatinine is only raised after substantial kidney damage has occurred.  Recently, cystatin C was proposed as a potential marker for kidney disease but this has not been studied thoroughly in Malaysia.  Glomerular Filtration Rate is the best method for measuring kidney function and is widely estimated using the Modification of Diet for Renal Disease equation. Another equation, the Chronic Kidney Disease Epidemiology Collaboration Creatinine equation was introduced in 2009. The new equation retained the precision and accuracy of the Modification of Diet for Renal Disease equation at GFR < 60ml/min/1.73m2, showed less bias and improved precision at GFR>60ml/min/1.73m2. In Asian countries, adding an ethnic coefficient to the equation enhanced its performance. In Malaysia, a multi-ethnic Asian population, the Chronic Kidney Disease Epidemiology Collaboration equation should be validated and the Glomerular Filtration Rate should be reported whenever serum creatinine is ordered. Reporting estimated Glomerular Filtration Rate will help diagnose patients who would have been otherwise missed if only albuminuria and serum creatinine are measured.

Hypertension in kidney transplantation is associated with an early renal nerve sprouting

PubMed Central

Rovella, Valentina; Borri, Filippo; Anemona, Lucia; Giannini, Elena; Giacobbi, Erica; Saggini, Andrea; Palmieri, Giampiero; Anselmo, Alessandro; Bove, Pierluigi; Melino, Gerry; Valentina, Guardini; Tesauro, Manfredi; Gabriele, D’Urso; Di Daniele, Nicola

2017-01-01

Abstract Background. Normalization of arterial pressure occurs in just a few patients with hypertensive chronic kidney disease undergoing kidney transplantation. Hypertension in kidney transplant recipients may be related to multiple factors. We aimed to assess whether hypertension in kidney-transplanted patients may be linked to reinnervation of renal arteries of the transplanted kidney. Methods. We investigated renal arteries innervation from native and transplanted kidneys in three patients 5 months, 2 years and 11 years after transplantation, respectively. Four transplanted kidneys from non-hypertensive patients on immunosuppressive treatment without evidence of hypertensive arteriolar damage were used as controls. Results. Evidence of nerve sprouting was observed as early as 5 months following transplantation, probably originated from ganglions of recipient patient located near the arterial anastomosis and was associated with mild hypertensive arteriolar damage. Regeneration of periadventitial nerves was already complete 2 years after transplantation. Nerve density tended to reach values observed in native kidney arteries and was associated with hypertension-related arteriolar lesions in transplanted kidneys. Control kidneys, albeit on an immunosuppressive regimen, presented only a modest regeneration of sympathetic nerves. Conclusions. Our results suggest that the considerable increase in sympathetic nerves, as found in patients with severe arterial damage, may be correlated to hypertension rather than to immunosuppressive therapy, thus providing a morphological basis for hypertension recurrence despite renal denervation. PMID:28498963

Hydrogen Sulfide in Renal Physiology and Disease.

PubMed

Feliers, Denis; Lee, Hak Joo; Kasinath, Balakuntalam S

2016-11-01

Hydrogen sulfide (H2S) has only recently gained recognition for its physiological effects. It is synthesized widely in the mammalian tissues and regulates several biologic processes ranging from development, angiogenesis, neurotransmission to protein synthesis. Recent Advances: The aim of this review is to critically evaluate the evidence for a role for H2S in kidney function and disease. H2S regulates fundamental kidney physiologic processes such as glomerular filtration and sodium reabsorption. In kidney disease states H2S appears to play a complex role in a context-dependent manner. In some disease states such as ischemia-reperfusion and diabetic kidney disease it can serve as an agent that ameliorates kidney injury. In other diseases such as cis-platinum-induced kidney disease it may mediate kidney injury although more investigation is needed. Recent studies have revealed that the actions of nitric oxide and H2S may be integrated in kidney cells. Further studies are needed to understand the full impact of H2S on kidney physiology. As it is endowed with the properties of regulating blood flow, oxidative stress, and inflammation, H2S should be investigated for its role in inflammatory and toxic diseases of the kidney. Such in-depth exploration may identify specific kidney diseases in which H2S may constitute a unique target for therapeutic intervention. Antioxid. Redox Signal. 25, 720-731.

High dietary fiber intake is associated with decreased inflammation and all-cause mortality in patients with chronic kidney disease

PubMed Central

Raj Krishnamurthy, Vidya M.; Wei, Guo; Baird, Bradley C.; Murtaugh, Maureen; Chonchol, Michel B.; Raphael, Kalani L.; Greene, Tom; Beddhu, Srinivasan

2016-01-01

Chronic kidney disease is considered an inflammatory state and a high fiber intake is associated with decreased inflammation in the general population. Here, we determined whether fiber intake is associated with decreased inflammation and mortality in chronic kidney disease, and whether kidney disease modifies the associations of fiber intake with inflammation and mortality. To do this, we analyzed data from 14,543 participants in the National Health and Nutrition Examination Survey III. The prevalence of chronic kidney disease (estimated glomerular filtration rate less than 60 ml/min per 1.73 m2) was 5.8%. For each 10-g/day increase in total fiber intake, the odds of elevated serum C-reactive protein levels were decreased by 11% and 38% in those without and with kidney disease, respectively. Dietary total fiber intake was not significantly associated with mortality in those without but was inversely related to mortality in those with kidney disease. The relationship of total fiber with inflammation and mortality differed significantly in those with and without kidney disease. Thus, high dietary total fiber intake is associated with lower risk of inflammation and mortality in kidney disease and these associations are stronger in magnitude in those with kidney disease. Interventional trials are needed to establish the effects of fiber intake on inflammation and mortality in kidney disease. PMID:22012132

Diet for Kidney Stone Prevention

MedlinePlus

... Diet, & Nutrition Clinical Trials Eating, Diet, & Nutrition for Kidney Stones Can I help prevent kidney stones by changing what I eat or drink? ... help you lose weight. Does the type of kidney stone I had affect food choices I should ...

Role of Magnetic Resonance Elastography as a Noninvasive Measurement Tool of Fibrosis in a Renal Allograft: A Case Report.

PubMed

Kim, J K; Yuen, D A; Leung, G; Jothy, S; Zaltzman, J; Ramesh Prasad, G V; Prabhudesai, V; Mnatzakanian, G; Kirpalani, A

2017-09-01

A major reason for poor long-term kidney transplant outcomes is the development of chronic allograft injury, characterized by interstitial fibrosis and tubular atrophy. Currently, an invasive biopsy that samples only <1% of the kidney is the gold standard for detecting kidney allograft fibrosis. We report the use of magnetic resonance elastography (MRE) to quantify tissue stiffness as a noninvasive and whole-kidney measurement tool of allograft fibrosis in a kidney transplant patient at 2 time points. The MRE whole-kidney stiffness values reflected the changes in fibrosis of the kidney allograft as assessed by histologic examination. To our knowledge, this technique is the first observation of change over time in MRE-derived whole-kidney stiffness in an allograft that is consistent with changes in histology-derived fibrosis scores in a single patient. Copyright © 2017 Elsevier Inc. All rights reserved.

Age and treatment of kidney failure.

PubMed

Elliott, Meghan J; Tam-Tham, Helen; Hemmelgarn, Brenda R

2013-05-01

This review discusses issues related to treatment of chronic kidney disease, and kidney failure in particular, among older adults. A substantial proportion of older adults have chronic kidney disease and progress to kidney failure. There is considerable variability in treatment practices for advanced kidney disease among older adults, and evidence that treatment decisions such as dialysis initiation may be made without adequate preparation. When initiated, survival among older adults on chronic dialysis remains poor, and is associated with a significant decline in functional status. There is also evidence to suggest that dialysis initiation may not reflect overall treatment goals of elderly patients, but rather a lack of clear communication between patients and health practitioners, and underdeveloped conservative care programs in many centers. Kidney failure is common among older adults. When considering treatment options for kidney failure, patient priorities, preferences, and symptoms should be taken into account, using a shared decision-making approach.

Relay kidney transplantation in Korea--legal, ethical and medical aspects.

PubMed

Park, Jong-Hyun; Park, Joong-Won; Koo, Young-Mo; Kim, Jang Han

2004-07-01

Living kidney transplantations constitute the majority of kidney transplantations in Korea. Recently, relay kidney transplantation, which is a modified form of both 'exchange transplantation' and 'living anonymous donation', has become at issue. After a living anonymous donor makes the initial donation, the next donor, who is related to the first recipient, makes the second donation; the third donor, who is related to the second recipient, makes the third donation; and so on. In relay kidney transplantation, organ trafficking, coercion of donation, assessment order, breach of agreement, and recipient burden should be evaluated with respect to ethical, legal and medical considerations. Despite these problems, a non-governmental body, the Korean Organ and Tissue Donor Program, has been promoting relay kidney transplantations to address the shortage of cadaveric kidney donations. Acceptance of the method of relay kidney transplantation requires the institution of supplementary measures to minimize the related problems.

40 CFR 180.459 - Triasulfuron; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., grain 0.02 Barley, straw 2.0 Cattle, fat 0.1 Cattle, kidney 0.5 Cattle, meat byproducts, except kidney 0.1 Cattle, meat 0.1 Goat, fat 0.1 Goat, kidney 0.5 Goat, meat byproducts, except kidney 0.1 Goat, meat 0.1 Grass, forage 7.0 Grass, hay 2.0 Hog, fat 0.1 Hog, kidney 0.5 Hog, meat byproducts 0.1 Hog...

40 CFR 180.459 - Triasulfuron; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., grain 0.02 Barley, straw 2.0 Cattle, fat 0.1 Cattle, kidney 0.5 Cattle, meat byproducts, except kidney 0.1 Cattle, meat 0.1 Goat, fat 0.1 Goat, kidney 0.5 Goat, meat byproducts, except kidney 0.1 Goat, meat 0.1 Grass, forage 7.0 Grass, hay 2.0 Hog, fat 0.1 Hog, kidney 0.5 Hog, meat byproducts 0.1 Hog...

Targeted Nanoparticles for Kidney Cancer Therapy

DTIC Science & Technology

2013-10-01

AD_________________ Award Number: W81XWH-10-1-0434 TITLE: Targeted Nanoparticles for Kidney Cancer Therapy PRINCIPAL...Targeted Nanoparticles for Kidney Cancer Therapy 5b. GRANT NUMBER W81XWH-10-1-0434 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...lines following treatment with D5 nanotubes. Tthermoablation will be studied initially. Human kidney cancer cells will be injected into the kidney

40 CFR 180.459 - Triasulfuron; tolerances for residues.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., grain 0.02 Barley, straw 2.0 Cattle, fat 0.1 Cattle, kidney 0.5 Cattle, meat byproducts, except kidney 0.1 Cattle, meat 0.1 Goat, fat 0.1 Goat, kidney 0.5 Goat, meat byproducts, except kidney 0.1 Goat, meat 0.1 Grass, forage 7.0 Grass, hay 2.0 Hog, fat 0.1 Hog, kidney 0.5 Hog, meat byproducts 0.1 Hog...

40 CFR 180.459 - Triasulfuron; tolerances for residues.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., grain 0.02 Barley, straw 2.0 Cattle, fat 0.1 Cattle, kidney 0.5 Cattle, meat byproducts, except kidney 0.1 Cattle, meat 0.1 Goat, fat 0.1 Goat, kidney 0.5 Goat, meat byproducts, except kidney 0.1 Goat, meat 0.1 Grass, forage 7.0 Grass, hay 2.0 Hog, fat 0.1 Hog, kidney 0.5 Hog, meat byproducts 0.1 Hog...

40 CFR 180.459 - Triasulfuron; tolerances for residues.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., grain 0.02 Barley, straw 2.0 Cattle, fat 0.1 Cattle, kidney 0.5 Cattle, meat byproducts, except kidney 0.1 Cattle, meat 0.1 Goat, fat 0.1 Goat, kidney 0.5 Goat, meat byproducts, except kidney 0.1 Goat, meat 0.1 Grass, forage 7.0 Grass, hay 2.0 Hog, fat 0.1 Hog, kidney 0.5 Hog, meat byproducts 0.1 Hog...

The experiences of close persons caring for people with chronic kidney disease stage 5 on conservative kidney management: Contested discourses of ageing

PubMed Central

Myers, Jason; Smith, Glenn; Higgs, Paul; Burns, Aine; Hopkins, Katherine; Jones, Louise

2014-01-01

Chronic kidney disease stage 5 is a global health challenge in the context of population ageing across the world. The range of treatment options available to patients at all ages has increased and includes transplantation and dialysis. However, these options are often seen as inappropriate for older frailer patients who are now offered the option of conservative kidney management, which is presented as a non-invasive alternative to dialysis, involving symptom management and addressing psychosocial needs. In this study, we conducted qualitative interviews with 26 close persons caring for someone with chronic kidney disease stage 5 in the United Kingdom to investigate how conservative kidney management interacted with implicit ideas of ageing, in both the experience of conservative kidney management and the understanding of the prognosis and future care of the kidney disease. Our findings highlighted participant confusion about the nature of conservative kidney management, which stems from an initial lack of clarity about how conservative kidney management differed from conventional treatments for chronic kidney disease stage 5. In particular, some respondents were not aware of the implicit palliative nature of the intervention or indeed the inevitable end-of-life issues. Although these findings can be situated within the context of communication failure, we would further argue that they also bring to the surface tensions in the discourses surrounding ageing and old age, drawing on the use of a ‘natural’ and a ‘normal’ paradigm of ageing. In the context of chronic kidney disease stage 5, more patients are being dialysed at older ages, but conservative kidney management is being advanced as a better option than dialysis in terms of quality of life and experience. However, in doing so, conservative kidney management implicitly draws on a notion of older age that echoes natural ageing rather than advocate a more interventionist approach. The role of discourses of ageing in the provision of treatments for conservative kidney management has not previously been acknowledged, and this article addresses this gap. PMID:24695386

Acute Kidney Injury in Patients Undergoing the Extracardiac Fontan Operation With and Without the Use of Cardiopulmonary Bypass.

PubMed

Algaze, Claudia A; Koth, Andrew M; Faberowski, Lisa W; Hanley, Frank L; Krawczeski, Catherine D; Axelrod, David M

2017-01-01

To describe the prevalence and risk factors for acute kidney injury in patients undergoing the extracardiac Fontan operation with and without cardiopulmonary bypass, and to determine whether acute kidney injury is associated with duration of mechanical ventilation, cardiovascular ICU and hospital postoperative length of stay, and early mortality. Single-center retrospective cohort study. Pediatric cardiovascular ICU, university-affiliated children's hospital. Patients with a preoperative creatinine before undergoing first-time extracardiac Fontan between January 1, 2004, and April 30, 2012. None. Acute kidney injury occurred in 55 of 138 patients (39.9%), including 41 (29.7%) with stage 1, six (4.4%) with stage 2, and eight (5.8%) with stage 3 acute kidney injury. Cardiopulmonary bypass was strongly associated with a higher risk of any acute kidney injury (adjusted odds ratio, 4.8 [95% CI, 1.4-16.0]; p = 0.01) but not stage 2/3 acute kidney injury. Lower renal perfusion pressure on the day of surgery (postoperative day, 0) was associated with a higher risk of stage 2/3 acute kidney injury (adjusted odds ratio, 1.2 [95% CI, 1.0-1.5]; p = 0.03). Higher vasoactive-inotropic score on postoperative day 0 was associated with a higher risk for stage 2/3 acute kidney injury (adjusted odds ratio, 1.9 [95% CI, 1.0-3.4]; p = 0.04). Stage 2/3 acute kidney injury was associated with longer cardiovascular ICU length of stay (mean, 7.3 greater d [95% CI, 3.4-11.3]; p < 0.001) and hospital postoperative length of stay (mean, 6.4 greater d [95% CI, 0.06-12.5]; p = 0.04). Postoperative acute kidney injury in patients undergoing the extracardiac Fontan operation is common and is associated with lower postoperative renal perfusion pressure and higher vasoactive-inotropic score. Cardiopulmonary bypass was strongly associated with any acute kidney injury, although not stage 2/3 acute kidney injury. Stage 2/3 acute kidney injury is a compelling risk factor for longer cardiovascular ICU and hospital postoperative length of stay. Increased attention to and management of renal perfusion pressure may reduce postoperative acute kidney injury and improve outcomes.

The experiences of close persons caring for people with chronic kidney disease stage 5 on conservative kidney management: contested discourses of ageing.

PubMed

Low, Joe; Myers, Jason; Smith, Glenn; Higgs, Paul; Burns, Aine; Hopkins, Katherine; Jones, Louise

2014-11-01

Chronic kidney disease stage 5 is a global health challenge in the context of population ageing across the world. The range of treatment options available to patients at all ages has increased and includes transplantation and dialysis. However, these options are often seen as inappropriate for older frailer patients who are now offered the option of conservative kidney management, which is presented as a non-invasive alternative to dialysis, involving symptom management and addressing psychosocial needs. In this study, we conducted qualitative interviews with 26 close persons caring for someone with chronic kidney disease stage 5 in the United Kingdom to investigate how conservative kidney management interacted with implicit ideas of ageing, in both the experience of conservative kidney management and the understanding of the prognosis and future care of the kidney disease. Our findings highlighted participant confusion about the nature of conservative kidney management, which stems from an initial lack of clarity about how conservative kidney management differed from conventional treatments for chronic kidney disease stage 5. In particular, some respondents were not aware of the implicit palliative nature of the intervention or indeed the inevitable end-of-life issues. Although these findings can be situated within the context of communication failure, we would further argue that they also bring to the surface tensions in the discourses surrounding ageing and old age, drawing on the use of a 'natural' and a 'normal' paradigm of ageing. In the context of chronic kidney disease stage 5, more patients are being dialysed at older ages, but conservative kidney management is being advanced as a better option than dialysis in terms of quality of life and experience. However, in doing so, conservative kidney management implicitly draws on a notion of older age that echoes natural ageing rather than advocate a more interventionist approach. The role of discourses of ageing in the provision of treatments for conservative kidney management has not previously been acknowledged, and this article addresses this gap. © The Author(s) 2014.

Cold preservation with hyperbranched polyglycerol-based solution improves kidney functional recovery with less injury at reperfusion in rats

PubMed Central

Li, Shadan; Liu, Bin; Guan, Qiunong; Chafeeva, Irina; Brooks, Donald E; Nguan, Christopher YC; Kizhakkedathu, Jayachandran N; Du, Caigan

2017-01-01

Minimizing donor organ injury during cold preservation (including cold perfusion and storage) is the first step to prevent transplant failure. We recently reported the advantages of hyperbranched polyglycerol (HPG) as a novel substitute for hydroxyethyl starch in UW solution for both cold heart preservation and cold kidney perfusion. This study evaluated the functional recovery of the kidney at reperfusion after cold preservation with HPG solution. The impact of HPG solution compared to conventional UW and HTK solutions on tissue weight and cell survival at 4°C was examined using rat kidney tissues and cultured human umbilical vein endothelial cells (HUVECs), respectively. The kidney protection by HPG solution was tested in a rat model of cold kidney ischemia-reperfusion injury, and was evaluated by histology and kidney function. Here, we showed that preservation with HPG solution prevented cell death in cultured HUVECs and edema formation in kidney tissues at 4°C similar to UW solution, whereas HTK solution was less effective. In rat model of cold ischemia-reperfusion injury, the kidneys perfused and subsequently stored 1-hour with cold HPG solution showed less leukocyte infiltration, less tubular damage and better kidney function (lower levels of serum creatinine and blood urea nitrogen) at 48 h of reperfusion than those treated with UW or HTK solution. In conclusion, our data show the superiority of HPG solution to UW or HTK solution in the cold perfusion and storage of rat kidneys, suggesting that the HPG solution may be a promising candidate for improved donor kidney preservation prior to transplantation. PMID:28337272

Awareness level of kidney functions and diseases among adults in a Nigerian population

PubMed Central

Okwuonu, C. G.; Chukwuonye, I. I.; Ogah, S. O.; Abali, C.; Adejumo, O. A.; Oviasu, E.

2015-01-01

The prevalence of kidney diseases is on the increase in Nigeria. The cost of its management is far beyond the reach of an average patient. Prevention is thus of paramount importance and awareness of kidney diseases will help in its prevention. The aim of this study is to assess the level of awareness of kidney functions and diseases among adults in a Nigerian population. A semi-structured, researcher – administered questionnaire was the tool for data collection. Four hundred and thirty-five questionnaires were analyzed. There were 160 males (36.8%) and 275 females (63.2%). The mean age was 42.8 ± 14 years with a range of 18–78 years. Among these, 82.1% were aware of the kidneys' involvement in waste removal from the body through urine while 36% and 29% were aware of kidneys' role in blood pressure regulation and blood production, respectively. Only 26.6% correctly identified at least two basic functions of the kidneys. Also, 32.6% of the respondents were aware of at least three common causes of kidney diseases in our environment. Majority of the respondents (70.7%) did not know that kidney diseases could be inherited. Furthermore, belief in alternative therapy for kidney disease was documented in 83.2%, while unawareness of dialysis as a treatment modality was recorded in 68% of the respondents. The awareness of kidney functions and diseases among the population is poor. Measures are needed to improve this to stem the rising prevalence of chronic kidney disease in Nigeria. PMID:26060365

Conserved and Divergent Features of Human and Mouse Kidney Organogenesis.

PubMed

Lindström, Nils O; McMahon, Jill A; Guo, Jinjin; Tran, Tracy; Guo, Qiuyu; Rutledge, Elisabeth; Parvez, Riana K; Saribekyan, Gohar; Schuler, Robert E; Liao, Christopher; Kim, Albert D; Abdelhalim, Ahmed; Ruffins, Seth W; Thornton, Matthew E; Basking, Laurence; Grubbs, Brendan; Kesselman, Carl; McMahon, Andrew P

2018-03-01

Human kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron number is linked to disease. Human kidney development initiates around 4 weeks of gestation and ends around 34-37 weeks of gestation. Over this period, a reiterative inductive process establishes the nephron complement. Studies have provided insightful anatomic descriptions of human kidney development, but the limited histologic views are not readily accessible to a broad audience. In this first paper in a series providing comprehensive insight into human kidney formation, we examined human kidney development in 135 anonymously donated human kidney specimens. We documented kidney development at a macroscopic and cellular level through histologic analysis, RNA in situ hybridization, immunofluorescence studies, and transcriptional profiling, contrasting human development (4-23 weeks) with mouse development at selected stages (embryonic day 15.5 and postnatal day 2). The high-resolution histologic interactive atlas of human kidney organogenesis generated can be viewed at the GUDMAP database (www.gudmap.org) together with three-dimensional reconstructions of key components of the data herein. At the anatomic level, human and mouse kidney development differ in timing, scale, and global features such as lobe formation and progenitor niche organization. The data also highlight differences in molecular and cellular features, including the expression and cellular distribution of anchor gene markers used to identify key cell types in mouse kidney studies. These data will facilitate and inform in vitro efforts to generate human kidney structures and comparative functional analyses across mammalian species. Copyright © 2018 by the American Society of Nephrology.

Inpatient health care utilization by children and adolescents with systemic lupus erythematosus and kidney involvement.

PubMed

Tanzer, Marie; Tran, Cheryl; Messer, Kassandra L; Kroeker, Amber; Herreshoff, Emily; Wickman, Larysa; Harkness, Courtney; Song, Peter; Gipson, Debbie S

2013-03-01

To evaluate inpatient health care utilization for children with systemic lupus erythematosus (SLE) with and without kidney disease. The Healthcare Cost and Utilization Project Kids' Inpatient Database for the years 2000, 2003, and 2006 was used for this analysis. SLE hospitalizations from the 2006 cohort were identified and classified as those with versus without kidney involvement by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Analyses were performed to examine determinants of hospitalization charges and changes in charges over time. In the US, 7,390 SLE-related pediatric hospitalizations generated $267 million in total charges in 2006. Of these, 4,193 discharges had kidney involvement. The average hospitalization charge was greater for SLE patients with kidney involvement compared to those without kidney involvement ($43,100 versus $28,500; P < 0.0001). In multivariate analysis, kidney involvement remained a significant predictor of hospitalization charges, independent of demographic and hospital characteristics (P < 0.0001). SLE-associated acute kidney failure, transplant, and end-stage kidney disease resulted in greater hospitalization charges than SLE without kidney involvement by $74,900 (P < 0.0001), $32,700 (P = 0.0002), and $27,400 (P < 0.0001), respectively. In the US, >7,000 hospitalizations occurred in 2006 among children with SLE, with nearly 57% demonstrating kidney involvement. Kidney involvement is a major determinant of hospitalization charges for these children. This study represents one of the first large-scale assessments of in-hospital health care utilization by children with SLE. Copyright © 2013 by the American College of Rheumatology.

Thermal Analyses of a Human Kidney and a Rabbit Kidney During Cryopreservation by Vitrification.

PubMed

Ehrlich, Lili E; Fahy, Gregory M; Wowk, Brian G; Malen, Jonathan A; Rabin, Yoed

2018-01-01

This study focuses on thermal analysis of the problem of scaling up from the vitrification of rabbit kidneys to the vitrification of human kidneys, where vitrification is the preservation of biological material in the glassy state. The basis for this study is a successful cryopreservation protocol for a rabbit kidney model, based on using a proprietary vitrification solution known as M22. Using the finite element analysis (FEA) commercial code ANSYS, heat transfer simulations suggest that indeed the rabbit kidney unquestionably cools rapidly enough to be vitrified based on known intrarenal concentrations of M22. Scaling up 21-fold, computer simulations suggest less favorable conditions for human kidney vitrification. In this case, cooling rates below -100 °C are sometimes slower than 1 °C/min, a rate that provides a clear-cut margin of safety at all temperatures based on the stability of rabbit kidneys in past studies. Nevertheless, it is concluded in this study that vitrifying human kidneys is possible without significant ice damage, assuming that human kidneys can be perfused with M22 as effectively as rabbit kidneys. The thermal analysis suggests that cooling rates can be further increased by a careful design of the cryogenic protocol and by tailoring the container to the shape of the kidney, in contrast to the present cylindrical container. This study demonstrates the critical need for the thermal analysis of experimental cryopreservation and highlights the unmet need for measuring the thermophysical properties of cryoprotective solutions under conditions relevant to realistic thermal histories.

Averting the Legacy of Kidney Disease-Focus on Childhood.

PubMed

Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

2016-02-08

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults if they receive kidney replacement therapy, including dialysis and transplantation, while only a minority of children may require this ultimate intervention.  Since there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. "For in every adult there dwells the child that was, and in every child there lies the adult that will be."-John Connolly, The Book of Lost Things.

Women and kidney disease: reflections on World Kidney Day 2018

PubMed Central

Piccoli, Giorgina B; Alrukhaimi, Mona; Liu, Zhi-Hong; Zakharova, Elena

2018-01-01

Abstract Chronic kidney disease affects ∼10% of the world’s adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women’s Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women’s health, and specifically their kidney health, to the community and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women, so that we may apply those learnings more broadly. Girls and women, who make up ∼50% of the world’s population, are important contributors to society as a whole and to their families. Gender differences continue to exist around the world in access to education, medical care and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, and also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for child bearing, and for the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we do and do not know about women, kidney health and kidney disease, and what we might learn in the future to improve outcomes worldwide. PMID:29435267

Urinary sodium excretion and kidney failure in non-diabetic chronic kidney disease

PubMed Central

Fan, Li; Tighiouart, Hocine; Levey, Andrew S.; Beck, Gerald J.; Sarnak, Mark J.

2014-01-01

Current guidelines recommend under 2g/day sodium intake in chronic kidney disease, but there are few studies relating sodium intake to long-term outcomes. Here we evaluated the association of mean baseline 24-hour urinary sodium excretion with kidney failure and a composite outcome of kidney failure or all-cause mortality using Cox regression in 840 participants enrolled in the Modification of Diet in Renal Disease Study. Mean 24-hour urinary sodium excretion was 3.46 g/day. Kidney failure developed in 617 and the composite outcome was reached in 723. In the primary analyses there was no association between 24-hour urine sodium and kidney failure [HR 0.99 (95% CI 0.91–1.08)] nor on the composite outcome [HR 1.01 (95% CI 0.93–1.09),] each per 1g/day higher urine sodium. In exploratory analyses there was a significant interaction of baseline proteinuria and sodium excretion with kidney failure. Using a 2-slope model, when urine sodium was under 3g/day, higher urine sodium was associated with increased risk of kidney failure in those with baseline proteinuria under 1g/day, and lower risk of kidney failure in those with baseline proteinuria of 1g/day or more. There was no association between urine sodium and kidney failure when urine sodium was 3g/day or more. Results were consistent using first baseline and time-dependent urine sodium. Thus, we noted no association of urine sodium with kidney failure. Results of the exploratory analyses need to be verified in additional studies and the mechanism explored. PMID:24646858

What we know and do not know about women and kidney diseases; Questions unanswered and answers unquestioned: Reflection on World Kidney Day and International Woman’s Day

PubMed Central

Piccoli, G.B.; Al Rukhaimi, M.; Liu, Zhi-Hong; Zakharova, E.; Levin, A.

2018-01-01

Chronic kidney disease affects approximately 10% of the world's adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women's health and specifically women’s kidney health on the community and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world's population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state in which acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. Various autoimmune and other conditions are more likely to impact women, with profound consequences for child bearing and the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we know and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide. PMID:29791583

What we know and do not know about women and kidney diseases; Questions unanswered and answers unquestioned: Reflection on World Kidney Day and International Woman's Day.

PubMed

Piccoli, G B; Al Rukhaimi, M; Liu, Zhi-Hong; Zakharova, E; Levin, A

2018-01-01

Chronic kidney disease affects approximately 10% of the world's adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women's health and specifically women's kidney health on the community and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world's population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state in which acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. Various autoimmune and other conditions are more likely to impact women, with profound consequences for child bearing and the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we know and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.

Red Kidney: Kidney Transplant From a Deceased Donor Who Received Massive Blood Transfusion During Cardiopulmonary Bypass.

PubMed

Bell, Richard; Hanif, Faisal; Prasad, Padmini; Ahmad, Niaz

2016-06-01

Here, we present a case of a deceased-donor kidney transplant. The brain-dead donor had received a massive blood transfusion during cardiopulmonary bypass, which lead to hemolysis, hemoglobinuria, acute kidney injury, and renal replacement therapy. The kidney appeared red after in situ flush. Postoperatively, the recipient developed delayed graft function. Protocol biopsy during the postoperative period revealed the widespread deposition of heme pigment in the renal tubules. Massive blood transfusion and cardiopulmonary bypass surgery are associated with hemolysis and heme pigment deposition in the renal tubules, which subsequently lead to acute kidney injury. Kidneys from such donors appear red and, while this does not preclude transplant, are likely to develop delayed graft function.

Stem cells in kidney regeneration.

PubMed

Yokote, Shinya; Yokoo, Takashi

2012-01-01

Currently many efforts are being made to apply regenerative medicine to kidney diseases using several types of stem/progenitor cells, such as mesenchymal stem cells, renal stem/progenitor cells, embryonic stem cells and induced pluripotent stem cells. Stem cells have the ability to repair injured organs and ameliorate damaged function. The strategy for kidney tissue repair is the recruitment of stem cells and soluble reparative factors to the kidney to elicit tissue repair and the induction of dedifferentiation of resident renal cells. On the other hand, where renal structure is totally disrupted, absolute kidney organ regeneration is needed to rebuild a whole functional kidney. In this review, we describe current advances in stem cell research for kidney tissue repair and de novo organ regeneration.

Risk factors associated with post-kidney transplant malignancies: an article from the Cancer-Kidney International Network.

PubMed

Sprangers, Ben; Nair, Vinay; Launay-Vacher, Vincent; Riella, Leonardo V; Jhaveri, Kenar D

2018-06-01

In kidney transplant recipients, cancer is one of the leading causes of death with a functioning graft beyond the first year of kidney transplantation, and malignancies account for 8-10% of all deaths in the USA (2.6 deaths/1000 patient-years) and exceed 30% of deaths in Australia (5/1000 patient-years) in kidney transplant recipients. Patient-, transplant- and medication-related factors contribute to the increased cancer risk following kidney transplantation. While it is well established that the overall immunosuppressive dose is associated with an increased risk for cancer following transplantation, the contributive effect of different immunosuppressive agents is not well established. In this review we will discuss the different risk factors for malignancies after kidney transplantation.

The Kidney Disease Screening and Awareness Program (KDSAP): A Novel Translatable Model for Increasing Interest in Nephrology Careers

PubMed Central

Wu, Jingshing; Yeh, Albert C.; Shieh, Eric C.; Cui, Cheryl; Polding, Laura C.; Ahmed, Rayhnuma; Lim, Kenneth; Lu, Tzong-Shi; Rhee, Connie M.; Bonventre, Joseph V.

2014-01-01

Despite the increasing prevalence of CKD in the United States, there is a declining interest among United States medical graduates in nephrology as a career choice. Effective programs are needed to generate interest at early educational stages when career choices can be influenced. The Kidney Disease Screening and Awareness Program (KDSAP) is a novel program initiated at Harvard College that increases student knowledge of and interest in kidney health and disease, interest in nephrology career paths, and participation in kidney disease research. This model, built on physician mentoring, kidney screening of underserved populations, direct interactions with kidney patients, and opportunities to participate in kidney research, can be reproduced and translated to other workforce-challenged subspecialties. PMID:24876120

Studying the Genetic Basis of Kidney Cancer - TCGA

Cancer.gov

Dr. Marston Linehan, NCI's Chief of Urologic Surgery, has spent the last several decades studying kidney cancer genes and treating kidney cancer patients. Learn more about his experience as a kidney cancer physician scientist and TCGA contributor in this

Aging changes in the kidneys and bladder

MedlinePlus

... fluid from the body. The kidneys also help control the body's chemical balance. The kidneys are part of the urinary system, which also includes the ureters, bladder, and urethra. Muscle ... bladder control. AGING CHANGES AND THEIR EFFECTS ON THE KIDNEYS ...

Kidney Failure and ESRD in the Atherosclerosis Risk in Communities (ARIC) Study: Comparing Ascertainment of Treated and Untreated Kidney Failure in a Cohort Study

PubMed Central

Rebholz, Casey M.; Coresh, Josef; Ballew, Shoshana H.; McMahon, Blaithin; Whelton, Seamus P.; Selvin, Elizabeth; Grams, Morgan E.

2015-01-01

Background Linkage to the US Renal Data System (USRDS) registry is commonly used to identify end-stage renal disease (ESRD) cases, or kidney failure treated with dialysis or transplantation, but it underestimates the total burden of kidney failure. This study validates a kidney failure definition that includes both kidney failure treated and not treated by dialysis or transplantation. It compares kidney failure risk factors and outcomes using this broader definition to USRDS-identified ESRD risk factors and outcomes. Study Design Diagnostic test study with stratified random sampling of hospitalizations for chart review. Setting & Participants Atherosclerosis Risk in Communities Study (N=11,530; chart review n=546). Index Test USRDS-identified ESRD; treated or untreated kidney failure defined by USRDS-identified ESRD or International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)/ICD-10-CM code from hospitalization or death. Reference Test For ESRD, determination of permanent dialysis or transplantation; for kidney failure, determination of permanent dialysis, transplantation, or eGFR <15 mL/min/1.73 m2. Results Over 13 years' median follow-up, 508 kidney failure cases were identified, including 173 (34.1%) from the USRDS registry. ESRD and kidney failure incidence were 1.23 and 3.66 cases per 1,000 person-years in the overall population, and 1.35 and 6.59 cases per 1,000 person-years among participants older than 70 years, respectively. Other risk factor associations were similar between ESRD and kidney failure, except diabetes and albuminuria which were stronger for ESRD. Survival at 1 and 5 years were 74.0% and 24.0% for ESRD and 59.8% and 31.6% for kidney failure, respectively. Sensitivity and specificity were 88.0% and 97.3% comparing the kidney failure ICD-9-CM/ICD-10-CM code algorithm to chart review; for USRDS-identified ESRD, sensitivity and specificity were 94.9% and 100.0%. Limitations Some medical charts were incomplete. Conclusions A kidney failure definition including treated and untreated disease identifies more cases than linkage to the USRDS registry alone, particularly among older adults. Future studies might consider reporting both USRDS-identified ESRD and a more inclusive kidney failure definition. PMID:25773483

Common Elements in Rare Kidney Diseases: Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

PubMed

Aymé, Ségolène; Bockenhauer, Detlef; Day, Simon; Devuyst, Olivier; Guay-Woodford, Lisa M; Ingelfinger, Julie R; Klein, Jon B; Knoers, Nine V A M; Perrone, Ronald D; Roberts, Julia; Schaefer, Franz; Torres, Vicente E; Cheung, Michael; Wheeler, David C; Winkelmayer, Wolfgang C

2017-10-01

Rare kidney diseases encompass at least 150 different conditions, most of which are inherited. Although individual rare kidney diseases raise specific issues, as a group these rare diseases can have overlapping challenges in diagnosis and treatment. These challenges include small numbers of affected patients, unidentified causes of disease, lack of biomarkers for monitoring disease progression, and need for complex care. To address common clinical and patient issues among rare kidney diseases, the KDIGO Controversies Conference entitled, Common Elements in Rare Kidney Diseases, brought together a panel of multidisciplinary clinical providers and patient advocates to address five central issues for rare kidney diseases. These issues encompassed diagnostic challenges, management of kidney functional decline and progression of chronic kidney disease, challenges in clinical study design, translation of advances in research to clinical care, and provision of practical and integrated patient support. Thus, by a process of consensus, guidance for addressing these challenges was developed and is presented here. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Pathogenesis of renal failure in multiple myeloma: any role of contrast media?

PubMed

Mussap, Michele; Merlini, Giampaolo

2014-01-01

The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function.

Biodegradable nanoparticles for improved kidney bioavailability of rhein: preparation, characterization, plasma, and kidney pharmacokinetics.

PubMed

Wei, Yinghui; Luo, Xiaoting; Guan, Jiani; Ma, Jianping; Zhong, Yicong; Luo, Jingwen; Li, Fanzhu

2017-11-01

The aim of this work is to develop biodegradable nanoparticles for improved kidney bioavailability of rhein (RH). RH-loaded nanoparticles were prepared using an emulsification solvent evaporation method and fully characterized by several techniques. Kidney pharmacokinetics was assessed by implanting a microdialysis probe in rat's kidney cortex. Blood samples were simultaneously collected (via femoral artery) for assessing plasma pharmacokinetics. Optimized nanoparticles were small, with a mean particle size of 132.6 ± 5.95 nm, and homogeneously dispersed. The charge on the particles was nearly zero, the encapsulation efficiency was 62.71 ± 3.02%, and the drug loading was 1.56 ± 0.15%. In vitro release of RH from the nanoparticles showed an initial burst release followed by a sustained release. Plasma and kidney pharmacokinetics showed that encapsulation of RH into nanoparticles significantly increased its kidney bioavailability (AUC kidney /AUC plasma  = 0.586 ± 0.072), clearly indicating that nanoparticles are a promising strategy for kidney drug delivery.

Kidney Stones as an Underrecognized Clinical Sign in Pediatric Cushing Disease.

PubMed

Rahman, Sara H; Papadakis, Georgios Z; Keil, Margaret F; Faucz, Fabio R; Lodish, Maya B; Stratakis, Constantine A

2016-03-01

To investigate the prevalence of kidney stones in a population of children with Cushing disease (CD) and to compare it with the prevalence of kidney stones in healthy children. Clinical and biochemical data from 139 pediatric patients with CD (68 females, 71 males) were analyzed retrospectively. Computed tomography scans were reviewed for kidney stones. Among 139 patients, 27 with CD (19.4%) had either radiographic evidence and/or a history of kidney stones. Those with kidney stones had higher urine free cortisol (P = .008) and transsphenoidal surgery at an older age (P = .007). The average urinary calcium/creatinine ratio was elevated in patients with CD (0.22 ± 0.11). The prevalence of kidney stones was higher in children with CD than in normal children (19.42% vs 1.0%; P < .001). Our results illustrate that kidney stones are an underestimated complication of pediatric CD, especially when compared with the prevalence of nephrolithiasis in the general pediatric population. Long-term consequences for kidney function are not known and need to be studied. Published by Elsevier Inc.

[Outcome of living kidney donors for transplantation].

PubMed

Lanot, Antoine; Bouvier, Nicolas; Chatelet, Valérie; Lecouf, Angélique; Tillou, Xavier; Hurault de Ligny, Bruno

2017-11-01

Nowadays, several treatments exist to treat terminal chronic renal failure. Best results for the recipients are obtained with kidney transplantation concerning mortality and quality of life. Transplantation is also the cheaper option for society. Living kidney donation raises the issue of the becoming of the donor, an absolutely healthy subject who gets to a surgical procedure. The becoming of living kidney donors has been compared with the one of controls subjects in several studies. The evaluations focused on the complications of nephrectomy in the short and long-term: kidney failure, hypertension, proteinuria, possibility of pregnancy, quality of life, and mortality. The first results did not show any risk linked to kidney donation, compared to general population. However, since 2013, kidney donors were found at higher risk for kidney failure and even for mortality, compared with controls selected like donor candidates. The risk of kidney donation is nevertheless acceptable and minimal, on the condition of rigorous selection of candidates and regular follow-up. Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.